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Bacteria     Virus          Fungus       Parasites              [Quick Tables]                           

 

 

Bacteria

 

Gram Positives   

Staphylococcus (MRSA), Streptococcus, Pneumococcus, Enterococcus, Corynebacteria

Listeria, E. rhusiopathae

 

Gram Negatives 

Bacillus (B. anthracis, B. cereus), N. gonorrhea, N. meningitis

 

Anaerobes  GPR:   Clostridium (C. perfringens, C. botulinum, C. tetani, C. difficile)

Actinomyces, Proprionibacterium, Lactobacillus, Eubacterium

GNR:  Bacteroides, Prevotela, Fusobacterium

Other:   Veillonella (GNC), Peptostreptococcus (GPC)

 

Enteric                     E. Coli, Shigella, Salmonella, Klebsiella, Vibrio, Campylobacter, H. pylori

SPACE

 

Pneumonia             GNCB – H. influenza et al, B. pertussis, Pseudomonas, Legionella

Chlamydia, Mycoplasma, HACEK

AFB - M. tuberculosis, M. avium, other AFB, Actinomyces, Nocardia

 

Zoonotic                  Francisella, Brucella, Yersinia, Pasteurella, Rickettsia, Coxiella, Ehrlichia, Bartonella, Mycoplasma, Borrelia, Leptospira

 

STD                          Syphilis, Chlamydia, Mycoplasma, HSV

 

Other Bacteria

 

Fungus

 

Superficial                              T. versicolor, dermatophytes

Subcutaneous

Systemic                                 coccidioides, histoplasma, blastomyces, paracoccidioides

Opportunistic             Candida, Cryptococcus, Aspergillus, Zygomycetes, PCP

 

Virus

 

HIV/AIDS

Respiratory                            RSV, influenza, parainfluenza, rhinovirus, coronavirus, adenovirus

Childhood Exanthems            measles, mumps, rubella, roseola, chicken pox

Hepatitis [A, B, C, D, E]

Diarrhea

Herpes                                    HSV, VZV, EBV, CMV)

Zoonotic                                  EEE, WEE, hemorrhagic fevers, rabies

 

Tumor Viruses           Other virus

 

Parasites

 

Protozoa                      Giardia, Isospora, Cryptosporidium, Toxoplasma, Plasmodium (malaria), Trichomonas

Nematodes                 Ascaris, Strongyloides, CLM, VLM, Echinococcus

                                    Tapeworms: Beef, Pork, Fish, Dog

Trematodes                Schistosomiasis

 

Insects

 

·          Case Presentations from Johns Hopkins Infectious Diseases

 

 

Gram Positives

 

Staphylococcus

Treatment: nafcillin/oxacillin, amp/sul, vancomycin, doxycycline, clindamycin, fluoroquinolones, cephalosporins (more 1st), bactrim

 

S. aureus        

Labs: B-hemolysis, catalase + / hemolysin, coagulase / protein A (binds Fc-Ig, hinders C3b opsonization)

Diseases:

 

Abscesses

            Stop reading this and go drain that M-F / can cause hot or cold (indolent) abscesses

 

Impetigo [pic]

 

Scalded skin (Ritter’s) [pic] [pic]

usually < 5 yrs, extreme tenderness, Nikolsky’s sign (involved and uninvolved skin), usu. spares oral mucosa, recovery without scarring, differentiate from TEN

exfoliative toxins A and B, cultures negative, superficial split in granular layer

 

Toxic Shock Syndrome (TSS) [pic] [pic]

300 cases/yr / ½ from females/tampons / can also be caused by Group A strep

Micro: superantigen, IL-1,2 / TSST 1 similar to enterotoxin B and C (occurs in 20% of S. aureus)

Presentation: fever, vomiting, diarrhea, diffuse erythroderma with desquamation (7-10 d), non-purulent conjunctivitis, hyperemia of mucosal surfaces, myalgia

Rash: almost always seen within first 24 hrs, purpural lesions can even look like RMSF, meningococcemia, cleavage pattern of lesions differentiates from ?strep SS and other causes

Complications: abnormalities of 3 or more organ systems including rhabdomyolysis, encephalopathy, azotemia, elevated ALT/AST, thrombocytopenia

Ddx: TSS from Group A (rarely B) Strep, RMSF, meningococcemia, EM, others

Treatment: anti-staph B-lactams (nafcillin or possible vancomycin until negative nasal swab for MRSA is obtained) and clindamycin for “eagle effect” (large number of organisms reach a slowed growth curve and this lack of cell division necessitates use of anti-anabolic agent such as clindamycin

Supportive: IV fluids and management of sepsis / ?vancomycin for MRSA strains?

Surgical debridement/drainage of any obvious source

 

Pneumonia

            recovery 3-6 wks / CXR resolution by 3-6 months

 

Food poisoning

preformed toxin, 2 hrs / Pappasito’s Mexican restaurant

 

Bacteremia

must treat 4-6 wks (with positive cultures) unless you have an obvious source that is quickly removed (see Harrison’s) – otherwise the infection may recur later as endocarditis et al.

 

Osteomyelitis (see other)

 

Endocarditis (see other)

 

Arthritis

 

MRSA (methicillin resistant Staph aureus)

            Current thinking is that nasal carriage predicts MRSA infection / A nasal swab can help

determine whether a person is colonized with MRSA, and guide empiric abx coverage for

presumed or culture-negative S. aureus infection (i.e. if nasal swab is positive, you need to use vancomycin) / it follows that contact precautions may not be all that useful to prevent transmission

Treatment: vancomycin, linezolid, synercid, (sometimes, if sensitive, rifampin, bactrim) / quinolones and carbapenems not effective on MRSA

Note: you can usu. trust sensitivities (e.g. if it says bactrim sensitive, you can use bactrim)

                       

S. epidermidis

catalase +

protective slime / adherent slime / line or device related

 

S. saprophyticus

catalase +

UTI in young women / more resistant

 

S. hemolyticus

more resistant

 

Streptococcus

GP diplococci

 

Strep pyogenes (Group A)

Micro: catalase negative, B-hemolysis, bacitracin (A disc) / M protein for attachment (anti-M is protective) / anti-phagocytic

Diseases: impetigo, cellulitis (erysipelas), pharyngitis, tonsillitis, purpural sepsis, TSS (exotoxin), necrotizing fasciitis/myositis, scalded skin, septic joint (via transient bacteremia, culture from blood and joint only ~66% sensitive), pyoderma, bacteremia

Reactive: scarlet fever (erythrogenic superAg), rheumatic fever (anti-ASO, streptolysin O), glomerulonephritis, reactive arthritis (not necessarily rheumatic fever)

Clinical: the lymphadenopathy of Staph and Strep infections usu. produces warn, red, tender nodes, but can be cold when the purulence is deep within the node

Treatment: Penicillins (and other)

 

S. agalactiae (Group B Strep)          

CAMP +,  B-hemolysis

mother to child via vaginal delivery / pneumonia, neonatal bacteremia, meningitis (esp. neonates), UTI

Treatment: ampicillin

 

Group C Strep

pharyngitis / bacteremia / endocarditis / (animals)

Treatment: same as Group A Strep

 

Enterococcus (Group D Strep)

Micro: g-hemolytic (non) / bile esculin /  PYR positive / 6.5 NaCl (not other group D)

Diseases:

·        Urinary

·        Biliary

·        Wound

·        Bacteremia

·        Endocarditis (for PCN allergic patients, some say linezolid not enough,)

Transmission: VRE is generally a nosocomial infection that is selected by prior antibiotic treatment (with vancomycin as well as other agents) and is not a community-acquired infection (people do get colonized by fecal matter contamination)

 

E. faecium

more commonly resistant to amp and vanc / also has endogenous anti-AG enzyme

E. faecalis

 

Treatment:    

 

VRE à linezolid and synercid / chloramphenicol, doxycycline may have

some efficacy /evernimycin and daptomycin also in clinical trials?

 

Non VRE à ampicillin for simple infection / amp + gentamicin for severe infection

 

·        Aminoglycoside resistance

both sp. / high level resistance to gentamicin predicts resistance to all others (except not necessarily streptomycin) / sometimes, Enterococci can have an enzyme that chews up all AG’s except gentamicin

·        B-lactamase

only E. faecalis (and but one strain of E. faecium)

·        Penicillin resistance

altered/over-production of PBP’s – both sp. / note: if resistant to one B-lactam via altered PBP’s, then it’s usually resistant to all of them

 

Note: Do Not trust all sensitivities (e.g. never use bactrim even if it says you can, but on the other hand, I have seen some ID people say nitrofurantoin is okay if listed as sensitive) / Note: imipenem does not have enough activity to treat Enterococcal bacteremia

 

Note on aminoglycosides: some data suggests gentamicin is actually more synergistic than other AG’s (e.g. tobramycin) against Enterococcus

 

Note on ampicillin resistance: if MIC at 64 ug/ml, and you don’t have access to linezolid, there are reports of using 18-30 g amp a day (to reach 100-150 ug/ml), plus gent and achieving success

 

Group G Strep

pharyngitis / puerperal sepsis / bacteremia, endocarditis

 

S. pneumoniae (Pneumococcus)

Micro: optochinin (P disc) / capsule (positive quelling reaction), pneumolysin, a-hemolysis

Diseases: otitis media, pneumonia (rusty sputum), bacteremia (sepsis with anemia), meningitis

type 3 is most severe (can produce abscess, pleural effusion)

Clinical: 30% become bacteremic (can cause dry gangrene [pic])

Diagnosis: culture from sputum, ear, blood (sensitivity ~50%), CSF, sinus / serum PCR may be coming soon

Treatment:

·        Pneumonia: ceftriaxone or cefotaxime or cefepime / levofloxacin or  moxifloxicin / vanc +/- rifampin

Note: macrolides actually are active against pneumococcus, the issues is that they may be more active in tissue, and not provide adequate blood/CSF coverage (given high propensity of Pneumococcus toward bacteremia)

·        Meningitis: must get CSF levels > 10 x MIC / ceftriaxone 2 g q 12

Resistance [NEJM]

Note: about ⅓ are resistant to penicillins (altered penicillin binding proteins), of these, some are also resistant to 3rd generation cephalosporins (15%), bactrim (30%), meropenem (15%) and erythromycin (15%) / pen sensitivity is not related to sensitivity of cipro (4%), rifampin (1%), chloramphenicol (3%)

Course: improvement in 1-2 days (up to 7 in elderly) / asplenic patients have mortality up to 45%

Vaccine available

Note: the vaccine is effective against many MDR strains (but not all ~12)

 

S. viridans

Micro: a-hemolysis / polysaccharides adhere

Diseases: endocarditis, dental carries, bacteremia

Treatment: penicillin (1st), erythromycin (2nd)

 

S. (deficient)  

satellite around S. aureus (need B6, L-cysteine)

Diseases: bacteremia, endocarditis

                                   

S. milleri        

grow in abscesses, blood, wound

 

Corynebacteria

 

C. diptheriae                          

Micro: GPR / H2S / Elek test / cat+ (tellurite med.) / “Chinese characters” / DT on B-phage (inactivates EF-2) / phospholipase D

Source: cutaneous colonization (humans reservoir)

Diseases: pseudomembranous pharyngitis with lymphadenopathy, Guillain-Barré syndrome, may cause exanthematous rash, DT causes myocarditis, paralysis of soft palate (common) and phrenic nerve (sometimes, requiring mechanical ventilation)

Note: Corynebacterium is often a contaminant of blood cultures

Treatment: macrolides / anti-toxin available for DT 

           

C. ulcerans                

diptheroids are commensal for skin, pharynx, urethra / causes mild infection

 

C. jeikeium    

nosocomial infections    / bacteremia, endocarditis / use vancomycin

 

Other GPR

 

Listeria monocytogenes       

Micro: GPR, tumbling motility, catalase + / slight B-hemolysis / internalin, LLO, PLA

can multiply at low temperatures / intracellular (CMI) and extracellular growth

Source: food (dairy, deli meats), animals, human gut

Incubation: 2-6 weeks

Risk factors: elderly, diabetes, renal disease, immunocompromised

Diseases:

            Chorioamnionitis (usu. FUO in 3rd trimester)

Neonatal:          early onset (transmitted in utero) à granulomatosis infantisepticum

late onset (birth canal) à meningitis

Bacteremia: steroids, malignancy, AIDS

Meningitis: neutrophilic meningitis (CSF can be negative, but blood culture positive)

Rhombencephalits

Diagnosis: culture blood, amniotic fluid

Treatment: ampicillin (1st) (Listeria resistant to all cephalosporins) (can add aminoglycoside for synergy; but not rifampin which would decrease efficacy of ampicillin) or bactrim (2nd)

 

E. rhusiopathae         

Micro: GPR, catalase negative, H2S

Transmission: mammals, poultry, fish (Wailer’s granuloma) / wound or even oral entry

Diseases: painful violet lesion (common), septicemia, endocarditis, arthritis (less common)

 

Bacillus

 

B. anthracis - vaccine available [wiki]

Micro: capsule / animals / soil (spores) / EF, LF, PA / capsule on a different plasmid / endospores introduced into skin via abrasion, inhalation, ingestion then transported to lymph nodes (germination occurs in lymph nodes; then bacteremia)

·        cutaneous anthrax (caused by handling infected animals, wool, hides, bioterrorism): small papule at 3-5 days then black and necrotic over 1-2 days [pic][pic][pic][pic][pic][pic][pic][pic] / 20% mortality if untreated (otherwise can be self-limited) / can biopsy and see gram-positive rods

Ddx: ecythema gangrenosum (Pseudomonas), brown recluse spider, plague

Treatment: quinolones (recommended but might not be required)

·        respiratory anthrax (bioterrorism)

will progress to sepsis and cardiovascular collapse in 24-48 hrs if not recognized and treated early

Diagnosis: widened mediastinum on CXR, bilateral infiltrates and effusions (which are hemorrhagic on thoracentesis)

Treatment: can use ciprofloxacin, doxycycline plus rifampin, clindamycin but because spores can persist a long time, recommended treatment is doxycycline100 mg bid for 60 days

·        GI / oropharyngeal

Prevention: vaccine available

 

B. cereus                   

motile, no capsule, ubiquitous / food poisoning (LT) (toxin-mediated disease occurs when heat-resistant spores germinate after boiling; re-cooking before serving may not destroy spores) / emetic illness within 6 hrs of eating, self-limited / heat-stabile (pyogenic)

opportunistic infections (rare)

 

Neisseria sp.

                                                                               

Neisseria gonorrhoeae         

Microbiology: GNR / diplococci / oxidase +, speciate with fermentation, chocolate agar with CO2 / Thayer-Martin media (inhibits normal flora) / Pili (attach/invade), OPA1 (adhere), LOS (endotoxin/core variability) / switches from invade to evade / OMP1 (endocytosis) / IgA protease

Diseases: urethritis, cervicitis, pharyngitis (from oral sex), anorectal, PID, septic arthritis, disseminated, bacteremia (IV drug users)

Transmission:

Females à male 25% (infected women are often asymptomatic)

Male à female 75%

Incubation: 2-7 days  

Presentation:

·        arthritis/dermatitis (biphasic illness)

        • constitutional and migratory arthritis usu. upper extremities (knee, shoulder, wrist, hand), tenosynovitis, vesiculopustular skin lesions
        • may abate or progress to purulent mono or polyarticular septic arthritis

·        causes vaginitis rather than arthritis in prepubertal females (discharge, bleeding, pelvic pain, dysuria)

·        causes increased burning/discharge rather than hematuria/retention in males

·        meningitis

·        osteomyelitis

·        conjunctivitis (neonatal)

Diagnosis: blood culture (if disseminated, positive in 50%; usu. only early on), culture of joint usually negative (may be positive late), but gram stain and/or culture (tell lab to use T-M media) of other areas (cervix, urethra, rectum, throat, skin lesions) may be positive // DNA probe // endocervical culture is 80-90% sensitive / test for syphilis and HIV also

Treatment: ceftriaxone 125 mg IM single dose or cefixime 400 mg PO x 1 or doxycycline

100 mg PO bid x 7 d or ciprofloxacin 500 mg PO x1 or ofloxacin 400 mg PO x1

Note: always cover for possible co-existing chlamydia (doxycycline); reverse not true, pts diagnosed with chlamydia do not have to be covered for Neisseria

Note: all newborns (regardless of status of mother) get silver nitrate ointment one time; conjunctivitis would occur day 2-5 (if drops not given); if newborn emerges with conjunctivitis, it is most likely not Neisseria (too soon)

 

Disseminated Gonococcal infection

Presentation: fever, rash (~nodular) [pic], endocarditis, hepatosplenomegaly / suspect compliment deficiency in chronic cases / females can be chronic carriers

Diagnosis: can culture from synovial fluid (usually not skin) [use normal media]

Treatment IV cephalosporins

           

 

Neisseria meningitidis           -vaccine available

GNR, 13 serogroups, CSF (high WBC, low glucose) / pilus, IgA protease, capsule / endotoxin / 5-15% are upper respiratory carriers (humans only reservoir)

      • bacteremia (may cause DIC)
      • meningitis (mostly children, due to lack of Ab’s) / case fatality rate 13% / ⅓ o ½ with permanent CNS sequelae

Treatment: high-dose ceftriaxone or penicillin G

·        chemoprevention for all contacts with rifampin or sulfonamide (about 2-3 days for at risk family members)        

Vaccine available (recommended for college dormitories and military)

 

Meningococcemia – rapidly progressive

subgroup B causes most of outbreaks (not covered by vaccine)

autoimmune disease predisposes patients to meningococcal infection

 

 

Anaerobes

-SC fatty acids / no sputum / analysis by GLC / E strips to get MIC (Kirby-Bauer gives false positives)

 

Gram Positive Rods (spores)

 

Clostridium                

 

C. perfringens           

GPR in pus, double zone of hemolysis / soil, intestinal tract / alpha toxin or enterotoxin

gas gangrene, food poisoning, sepsis (hemolytic anemia)

Risk factors for sepsis: septic abortion, diseased biliary tree, traumatic wound infections, cancer, leukemia, endocarditis, GI AV malformations, or the NEC of newborn

Treatment: new B-lactams (large doses), clindamycin, metronidazole, chloramphenicol (careful of aplastic crisis)

 

Gastroenteritis

classic food poisoning (incubation 8 to 24 hours)

preformed toxin of C. perfringens / meats, stew, hash

Presentation: gastric pain, watery diarrhea, no vomiting (unlike B. cereus)

 

Enteritis necroticans (pigbel)

Beta toxin of C. perfringens / high protein meal with trypsin inhibitors (sweet potatoes) in a

host with limited proteolytic activity in intestine

Presentation: acute abdominal pain, bloody diarrhea, vomiting, peritonitis

Complications: small intestine ulcerations

 

C. botulinum  

Source: ubiquitous soil, home canned foods (vegetables, fruit, occ. meat or fish), outbreaks (baked potatoes, day-old stew)

Diseases:

Food-borne: ingestion of toxin à mild gastroenteritis (nausea, vomiting, abdominal pain) / incubation for 18-36 hrs / cranial nerves (blurred or double vision, voice changes) then symmetric descending paralysis, then respiratory failure

Infant botulism from honey (spores germinate in the intestine) causes floppy baby

Wound botulism (rare, 10 day incubation, same disease as food-borne, often from IVDA and intranasal cocaine)

Mechanism: LT neurotoxins A-G (only A,B,E cause human illness) / neurotoxin enters spread hematogenously to cholinergic nerve terminals, NMJ, and ganglia, internalized into neurons, inhibit release of acetylcholine / CNS not involved

Note: toxin is inactivated by cooking    

Presentation: dilated pupils / repetitive nerve stimulation gives incremental response

Diagnosis: detect toxin or organism in stool or blood

Ddx: GBS, Lambert-Eaton, polymyositis, tick paralysis, diptheria, chemical intoxication

Treatment: Trivalent horse anti-toxin (made in Los Angeles and Atlanta only) must be given immediately; in absence of ileus, cathartics should be given to purge toxin (GI lavage only if recent ingestion); antibiotics only if ongoing activate infection (not solely toxin)

Course: 20% mortality or self-remission by 1 week

 

C. tetani

Micro: anaerobic GPR, spore forming (tennis racket)

Source: ubiquitous, soil and feces

Epidemiology: 50 cases/yr, non-immunized

Mechanism: retrograde transport along peripheral motor neuron to brainstem and spinal cord, toxin blocks release of GABA, suppresses glycine release in motor nuclei causing lockjaw (trismus), spasms [pic]

Diseases:

Generalized: onset~7 days / trismus, then shoulders/back, then abdomen/limbs / risus sardonicus, opisthotonos, ANS dysfunction

Neonatal: unsterile treatment of umbilical cord stump / generalized spasms in first two weeks of life IP

Local

Diagnosis: clinical / serum antitoxin levels ( > 0.01 is protective, and also rules out Tetanus)

Treatment: tetanus immune globulin (TIG) / flagyl (penicillin is 2nd line as it may antagonize GABA) / BZ for spasms, supportive care (tracheostomy, quiet room)

vaccine available

 

C. difficile

pseudomembranous colitis or C. difficile associated diarrhea (CDAD) / can happen with even one dose / wide range of severity / 50% of people are carriers of non-toxin producing strain (geographical component)

Presentation: frequent, loose, foul-smelling stools, abdominal cramps / can have some blood, but usually not frank hematochezia / fever usually low-grade (can be high) /

Prevalence: 3% of healthy adults are colonized; 20-40% of hospital patients are colonized

Diagnosis:

·        cytotoxin A or B (in stool) / very insensitive; requires multiple samples

·        fecal leukocytes (usually positive)

·        flexible sigmoidoscopy [pic][pic] (can miss only proximal lesions; 10% of cases spare rectum; 50% have pseudomembranes in colon)

Complications: loss of fluids, albumin, electrolytes / can get polyarthritis (rare) / osteomyelitis (nosocomial) / watch out for toxic megacolon with perforation

Treatment: Guidelines from the American College of Gastroenterology

·        PO or IV metronidazole 250 mg qid for 10 days (I say 14-21)

·        PO (not IV) vancomycin (trend now is to use PO vancomycin 1st line if possible 9/06) / some studies show benefit of adding rifampin

·        NEW tactic to prevent relapse: follow initial CDAD treatment with 2 wk “chaser” course of rifaximin

·        if possible avoid/stop antibiotics active against normal GI flora (of course, GNR coverage will be necessary if patient does perforate)

·        replace fluid and electrolyte losses, avoid antiperistaltic agents (duh!)

·        some advocate cholestyramine or colestipol to attempt to bind toxin in gut

Note: relapse is treated with same agents (resistance is not the issue, but perhaps ½ of relapse is with different strains)

Note: do not treat asymptomatic patients colonized with C. difficile

Course: mortality 5-10% of those affected / should improve within 48-72 hrs but relapse is common (5-15%), often occurs early, risk factors: age, surgery, leukocytosis, CRF, females, spring time infection / how to prevent relapse/recurrence (always under investigation)

Note: patient needs to be in contact isolation

Note: North American isolate is emerging 9/06 à more virulent, responds better to PO vancomycin (recommendation now is to change if 2 days metronidazole does not show improvement)

 

C. septicum

 

Suppurative deep tissue infections

·        Intraabdominal abscess, frostbite and gas gangrene, stump infection

·        Female genital tract, especially pelvic abscess

·        Emphysematous cholecystitis

 

Skin and soft tissue infection

·        Wound contamination (no antibiotic treatment needed)

·        Cellulitis (heroin addicts)

·        Fasciitis (rapid progression, massive hemolysis due to toxin)

·        Myonecrosis (gas gangrene) needs surgery

 

Bacteremia

·        C. perfringens bacteremia usually transient and benign / look for other predisposing factors or illness elsewhere

·        C. septicum bacteremia associated with intestinal malignancy (like S. Bovis)

·        primary pathogen of neutropenic enterocolitis

 

Diagnosis: culture and clinical findings / X-rays showing gas

Treatment: PCN plus clindamycin / surgery / hyperbaric oxygen

 

Gram Positive Rods

 

Actinomyces                oral, GI, soil

Proprionibacterium    skin flora         

Lactobacillus               vaginal flora

Eubacterium               colon

 

Gram Negative Rods

 

Bacteroides fragilis   

colon / B-lactamase

abscesses in peritoneum / endometritis

Micro:  bile / safety pin appearance / SOD / catalase +

Treatment: new B-lactams (pip/tazo, meropenem, cefotetan, cefoxitin), clindamycin, flagyl, chloramphenicol

           

Prevotela                   

Vitamin K and hemin

oral / aspiration pneumonia / B-lactamase     

 

Fusobacterium necrophorum

needleshape morphology [pic] / oral / lysis tubes help for culture / aspiration pneumonia / same + penicillin G       

 

leukocidin, hemolysin, platelet aggregation

 

Lemmiere syndrome (also Prevotela, Peptostreptococcus, Eikenella) (see other)

 

Gram Negative Cocci

 

Veillonella                 

gram stain/failure to grow

abscesses from aspiration or trauma / URI, GI, GU

            Treatment: penicillin G, etc.      

                                   

Gram Positive Cocci

 

Peptostreptococcus   

gram stain/failure to grow

abscesses from oral, skin, GI, GU

            cannot use penicillin G if B. fragilis is present

metronidazole not effective

 

 

Gram Negatives

 

 

Enterobacteriaceae

 

Lactose fermentation: this information is useful because it may come back before the actual species/susceptibilities are determined

non lactose fermentors (Shigella, Salmonella)

lactose fermentors (E. coli, Klebsiella, SPACE bugs)

-MacConkey selects enteric bugs with bile salts/gram negative/lactose + turn pink (less pathogenic)

-APE tests color change/gas production

-serotyping below species level - O cell wall / H flagellar / K capsular

 -resistance unpredictable / K1 causes neonatal meningitis / oxidase - / catalase -

 -virulence factors: endotoxin, capsule, phase variation, exotoxins, adhesion factors, growth factors, resistance, antibiotic resistance plasmids

 

Shigella

Pathology: large intestine, non-motile, does not penetrate beyond epithelium / intra/extracellular replication

Epidemiology: humans are the only reservoir / very low ID50 (only need a tiny amount)

Course: 1-4 days incubation / severe febrile illness, bloody diarrhea / can cause tenesmus in distal colon

Complications:

·        Hemolytic Uremic Syndrome (HUS), Seizures (produces a neurotoxin), Toxic Encephalopathy (rare, rapid, watch for headaches), Ekari syndrome (overwhelming shock and collapse, unrelated to fluid loss, toxin-mediated)

·        Toxic megacolon

·        Reiter’s (HLA B27, more in adults than children & more common than reactive arthritis)

·        Vaginitis

·        chronic diarrhea with malnutrition (less in US)

Labs:   serum chemistries, low CO2, acidotic, low bicarbonate

CBC with differential (often produces bandemia)

Fecal leukocytes – may get false negatives

Fecal Blood – watery then bloody or always bloody

Stool culture – rectal swab, 50% positive

Treatment: must be careful with anti-motility agents – in adults, they can relieve cramps when given with antibiotics (just be careful not to give with C. difficile) / and do not give them without antibiotics / rehydration, TMP-SMX (some resistance), Suprax (cefixime), ceftriaxone, quinolones

 

Shigella dysenteriae

Shiga toxin (neurotoxin) / most severe disease / more in developing countries

 

Shigella sonnei (causes most shigellosis in U.S.)

 

S. flexneri (Africa)

Sensitive to ciprofloxacin, ceftazidime, cefotaxime, cefoxitin / one study of resistance to ampicillin (82%), chloramphenicol (73%), tetracycline (97%), co-trimoxazole (88%)

 

S. boydii

 

Salmonella

 

Lab: stool culture, motile, lac-, suc-, H2S                     

Transmission: fecal-oral, uncooked meat and dairy products (high ID50), pet rodents

Pathology: invade mucosa / gastroenteritis, even bacteremia

Clinical: leukopenia, bradycardia (or relative bradycardia)

Complications: meningitis, arthritis, osteomyelitis (sickle cell patients), infect aneurysms

Treatment: antibiotics may prolong carrier state (only treat systemic infections)

           

Salmonella (non-typhoid)

More in children, animal reservoir, sanitation, summer peaks, food-borne, infectious dose is high, gastric acidity is protective

Note: immunocompromised (HIV, sickle, cancer) more likely to become bacteremic (often without GI symptoms)

Treatment: usually self-limiting in adults, antibiotics, other?

 

S. typhi

travel outside US

Mechanism: invasive, survives in phagocytes, proliferation in Peyer’s patches, transient bacteremia, seeding of RES/distant sites

Diseases: enteric fever (rose spots on lower chest, abdomen) / chronic carrier in biliary tract

Presentation: usually presents as fever of unknown origin (FUO)

Labs: transient positive stool cultures

Treatment: chloramphenicol / ampicillin / TMP/SMX

 

S. enteritica (serotype Typhimurium) (same thing as below?)

Transmission by human-human, and pet rodents [NEJM]

May have multidrug resistance

 

S. enteritidis

                        milder version / can also seed bloodstream

·        Study à azithromycin, cefixime not that useful for uncomplicated S. enteritidis

·        quinolones and new macrolides might be useful

 

 

S. choleraesuis

most common cause of septicemia

Treatment: chloramphenicol, ampicillin, TMP/SMX                

           

E. Coli

 

most common cause of UTI / K1 neonatal meningitis / GN septicemia (ceftriaxone?)

Treatment (except EHEC): ampicillin (60-70%), amp/sul (80%), cipro, cephs, all broad spectrum B-lactams, TMP/SMX

Note: some E. coli strains can get pretty nasty and even require carbapenems

 

EHEC Hemorrhagic (large intestine, distal ileum)

0157:H7 / verotoxin (Shiga-like STx 1 or 2 – blocks EF-1 binding 60s), EHEC-hemolysin, heat-stabile enterotoxin / A & E lesions

Transmission: fast food burgers, beef products, raw milk, fecal-oral

Course: 4 days after exposure (range 1 to 8 d), watery diarrhea, intense abdominal pain, followed 1-2 days later by bloody diarrhea, fever is not prominent, 3-10 day resolution, infectious shedding (up to 3 weeks)

Complications: Hemolytic Uremic Syndrome (HUS) (5-10%, mostly < 5 yrs) (circulating toxin)

Treatment: some think patients with bloody diarrhea are put at increased risk for HUS with abx (i.e. don’t treat with antibiotics)

 

ETEC Toxic (small intestine)   

CFA Pili / heat-stable (ST, cGMP) and heat-labile, cholera-like (LT, cAMP) / strains may have one (less severe) or both plasmids (most severe diarrhea)

Course: profuse, watery diarrhea // commonly causes post-infectious irritable bowel syndrome (occurs in 10% of ETEC cases during 6 months following)

Montezuma’s/Traveler’s Diarrhea (immunity to develops to CFA and LT)

primary cause of infant diarrhea / fever is not prominent

Prevention: rifaximin prophylaxis reduced incidence by 5x

Treatment: rehydration therapy, TMP/SMX (bactrim) or quinolones

 

EPEC Pathogenic (small intestine)

foes not have pili / BFP and intimin (homologs in Yersinia, EHEC, etc.)

A & E lesions cause watery diarrhea, fever (sometimes) (usually self-limiting, chronic in infants)

Nursery outbreaks / childhood diarrhea in developing countries

Treatment: TMP/SMX (bactrim) or quinolones

 

EIEC Invasive (large intestine)           

Facultative intracellular/endocytosis causes inflammation, ulceration, necrosis

Similar but less severe than Shigella (mostly in children under 5 yrs) / fever +

Treatment: TMP/SMX (bactrim) or quinolones

           

EAEG Aggregative

Watery diarrhea, epidemics, prolonged diarrhea, developing countries

           

Klebsiella pneumoniae

Micro: non-motile,  lactose + / encapsulated (India ink) / intestinal flora

Diseases: 3% of acute pneumonias / 2nd leading cause of UTI / more in infants, elderly,  alcoholics, immunocompromised

·        Friedländer's pneumonia: upper lobes, currant jelly sputum, early to abscess, rapid decline

Treatment: very important, depends on whether organism has ESBL (extended spectrum b-lactamase) gene / if so, the in vitro sensitivity to cephalosporins will be misleading, and no cephalosporin will be effective / in these cases, the drug of choice is meropenem/imipenem and possibly double coverage with a quinolone / in non-ESBL strains, one might get by with amp/sul (80%), cipro, carbapenems

 

Klebsiella oxytoca

being studied as potential causative organism in C. difficile-negative cases of antibiotic-associated colitis 11/06

 

SPACE Bugs and friends

 

·        intestinal flora that cause nosocomial infections (IV lines, etc.)

·        must be treated with 2 antibiotics such as a cephalosporin (cefepime) + aminoglycoside (GM or tobramycin)

 

Serratia

Proteus

Acinetobacter

Citrobacter      

Enterobacter

 

 

Serratia          

often MDR  to penicillins, cephalosporins and aminoglycosides

Treatment: amikacin, newer B-lactams, quinolones

 

Proteus          

            10% of uncomplicated UTI’s / also produces urease, which raises pH and produces Struvite

stones or “staghorn calculi”

diseases: UTI, wound infection, septicemia

Treatment: amikacin, newer B-lactams, quinolones

 

Acinetobacter

Extremely rare cause of community-acquired pneumonia (associated with bacteremia) / nosocomial acinetobacter pneumonia is not associated with bacteremia

 

Citrobacter    

enteric flora, causing opportunistic infections (not diarrhea) / citrobacter can often cause brain abscesses associated with neonatal meningitis

 

Enterobacter

Must hit 2 different targets to treat this very resistant organism (must have synergy)

Cell wall: cefepime (not the others: you cannot use 3rd generation cephalosporins no matter what

the c/s says because they will turn on the genes during therapy, under pressure), tic/sul, pip/tazo,

aztreonam, meropenem, ?vancomycin

            Protein synthesis: AG gentamicin, tobramycin, amikacin (less chance of AG resistance),

streptomycin

Others: can use bactrim and cipro if c/s reads sensitive

            Rifampin?

 

Providencia

            Common cause of catheter associated UTI’s (nosocomial UTIs)

            does not produce uricase, most resistant to antibiotics /

 

Morganella

 

Vibrios

gram negative, oxidase +, facultative anaerobes, marine

single polar flagellum vs. peritrichous (E. coli, Salmonella)

 

Vibrio cholerae 01

Micro: grow in 0-1% NaCl, yellow colonies, sucrose + on TCBS

non-invasive, often no fever, 8-72 hr incubation, severity depends on host

Toxin: LT-like choleratoxin (ADP-rib. of Gs)

Treatment: oral rehydration / maybe tetracycline / vaccine promising   

                                                                       

V. parahaemolyticus

~ invasive / halophilic, seafood / enterotoxin, 5-24 hr incubation à watery or bloody diarrhea

 

V. vulnificus               

lac + / invasive / ingestion: fatal sepsis with liver disease (hemochromatosis), diabetes,

immunosuppressed / wound infection (gangrene) / mortality up to 50% in        

                                                                       

V. alginolyticus

septicemia or wound infection

 

V. damsela

Gulf Coast / toxin / may be rapidly fatal / septicemia or wound infection

 

Campylobacter          

microaerophilic, non-fermenting, non spore forming, not halophilic, 0.45 microns (tiny), grows at 45 degrees / highly antibiotic resistant

 

C. jejuni         

Source: GI tract of animals / often spread by undercooked meats (retail poultry >> beef) or direct contact with infected animals

Disease: similar to salmonella / usu. self-limited enteritis (watery or gross bloody stool; appears identical to IBD on biopsy) but can lead to bacteremia

Complications:

·        local suppurative infections (peritonitis, pancreatitis, endocarditis, cystitis, meningitis, septic arthritis)

·        1 in 1000 cases leads to GBS

·        recurrence in 5-10% of untreated patients (much more likely to be confused for chronic, relapsing case of IBD than other GI pathogens)

Diagnosis: clinical, culture from stool, fecal leukocytes (ETEC and viruses usu. do not have fecal WBC)

Treatment: clindamycin (1st) / often resistant to quinolones / sometimes bactrim can work (but often resistant to that too)

 

C. fetus          

found in sheep and cows / bacteremia in immunocompromised patients

resistant to humoral immunity                            

 

Helicobacter pylori (type 1)                                                                                                                   vaccine promising?

            GNR, spiral, microaerophilic / urease positive (breath test), attachment

            vac A (vaculating cytotoxin) / mostly asymptomatic / host response damages tissue

            gastritis, peptic and duodenal ulcers / may lead to carcinomas, lymphomas 

            Treatment: tetracycline or amoxicillin, metronidazole, bismuth subsalicylates

 

            H. cinaedi

Causes gastroenteritis, bacteremia, soft-tissue infections, pericarditis/myocarditis / fecal-oral, well-water, hamsters / can be resistant to FQ and AG / likely sensitive to meropenem           

 

Haemophilus 

            GNCB, non-motile, oxidase +, facultative anaerobes, obligate parasites

            requires chocolate agar - hematin (factor X), NAD (factor V), and CO2 for growth

            use HMW1,2 and pili to adhere to epithelium / LPS / IgA protease / Hib has PRP capsule

            encapsulated: meningitis, conjunctivitis, epiglottitis, arthritis (last 3 maybe for other one)

            unencapsulated: otitis media (2nd to pneumococcus), sinusitis, pneumonia, bronchitis

 

H. influenza   

Vaccine widely used

causes purulent meningitis (children under 5), epiglottitis / most children are non-Hib carriers

T-cell immunity doesn’t work well until 18 months / maternal Ab’s work up to 2 mos.

PRP conjugate vaccine given > 2 months / prophylaxis with rifampicin

Treatment: cefotaxime

 

-H. ducreyi                  chancroid genital ulcers [pic]

-H. parainfluenzae      upper and lower respiratory infections

-H. haemolyticus         upper and lower respiratory infections

-H. aegyptius               conjunctivitis

 

Moraxella catarrhalis

GNC / otitis media in children / typical pneumonia in adults / common colonizer in chronic lung diseases (may consider pathogenic on sputum if WBC > 25 and epithelials < 10)

Treatment: cephalosporin or amp/AG

 

Bordetella pertussis (see pediatric ID)

GNCB, strict aerobe, non-motile, chocolate agar

A-B toxin (cAMP) / invasive AC, tracheal cytotoxin, dermonecrotic, LPS / adherence:

pili, Fha, pertactin / coordinated transcription (BvgS his kinase, BvgA response regulator)

colonize ciliated mucosal cells (humans only reservoir) / infection worst in infants (may be afebrile

3 stages: catarrhal 1-2 wks / paroxysmal (whooping cough) 2-4wks / convalescent                               

Labs: WBC 20-30 with high lymphocyte fraction

Acellular vaccine commonly used (DTaP)

Treatment helps only stage one (erythromycin 5-7 days)

           

Legionella

 

GNCB (maybe AFB), aerobic / multiply inside macrophage and lyse it (cell mediated immunity)

19 species / L. pneumophila (85 to 90% of cases), followed by L. micdadei (5 to 10%), then L. bozemanii and L. dumoffii

Transmission: water source, aerosolization / (not person-to-person) / late summer and early fall

RF: middle-aged man, smoking, alcohol, immunosuppression

Diseases:

1.      asymptomatic

2.      Pontiac fever: self-limited, flu-like illness without pneumonia

3.      Legionnaire’s disease (20% mortality) / pneumonia / 1-8% of community-acquired pneumonias that result in hospitalization / 4% of lethal nosocomial pneumonias / clue is pneumonia + GI symptoms

4.      rare localized soft tissue infections

Presentation: incubation: 2 to 10 days / prodromal phase (malaise, fever, headache, and myalgias, cough initially nonproductive, then mucoid)

More common: high fever (sometimes with relative bradycardia), and diarrhea is common (stool is guaiac negative and no fecal WBC)

Less common: altered mental status with confusion, lethargy, or delirium (normal LP)

Complications: bacteremia (38%) and can cause myocardial abscess

CXR: unilateral, patchy segmental or lobar alveolar infiltrate / can progress to bilateral with pleural effusions / occasional lung abscesses and multiple rounded densities suggesting septic emboli

Labs: WBC 10-15 / hyponatremia (more likely than other atypical pneumonias),  hypophosphatemia, and elevated ALT/AST / occasionally microscopic hematuria, sometimes with impaired renal function

Diagnosis: urine Ag (86% sensitivity, 99% specificity), BAL Assay (46% sensitivity)

1. urine Ag – remains positive long after treatment initiated, only detects serogroup 1 (80% of strains)

2. culture (may grow from any fluid collected, including blood) / 30-70% yield (must use BCYE agar)

3. direct immunofluorescent Ab stain of sputum, exudates (DFA staining is specific but not sensitive)

4. serology (4-fold rise, but usually it occurs already well into illness)

Course: 15% mortality (even with treatment) / slow convalescence of CXR

Treatment: fluoroquinolones or macrolide ?+/- rifampin / duration over 3 weeks / IV can be changed to oral after acute symptoms have resolved

 

Pseudomonas aureugenosa              

GNR, aerobe / lactose -, oxidase + / pyocyanin (blue-green pigment) / endotoxin A (EF-2)

Diseases: wound, burn, UTI, pneumonia (cystic fibrosis), osteomyelitis / sepsis (black? skin lesions) / hot tub folliculitis / external otitis (swimmer’s ear) – especially in older patients with DM

 

Ecythema gangrenosum

round/oval, 1 to 5 cm, raised halo/rim of erythema/induration surrounds central area, a vesicle that evolves into a necrotic ulcer / occurs in 5-20% of pseudomonal bacteremia (and also aeromonas and several other bacteria)

 

Treatment:

Cefepime + AG (+++ synergy) [probably the best for resistant strains]

Zosyn or Timentin + AG (++ synergy)

Ceftazidime/ceftriaxone + AG (+ synergy)

Meropenem [good coverage, ?synergy]

Ciprofloxacin [good if sensitive]

 

Aeromonas hydrophila

Myonecrosis / Sepsis / endocarditis

aeromonas / resistant to many antibiotics use quinolones

 

Stenotrophomonas maltophilia

            Nosocomial infection (pneumonia, UTI, wound infection, bacteremia)

Resistance: usually resistant to imipenem, pip/tazo

Treatment: drug of choice IV Bactrim, also ticarcillin/CA (Timentin)

 

Burkholderia pseudomallei

Causes melioidosis / water, soil in SE Asia, N. Australia, Central and S. America / can infect any organ, but most likely lungs / can be latent for months to years with reactivation in form of chronic pneumonitis

 

Burkholderia cepacia

opportunistic pathogen (cystic fibrosis, sickle cell, chronic granulomatous disease) / nosocomial outbreaks / may cause necrotizing pneumonia

                        Resistance: highly resistant to many B-lactams and AGs

                        Treatment: bactrim

 

Mycobacterium

 

Mycobacterium tuberculosis (MTB)                        [non-tuberculous mycobacteria]

 

Micro: slender AFB, non-motile, obligate aerobe / droplet nuclei in milk, wounds (rarely)

Pathology: 90% asymptomatic exposure / 90% active TB are reactivated cases (90% pulmonary)

MTb first settles mid/lower lung / may become walled off in apex of lung, bone, kidney, brain

Infectivity: not coughing reduces infectivity / takes about 1 month to become smear negative on 4 drug therapy (no differences in AIDS pts) / droplet precautions should be practiced / document negative sputum smears before moving out of isolation (hospital, work, half-way house)

Babies contacted at home given 3 months INH before completing work-up

Presentation:

·        fever, night sweats, malaise, weight loss, hemoptysis

·        pleural effusion (30% with negative PPD, most have spontaneous resolution, high eosinophils, low mesothelial cells)

·        Rasmussen aneurysm (rupture of dilated vessel in cavitary lesion)

·        systemic disease (arthritis, meningitis, rashes) (see disseminated)

Specific syndromes:

·        Primary Tb

·        Reactive Tb

·        Miliary Tb (disseminated Tb): 1-2 mm granulomas

·        Pott’s disease (spine): osteoarticular Tb usu. has radiographic changes

·        Scrofula (cervical nodes)

·        Reactive Tb: Poncet’s (arthritis) / organism not in joints

·        Adrenal tuberculosis: cause of primary adrenal insufficiency       

Labs: can have lymphopenia (which can be a true state of immunosuppression, just like AIDS), leukocytosis, anemia, hyponatremia (SIADH)

Diagnosis:

Culture: must have for definitive diagnosis (Zhiel-Neelson/Kinyoun) / granuloma formation may be prevented by immunosuppression / culture takes about 3 to 6 weeks

·        Note: new technique called MODS (microscopic-observation drug-susceptibility) only takes 7 days and has 97% sensitivity (but only available now in very specialized labs 10/06)

AFB stains for CSF have very low sensitivity / get as many early morning AFB samples as you can (as cultures may not grow) / beware of M. Saphrophytes from water, upper GI, urinary

PCR – low sensitivity / mainly useful to distinguish different mycobacterial sp. (not initial diagnosis) / check CSF, ascites, ?pleural effusion

ADA (enzyme) – elevated with Tb / check in CSF, ascites, ?pleural effusion, ?blood

CSF: 10-500 WBC / glucose 20-40 / protein 4000-5000

may have left shift early on and then lymphocyte predominance later (like viral)

Pleural effusion: 20-30% culture yield [leave some fluid in case you need to take a biopsy later, which has a 60% yield and 80% with multiple biopsies]

Skin Testing [pic] (Mantoux positive [pic] at):

        • ≥ 5 mm (HIV or immunocompromised or close contact)
        • ≥ 10 mm (at risk: diabetes, ESRD, blood disorders, IVDA, rapid weight loss)
        • ≥ 15 mm (normal)

Note: sarcoid, lymphoma, immunosuppression may cause anergy / up to 20% of cases may have negative skin testing even with normal immune system

Note: HIV converters have 15%/yr chance of developing Tb whereas normal is 3%/yr

Note: new test called IGRA may be better for detecting latent Tb (esp. in BCG-exposed patients)

CXR:  classical teaching is apical à recurrence and atypical à primary infection; however, the most important factor in CXR appearance is host immunity status

CT can help distinguish disseminated tuberculosis vs. lung metastases and diffuse interstitial diseases [CT] [CT]

            Ddx: M. kansasii, many others

Treatment: (see TB drugs)

Chemoprevention (for patients with positive PPD and no active disease): 6-12 months INH (some say treat all pts < 35 yrs with no contraindications to INH)

Active TB: INH + rifampin + PZA + ethambutol for 2 months then INH + rifampin for 4 months

Note: fever resolution at 1 week of treatment for regular TB (85%), MDR TB (50%), MAC (20%) / rapid defervescence does not rule out MDR strains

Resistance: growing (often occurs in people from TB prevalent countries) / treatment failure = positive cultures after 3 months or positive AFB stains after 5 months

 

Disseminated mycobacteria (as in HIV/AIDS)

Major cause of FUO in HIV/AIDS pts / Tb is more common in HIV as consequence of immunosuppression (not necessarily from co-infection and/or socioeconomic factors)

Presentation: lymphadenopathy, miliary Tb in lungs, mucosal ulcers

Note: microabscesses detected by high resolution but not conventional ultrasound, also useful for follow-up (90% resolution of microabscesses after clinical resolution)

Ddx: M. tuberculosis, M. kansasii, M. genavense, M. intracellulare, M. haemophilum, M. simiae, M. celatum, M. malmoense, M. marinum, and rapidly growing mycobacteria

 

Differentiating sputum positive AFB infections

MAI: lower CD4 count, dyspnea, normal CXR

Blood cultures positive in MTB (58%) and MAI (80%)

Liver biopsy (70%) sensitivity

Note: in cases of suspected pulmonary infection, a single culture can be a colonizer (esp. in patients with abnormal lungs) rather than active infection (except M. kansasii is usually pathogenic) / One study (n=34): 20 MTB (1/2 disseminated), 9 MAI (⅓ disseminated), 3 M. kansasii, 1 M. malmoense, 1 M. fortuitum

           

M. Avium-Intracellulare       

·        AIDS / disseminated disease or focal infection

·        Lady Windermere syndrome / elderly women, chronic, indolent cough

Diagnosis: stool culture for MAI (GI is most common route of entry), blood culture, tissue biopsy (best for definitively proving active, focal infection)

·        CXR/CT: may show small nodular infiltrates cylindrical bronchiectasis / often middle lobe involvement

Treatment: multi-drug resistance is expected / may take several months up to an entire year of ethambutol and clarithromycin (or azithromycin) / add streptomycin/amikacin (if really sick) / may also add rifampin

·        Note: prophylactic doses with disseminated MAI will only generate resistant MAI / if you’re not sure about diagnosis, either treat or don’t treat and wait for positive blood cultures

 

M. lepra                     

AFB enters the skin?

Transmission: men, milk, insects, armadillos

Presentation: nerve involvement / lymphadenopathy

            Lepromatous: failed cell-mediated immunity, bad prognosis

Tuberculoid leprosy: self-limited disease / associated with vitiligo (anesthesia, anhidrosis, alopecia) / biopsy reveals granulomas

            Treatment: long-term oral dapsone or clofazimine, dapsone, rifampin

 

Non-Tuberculous Mycobacteria (NTM)

 

Note: all produce B-lactamase

Diagnosis: rapid detection with DNA probe (ask lab, often can do Tb, MAI, M. kansasii, M. gordoneii)

·        Rapid growers (2 weeks): M. abscessus, M. fortuitum, M. chelonae

·        Slower growers (4 weeks): M. avium complex, M. kansasii, M. terrae/M. nonchromogenicum complex

 

M. smegmatis           

UG flora

 

M. kansasii

pulmonary infection (similar to MTb) / still need PMN’s / 18 months of INH 300 mg/day, rifampin and ethambutol / alternative: clarithromycin

 

M. fortuitum  

bone and soft tissue / can become disseminated in compromised host affecting lungs, joints, and even CNS / soil, dust, water, instrumentation (catheters, surgery) / rapid grower

Treatment: clarithromycin, amikacin, doxycycline, bactrim, cefoxitin, imipenem, some quinolones

 

M. scrofulaceum

cervical lymphadenitis in children / pulmonary disease / superficial, skin infection

 

M. marinum               

fish tank granuloma / grows in cold temperatures / 1-2 months (usu. 2-3 wks) after contact / small, violet nodule at site of minor trauma / can be self-limited

Ddx (for finger-hand-arm): cellulitis (staph or strep), finger-hand-arm disease, Vibrio, M. marinum, E. rhusiopathae, Sporothrix

Treatment: surgical debridement / clarithromycin or minocycline or (rifampin + ethambutol) / some success with bactrim, doxycycline

 

M. haemophilum

Infects skin and soft tissue in immunocompromised patients / clarithromycin and rifampin

 

Rhodococcus equi

AFB / causes cysts (can be size of basketball in some medical journals)

 

Actinomyces

filamentous GPR or AFB, grows slowly in anaerobic or microaerophillic (EOS) / infection may disregard normal fascial planes causing sinus tracts

Source: oral, GI flora, soil

      • craniofacial abscesses (lumpy jaw)
      • genito-urinary/chronic
      • pneumonia / head/neck à thorax (unless traumatic entry)
      • sulfur granules (purple lesion, fistula, painless)
      • Whipple’s disease

Labs: cultures will often be contaminated with GNRs

Treatment: penicillin (at least one year, high dose; first 2-6 weeks IV) / tetracycline / surgery if needed

 

Nocardia [NEJM]         

GPR, weakly AFB branching, beaded rod, aerobic

Transmission: from soil to lungs, skin (wounds), CNS

Diseases:

·        Pneumonia – cavitary lesion on CXR, thick sputum, fever

·        CNS

·        disseminated infection (immunocompromised) / must always be on guard for this possibility (brain, kidneys, bones, skin, muscle)

Note: one third of patients are immunocompetent

Diagnosis: silver staining of tissue specimens / actually does often grow on routine lab mediums (2 to 7 days; so must notify lab of suspicion)

Treatment: sulfadiazine or sulfisoxazole 6 to 8 g/d qid up to 12 g/d / others: TMP/SMX, minocycline, amikacin / B-lactams not as well studied

·        duration of treatment: 6 to 12 months

 

N. asteroides   80-90% of cases

N. brasiliensis

N. farcinia

N. nova

N. transvalensis

 

Chlamydia

            most common infectious disease in U.S.

            obligate intracellular parasite (no cytochromes or ATP synthetase) - relative bradycardia

            non-motile, no pili, no peptidoglycan wall (lacks muramic acid)

EB (elementary body, small/infectious) / RB (reticulate body, replicates by fission) / 24 hr life cycle is why you have to have antibiotic levels for a long time

            antigen detection by IF, Giemsa, DNA probe / culture difficult, slow, insensitive

 

Chlamydia trachomatis

Transmission: human sexual transmission or vertical

ABC cause trachoma

·        UTI

§         endocervicitis – most common presentation mucopurulent

§         acute urethral syndrome (most common cause of nongonoccocal urethritis (NGU) in men

§         acute dysuria, pyuria, voided urine < 10e5 / non-GC urethritis that may remain asymptomatic (PID, infertility) / must differentiate from HSV

§         nonpuerperal endometritis

§         acute salpingitis

§         postpartum endometritis

§         neonatal pneumonia, conjunctivitis, otitis media:  25-75% transmission rate / presents at 3-4 months / types D-K / macrolide treatment in children – 1st course 80% effective

§         LGV: types L1-3 (positive Frei test)

·        Conjunctivitis: must swab cells on lower eyelids

·        Arthritis (see Reiter’s)

·        Conjunctivitis: must swab cells on lower eyelids / major cause of neonatal blindness in Africa

·        Diarrhea

Treatment: azithromycin 1g PO x 1 [GI upset with huge dose] or doxycycline 100 mg

PO bid x 7d or erythromycin 500 mg PO qid x 7d or amoxicillin 500 mg PO tid x 7-10d

 

Chlamydia psittaci (psittacosis)

Diseases: pneumonia, abortions

Source: mainly infected psittacine birds (parrots, parakeets, lovebirds), less often in poultry, pigeons, and canaries, and occasionally in snowy egrets and some seabirds (e.g., herring gulls, petrels, and fulmars) / note: bird is sick too

Transmission: inhalation of dust from feathers/excreta or being bitten by infected bird / human à human is rare (coughing, venereal) / incubation: 1-3 wks

Presentation: abrupt or insidious fever, chills, malaise, anorexia then variable cough / wk 2, pneumonia with consolidation / temperature stays high 2-3 wks then slowly falls / may have splenomegaly

Diagnosis: clinical picture +/- serology

·        CXR: pneumonitis radiating from hilum

Pathology: pneumonitis with mononuclear cell exudate (similar to Mycoplasm, viral, Q fever)

Ddx: influenza, typhoid fever, mycoplasma, legionella, Q fever

Treatment: tetracycline 250-500 mg qid or doxycycline 100 mg po bid

Prognosis: improvement usually within 48 to 72 h (continue antibiotic at least 10 d) / untreated mortality from 30% and higher (severity depends on host and virulence of strain)

Prevention: avoidance of birds and infected people / imported birds often get 4-5 course of tet-feed.

 

Chlamydia pneumoniae

human (aerosol) / pneumonia, pharyngitis?, relative bradycardia / doxycycline, azythromycin or erythromycin

Treatment: clarithromycin for neonates

 

 

Zoonotic Diseases        (all may be aerosols / facultative intracellular)

 

Francisella tularensis (Tularemia)   

Presentation: localized or disseminated rashes / humoral and cell-mediated response / relative bradycardia, causes RES granulomas

Micro: GNCB, aerobe, facultative intracellular

Transmission: ticks, deer flies / less commonly (infected meat, animals bites (rabbits), water, aerosol) / infecting does very low 10 - 50 (can penetrate skin) / oral challenge requires 10e8

Course: incubation (2-5 days) / primary (1-4 days) / remission (1-3 days) / chronic relapse (2-3 weeks)

Primary Diseases: ulceroglandular (45%), enteric tularemia (5%), pulmonary tularemia (via inhalation)

Complications: oculoglandular, meningitis, endocarditis, osteomyelitis, pneumonia (primary or sequela)

Diagnosis: there is an agglutination assay (culture is dangerous, difficult)

Treatment: streptomycin, tetracycline or chloramphenicol (up to 30% mortality if left untreated) / vaccine available

                       

Brucella

 

B. suis             most common

B. abortus        cattle

B. melitensis     most invasive

B. canis            recent pathogen

           

GNCB, aerobe, facultative intracellular parasite

use culture (takes forever) since serology is problematic (replicates within macrophages)

animals / infected cheese or milk / inhalation

Transmission: penetrates skin or mucous membrane to reach RE system

Presentation: fever, symmetric lymphadenopathy, joint swelling, hepatosplenomegaly

Primary Diseases: bone marrow (sacroiliitis), liver, kidney, endocardium, brain (see below)

Labs: leukopenia

Complications:

Neuro (2-5%): meningitis, vasculitis, parenchymal CNS lesions, and diseases of the roots and peripheral nerves

Course: longer incubation (7-21 days) / acute (like typhoid) / localized (more in females) / chronic / may relapse

Treatment: tetracycline/streptomycin or doxycycline/rifampin (only 2% mortality untreated, high morbidity) / strain 19 (avirulent) vaccine used for cattle and workers

 

Neurobrucellosis

culture of tissue with CO2 incubation or serology, CSF analysis

Treatment: doxycycline, rifampin, and possibly bactrim for 2 to 4 months +/ corticosteroids

 

Yersinia

GNR, aerobe, facultative intracellular   

 

Yersinia pestis (Plague)                                                                                

bubonic plague from fleas / pneumonic plague from droplet spread (or from bubo)

Transmission: sylvatic cycle: rodent to rodent via flea (endemic) / urban cycle: rat to rat via flea (epidemic)

Course: spreads rapidly, systemically ill with tender lymphadenopathy

YOP proteins made in host cells: H (tyr phosphatase), E (cytotoxic), M (prevents coagulation)

Diagnosis: gram smear from bubo, blood, sputum / culture on MacConkey  / direct IF

Treatment: streptomycin (tetracycline for prophylaxis) / chloramphenicol, sulfonamides / killed vaccine available

 

Yersinia pseudotuberculosis 

acute mesenteric lymphadenitis (usually self-limiting) / fever, abdominal pain mimics appendicitis / causes pseudoTB in lymph nodes, spleen, liver (uncommonly causes bacteremia)

Treatment: ampicillin, cephalosporins, aminoglycosides, tetracyclines, chloramphenicol

 

Yersinia enterocolitica

invasin, ST-like, AIL (complement resistance), various YOPs, 03 and 09 serotypes

fecal oral transmission

Diseases: enterocolitis and/or terminal ileitis (fever, diarrhea, abdominal pain)

Course: more mild in children than adults

uncomplicated enteritis (65%), complicated (15%), appendicular syndrome (10%), ileitis (3%), colitis (5%)

Complications: lymphadenitis (pseudoappendicitis), reactive arthritis (HLA B27), septicemia, erythema nodosum (25%)

Diagnosis: positive stool culture (80%)

Treatment: quinolones, TMP/SMX, AG (streptomycin), chloramphenicol, tetracycline, resistant to penicillins and cephalosporins

 

Pasteurella multocida           

GNCB / animal bites (80% of cat bites) / cellulitis

Rarely occurs without bites / ~10% of patients hospitalized for animal bites

Can lead to sepsis (but not as fast as DF2)

Treatment: ?

 

Capnocytophaga canimorsus (DF2) 

GNR (fastidious, slow-growing) / from dog or cat bites/scratches (and others)

Complications: overwhelming sepsis in asplenic and otherwise immunocompromised, hemolytic anemia (HUS)

Treatment: penicillin

 

 

Rickettsia (all arthropod vectors except Coxiella)

 

small GNCB, aerobic, obligate intracellular parasite

replicate in cytoplasm (Rickettsia) or vacuoles (Coxiella and Ehrlichia)

penetration, incubation, dissemination (rash from vascular effects)

Clinical: patients will exhibit systemic symptoms, thrombocytosis is almost mandatory

Labs: Weil-Felix rxn (proteus agglutination; can be used as screening test) / specific IF (culture dangerous/difficult)

Treatment: tetracycline or chloramphenicol

 

Louse-borne typhus: human reservoir // all others: humans are accidental hosts

 

R. rickettsii                           

large ticks

(usu. dog tick and wood tick)

 

 

Rocky Mountain Spotted Fever (see below)

 

R. akari                                 

mites / mouse

rickettsialpox (mild febrile illness)

 

R. prowazekii            

human louse

epidemic typhus (Brill-Zinsser is recrudescent disease-usually effects elderly)

 

R. typhi                                              

Fleas

endemic / murine typhus (milder typhus)

R. tsutsugamushi

Mites

scrub typhus

 

 

 

Rocky Mountain Spotted Fever or RMSF

South-Central-mid-Atlantic / spring and summer (April to Sept. 95%)

Course:

·        2 to 14 (avg. 7) days:  fever, severe frontal headache, fatigue, myalgia, nausea, vomiting, abdominal pain, anorexia

·        macular or petechial rash (~85%) of palms and soles rash (similar to syphilis, coxsackie) // centripetal spread (limbs à trunk) [pic] [pic][pic][pic]

·        CNS: marked mental changes, meningismus, ataxia, seizures, hallucinations, focal cerebral deficits, and variable PNS involvement / 25% with encephalitis (delirium, stupor, coma)

Diagnosis: serology and antiendothelial antibody studies that take 1 to 2 weeks to reach detectable levels, immunohistologic, PCR of skin lesion biopsies

Labs: reduced WBC’s (increased bands), anemia, thrombocytopenia, hyponatremia, increased AST/ALT

·        CSF à mononuclear pleocytosis, increased protein, glial nodules (enlarged endothelial cells, lymphocytes, macrophages containing organisms by IF) , direct effects and immunologic injury (including antiendothelial antibodies)

Prognosis: rapidly progressive, 20% mortality untreated (5% overall)

Treatment: doxycycline and others

 

Ehrlichia chaffeensis

deer tick / monocytic or granulocytic ehrlichiosis (different organisms)

Presentation: fever, headache, usually no rash

Labs: causes low WBCs, but thrombocytosis is almost mandatory (one text said

thrombocytopenia? I think that was an error?)

 

Bartonella (Rochalimaea)                    facultative intracellular parasite

 

B. henselae                

flea bite

Diseases:

·        cat scratch disease / systemic symptoms and tender regional lymphadenopathy can be debilitating

·        peliosis hepatitis

·        relapsing fever

·        bacillary angiomatosis (purple, vascular appearing lesions on extremities [pic][pic]; more common, but not always in AIDS)

o       biopsy to differentiate from Kaposi’s sarcoma (requires Warthin-Starry silver stains)

·        CNS (< 10%): encephalopathy, neuroretinitis (Parinaud’s oculoglandular disease is rare), cerebral arteritis (rare)

Diagnosis:  serology (method of choice), culture (1-4 wks), PCR (may not yet be available),

Course: may take 2-4 months to resolve

Treatment: optimum antibiotics unclear but current thinking is 5 days azithromycin +/- aminoglycosides for severe disease / other possible options (doxycycline, macrolides, bactrim or rifampin)

 

B. quintana    

human louse / trench fever / can also cause angiomatosis (but not liver disease) and frequently boney invasion

Treatment: similar to B. henselae (oral if mild, IV if systemic/severe disease)

 

            B. bacilliformis (Peru)

Carrion disease (named for medical student who lost his life researching it)

·        acute - Oroya fever / malaise, headache, muscle pains, remittent fever/chills, rapidly developing anemia (extravascular)

·        chronic (eruptive) - verruca peruviana or veruga peruana / benign condition characterized by wart like lesions of the skin and no hematologic manifestations

 

Coxiella burnetii (Q Fever)

facultative intracellular parasite / animals / inhalation, ingestion

Diseases:

·        Q fever / incubation 9 to 28 days, high fever, headache, myalgia, atypical pneumonia, hepatitis, rash? (conflicting accounts)

·        chronic hepatitis (occurs in ⅓)

·        endocarditis [NEJM] (may occur 1 to 20 yrs after exposure)

Weil-Felix reaction

Diagnosis: can test for antibodies to Coxiella (cross-react with Bartonella ones) / clinical diagnosis / tissue pathology (vacuolated histiocytes)

 

Mycoplasma

- no cell wall (no penicillin sensitivity) / only bacteria with cholesterol

- Eaton’s agar, smallest free living bacteria / found in respiratory/UG secretions

 

Mycoplasma pneumoniae

no cell wall / strict aerobe / adherence P1 / slower than S. pneumo

Common diseases:  tracheobronchitis, pharyngitis, non-purulent otitis media

Uncommon diseases: carditis, meningitis, encephalitis

Epidemiology: 20% community acquired pneumonia (i.e. military, prisons) / 33% of teenage pneumonia / peak age 5-20 yrs and elderly

Transmission: usually close contacts, epidemics every 4-6 yrs in temperate climates

Clinical: most cases do not require hospitalization / immunity is incomplete, reinfection is common

Course: incubation 2-21 days à 2-4 days low-grade fever, headache, sore throat, malaise, dry cough (may be purulent, blood-tinged) à 1-2 days cough worsens for 1-2 weeks then gradual recovery; some will persist with malaise-type symptoms for weeks; others will develop severe illness with pneumonia +/- various systemic manifestations

·        Tracheobronchitis or pneumonia (5-10%) / productive cough (yellow +/- blood tinged) / pleural effusion (5-20%) / pleuritis usually minimal / rarely causes chills (like S. pneumo) or nausea, vomiting, myalgias (like influenza) or diarrhea (like adenovirus)

·        Pharyngitis: usually with minimal LAD

·        non-purulent otitis media or bullous myringitis (15%)

·        Skin: younger, males at more risk for erythema multiforme major or Steven’s Johnson Syndrome (up to 7%) involving GI, GU, joints

·        Joint: polyarthralgia (can be mono, frank arthritis is rare) / mysositis

·        Vascular: Raynaud’s and other vascular occlusive occurrences

·         Cardiac: very common (↑10%) complication à chest pain, CHF, conduction defects

·        Neuro: uncommon (1 in 100; ~7%, children/young adults, 3-30 days +/- after pneumonia resolves) // various syndromes (e.g. peripheral neuropathy, meningitis, meningoencephalitis, transverse myelitis, hemiplegia, cerebellar ataxia, acute polyradiculoneuritis, cranial nerve palsy, vasculitis of small arteries, veins, capillaries

CXR: unilateral or patchy, usu. lower lobe, sometimes bilateral, pleural effusions (25%)

Labs:

·         WBC count usually only mildly elevated

·        IgM and IgG specific immunoassay (4-fould rise in serum antibody or single high IgM) // single high IgG titer not useful because titers can remain elevated for a year or more

·        cold hemagglutinins (by 7-10 days, peak 2-3 weeks, duration 2-3 months)

sub-clinical hemolysis (RBC I antigen) is the norm / 1:32 is highly suggestive (1:64 is positive), or a 4-fold rise over time) / severe cases 1:20,000 titer (associated with Raynaud’s) / test not very specific, also reacts with EBV (anti-I), CMV (anti-I), adenovirus et al, lymphoma

·        complement fixation (levels peak 2-3 weeks, duration 2-3 months)

assay is more specific

·        cultures take 7-10 days (gram stain not helpful)

·        elevated CK (myositis)

·        RBC clumping can cause false positive MCV elevation (with high RDW)

Transmission: prolonged shedding (2-8 days before symptoms and up to 14 weeks after), droplet spread, low infective dose

Immunology: asplenism increases risk of severe infection, complement fixing antibody titres peak 2-4 weeks, last 6 to 12 months, 66% of symptomatic patients develop IgM that cross reacts with I antigen of human red blood cells (can produce hemolytic anemia), other non-specific immune reactions occur

Treatment: azithromycin, clarithromycin >> quinolones > doxycycline / treatment hastens recovery but pts continue to shed infective organisms for weeks

 

M. hominis                

Facultative anaerobe, many serotypes, common GU flora

Diseases: post-partum fever (isolated from 10% of cases), usually self-limiting

Complications: PID, pyelonephritis

Treatment: same as above (but will be resistant to erythromycin)

 

U. urealyticum           

Facultative anaerobe / GU flora in 80% of sexually active people

Diseases: pneumonia (neonates), chorioamnionitis, post-partum fever, non-GC non-chlamydia urethritis

Treatment: tetracyclines (cross-cover chlamydia) / spectinomycin or quinolones for tetracycline resistance

 

Spirochetes (Treponema and Borrelia)

periplasmic flagella / only by darkfield microscopy, silver impregnation, IF

obligate parasite of humans / non-pathogenic strains found to inhabit oral/anal

 

T. Syphilis

Primary: 2-4 wks incubation (extreme range of 10-90 days), then painless chancre (days to weeks, one week with therapy; can be located anywhere at primary site of inoculation); ⅓ will have negative serology at this stage

Secondary (weeks to months) [dermis]

·        classic lesions involving palms and soles (maculopapular squamous eruption, scattered reddish-brown lesions, thin scale; can mimic almost all dermatological conditions) [pic][pic] / Ddx: atypical pityriasis rosea or erythema multiforme

·        may get meningovascular syphilis

·        fever, soar throat, mucosal ulcerations, malaise, generalized lymphadenopathy, patchy alopecia, thinning of lateral third of eyebrow

·        obliterative endarteritis (involvement of vasa vasorum leads to saccular aneurismal dilatation of aorta; aortic insufficiency)

·        condyloma lata (perianal wart like lesions, more stuck-on, full of organisms, will regress)

·        Other: arthritis, hepatitis, glomerulonephritis

Latent (early latent < 1 yr, late latent > 1 yr)

asymptomatic (persists in ⅓ of patients) ⅓ of them will heal without treatment

Tertiary or late - years later: may have severe sequelae / damage is autoimmune

 

Neurosyphilis (8-40% if untreated; > 40% with HIV) can occur during any stage

can present like Pick’s disease (loss of judgment, insight, memory, delusions, hallucinations, changes in personality) / demyelination of posterior column (wide gait, foot slap, paresthesias, incontinence, loss of position/vibratory, impotence) and dorsal root ganglia causes paresis and tabes dorsalis (involves more organisms), Charcot’s joints, Argyll-Robinson  pupil (accommodates but doesn’t react to light?), “gun-barrel” site (loss of optic nerve) / CN VII-VIII most commonly (vertigo, tinnitus, loss of facial expression)

o       can use LP (but negative VDRL)

Gummatous (9-16% untreated) – mega-immune response to only a few organisms

 

Congenital syphilis:

            100% preventable with screening and treatment / primary/secondary, early latent:

50% vertical transmission rate / late latent, tertiary: 25% vertical transmission rate /

nephrotic syndrome, fibrosis (pancreatitis, GI inflammation, interstitial pneumonia), excess extramedullary hematopoeisis, osteochondritis (undulating growth plate), hepatomegaly, splenomegaly, mucocutaneous lesions, jaundice, lymphadenopathy, “snuffles”/ early: Parrot’s pseudoparalysis / 8-15 yrs develop Clutton’s joints / Hutchinson triad (Hutchinson teeth or blunted upper incisors, interstitial keratitis, 8th nerve deafness)

 

Screening: seroconversion occurs from 1-4 weeks after primary chancre

Non-treponemal: Ab to cardiolipin (VDRL), RPR (1:2 low, 1:16 moderate, 1:64 high)

·        false positives:  EBV, HBV, leprosy, lyme disease, endocarditis (RF), connective tissue disease (RA, SLE, APA), drugs

Treponemal: FTA-ABS or TPI (test directly for organism) / MHA-TP (false positive mainly with lyme disease, remains positive for life)

CSF Studies:

·        CSF VDRL (only 60% sensitive, then look at protein/WBCs) [preferred]

·        CSF FTAB (too sensitive, ↑ false positives, even from serum contamination of LP)

·        MHA-TP (supposedly very high negative predictive value for neurosyphilis)

Screen for other sexually transmitted disease: gonorrhea, chlamydia, HBV, HCV

Treatment:

·        Benzathine penicillin G recommended when CNS infection is ruled out / treatment may cause Jarisch-Herxheimer reaction (fever, chills, hypotension occurs within 1-2 hrs; resolves 24-48 hrs; usu. only requires NSAIDs and Tylenol; also occurs with treatment of rat bite fever, leptospirosis, ehrlichiosis) / titre should fall 4 fold within 3 months (negative or near-negative titre at one year) with successful treatment

Primary: penicillin G 2.4 mu IM x 1 [usually given ½ dose in each hip]

Secondary:

Latent (early): penicillin G 2.4 mu IM x 1

Latent (late): penicillin G 2.4 mu IM plus 2.4 mu IM once a week x 3 weeks

Tertiary: high-dose IV penicillin G x 2 wks in hospital (watch for inflammatory response to therapy?) then give one more shot

Alternatives: ceftriaxone or doxycycline 100 mg bid 2 wks or tetracycline 500 mg qid 2 wks or erythromycin mg qid 2 wks

VDRL on LP in patients with CNS signs, HIV or immunocompromised

In HIV patients, recheck titres q 6 months (to 18 months) (consider re-treatment if )

 

Treponema pallidum (relatively anaerobic)

 

-T. p. pallidum                        syphilis (microaerophilic)

-T. p. pertenue                        yaws (tropical Africa and Asia)

-T. p. endimicum         endemic syphilis (now rare)

-T. carateum               pinta (skin lesions) (L. America)

-T. vincentii                 Vincent’s disease or “trenchmouth”

 

Borrelia

visible by LM with Giemsa or Wright stain (because it’s larger)

arthropod vector (most common in U.S.)

VMP variable major proteins result in relapses / expression plasmid and storage plasmid (EPSP)

 

B. burgdorferi or Lyme disease

Deer tick (hard body, Ixodid or Ixodes tick; NE (Maine to Maryland), Midwest (Wisconsin to Minnesota), NW (northern California and Oregon) / 90% of vector-borne infections

Course: some say < 10% of inoculations become infected / 10-20% of infections are asymptomatic

Unusual syndromes: CNS vasculitis/infarction, increased ICP, psychiatric disease, myositis

Co-infection: 10% with either babesiosis (splenectomized) or ehrlichiosis (elderly)

 

Stage One

erythema migrans or erythema chronicum migrans (expanding red rash, central clearing; 20-30cm) occurs 3-32 days after bite / secondary rings may occur within original circle / may itch or burn and may see systemic symptoms during this phase (see below) /no rash noticed in 20%

 

Stage Two  (< 1 months)

 

Skin: malar rash, conjunctivitis, or, rarely, diffuse urticaria / EM and secondary lesions (similar to primary, but smaller) usually fade within 3 to 4 weeks (range, 1 day to 14 months)

Heart Block: 8% get various degrees of heart block (usu. resolve within a week) / usu. don’t really get much myocardial damage, but can get mild pericarditis with non-specific EKG changes / cardiac involvement usu. from 3 days to several weeks

Systemic: malaise and fatigue, headache, fever and chills, generalized aches, and regional lymphadenopathy

CNS/PNS (15% untreated): meningitis, encephalitis, encephalomyelitis, cranial nerve palsy (especially II and VII, Bell’s Palsy), acute painful radiculoneuritis, chronic polyradiculoneuropathy mononeuritis multiplex

Musculoskeletal: pain in joints, tendons, bursae, muscle, or bones, often without joint swelling / migratory polyarthritis (hours to days per location; most common in knees; may last months)

Eye: conjunctivitis >> retinal problems, other

 

Stage Three

migratory polyarthritis

can last several years / 500-100K WBC, no positive Cx, but DNA is there / HLA-DRB1*0401

neuro: psychological problems, peripheral neuropathies, encephalomyelitis (more in Europeans)

skin: acrodermatitis chronica atrophicans (more in Europeans)

autoimmune response similar to syphilis

 

Diagnosis: clinical diagnosis (30-40% will be seronegative at presentation; 60% seroconversion by 2-4 wks, 90% by 4-6 wks, then usually positive for several years) / sensitivity for PCR in synovial fluid ~85%, lower in CSF

Labs (stage two): positive MHATP, high ESR, elevated IgM, elevated ALT, GGT, LDH, mild anemia

CSF: normal glucose, elevated protein, lymphocytic pleocytosis ~100,

Treatment:

Stage I/II: 20-30 days doxycycline or amoxicillin or cefuroxime or ceftriaxone / macrolides 2nd choice / IV ceftriaxone with heart block, and possibly steroids if not better < 24 hrs / 15%  have Jarisch-Herxheimer-like within 1st 24 hrs of treatment

Late: IV ceftriaxone / IV penicillin

Treatment failure is rare and recurrence of non-specific symptoms may not be due to ongoing infection

 

B. recurrentis            

Tick (endemic) or louseborne (epidemic) relapsing fever / antigenic variation causes reemergence

                        Presentation:

·        CNS (10%): hemorrhage, perivascular infiltrates, degenerative lesions

·        CNS (2% to 5%): meningitis, vasculitis, parenchymal lesions, nerve roots and PNS

·        Secondary vasculitis with mycotic aneurysm formation, subarachnoid/intraparenchymal bleeding

Diagnosis: microscopic detection in peripheral blood during a febrile episode / serology is supportive

Treatment:  tetracyclines, chloramphenicol, penicillins, erythromycin

 

B. hermsi                   

tickborne relapsing fever

 

Leptospira interrogans

            animals / contaminated urine (rodent urine), water

Diagnosis: culture urine / blood / CSF

Biphasic illness

Primary

Secondary (immune phase) / late uveitis

            Treatment: tetracycline or penicillin (early ~)

 

Weil’s syndrome (severe) (5 to 10%)

more severe icteric form of Leptospirosis / significant hepatic and renal involvement Incubation: 7 to 12 days

Presentation: biphasic illness, fever, severe HA, myalgia, conjunctival injection, spontaneous defervescence after several days

·        first phase: blood and CSF cultures positive

·        second phase: immune response, days later, meningitis in 70-90% (can be subclinical)

note: uveitis often occurs months to years into the infection / ~7% show additional neurologic syndromes

·        CNS: subarachnoid, parenchymal, subdural, spinal hemorrhage, can have vasculitis with widespread capillaritis and multiple vessel occlusions

·        bleeding worsened by thrombocytopenia, coagulopathy, and renal disease

Diagnosis: culture or IF staining of blood/CSF/tissue

Treatment: tetracycline or B-lactams

 

Spirillum minor          

rat bite fever (also caused by Streptobacillus monoformis)

 

Other Bacteria

 

 

 

Fungi

 

 

Superficial

 

Non-Tinea Tinea

 

Tinea versicolor (Malassezia furfur) [dermis]

Appearance: hypopigmented or hyperpigmented, oval, scaling or non-scaling, coalescent macules on trunk and proximal extremities / lesions can be inflammatory and/or vesicular and mimic other infectious processes

Diagnosis: KOH prep / green fluorescence on Wood’s light (routine fungal cultures will not grow; also may have false negative if patient recently showered) 

Pathology: KOH reveals ‘spaghetti and meatballs’ (short hyphae and yeast forms)

 

Tinea nigra                 Exophialia werneckii

Black piedra               Piedriae hortae

White piedra               Trichosporon beigelii

 

Dermatophytes (Tinea sp.)

Dermatophyte test media - they will turn red / others yellow

Treatment: griseofulvin, some people use fluconazole/itraconazole instead (2 week therapy)

 

Epidermophyton           macroconidia (smooth)

Microsporum                macroconidia (rough)

Trichophyton                microconidia

 

Tinea capitis

Treatment: requires oral griseofulvin or itraconazole or terbinafine

 

Endothrix

T. tonsurans               black dot / may present in 4 different ways / common in Houston

T. violaceum

T. schoenleinii             favus

 

Ectothrix

M. audouinii                epidemic tinea

M. canis                       zoophilic

T. mentagrophytes      zoophilic

 

Tinea barbae

 

T. verrucosum             cattle

T. mentagrophytes      zoophilic

 

Tinea unguinum

Note: use itraconazole

 

Kerion

Trychophyton spp.

 

Tinea corporis  [dermis]

Treatment: topical antifungal

 

Erythematous scaly plaque with central clearing and serpiginous border

Transmission: infected animal or person-to-person

 

M. canis, rubrum, mentagrophytes, concentricum

 

Tinea cruris

E. floccosum, T. rubrum

            the groin and beyond

 

Tinea pedis [dermis]    

T. rubrum      

            classic pattern of (2 hands + 1 foot) or (2 feet + one hand) / often resistant to treatment

T. mentagrophytes

 

Sub-Cutaneous

 

Sporothrix shenckii (sporotrichosis)

lymphocutaneous, pulmonary / Central/South America, Mexico / worse with alcoholics,

immunocompromised

Micro: dimorphic / rosette conidia / asteroid bodies / unequal budding

Treatment: KI therapy

 

Chromomycosis

painless / cauliflower-like / black fungi / sclerotic bodies

 

Mycetomas

Madura foot / sulfur granules / lollipop conidia

Diagnosis: histological exam distinguishes (broad, eumycetoma elements) vs. (narrow, actinomycete elements) / geography and culture for confirmation / serology not used

Complications: can cause substantial regional destruction (along fascial planes), but distant spread is uncommon / may require amputation of extremities

 

Eumycetoma

slower progression / usually starts hurting when bone becomes involved

Treatment: may respond to some antifungal therapy, but without complete surgical debridement, relapse is almost certain

 

Pseudallescheria boydii – most common in US, Canada

Madurella mycetomatis

 

Actinomycetoma

faster progression / lesions may spread

Treatment: bactrim + (streptomycin or rifampin) / dapsone + streptomycin / alternative à augmentin / 9 months of treatment

 

N. brasiliensis, Actinomadura madurae

 most common in S. and Central America, Caribbean

 

lumpy jaw                                 sulfur draining tracts

pulmonary nocardiosis (WAF)AIDS / may disseminate

cutaneous nocardiosis   (WAF) soil in you

 

 

Systemic

 

Coccidioides immitis (San Joaquin Valley Fever) [MRI]

barrel arthroconidia (inhaled) / spherule ruptures (~yeast) / erythema

Southwest US, Mexico, Columbia, Paraguay, Venezuela (not Brazil)

Risk factors: archaeological excavation, rock hunting/climbing, military maneuvers, construction work

 

Presentation:

 

40% symptomatic

(60% asymptomatic!)

can cause thin walled, pyogenic granuloma, may cause pleural effusion +/- hemoptysis

Other: hypersensitivity reaction, erythema nodosum, erythema multiforme, arthritis, conjunctivitis

 

5% pulmonary residual

 

 

1% disseminated                      

⅓ get meningitis (see below)

Filipino men are uniquely susceptible

 

Diagnosis: eosinophilia / CSF culture (50%), sputum culture (must warn lab; biohazard), specific antibodies helpful (may take 8 weeks to be formed)

·        CXR findings same as chronic cavitary Tb (small, irregular, single or multiple cavities, upper lobes)

 

Coccidioides meningitis

basilar meningitis (40% sensitivity of CT/MRI) > encephalitis, lesions, CNS vasculitis / granulomata may be found in blood vessel walls / necrosis may occur due to endarteritis obliterans

Treatment: prolonged intrathecal amphotericin B + dexamethasone

 

Histoplasma capsulata (Darling’s)

tuberculated microconidia / infective macroconidia (bird, bat guano) / intracellular growth

Mississippi River Valley

Presentation: primary infection via inhalation often non-specific (subacute illness with fever, hepatosplenomegaly, pain from GI ulcers, may have meningitis/endocarditis/Addison’s) / commonly have enlarged spleen (even larger than MAI or MTB, may show some splenic infarcts on CT)

Labs: leukopenia or pancytopenia, very high LDH

Complications: hypotension, mental status changes, coagulopathy, rhabdomyolysis, adrenal insufficiency / chronic cavitary histoplasmosis and fibrosing mediastinitis (rare, can lead to progressive respiratory/circulatory dysfunction)

Diagnosis:

·        culture from any body fluid (sputum, bone marrow, mucosal lesions, BAL, liver biopsy, skin lesions) / lysis-tubes or buffy helps; 15 ml min sample required; may take 2 wks

·        GMS stain on tissues

·        urine Ag tests (more concentrated than blood, thus higher sensitivity)

·        fungal serology panel (should be informative but may not determine active infection)

Ddx: disseminated Tb, PCP

Treatment: primary usually self-limited (immunocompetent patients can be observed only) / immunosuppressed or severe/chronic patients require amphotericin B or itraconazole 10-12 wks / lifelong suppression with itraconazole or even intermittent ampho B / CNS histoplasmosis requires amphotericin B followed by fluconazole (because itraconazole does not penetrate CSF)

 

Blastomyces dermatitidis (Gilchrest’s)

broad based bud / oval microconidia / Appalachia line / skin and bones

Source: SE, south-central, midwestern US and Canada; decaying vegetation, close to water, high humidity

Presenation:

·        often as asymptomatic or chronic respiratory infection; fulminant respiratory failure (including ARDS) may occur and usu. does so in immunocompetent hosts with 50% mortality

·        skin lesions in exposed areas become crusted [pic], ulcerated [pic], verrucous, papulopustular, subcutaneous

·        genitourinary lesions (20-30%; usu. prostate, epididymis)

·        bone and joint pain from osteolytic lesions

Diagnosis:

·        CXR with air-space infiltrates

·        antibody assays unhelpful due to false negative and false positive (other fungi)

Treatment: itraconazole or amphotericin B (severe cases; immunocompromised; CNS)

 

Paracoccidioides brasiliensis

Micro: ship’s wheel blastoconidia / oval microconidia / chronic / mild / dissemination

Epidemiology: usu. infects male agricultural workers > 30 yrs old / occurs in Brazil / long incubation period (weeks to over 30 years)

Pathology: pulmonary infiltrates, oral/mucosal lesions

Presentation: fever, cough, lymphadenopathy, hepatosplenomegaly, and may have bony lesions, arthritis / children have more acute form (juvenile or disseminated parracoccidioidomycosis)

 

 

Opportunistic Fungal Infections [see anti-fungal drugs]

 

 

Candida albicans       

Micro: budding yeast with pseudohyphae (germ tubes at 37 degrees) / chlamydoconidia

chronic mucocutaneous candidiasis (T-cell defect) / adherence, protease

Diseases:

·        oral thrush [dermis]

·        esophagitis

·        UTI (see other)

·        vaginitis, diaper rash

·        endocarditis (IVDA)

·        retinitis (10% of patients with candidemia) [pic] / range from asymptomatic to blurred vision, ocular pain, scotoma

·        vasculitis (rare)

·        chronic meningitis

·        Line infection: common cause of line infections (rule of thumb for a cath tip culture is that you can downplay < 15 colonies as long as the blood never grows any fungus and you don’t suspect candidemia)

Note: it is debatable whether all lines must be removed with candidemia (unless C. paraps., in which case you must always remove the line)

Treatment:

·        oral candidiasis (first try nystatin, fluco suspension, itra suspension; if recurrent, unresponsive or severe use IV fluconazole or itraconazole (voriconazole for refractory cases)

·        other conditions start with oral or IV azoles (specifics and duration depending on particular organism, resistance patterns, response to treatment, etc.)

 

Systemic Fungal Infections

 

Risk Factors:

prior antibiotics (especially broad, gram-negative agents)

steroids (other immunosuppressive agents)

HIV

gut wall surgery

hyperglycemia (via host and organism immunomodulation)

TPN (fungus grows in the medium and is then introduced IV)

lines/catheters/ventilator

IVDA

colonization (40% incidence)

Diagnosis: only need one positive culture from sterile site (i.e. blood) / sensitivity of candidemia can be anywhere from 60% as low as 10%

Findings: endopthalmitis in 10% of cases (use fundoscope)

Complications:

Eyes: ophthalmology consult – retina only vs. intravitreous (very serious)

Treatment: see anti-fungal agents

Prophylaxis: fluconazole for very select patients (ex. GI perforation, post-transplant patients)

 

Resistance Patterns

 

C. albicans (50%)                     can develop resistance to azoles after months to yrs of treatment

C. paraps. (10-20%)                usually sensitive to F/I or ampho B

C. tropicalis (10-20%)              usually sensitive to F/I or ampho B

C. glabrata (10-30%)               resistance to F/I, partial resistance to Ampho B

C. kruseii (1%)             resistance to F/I, partial resistance to Ampho B

C. lusitanei (1%)                       resistance to Ampho B, partial resistance to F/I

 

Note: resistance to F/I can be dose-dependent or 100%

 

Cryptococcus  neoformans    

6-10% incidence of Cryptococcal infection when CD4 < 100

Source: pigeons, soil

·        Pneumonia: five histologic forms (fibrocaseous cryptococcoma, granulomatous pneumonia, histiocytic pneumonia, mucoid pneumonia, intracapillary cryptococcosis) / hilar/mediastinal lymph nodes are unusual, pleural effusions uncommon

can lead to ARDS, BOOP

20-70% will also have meningitis

·        Meningitis: headache, nausea, gait disturbance, confusion, visual changes (fever and nuchal rigidity often mild or absent), papilledema (30%), asymmetric cranial nerve palsies (25%) / headache relieved by CSF tap / AIDS < 100 / CSF (low sugar, high protein, lymphocytic predominance)

·        Skin: ulcers, cellulitis, nodules, pustules, lesions with appearance of molluscum

Diagnosis: CSF cryptococcal Ag (90% sensitive, small false positive rate), serum Ag, India ink (30% sensitivity), fungal culture (grows readily on blood agar; from urine also), mucicarmine (stains for heavy capsule in tissue samples), phenol oxidase

·        CXR: findings vary from consolidations, nodules, infiltrates, miliary [CXR][CT]

·        MRI: may show cryptococcomas in basal ganglia or caudate nucleus (usu. more in immunocompetent patients with C. neoformans var. gattii)

Treatment:

 

HIV/AIDSgoal is control, not cure

 

Ampho B (0.7 mg/kg/d IV)  +/- 5 FC (100 mg/kg/d PO) ~ 2 wks

400 mg/d fluconazole ~ 6-8 wks [consider repeat LP before switching]

200 mg/d lifelong fluconazole (crypto never eradicated, Ag positive in CSF for life)

Note: 5FC requires checking levels with renal impairment

 

Non HIV/AIDSgoal is cure, not control

10 weeks IV amphotericin B / until serial LP for 6 weeks, with at least 4 weeks of sterile cultures, clearing of India Ink, decreasing cryptococcal Ag titer and normalization of CSF glucose / followed by 6-12 months oral fluconazole

 

Elevated CSF pressure defined between 20 and 25 cm/H2O

brain imaging has not shown obstruction – theory à fungal products occlude arachnoid granulations / 1 or 2 per day large volume LP or placement of CSF shunts until opening pressure < 20 cm/H2O

 

Aspergillus    

Epidemiology: very important for post-lung transplant patients / neutropenic hosts

Micro: 45 degree branching, hyphal forms

Diseases: (pulmonary > other)

·        aspergilloma

·        disseminated Aspergillus (immunosuppressed host; invades across tissue planes)

·        contiguous from sinus and orbital foci

·        single/multiple abscesses or microabscesses

·        allergic bronchopulmonary aspergillosis (ABPA)

§         presents like asthma; intermittent wheezing, bilateral pulmonary infiltrates, brownish sputum, causes bronchopulmonary fistulas, peripheral eosinophilia / IgE may be elevated and skin testing may be positive to antigens / central bronchiectasis is common but usu. do NOT see peripheral cavitation

·        hyphal angiitis à small/large vessel thromboses, cerebral infarction/hemorrhage, and mycotic aneurysms

Diagnosis:

·        bronchoscopy (can get contaminants in sputum but true infection should be diagnosed by pathology and clinical picture)

·        CSF culture rarely positive / need tissue histology / special Ag assay for CSF, urine, serum

Treatment: Ampho B and liposomal ampho B historically, but some studies show better results with IV voriconazole (2 doses 6 mg/kg day 1 then 4 mg/kg x at least 7 days) / must be drained/removed / mortality 50-70%

Resistance: only the rarely occurring A. terreus is resistant to Ampho B (this may have changed)

 

Mucormycosis

Caused by Zygomycetes: Rhizopus, Rhizomucor, Cunninghamella, Absidia / irregular, broad, non-septate, 90 degree branching, sporangiospores, rhizoids

Risk factors: diabetes (esp. DKA), organ transplant patients, hematologic malignancies, patients receiving deferoxamine therapy

Diseases:

·        rhinocerebral disease / septic thrombosis of cavernous sinus and internal carotid à vision loss, unilateral face pain, lethargy, headache, periorbital swelling, proptosis, and opthalmoplegia // mycotic aneurysm formation is rare

·        pulmonary, GI, cutaneous

Diagnosis:

·        neuroimaging: sinus opacification, bone erosion, and obliteration of deep fascial tissue planes (not for diagnosis but to guide prognosis and therapy)

·        CSF may be normal or show nonspecific changes

·        biopsy/culture of nasal turbinate et al à characteristic broad, nonseptate, irregularly branching hyphae on KOH wet mount

Treatment: amphotericin B (10-12 wks), local debridement including possible orbital exenteration, ?hyperbaric oxygen

Prognosis: mortality 30% to 80% (residual morbidity ~70%)

 

Pneumocystis carinii  (PCP)

General: 1st AIDS-defining illness in 30% of HIV (80% lifetime incidence in HIV) / vulnerable at CD4 < 200/µL / incidence 40-60%/yr after one episode / 40-50% incidence with CD4 < 100

Presentation: fever, dyspnea, nonproductive cough evolves over weeks or even acutely over days; classic presentation is dyspnea on exertion out of proportion to CXR

Complications: bullae, bronchopulmonary fistula with a pneumothorax that won’t heal until one stops giving steroids

Diagnosis: GMS or silver methenamine stain of sputum (sensitivity 30-75%) or BAL cytology (sensitivity ~90% but must send in separate container for immediate fixation; also still usu. sensitive even up to week after initiation of treatment)

CXR à 20-30% with normal CXR or diffuse, bilateral perihilar infiltrates

Labs: LDH < 220 very unlikely to have PCP

Ddx

·        diffuse interstitial infiltrates: Histoplasma, MTb, M. kansasii

·        patchy/pleural-based: MTb, Cryptococcus

·        cavitary: MTb, coccidiomycosis

Treatment: [current recommendations]

·        All regimens for 21 days / bactrim (20 mg/kg/day IV or PO) / pentamidine (3 to 4 mg/kg IV once daily) / clindamycin 300 to 450 mg po qid + primaquine 15 mg/day po / dapsone plus pyrimethamine / atovaquone 750 mg po bid / TMP 20 mg/kg/day po + dapsone 100 mg/day po

·        if PaO2 < 70 or A-a gradient > 35 mmHg (prednisone 40 mg bid x 5 days, 20 mg bid x 5 days, 20 mg qd x remainder); reduces hypoxemia acutely and the amount late fibrosis

Prognosis: mortality for given episode 15-20% if requiring hospitalization mortality in AIDS patients after PCP is 50% by 1 yr (60% if required ventilation)

Prevention: Bactrim 80/400 mg/day for AIDS with CD4 < 200 (or dapsone 100 mg/day or aerosolized pentamidine)

o       some say can discontinue prophylaxis if sustained CD4 above 200 ( > 3 months )

 

            P. jeroveci

                        Usu. presents as diffuse pneumonia / can less commonly present as upper-lobe cavitary infiltrate

 

Fusarium

disseminated infections occur in immunocompromised (neutropenic) patients by Fusarium solani complex, Fusarium oxysporum, Fusarium verticillioides, Fusarium proliferatum and rarely other fusarial species

Treatment: possibly posaconazole

 

 


Virology

 

HIV

 

Respiratory                   RSV, influenza, parainfluenza, rhinovirus, coronavirus, adenovirus

Childhood exanthems   measles, mumps, rubella, roseola, chicken pox

Enteroviruses                    Coxsackievirus, Echovirus

Zoonotic                        Arbovirus, Arenavirus

Hepatitis

Diarrhea

Rabies

Herpes (HSV, VZV, EBV, CMV)

Tumor Viruses

Other virus

 

         Naked                                    Circular                                      Huge

 

Parvovirus        ss DNA            Hepatitis B - ds DNA               Herpesvirus - ds DNA

Papovavirus      ds DNA           Papovavirus - ds DNA             Poxvirus - ds DNA

Adenovirus       ds DNA           Hepatitis D - ss RNA               Arenavirus - ss RNA

Picornavirus      ds RNA           Arenavirus - 2 ss RNA             Rhabdovirus - ss RNA

Calicivirus         ss RNA            Bunyavirus - ss RNA                Filovirus - ss RNA

Reovirus           ds RNA                                                           Paramyxovirus - ss RNA

 

 

Viruses associated with cancer

Direct neoplastic transformers: HPV, EBV, HHV-8, HTLV-1

Indirect transformers (enablers): HIV, HBV, HCV

 

 

Respiratory Viral Infections

 

RSV   

paramyxovirus, pleomorphic, non-segmented, ss (-) RNA / contact spread

            upper (more) and lower respiratory tract invasion / G - attachment / F - fusion, syncitium

            respiratory epithelium / IF is green, Elisa / ribavirin (SPAG)

            vaccine very expensive / RSV hyperimmune IgG given to preterm infants

 

Influenza        

orthomyxovirus, pleomorphic, segmented, ss (-) RNAVirus A,B,C / hemagglutinin and neuraminidase / drifts (all) and shifts (A)

primary pneumoniae (A) / bacterial superinfections / TSS (B) / myositis (B)

Reye’s syndrome (no aspirin) / Neuro (Guillain-Barré) / cardiac

vaccine: yes (mixture) / amantadine, rimantadine (only type A) curative/prevention

 

Parainfluenza  (types 1 – 4)

paramyxovirus, non-segmented, ss (-) RNA, H N and F proteins

Spread by contact or aerosolization

Type 1 causes croup (laryngeotracheobronchitis) / late summer-fall (early childhood)

Type 2 less severe croup and other URI stuff / late summer-fall (early childhood)

Type 3 causes bronchiolitis, pneumonia in infants / late spring-summer (babies)

Type 4 mild

Treatment: Ribavirin under investigation / vaccine: in progress

 

Rhinovirus      picornavirus, naked, ss (+) RNA

contact or aerosolization / 100 serotypes / grows in cold / incubation 2-3 / shed 1 month / IgA by 1 wk / IgG 1 wk-1 mo / treat symptoms / interferon promising?

 

Coronavirus    large, ss (+) RNA

                        contact or aerosol / winter peak in U.S. / nucleocapsid and 2 envelope proteins

                        (peplomers) are major Ag’s / 229E and OC43 / URI, LRI & GI (watery diarrhea)

                        Treatment: supportive

 

                        SARS-CoV

CXR shows diffuse opacification in advanced stage

                        Treatment: supportive only / respiratory isolation imperative

 

Adenovirus     large, naked, icosohedral, ds (+) DNA / 47 types / type 7 is worst / 40 & 41 are ?

Transmission: secretion contact or fecal-oral

Diseases: pneumonia (smudge cells), diarrhea, GU (hemorrhagic cystitis), conjunctivitis [pic], CNS, endocarditis?, disseminated, congenital

Presentation: rash may or may not be apparent / periauricular nodes / hemorrhagic cystitis (blood in urine lasts one day)

                        Diagnosis: grape-like clustering / hemagglutinin

Treatment: symptomatic and IgG for immunocompromised

 

Childhood Exanthems

 

 

Measles (rubeola) [dermis]               

paramyxovirus, enveloped, H & F

Transmission: infective secretions (5 days prior / 4days after) / kids over 6 months / respiratory or conjunctiva to viremia

·        1-10 day incubation / severe cough (destruction) / high fever (40.6 or 105)

·        1st to 3rd day - Koplik’s spots on mucous membranes (blue-white on reddish background)

·        3 to 4th day exanthem from head then trunk then extremities

Complications:

·        subacute sclerosing panencephalitis or SSPE (chronic condition involves CNS; occurs rarely in children contracting measles at age < 2 yrs)

·        concurrent pneumonitis

·        invades WBC causing immune impairment (can cause TB relapse)

Diagnosis: clinical but pathology of respiratory secretion might show multinucleatd giant cells with inclusion bodies / IgM positive 1-2 days after rash

Treatment: ribavirin? / vitamin A therapy shown to reduce mortality (recommended for severe cases, immunodeficiency, vitamin A deficient or malnourished, impaired intestinal absorption, recent immigrants)

Prevention: vaccine - live attenuated

 

Mumps                      

paramyxovirus, enveloped, head and neck

Transmission: infective secretions (7 days prior to 9 days after resolution) / kids, late winter / inhalation begets viremia

Course: 6-18 day incubation / asymptomatic or fever, glands / parotid gland(s), heart, kidneys, orchitis, breasts, aseptic meningitis (10%) / encephalitis (10-20%)

vaccine - live attenuated

 

Rubella (German Measles) [dermis]                

togavirus (see EEE, WEE), enveloped, icosohedral, ss (+) RNA

Transmission: oral secretions / congenital / respiratory to viremia

Course: 16 day incubation à mild illness, fever, macular/maculopapular rash on head/neck/trunk, reddish spots/petechial lesions on soft palate / cervical lymphadenopathy / arthralgia or arthritis (more in women, adults) / up to 25% can be asymptomatic

Congenital (deafness, cataracts, congenital heart disease, hepatomegaly, splenomegaly, growth retardation) / 39% aborted, 25% gross anomaly, 36% normal

Labs: mild decreased WBC’s and platelets

vaccine: live attenuated / no treatment

 

5th Disease (Parvovirus B19) (erythema infectiosum) [dermis]          

micro: naked, icosohedral, ss DNA

Transmission: respiratory / children (5-14 yrs) to young adults / replication in pronormoblast (RBC)

Course: 4-12 d incubation à mild febrile illness followed by lacey-appearing facial rash “slapped cheek” (and sometimes extremities in adults)

Complications: aplastic crisis (with underlying hemoglobinopathy, immunocompromised, and pregnancy (leading to spontaneous abortion, hydrops faetalis)), arthralgias, arthritis due to production of IgM (transiently positive RF, ANA) may be persistent (more in young women, usu. resolves within 2-4 weeks)

Diagnosis: may see giant pronormoblasts in peripheral smear, serology not reliable (IgM or IgG usually fades by 2-3 months and is often negative in HIV patients)

Treatment: no vaccine / IVIG infusions may help in protracted cases (esp. in cases of severe red cell aplasia)

 

Roseola (exanthem subitum) [dermis]  

Human Herpesvirus 6 (HHV-6)

Course: several days (3-5) high fever / after fever resolves (occasionally before), rash (neck, trunk then face, scalp, extremities) called exanthem subitum

Presentation: rash lasts 2-48 hrs / febrile seizures in infants / anorexia, irritability in 6-36 months

no vaccine, no treatment

 

Picornaviruses

naked / icosohedral / ss (+) DNA / enterocytes replicate at lower pH and higher T than rhinos

VPg genome / viral encoded RNA polymerase / P1 (capsid) becomes VP1-4 / P2, P3 for replication

 

Enteroviruses (Coxsackievirus, Echovirus, Poliovirus)

 

Coxsackievirus, Echovirus

Diseases:

·        Coxsackievirus A/B self-limiting or aseptic meningitis (rare outside of neonates, except more serious in patients with hypogammaglobulins, for whom IVIG may help)

·        Coxsackievirus A à hand, foot, mouth (⅔ have exanthem)

·        Coxsackievirus B

§         URI evolving into pericarditis/myocarditis (usually both and not just pericarditis)

§         herpangina if only oral lesions occur

§         pleurodynia (Bornholm disease) / paroxysms of sharp stabbing pain in chest/abdomen (15-30 mins) accompanied by fevers, diaphoresis, tachycardia / Treated with NSAIDs

·        Echovirus à common cold, aseptic meningitis, acute hemorrhagic conjunctivitis

Course:

·        prodrome: brief period of low-grade fever, malaise, sore throat, anorexia / lesions absent

·        1-2 days later à rash (morbilliform vesiculopustular, often hemorrhagic component) affects palms and soles (erythematous on palmar hands, finger, plantar feet, in between toes), oral lesions (shallow yellow with red halos, mildly painful; 90% with A16 coxsackievirus oral lesions)

Labs: can produce meningitis with CSF resembling bacterial meningitis (high WBCs, etc.)

 

Poliovirus       

fecal-oral / replication in lymphoid tissue / viremia / seeds RE and CNS / autoimmune damage

via molecular mimicry / 99% asymptomatic / dirt and disease paradox / more severe for older victims

Killed Salk (IPV) - injection / humoral immunity

Live Sabin (OPV) - oral and cheap / IgG and IgA / can mutate / contraindicated in immunocompromised / may not work if you’ve got another GI virus at time of vaccination)

 

 

Zoonotic Diseases     (all enveloped except reovirus)

 

Arbovirus

                       

general            

mild or asymptomatic 2 - 3 / prodrome 3-7 / severe rechallenge

transovarial transmission / extrinsic incubation period /

usually have sylvatic cycles (exc. urban dengue and urban yellow and sometimes SLE)

vaccines for Yellow Fever (live attenuated) / WEE and EEE and Powasan (inactivated)

 

Togavirus      

alphavirus / (+) ss RNA / early (enzymes) and late (structural) translation

 

Eastern equine encephalitis (EEE)5% mortality

 

Western equine encephalitis WEE20% mortality

                       

Flavivirus

genome translated to single polypeptide / RNA dependent RNA polymerase / budding - lysis

·        Yellow Fever (aedes mosquito)

high fever, black vomitus, jaundice, councilman bodies (acidophilic) in liver / severe systemic / fever, hepatitis

·        St. Louis encephalitis (culex mosquito)  (10%)

·        Japanese encephalitis

·        West Nile Virus

summer, community outbreaks, dead crows / IgM produced intrathecally in acute infection might be detected in CSF / MRI abnormal in 30% of cases (unlike HSV)

·        Powasan fever (tick)

·        Dengue fever (aedes mosquito)

        • mild (myalgia, petechiae, epistaxis)
        • severe (fever, rash, GI hemorrhagic, shock) [Ab’s work against you]

Diagnosis: IgM ELISA or paired serology

Ddx: Rickettsial disease, acute HIV, other hemorrhagic viral illness

 

Bunyavirus

(-) ss RNA / do NOT have a matrix protein (unlike other (-) sense RNA)

attach by G1 glycoprotein / endocytosis / budding (lysis or exocytosis)

o       California encephalitis (mosquitoes, flies, ticks) (seizures)

o       Lacrosse encephalitis (same) (5-18 yrs - seizures)

 

Reovirus

naked ds RNA / segmented

Colorado Tick Fever (fever, myalgia)

 

Rodent-Borne Viruses

 

Arenaviruses 

enveloped, spherical, pleomorphic / 2 circular ss RNA and transcriptase

 

Lymphatic Choriomeningitis Virus (LCV)

Transmission: aerosols

acute fever: headache, myalgia / sub-acute: up to 3 months of meningitis

 

Hemorrhagic Fevers (level IV agents) [acp]

symptoms are many

Treatment: ribavirin, IgG and possibly IFN-alpha for Lassa, Junin ?New World Fever (anecdotal/small studies only)

                       

Bunyavirusesmortality 67%

Hantavirus

Diseases: hemorrhagic, pneumonia

Transmission: inhalation, conjunctiva, skin breaks

o       California encephalitis

o       Korean hemorrhagic fever

o       Sin-Nombre

o       Crimean-Congo

o       Sandfly-Rift Valley

Treatment: ribavirin

 

Hantavirus pulmonary syndrome

Transmission: aerosolization of urine from infected rodents

Presentation: similar to Influenza then progresses to ARDS-like (within one week; mortality 30-40%; if you survive first 48 hrs, good chance will recover fully)

Labs: thrombocytopenia, IgM may be positive during acute phase, BAL will be non-specific

            Ddx: rickettsial disease, meningococcemia, plague, tularemia, sepsis

 

Filoviruses – mortality 90%

filamentous, enveloped, (-) ss RNA / seven proteins / rep like rhabdoviruses / 4 - 6 day incubation / eosinophilic inclusions / Marburg, Ebola

 

Poxviruses

            Micro: orthopoxviruses - complex lipid-containing envelope / ds DNA / nucleoprotein Ag

common to all / replication unique among DNA viruses (takes place in host cytoplasm) /

parapoxviruses - ORF (granulomatous)

Diseases:  milker’s node - nodular lesions on fingers, face / small pox

Transmission: direct contact with lesions (exc. smallpox or variola, which is inhaled) / vaccinia (direct?)

 

eosinophilic cytoplasmic inclusions, papules with whitish material inside, usually arms and trunk, spread by direct contact, flesh colored / more prevalent in HIV patients (should improve as HIV better controlled)

 

                                    lesions at same stage of development / hands and soles / face

Treatment: vaccine available (can cause eczema vaccinatum à contraindicated for patients with eczema)

 

Molluscum contagiosum - unclassified poxvirus

eosinophilic cytoplasmic inclusions, papules with whitish material inside, usually arms and trunk, spread by direct contact, flesh colored / more prevalent in HIV patients (should improve as HIV better controlled) [pic][pic]

 

                        Smallpox

lesions at same stage of development (and patients become systemically ill before rash) / hands and soles / face / everywhere [pic]

Treatment: vaccine available

·        vaccinia necrosum or progressive vaccinemia [pic] (treat with vaccinia immune globulin / contraindicated with immune deficiencies or close contacts with those who are immunocompromised)

·        can cause eczema vaccinatum (severe vaccinia lesions appear in areas of eczema) [pic] // contraindicated for patients with eczema

 

 

Viral Hepatitis [A, B, C, D, E] [liver disease]

 

Transmission: [except HAV and HEV] fomites, blood-borne / intercourse or intimate contact NOS, parturition (infectivity when HBsAg positive, before symptoms)

Presentation: headache, nausea, vomiting, abdominal pain, diarrhea, anorexia, fatigue, fever lasting 3 to 7 days (wide range from asymptomatic to severe discomfort), sometimes pharyngitis with coryza

Physical Exam: scleral icterus and jaundice (absent in most children), enlarged, tender liver (70% Murphy’s), benign rash (sometimes present early in course)

Differential Diagnosis: EBV, CMV, enterovirus, other virus (often multi-organ involvement)

 

Hepatitis incubation periods

1.      HAV = 15-60 days

2.      HEV = 15-60 days

3.      HBV = 45-160 days

4.      HDV = 45 – 180 days

5.      HCV = 14 – 180 days

6.      HGV =

 

Hepatitis A (HAV)

            most common cause of acute viral hepatitis in US

picornavirus / naked / RNA

Transmission: fecal-oral, foreign travel, poor sanitation, contact with children in day-care

(only shed virus before symptoms develop)

Course: 2 - 7 week incubation / prodrome 1-7 days / jaundice, sickness / resolves by 14 days although can take up to 6 months (no chronicity or cirrhosis), very few develop fulminant hepatitis but chances much higher with existing HBV/HCV (50% mortality)

Note: actually can have CNS involvement in prodromal stage (uncommon)

Serology: IgM positive 3-65 months / IgG lifetime

Prevention: vaccine available (should give especially to people who already have HBV/HCV)

Treatment: mainly supportive / HAV Ig therapy reduces symptoms when given < 14 days (should be given to family members/exposees within 2 weeks of exposure)

Vaccine: should be given to HIV patients

 

Hepatitis B (HBV) [diagram][diagram]

 

circular ds DNA / transcriptase / 1 million

Presentation: arthritis (+/- urticarial rash) precedes liver findings

Course: 2.5 months incubation (ranges from 1.5 to 6 months), usually only 1 to 1.5 months of illness, but worse with higher age or inoculum (i.e. transfusion of .0001 uL enough)

Prognosis: 95% of adults recover completely / chronic liver disease in 5-10% (20% of HIV patients)

chronic persistent: resolves in 1 year

chronic active: progress to HCC, cirrhosis (most common cause in Asia)

chronic carrier state: more likely among children (90% among newborns)

            Complications: HCC / HBV associated vasculitis

Serology: HBsAg (shed from envelope) / core HBcAg (DNA) / viral core particles HBeAg (detergent treatment) / anti-HBc at 2 months (not protective) / anti-HBs at 5 months (protective) / window before 5 months with no HbsAg and you get anti-HBc IgM / HBeAg indicates acute phase / chronicity may mean no anti-HBs

Prevention: recombinant HBV vaccine, HBIg therapy given to at risk patients (needlestick, newborns within 4 hrs, HIV patients, patients with anti-HBc and negative HBV DNA replication)

Treatment:

·        INF-a is used to treat chronic HBV in adults (studies in children are less encouraging)

·        NtRTIs (lamivudine, adefovir, entecavir, telbivudine); but note, to decrease resistance development, patients with HBV but without HIV should not use agents with anti-HIV activity (adefovir, entecavir, interferon)

 

Treatment of HBV associated vasculitis: must use IFN-a/vidarabine therapy to control HBV while giving steroids (or plasma exchange) to control vasculitis

 

Hepatitis C (HCV)

 

flavivirus, ss RNA / very common in U.S. (4 million cases)

Presentation: often presents as chronic liver disease

Transmission: IV drugs, transfusions

Course: incubation (ranges from 1 to 6 months), chronicity (50%), may lead to cirrhosis (40%) and carcinoma / often subclinical, diagnosed because of chronic liver disease

Serology: anti-HCV takes 3 months to appear / can do PCR for HCV DNA (viral load has less prognostic value than simply as qualitative means of determining whether there is active viral replication going on) / can do qualitative or quantitative PCR for HCV RNA (again not often needed)

Treatment: INF-alpha-2b, ribavirin / treatment of acute seroconversion yield very high cure rate / treatment of chronic HCV follows the ⅓ rule (⅓ cure, ⅓ remission, ⅓ refractory) / can have chronic non-active hepatitis with small amount of viral replication / liver biopsy only sure way to determine effect of treatment

Prognosis: certain genotypes respond more and less to treatment (genotypes 1 and 4 require 48 wks therapy (50% success); 2 and 3 require 24 wks (80% success and can defer biopsy)

 

Extra-hepatic manifestations of HCV

Skin: purpura (5%), Raynaud’s (5%), cutaneous vasculitis (5%), psoriasis (2%), porphyria cutanea tarda (1%), lichen planus (1%)

Musculoskeletal: arthralgia (20%), arthritis (2%), myalgia (2%)

CNS: sensory (10%), motor (5%)

Other: lymphocyte sialadenitis +/- sicca (10%), HTN (10%), uveitis (1%), thyroiditis

 

Cryoglobulinemia (see labs)

present in 40% although clinical sequelae (vasculitis) only in 2-3% / when there is vasculitis, involvement is cutaneous/palpable purpura (80%), nerve (50%), renal (usu. MPGN) (30%)

positive cryoglobulinemia also portends HIV-positivity (20%) and other rheumatologic conditions (except not Sicca)

            Note: HCV cryoglobulinemia increases risk of NHL and HCC

Treatment: combination therapy with IFN-alpha and ribavirin [treatment of HCV should ameliorate amount and symptoms of cryoglobulinemia]

 

Autoantibodies in HCV

70% with one auto-Ab, 10% with 3 or more auto-Ab

ANA (40%), RF (40%), anti-cardiolipin (30%), c-ANCA (3%), anti-thyroglobulin

HCV-associated anti-cardiolipin Ab is not associated with the APA syndrome (although HIV/HCV is associated with a higher incidence of thrombocytopenia and hypercoagulability)

 

Hepatitis D

 

defective RNA virus / utilizes HBsAg for its shell / only infected hepatocytes

Transmission:  IV drug users / coinfection (5% chance of chronic HDV), superinfection (70%) / often produces fulminant hepatitis

Course: acute HDV has 2-20% mortality / 70% will develop cirrhosis in 2 - 15 yrs

Serology: easy to miss diagnosis of acute HDV (low Ab titres), chronic HDV is easier to detect (Ag in liver and high Ab’s)

 

Hepatitis E

 

calicivirus / fragile RNA virus / many genotypes / one serotype

Indian subcontinent, northwest China, former USSR

Transmission: enteric, water-borne epidemics / fecal-oral to HAV

Course: similar to HAV with viral shedding for a week after onset of jaundice / usu. self-limited 1-4 weeks (0.1 to 4% fatality) except in

3rd trimester of pregnancy (causes fulminant hepatitis with (10-20% fatality)

Serology: diagnose with anti-HEV

Prevention: vaccine under development 1/07

 

Viral Hepatitis Labs

 

Note: with dual hepatitis B and C infection, labs may be misleading. Also, IgM can actually be detected even in chronic hepatitis infection. (see below)

 

HBsAg            appears 1-10 wks after HBV / longer than 6 months indicated chronic carrier state / some strains of HBV are low surface antigen (can go undetected by HBsAg assay)

 

anti-HBc         may appear as IgM after HBsAg, but before anti-HBs appears / persists for a long time (some labs use too sensitive a test) / IgM can be detected even in chronic hepatitis infection, due to neo-antigen presentation and antibody response

 

anti-HBs         recovery and immunity ( > 10 ml U/ml is protective, some labs measure to 5 and are too generously called positive or protected) / levels used to guide treatment on exposure

 

HBeAg            appears 3-5 days after HBsAg / lasts 2-6 wks / associated with viral replication

 

anti-HBe         appears after anti-HBc / may indicate lessening of infectivity (only used with chronic HCV patients to make decisions about treatment)

 

anti-HAV        coincides with acute liver necrosis / remains indefinitely, so only diagnostic if IgM is found or it follows a high to low shift (30% positive IgG in population)

 

HCAg              useful for early diagnosis of HCV and monitoring therapy (RNA assay also available)

 

anti-HCV        weeks to months delay in onset

 

HCV PCR       designed to be better for early diagnosis / 20% false positives and negatives  (?FDA approved for use with initial diagnosis)

 

HCV Elisa-3   has a 50% false positive rate (way too sensitive) / use another 2nd line test

 

HGAg             almost available

 

 

Diarrhea

 

Rotavirus (6 mo to 2 years old)          

Reovirus / 3 serogroups / group A 1-4 is most important / icosohedral / naked / segmented ds RNA / RNA dep-RNA polymerase / viral replication: does not need a nucleus / ds event allows recombination

Epidemiology: major cause of infant diarrhea (15% of children under 2 may have 5 episodes, 50% incidence by 3-4 yrs /  follows geographical and seasonal (Winter) distribution pattern (more year round near equator)

Transmission: fecal-oral, only 10 particles needed

Pathology: local damage causes fluid loss / loss of brush border, flat mucosa / sIgA provides cross protection

Presentation:  fever (30-50%), vomiting (80-90%), explosive watery diarrhea, stools (non-bloody)

Diagnosis: rapid antigen test of stool sample (ELISA is cheapest and fastest) or EM

Course: 1-3 incubation / vomit (1-3) and diarrhea (3-9 days)

Treatment: supportive / rehydrate / electrolytes – pedialyte while vomiting – food when diarrhea persisting -

Prevention: oral vaccine awaiting FDA approval

 

Norwalk (older children, adults)

Calicivirus family (norovirus) / icosohedral / naked / + ss RNA / resistant virion / rep and assembly in cytoplasm

Epidemiology: any time of year / major cause of childhood and adult diarrhea (probably > ½ of cases of non-bacterial diarrhea)

Transmission: fecal-oral

Pathology: local damage causes fluid loss / sIgA provides cross protection

Course: 10-50 hour incubation and course self-limited / same as rotavirus plus fever, anorexia, respiratory

Diagnosis: RT-PCR ELISA

Treatment: supportive / rehydrate / electrolytes

Prevention: oral vaccine awaiting FDA

 

Astroviruses

five human pathogens / star-shaped morphology / + ss RNA

Epidemiology: fecal-oral / common cause of diarrhea in infants

Diagnosis: EM of stool

                       

Enteric Adenovirus               

types 40 and 41/ 8 - 10 day incubation and diarrhea / usually respiratory

too hard to culture (unlike other respiratory viruses)

                                   

Misc.   

            small, round viruses

coronaviruses

adenovirus

viral gastroenteritis in AIDS pts.

 

 

Rhabdoviruses (rabies)   

 

Micro: lipid envelope, gp peplomers surround helical capsid / ss RNA / 5 proteins

Epidemiology: domestic and wild animals / 40K to 100K a year / 1-2 in U.S.

Transmission: bites / mucous membranes / aerosols / transplants / intra-axonal retrograde spread

anterograde gets it to saliva

Presentation: 4 days - 19yrs pre-clinical / prodrome 2-10 days / pain or numb at site and other non-specific symptoms / neurological 2-7 days / furious / paralysis, coma, respiratory arrest

Diagnosis: negri bodies (old way) / dIFA preferred

Ddx:  herpes, EEE, Ca, SLE / paralytic: polio, tetanus

Treatment:

o       kill wild animal (send head to lab) or quarantine domestic animal 10 days

o       cleanse wound with 20% soap

o       tetanus toxoid and antibiotics

o       HRIG (10 units/kg into wound site and equal amount IM into gluteal

o       active immunization with 5 doses HDCV or RVA over 28 day period

            Vaccination: pre-exposure - HDCV 3 doses / post-exposure - 5 doses

 

Herpesvirus     ds DNA / icosohedral / lipid envelope / replication in nucleus

 

HSV-1            

humans only reservoir / transmitted by direct contact

Diseases:

·        gingivostomatitis

·        conjunctivitis – urgent optho consult

·        keratitis – dendritic  pattern on fluorescein staining of cornea / urgent optho consult

·        pneumonia (bilateral consolidations)

·        herpetic whitlow – when you get it on your finger

·        eczema herpeticum – usually with superinfection

·        HSV Encephalitismost common cause of acute viral encephalitis (70% mortality untreated)

Pathogenesis:

·        acute infection à multinucleate syncitia / primary can be asymptomatic, gingivostomatitis or other à multiple vesicles in localized area, may have fever, malaise / 1-2 weeks, then

shed for 10-15 days / primary usually more severe than recurrence

·        latent infection à DNA lies dormant in sensory ganglia then comes out / recurrent infection / unilateral x 1 week, shed for 3-5 days, careful to avoid autoinoculation of cornea

                        Note: HSV meningitis/pneumonia occurs in both normal and immunocompromised

Exam: vesicles more disseminated than herpangina (hand-foot-mouth)

Diagnosis:

·        PCR vesicles/CSF (takes a few days, more sensitive than culture, which takes ~2 wks

·        Tzanck smear is good but can’t distinguish VZV / cowdry A inclusions (eosinophilic body with halo) (also seen with VZV, CMV, PME, SSPE)

MRI: may produce characteristic unilateral temporal lobe lesion (MRI normal in ~10% and often normal early in course)

Treatment: acyclovir and similar agents, foscarnet for resistant cases / all of these agents seem to have some form of renal toxicity / ? nucleotide analogs - iododeoxyuridine and trifluorothymidine

Note: rapid screening test for acyclovir resistance (esp. with BMT patients and GVHD) being developed

 

HSV-2

Diseases: genital / neonatal / adult

·        Primary: vesicles and pustules / systemic symptoms / 3-4 weeks

·        Nonprimary

·        Recurrent: prodrome and vesicles / 1-2 weeks

Neonatal: 60% mortality - neurological - internal organs (disseminated)

lymphocytosis, bloody CSF

Treatment: IV acyclovir and others

 

HHV-6           

roseola / cytopathic for T-cells / most children have it by age 5 / contact or respiration

 

HHV-7

same thing / most by age 2

 

HHV-8 (all of these are seen more in immunocompromised, esp. HIV patients)            

·        Kaposi’s sarcoma

·        Castleman’s disease or angiofollicular lymphoid hyperplasia / can cause acute aplastic anemia/pancytopenia

·        Primary effusion lymphoma – fever, malaise, pleural effusions (+/- ascites, pericardial effusions) – prognosis very poor

 

Herpes B virus          

HSV of monkeys / lethal encephalitis for humans / acyclovir

 

Varicella-Zoster (VZV)

            Diseases: varicella (chicken pox) / herpes zoster (shingles) / habitat: ubiquitous

            Transmission: contact for both / respiratory for varicella

            Pathogenesis: ballooning degeneration / syncitia / inclusions

            Primary: respiratory mucosa, blood and lymphatics, RE

Latent: dorsal root ganglion

 

Varicella (Chicken Pox)

            Ddx: coxsackie, echovirus, rickettsialpox

Course: Incubation: 14 - 21 days / Prodrome: 1-3 days / successive crops, different stages of development, more on trunk / lesions are contagious about 10 days from eruption to crusting over / may have superinfection and/or scarring / less common in adults (20% of adults get VZV pneumonia)  / 20% mortality in immunocompromised patients

Complications: Pneumococcal sepsis

Treatment: benadryl / special baths

Note: should not have high fever > 101 beyond 2nd day (pt should come to ER)

Note: enanthem is painful / exanthem is itchy

Vaccine: probably needs boosting at least once, probably more than once over years

 

Shingles (Herpes Zoster)

Incidence: 30% lifetime incidence (assuming most people have been exposed to chicken pox) / risk increases with age beginning at 50 yrs
Presentation: b
urning pain typically precedes the rash (multiple vesicles, eruptions [pic]) by several days and can persist for several months after the rash resolves / usually only one single sensory ganglion (one dermatome; thoracic >> trigeminal, lumbar, cervical, nasociliary), but widespread disease can occur in immunocompromised patients [a basic difference from HSV being that HZ will just randomly choose a dermatome (the chicken pox was everywhere), whereas HSV is confined to original dermatomes it infected and tends to recur on a more periodic basis]

Note: if nasociliary or any suspicion of ocular involvement (immediate ophthalmology consult indicated)

Diagnosis: Tzanck smear of lesion / combination of PCR (of vesicle fluid) and IHC (immunoassay) increases specificity to 97%

Complications:

·        postherpetic neuralgia occurs after resolution of rash / may last weeks, months, years / 40% over 60 yrs will develop / very debilitating and difficult to treat / TCAs, Neurontin used with variable effect / vaccine more effective at preventing postherpetic neuralgia in > 70 yrs than in those < 70 yrs who develop shingles

·        encephalitis, myelitis, cranial nerve palsies, peripheral nerve palsies

Treatment:

·        acyclovir or famciclovir or valacyclovir (most effective < 72 hrs after onset)

·        corticosteroids can reduce pain and incidence of postherpetic neuralgia (treat as other neuralgias)

Vaccine: live attenuated vaccine / immunoprophylaxis with VZV IG (< 72 hrs of exposure) / less painful, more itchy with children

 

Other VZV Complications:

 

·        Ocular: VZV and HSV-1 may co-infect the cornea / consult ophthalmologist for ocular involvement

·        Postherpetic neuralgia (can be persistent and debilitating)

·        VZV myelitis [MRI] [MRI]

Diagnosis: PCR of CSF, VZV antibodies in CSF, viral cultures

Treatment: there are reports of failed acyclovir then treated with famciclovir

 

            Hemolytic anemia

                        Rare (anti-I or anti-Pr cold agglutinins)

 

Epstein-Barr Virus (EBV)

Diseases: EBV causes 80% of acute infectious mononucleosis (CMV causes 20%)

acute (infectious mononucleosis) / chronic active EBV is different from chronic fatigue syndrome (which is more broad) / associated with various malignancies (see below)

Presentation:

Infants and children – usually asymptomatic or non-specific

In adolescents and adults:          over 50% à fever, LAD, pharyngitis (~1 wk)

10% à splenomegaly, palatal petechiae, hepatomegaly

Course: primary: often asymptomatic / 3-7 week incubation / 3-5 day prodrome / sore throat

Complications (uncommon): hemolytic anemia, thrombocytopenia, neutropenia, aplastic anemia, myocarditis, hepatitis, genital ulcers, rash, neurological complications (Guillain-Barré, encephalitis, meningitis)

Emergency: splenic rupture, airway obstruction

Pathogenesis: B-cells infected via C3b receptor (~20% of them) / Downey cells (T-cells) / Cellular immunity more important for control of EBV / X-linked lymphoproliferative disease (Duncan’s) à over ½ die from EBV infection

Transmission: oral secretions / oral shedding abolished by Acyclovir (does not change EBV-infected cell count in blood)

Differential Diagnosis: toxoplasmosis, HHV 6 (roseola), HIV (usually no atypical lymphocytosis), other unidentified pathogens, Group A strep or Adenovirus (pharyngitis), acute leukemia (absence of pharyngitis)

Diagnosis:

elevated WBCs (elevated monos) / atypical lymphocytes (can sometimes be confused with acute leukemia or disseminated lymphoma)

Heterophile antibodies

monospot rapid heterophile Ab test, (sensitivity ~80%) (may also see cold agglutinins, cryoglobulins, antinuclear and RF)

serological test for EBV and CMV (more sensitive) / VCA (+ earlier), EBNA (+ later)

elevated ALT, atypical lymphocytes (responding T cells)

Note: causes false positive RPR test

Treatment:

·        restrict activity (splenomegaly), supportive for uncomplicated infection

·        Steroids for impending upper-airway obstruction, acute hemolytic anemia, severe cardiac involvement, neurological disease

·        Amoxicillin will give a drug reaction and maculopapular rash (90% of the time; not a B-lactam allergy)

Vaccination for EBV under investigation

 

Cancers associated with EBV

 

Nasopharyngeal carcinoma

IgA to EBV for early detection

 

Burkitt’s

limited Ag expression hides Downey’s

African à jaw, P. falciprum, EBV (90%)

USA à abdominal, from EBV

 

AIDS lymphomas (see other)

Burkitt’s (early), Immunoblastic (late)

 

Oral hairy leukoplakia

ubiquitous, saliva (asymptomatic shedding) / nonmalignant / active viral replication Treated with acyclovir

 

Hodgkin’s

40 to 60% with EBV DNA

 

Lymphoproliferative disease (congential/acquired)

EBV viral load can sometimes be detected  before disease – controls may have incidence of ~10%

Treatment: reduction of immunosuppressive medication can sometimes be curative / surgical removal or irradiation (esp. GI tract) / interferon alpha under investigation

Rituximab (monoclonal Ab) under investigation / cytotoxic chemotherapy in some refractory cases / BMT patients – unirradiated donor WBCs may help / EBV-specific cytotoxic T cells

 

Lymphoid interstitial pneumonitis ?

 

Cytomegalovirus (CMV)

Incidence: 50% to 90% (lower socioeconomic groups)

Diseases: mononucleosis-like in adults (heterophile negative), retinitis, encephalitis, pneumonitis [pic], adrenalitis, hepatitis, colitis with severe diarrhea

AIDS (CD4 < 50)

CNS (retinitis > encephalitis, myelitis), gastrointestinal system (colitis, esophagitis > gastritis), and pulmonary system

Source: ubiquitous / any and all secretions

Transmission: congenital, oral, sexual, blood transfusions, tissue transplants (bone marrow et al)

Congenital: most prevalent cause of congenital disease / 0.5-2.5% infected in utero / 10% causes clinical disease / 20% deaf and retarded / perinatal resolves

Diagnosis: antigenemia assay, cytomegalic cells with inclusions, culture, IgM (persists up to 4 months) and IgG (not very informative) / PCR (of body fluids) is best to distinguish invasive from latent / urine culture can determine if virus is being shed in urine

Prevention: condoms / screen transfusion, transplant donors/recipients / PCR to decide who needs prophylactic antivirals / hyper-immune globulin / vaccine under investigation

Treatment: ganciclovir or foscarnet (resistance will develop), topical agents, antisense DNA for retinitis

 

DNA Tumor Viruses

 

all families have examples except parvoviruses (ss DNA)

activate growth accelerators - retroviruses / HBV / EBV

remove growth suppressors - adenovirus / HPV / SV40

15% cancers from oncogenic viruses

Transformation:  for DNA tumor viruses, oncogene is of viral origin / may be cofactor / result of abortive infection

 

Papovirus

-BK                 renal                 no persistence / no human tumors

-JC                  PML                no persistence / no human tumors

-SV40              monkeys           no human tumors /  large T Ag binds p53 and RB / aerosols

-Papilloma       warts               E6 - p53 and E7 - RB  / sometimes persistence of virus in tumor

                                                no in vitro transformation

                                               

Adenovirus       no persistence / no human cancers  / binds RB and p53 by E1A and E1B

 

Herpesvirus      no persistence 

-HSV2            

-EBV               Burkitt’s lymphoma / viral protein LMP1

-CMV

 

Hepatitis B

primary hepatocellular carcinoma / no persistence / no transforming protein/ not in vitro

/complex structure / ? stimulation by viral protein X of transcription genes                      

           

Poxvirus (see other)

-molluscum contagiosum

no in vitro transformation / complex structure / pox growth factor suspected oncogene

 

RNA Tumor Viruses

 

Retroviruses (Basic Biology)

 

reverse transcriptase and integrase carried in virion / 2 copies of ss (+) RNA / uses template switching (interesting phenomenon) / integrates as a double stranded DNA molecule with LTR’s / transformation: promotor insertion,

enhancer insertion, PolyA site insertion (truncation), leader insertion ?, inactivation (p53, RB)

 

gag       structure

pol       enzymatic

env       envelope gp’s

 

mechanism of action:

 

Protease inhibitors prevent virus from cleaving its pro-proteins

            spliced - Vpr, Vpu, Vif (protease target)

            full - gag, pol, env (not protease target)

            viral protease cleaves gag and pol

            cellular protease cleaves gp160 to gp120 (binds CD4 and chemokine receptor) and gp41

 

Other possible targets

            Integrase – Merck is working on it

            tat / tax - increase transcription rate

            rev / rex - increase transport of unspliced mRNA

            nef - negative regulator of transcription

            vif - facilitates maturing during budding

 

HIV / AIDS [opportunistic infections]

 

·        Very informative HIV/AIDS web site

·        HIV/AIDS Case Presentations from Johns Hopkins Infectious Diseases AIDS Site

 

Primary HIV infection

Incubation: 2-4 weeks

Primary HIV infection: symptomatic in 30 to 60%

Presentation: EBV-like syndrome with various symptoms: fever, malaise, headache, pharyngitis, diarrhea, leukopenia, thrombocytopenia, anemia (see below), macular rash

Course: weeks to months – then latency for up to 10 or more years

Diagnosis: P24 Ag test most specific, HIV PCR may have false positives / p24 and gp160 Ab usually by 10-21 days, ELISA (initial test) and Western Blot (confirmatory) usually by 12 wks

Prevention: male circumcision shown to reduce HIV incidence by ½ (in Africa)

 

 

Treatment (see HIV meds)

           

            Normal CD4 count 600-1500 cells/mm3

 

Asymptomatic, CD4     > 400               wait

Asymptomatic, CD4     200 to 400       debatable (VL  > 20,000 à can treat)

Asymptomatic, CD4     < 200               treat

 

Note: many think that starting too early (esp. with poor compliance) will increase the resistance:benefit ratio / not treating also means lower cumulative side effects of anti-retrovirals (lipodystrophy, insulin resistance, pancreatitis, mitochondrial toxicity)

 

            HAART regimens

 

3 NRTI’s

2 NRTI’s + protease inhibitor(s)

2 NRTI’s + NNRT

 

Note: get viral resistance profile if treatment not working (also suspect non-compliance)

Note: never use single agent (guaranteed to generate resistance)

Note: “immune reconstitution syndrome” may occur 1-2 weeks after initiation of HAART (this is why it’s better to wait until any active infection resolved

 

            Complications in Advanced HIV/AIDS

           

Hemolytic Anemia

may be increased risk of thromboembolism in AIDS patients with autoimmune hemolytic anemia who receive RBC transfusions (some consider prophylactic anticoagulation)

 

Thrombocytopenia

can occur early or late / mechanism similar to ITP / when < 20,000, treatment becomes necessary / HAART increases platelets over weeks to months, but if need faster, must have platelet infusion / other options may include steroids, IVIG, anti-RhD Ig and even splenectomy

 

Pancytopenia

            can occur due to ineffective hematopoeisis / normal to hypercellular marrow


Renal Failure in HIV patient

HIVAN (FSGS) – usually occurs early in HIV with progressive course
TTP-like syndrome – HIV associated TMA (thrombotic microangiopathy)

 

DILS disease

3-4% incidence / parotid gland enlargement / sicca symptoms / predominance of CD8 T-lymphocytes in tissues / newly described disease

 

Aphthous ulcers

                        consider infectious causes (HSV, VZV?) / Treatment: thalidomide [NEJM]

 

HIV dementia

psychomotor slowing and focal CNS signs / HIV-associated cognitive motor complex is most common syndrome (usually comes late in course of HIV)

 

            Peripheral neuropathy

                        affects 30% of HIV patients / usually symmetric, bilateral sensory >> motor

 

            Myopathy

                        progressive, painless proximal muscle weakness

 

            Diffuse lymphadenopathy [Ddx]

can occur in early or late stages due to reactive lymphoid hyperplasia (due to B and T cell dysfunction) / Castleman’s

 

Malignancy associated with HIV: various types are increased, esp. lymphoma (Burkitt’s, large B-cell, primary CNS lymphoma, Castleman’s, plasmablastic lymphoma of oral cavity, primary effusion lymphoma, germinotropic lymphoproliferative disorder), Kaposi’s sarcoma, more

 

            Increased incidence of atopic reactions (to medications, allergens)

 

 

Differential Diagnoses for Various Presenting Symptoms

 

Constitutional (fever, weight loss, fatigue):

 MTb, MAI, HIV wasting syndrome, lymphoma, Bartonella

Visual changes, eye pain:

CMV retinitis, ophthalmic VZV

Headache, mental status changes:

Toxoplasma encephalitis, CNS lymphoma (primary or systemic), cryptococcal meningitis, PML (JC virus), HSV?

Work-up: LP, CT/MRI with contrast, EBV PCR may suggest lymphoma (will MRI be obvious?)

Cough, shortness of breath:

PCP, Tb, bacterial pneumonia, influenza

Oral lesions:

thrush, oral hairy leukoplakia, apthous ulcers, HSV

Odynophagia, dysphagia:

Candida, CMV, HSV esophagitis

Chronic diarrhea:

Cryptosporidium, Isosporidia, MAI?,

Genitourinary symptoms:

recurrent HSV infection, Syphilis, cervical

Skin lesions:

Dermatitis? that gets out of control, Kaposi’s sarcoma, Molluscum contagiosum, Bartonella (bacillary angiomatosis), scabies, pruritis nodularis, eosinophilic folliculitis

 

                        Vasculitis (10-30%)

can be secondary or primary / early primary can cause CVA, mycotic aneurysms

 

Lymphadenopathy in HIV Patient

 

Note: GI tract involvement by lymphoma is generally hard to see by radiology / skin usually last thing involved in HIV

 

Ddx with HIV

diffuse large cell lymphoma

MAI-disseminated – blood cultures often positive

Tb-disseminated – biopsy lymph node, bone marrow, etc.

Other disseminated NTM

Histoplasmosis - associated rash, blood cultures positive (50%)

Bartonella henslea – diffuse adenopathy

Blastomycosis – less granulomatous, might be more purulent (skin nodules)

Cryptococcal – expect meningitis

B-cell lymphoma -

T-cell lymphoma - lymphoblastic

Mycosis fungoides and Sezary syndrome

 

Ddx without HIV

Peripheral T-cell lymphoma

B-cell

Fungal

Syphilis

Tb

 

Focal Brain Lesion (FBL) in HIV patient

 

                        With mass effect

            Toxoplasmosis (20% even when seronegative)

                        Primary CNS lymphoma (PCNSL) (40% even with positive toxoplasma IgG)

           

                        No mass effect

            PML (30% even with negative JCV PCR)

                        HSV, VZV, CMV, HIV

            PCNSL (10%)

                        Toxoplasma (6%)

 

Opportunists with AIDS

 

Protozoa: PCP, Toxoplasma, Isospora belli, Cryptosporidium

Fungal: candidiasis, cryptococcus, coccidoides, histoplasma

Mycobacterial: disseminated TB, MAI

Viral: HSV, CMV, VZV, PML

 

Note: don’t stop just because you get one diagnosis.  Example, a patient with pericardial effusion positive for Tb might still have a fungal pneumonia (chest CT, BAL) and don’t miss the cryptosporidium (remember the diarrhea from the HPI), and now the patient has C. difficile too – DOH!

 

Recommendations for Treatment and Prevention of Opportunistic Infections as of 1999

 

           

Treatment

When to Prevent

Primary Prevention

Secondary Prevention

PCP

bactrim

(dapsone, pentamidine,

dapsone plus pyrimethamine)

CD4 < 200

FUO > 2 wks or oral candidiasis

Bactrim 1 DS 3 x week

 

same as Rx

MTb                                    

 

(H) isoniazid plus B6

(R) rifampin

(Z) PZA

(E) ethambutol

skin test > 5 mm

h/o + test w/out treatment

recent exposure to Tb

(H) isoniazid plus B6

(R) rifampin

None

MAI                                                    

(clarithromycin or azithromycin)

 

plus one or more of (rifabutin, ethambutol, clofazimine, ciprofloxacin)

 

CD4 < 75

clarithromycin 500 mg qd

 

Or

 

Azithro 1200 mg q wk

Same as Rx

Toxoplasmosis                                                    

sulfadiazine plus pyrimethamine plus leucovorin (clindamycin as alternative to sulfa)

IgG to toxoplasma and CD4 < 100

Bactrim 1 DS qd

or

dapsone plus pyrimethamine/leucovorin

(sulfadiazine or clindamycin)

plus pyrimethamine/leucovorin

Influenza                              

?

all patients

vaccine   

 

Pneumococcus

cephalosporins/quinolones/others

all patients

vaccine   

 

 

CMV                                         ?oral ganciclovir                               IV ganciclovir (IV        

IV ganciclovir (Foscarnet)

IgG to CMV and CD4 < 50

?oral ganciclovir

IV ganciclovir or IV Foscarnet or oral ganciclovir

HSV                     

acyclovir (famciclovir)

none

None

acyclovir or famciclovir

 

VZV                     

acyclovir (famciclovir)

recent exposure

VZV immune globulin

acyclovir or famciclovir

Candida

fluconazole (ketoconazole)

CD4 < 50               

fluconazole or ketoconazole

fluconazole (ketoconazole,

itraconazole, clotrimazole troches, nystatin)

Cryptococcus

amphotericin B (+/- flucytosine)

or

fluconazole (ketoconazole)

CD4 < 50

fluconazole or ketoconazole

fluconazole (itraconazole, weekly IV amphotericin)

Coccidoides

fluconazole (itraconazole)

CD4 < 50 / endemic

fluconazole or itraconazole

Fluconazole or itraconazole or weekly IV amphotericin

Histoplasma         

itraconazole (fluconazole)

CD4 < 50 / endemic

Itraconazole or fluconazole

itraconazole or fluconazole or weekly IV amphotericin

 

Note: can give measles vaccine (even though it’s live) / cannot give OPV or Typhoid

 

 

HTLV - I         HTLV-1 (tropics of Japan, IVDA) / (2% get necrotizing vasculitis, slowly progressive spastic paraplegia)

 

ATL (adult T-cell leukemia)

TSP (tropical spastic paraparesis)

HAM (HTLV-1 ass. myelopathy)

 

 

HTLV-II         Hairy cell leukemia


Parasitology

 

Protozoa

 

E. histolytica

           

Intestinal amebiasis

(4 cysts) / E. coli (8 cysts) / iodoquinol / symptoms and endoscopic features can mimic ulcerative colitis à but DO NOT give steroids (can cause life-threatening reaction)

 

Invasive amebiasis

can invade (liver, lungs, brain) / iodoquinol plus metronidazole

resistant: chloroquine (concentrates in liver), emetine (contraindicated with cardiac disease)

 

Balantidium coli

can invade / tetracycline and iodoquinol

 

Acanthamoeba [NEJM]

can cause granulomatous CNS lesions in immunocompromised host / subacute course / only chance for cure is successful surgical excision

 

Balamuthia

            similar to acanthamoeba

 

Naegleria fowleri

purulent meningoencephalitis / acute course (death within days) / may occur in healthy persons exposed to infected water source / none

 

Giardia lamblia           (small intestine, non-invasive)

more water-related outbreaks than any other organism / may portend IgA deficiency

Presentation: acute or chronic diarrhea with features of malabsorption / frequent, foul-smelling stools, watery stools (rarely contain blood, mucus), abdominal pain, nausea, vomiting, anorexia, flatulence, fever only in severe giardiasis, anemia (malabsorption in upper intestine)

Course: usually 5-7 days (up to 1 month, possibly more chronic in some cases), stool infective for much longer

Diagnosis: will not see trophs in stool (low yield) / can send for stool antigen / will not expect to see fecal WBC’s (since non-invasive)

Treatment: flurazolidone, metronidazole, quinacrine (most effective, but tastes awful) / harder to treat with HIV

 

Cryptosporidium        (small and large intestine)

Diagnosis: see sporocyte with oocysts in stool

Diseases: AIDS diarrhea (watery) / will often persist and is difficult to treat other than treating the AIDS

Treatment: paromomycin (maybe?)    

 

Cyclospora    

            AIDS diarrhea / differentiate from cryptosporidium (small, round)

Treatment: bactrim?

 

Plasmodium (malaria)   www.cdc.gov/travel/regionalmalaria

           

Presentation: intermittent paroxysmal fever (systemic illness)

Findings: hepatosplenomegaly from hyperreactive form (elevated IgM), released pigment and debris may darken skin

Complications: sepsis, DIC, end-organ ischemia/damage, renal disease (blackwater fever)

Diagnosis: thick and thin smear [pic][pic][pic]

Labs: smear, measure parasite level (>5% is severe; levels may rise after initiation of treatment so keep re-checking), hypoglycemia, thrombocytopenia, DIC markers

Acute treatment:

·        chloroquine (schizontocidal) [not for P. falciprum] / chloroquine resistance à quinine and doxycycline, clindamycin

·        Complications: supportive (monitoring, seizures, sepsis) // may even need to do exchange transfusions for moderate to severe cases

·        Duration: treat until parasitemia < 1% and longer (do not undertreat or it will relapse)

Anti-relapse/prophylaxis:

·        primaquine (gametocidal, sporocidal, hypnocidal) or mefloquine (qweek; start 1 week before to 4 weeks after return) or atovaquone plus proguanil (starting 1 to 2 days before to 1 week after return)

·        test fellow traveler’s

           

P. falciprum [NEJM]

multiply infected RBCs / RBC sequestration (in vascular beds) (may cause majority of end-organ damage)

Treatment: often resistant to chloroquine, use bactrim, quinine

 

P. vivax          

big RBC, Schuffner’s dots [pic] / 16-24 schizonts / may relapse (hypnozoites in liver)

 

P. ovale

may relapse (hypnozoites in liver)

 

P. malariae    

band in RBC / 8 schizonts

 

Babesiosis

B. microti / rodents à ticks à humans / northeast US

Presentation: fever, headache, malaise

Diagnosis: parasites in RBCs [blood smear] / can get serological confirmation

Complications: hemolytic anemia (ranges from mild to severe)

More severe with splenectomy, elderly, co-existing lyme disease

Treatment: doxycycline, clindamycin, quinine / exchange transfusions may be necessary

 

Pneumocystis (see fungus)

 

Toxoplasma gondii

            Most common CNS mass lesion in HIV

·        Acquired: fever, lymphadenopathy (tender/indurated), uveitis, meningitis/encephalitis (less common), seizures

·        Congenital: brain, eye, liver, lymphatics / intracerebral calcifications, microcephaly / immunocompromised (AIDS < 100-200)

Transmission: oocysts (cat feces), pseudocysts (infected meat) / tachyzoites infect liver cells / chronic (ocular)

Diagnosis: morphology, antibodies (~50% will have), serum Ag, CSF Ag

CSF: 15% normal / WBC > 20 (50%), increased protein (35-70%), decreased glucose (50%)

CT/MRI: often multiple ring-enhancing lesions (often in basal ganglia)

Note: do not confuse skin lesions of disseminated toxoplasmosis [dermis] with molluscum contagiosum! (skin biopsy can distinguish)

Ddx: CNS lymphoma (if 2 wks empiric antibiotic Rx fails, consider stereotactic brain biopsy)

Treatment: bactrim / pyrimethamine and dapsone (not dapsone alone) / pyrimethamine and sulfadiazine

Prophylaxis: bactrim 1 DS qd

 

Trichomonas vaginalis

no cysts, only trophs / only STD that is a parasite / can also cause urethritis

Diagnosis: wet prep with inflammation, lots of WBCs or culture

Treatment: metronidazole / treat partner

 

Helminthes (in general)

 

Diagnosis: stool cultures for O&P – for any intestinal parasite / best if taken spaced out over days / yield is often very low and you should always send at least 3 samples if you have any suspicion

 

Nematodes

 

·        most are susceptible to mebendazole (inhibits tubulin and glucose transport)

 

Enterobius vermicularis (pinworm)very itchy

scotch tape prep / flattened egg

 

Trichuris trichiura (whipworm)

invasive / diarrhea or even prolapsed rectum / adult or eggs

 

Ascaris lumbricoides  (roundworm)

ascariasis / intestinal obstruction (1 in 500) / eggs or adults / larva migrates to lungs (causes pneumonia) / type I IgE upon reinfection

 

Ancylostoma (americanus, duodenale) (hookworm) [NEJM]

 

Strongyloides stercoralis

Life-Cycle: only nematode which replicates within the body

·        filaraform larva is passed in the stool (infective)

·        rabditiform larva hatches deep in crypts (migrates to lungs, causes pneumonia)

o       causes hyperinfection syndrome in immunocompromised patients (worms everywhere!, life threatening gram negative sepsis, totally nasty)

o       infection can be quiescent/asymptomatic for up to 30 yrs and then comes back up when patient becomes immunocompromised

Pathology: hookworm causes malabsorption (anemia), altered motility, trauma

Diagnosis: strongyloides can be detected by duodenal aspirate

Treatment:

o       ivermectin (stimulates GABA, results in paralysis)     

o       thiabendazole (inhibits tubulin and fumarate reductase)

 

Trichinella spiralis

Transmission: infected pork containing cysts

o       1st week – gut invasion (nausea, abdominal pain, constipation or diarrhea)

o       2nd week – larval migration (local and systemic hypersensitivity with fever, eosinophilia, periorbital and facial edema; rarely may get myocarditis, encephalitis, pneumonitis during this phase)

o       3rd week – encystation (calcification) in muscle (edema, muscle weakness)

Treatment: anti-helminthics are ineffective against encysted larva / AIDS treat chronic inflammation with glucocorticoids

Prevention: cooking pork thoroughly should kill cysts (or freezing -15C x 3 wks)

 

Cutaneous larva migrans (CLM)

a. brasiliensis (cat) / a. caninum (dog) / tunnel under skin / thiabendazole

 

Visceral larva migrans (VLM)

toxocara canis (dog ascaris) / more variable invasion than ascariasis / cannot complete life cycle, which is why it searches around your viscera (hence the name) / causes pneumonia

 

Ocular larva migrans

            Invasin of Toxocara larva into eye (typically produces granulomatous mass, usu. in posterior pole of retina)

 

Leishmania brasiliensis

            endemic to Brazil / hepatomegaly, splenomegaly, pancytopenia / pneumonitis uncommon

 

Leishmania donovani

Indian subcontinent, NE Africa, Brazil / transmitted by sandfly / malnourishment increases  risk factor of progression to severe disease or kala azar

            Presentation: fever, cachexia, splenomegaly (hepatomegaly rare)

Diagnosis: splenic aspiration (98% sensitive) / can do slide or culture of biopsy / sometimes can pick up intracellular amastigotes in peripheral smear

            Ddx: malaria, miliary Tb, schistosomiasis

            Labs: may have pancytopenia, hypergammaglobulinemia, hypoalbuminemia

            Treatment: amphotericin, pentamidine / do not wait for diagnosis to begin treatment

 

Anisakis [wiki]

invades submucosa of GI tract causing (abdominal pain, nausea, vomiting, occasionally urticaria)

 

Gnathostoma

            associated with ingestion of raw fish / causes tender migratory subcutaneous nodules

 

Cestodes  (Tapeworms)

 

Definitive host – intestinal tapeworms

Intermediate host – larva hatch from eggs of intestinal worms, are ingested and migrate into tissues

 

Intestinal tapeworms

·        niclosamide (interferes with anaerobic ATP production)

·        praziquantel (Ca influx causes paralysis)

 

Larva

·        albendazole (blocks glucose uptake)

 

T. solium (pork)         

hooks / obstruction / eating eggs produces cysticercosis (larva can migrate anywhere)

Mexico and S. America, Africa, SE Asia, Eastern Europe

Intestinal tapeworms from eating intermediate hosts (pigs, dogs, cats, sheep and humans)

Presentation: usually asymptomatic / rarely causes epigastric discomfort, nausea, increased hunger, weight loss and diarrhea

Diagnosis: stool sample / scotch tape

Treatment: one dose praziquantel 5 mg/kg

Cysticercosis from fecal matter of infected humans (CNS, skeletal muscle, subcutaneous tissue, and eye)

Neurocysticercosis: seizures (partial, generalized, Jacksonian), focal neurological signs and/or increased intracranial pressure / unusual racemose form occurs in subarachnoid and base of brain causing chronic meningitis or arachnoiditis

o       basilar arachnoiditis (sub-arachnoid cysts) à lacunar infarction

o       Chronic cysticercosis meningitis à CVA

Labs: CT shows contrast enhancing rings (calcification is in the lesion itself) and MRI is best for detecting smaller cysts / CSF shows pleocytosis with many mononuclear cells, increased protein, decreased glucose / serological tests 91% sensitive, 98% specific

Treatment: if you think there are living cysts, you can give albendazole 15 mg/kg divided doses  for 8 to 28 days and high dose steroids (dying larva no longer secrete anti-inflammatory proteins, which allows your immune system to then damage your brain) / praziquantel 50 mg/kg divided doses for 15 days is another option (but steroids interfere with levels)

Ocular and spinal lesions require surgical resection as inflammation may be more damaging

Ventricular, obstructive lesions are best treated with surgical resection

Prognosis: size of lesions should decrease within 3 to 6 months / seizures et al may persist and require lifelong anticonvulsants

 

T. saginata (beef)

no hooks / humans only definitive host / may cause obstruction of gut

Africa and Middle East / undercooked beef

Presentation: perianal discomfort, mild abdominal pain, nausea, appetite changes, weakness, weight loss

Diagnosis: stool sample / scotch tape

Treatment: one dose praziquantel 5 mg/kg

 

D. latum (fish)           

3-5 weeks after eating raw fish /

usually asymptomatic, may cause abdominal pain, diarrhea, vomiting, weakness, weight loss

can cause B12 deficiency (2% of infected elderly) and/or GI obstruction (longest tapeworm)

copapod intermediate host (eating procercoid larva gives you sparganosis)

Diagnosis: stool ova

Treatment: one dose praziquantel 5-10 mg/kg

 

H. diminuta (rodents)

Similar to H. nana

 

H. nana (dwarf tapeworm)

chronic, often asymptomatic / most common tapeworm / institutionalized children

human feces (humans are intermediate and definitive host), larval meal-worms and fleas

Treatment: one dose praziquantel 25 mg/kg

 

D. caninum (dog)

Usually asymptomatic, may cause abdominal pain, diarrhea, urticaria, pruritis, eosinophilia,

Diagnosis: stool ova

Treatment: praziquantel

 

Echinococcus granulosus (dog tapeworm) [NEJM]

Hydatid disease / definitive hosts are dogs and intermediate hosts are farm animal, humans, etc.

Transmission: humans eat dog poo (definitive host poo)

Pathogenesis: can spread by invading tissue planes, single cyst > multiple cysts (20-40%)

Presentation: unusual in that it can progress silently for a long time (up to 15-20 yrs) / rupture or episodic leakage may produce fever, urticaria, pruritis, eosinophilia, fatal anaphylaxis

            Liver (mimics hepatocellular carcinoma) (grow 1 cm per year, grow faster in lung)

Lungs (may cause hemoptysis, cough, chest pain) [CXR] [CXR] [CT][CT]

Mostly in liver and lungs but can go anywhere including bone, CNS, heart

Diagnosis: CT, MRI, ultrasound / BAL may reveal ultrastructures (hooklets, etc.) and are

diagnostic 50-90% of time / be careful with biopsy not to spread infection, spilling cysts can cause anaphylaxis and/or re-seeding) / serology 80-90% sensitive, 50-75% specific, false positives from cysticercosis (can be used to follow treatment/relapse)

Treatment: albendazole 400 mg BID for 8-12 weeks (4 weeks pre and 4 weeks post resection)

(30-70% successful, 30% relapse) and praziquantel during cyst manipulation / PAIR procedure

 

Echinococcus multilocularis

            Multiple, locally invasive liver (98%) or alveolar lesions / rodents, foxes / Canada, U.S.

and other areas

 

Echinococcus vogeli                  S. America

Echinococcus oligarthrus           S. America

 

Sparganosis

Larva of D. tapeworms / contaminated water or infected animals

Slow migration in tissues / presents as subcutaneous swelling / periorbital sparganosis can cause blindness

 

Coenurosis

Rare infection by larval stage of dog tapeworm Taenia sp. / CNS and subcutaneous tissues / drugs not effective, requires surgical resection

 

Trematodes (blood flukes, schistosomiasis)

 

S. mansoni (Katayama fever)

S. America, Africa

Micro: hermaphroditic / man-snail-man / cercaria (penetrate skin) / migration through tissue (eosinophilic response) / granuloma response to eggs (cirrhosis) / pathogenic (mild rxn) / non-human spp. cause (swimmer’s itch)

Course: 4-8 wks after exposure, migration through portal and pulmonary tissue (much of damage from hypersensitivity response)

Diseases:

·        Liver – periportal fibrosis or “pipe stem fibrosis” (relatively less hepatocellular damage) / hepatomegaly, hypersplenism, esophageal varices (other stigmata of end-stage liver disease less prominent feature; spider nevi, ascites, jaundice, gynecomastia)

·        MPGN and nephrotic syndrome (renal failure) likely from immune complex deposition

·        CNS complications

Diagnosis: eosinophilia, stool studies likely negative, serology may be helpful

Treatment: praziquantel

 

S. japonicum (Far East)

S. haematobium (Mid East, Africa)

 

Paragonimiasis [NEJM]

            Endemic to Brazil

Presentation: chronic cough, intermittent hemoptysis > fever, night sweats, weight loss, hemoptysis, pleuritic chest pain > symptoms from ectopic foci (subcutaneous, CNS)

Course: symptoms usually occur 2-3 months after exposure to metacercariae (on raw shellfish)

Imaging: peripheral or nodular cystic lesions may be seen CXR

Labs: pleural effusion (< 2000 WBC, glucose < 10, elevated LDH)

Diagnosis: eggs in stool or sputum or biopsy or immunoassay (sent to CDC)

Treatment: praziquantel achieves cure ~100% by 3 days of treatment

 

P. Westermani

 

Clonorchis sinensis [wiki]

            Causes biliary tract disease (not pulmonary)

 

Fascioliasis [wiki]

            Infection usually involves bile ducts / can migrate to skin and lungs / rare in U.S.

 

            F. hepatica

            F. gigantica

 

unsorted: onchocerca volvulus – fibrotic subcutaneous nodules around the head / Africa, S. America

 

 

 

Insects

 

 

 

Scabies

            linear lesions [pic][pic][dermis] / worse at night / infected families

Treatment: 5% permethrin / adults and infants have reversed distribution / infants have more pustules (resembles atopic dermatitis), palms, soles and face not spared as in adults / lindane used to be fashionable but now 2nd line / other things like sulfa and benzyl benzoate are 3rd line

 

Brown recluse spider (Loxosceles sp.) [pic]

            necrotic, black lesion (with bullae, erythema) / painful / spreads rapidly (within hours) / bad

 

            Black Widow Spider

                        neurological signs, abdominal pain; no soft-tissue damage [pic]

 

 

 

 


 

Review Tables

 

 

Meningitis [age breakdown]

 

Food Poisoning

Toxin Producers

Capsule

Flora

Opportunists with AIDS

Vaccine Commonly Available

Animal Bites

 


 

SPACE Bugs

Cause nosocomial infections

(must be treated with 2 antibiotics – cephalosporin + aminoglycoside)

Serratia (can be MDR)

Pseudomonas

Acinetobacter

Citrobacter

Enterobacter

 

Resistance Patterns

 

Listeriacephalosporins – use ampicillin

Pseudomonascefotaxime – use ceftazidime

Klebsiellapenicillin’s including ampicillin – use Ceflex

C. difficile (macrolides?)

Campylobacterbactrim, quinolones – use macrolide

Yersinia enterolitica – cephalosporins and penicillins – use macrolide, quinolone

 

Food Poisoning

            S. aureus                      2-6 hrs             meat, dairy, other

            B. cereus                      6-15 hrs           reheated rice, other

            L. monocytogenes                                raw dairy, meats, vegetables (or after processing contamination)

            C. perfringens               8-12 hrs           reheated meat, etc.

            C. botulinum                                         home canned food

            E. coli                                                   various foods (0157:H7 in undercooked ground beef)

            Salmonella                    24-72 hrs         everything (poultry, eggs, meat milk)

            Campylobacter                         poultry

V. cholerae                   8-72 hrs.          seafood

            V. parahaemolyticus     15-24 hrs.        seafood

            Shigella                                     direct person to person

 

Produces Toxins

 

            S. aureus                                  TST (superAg) / exo A and exo B (exfoliation)

            S. pyogenes                              a-toxin

            B. anthracis                              LF / EF / PA (A-B toxin with 2 A components)

            B. cereus                                  pyogenic toxin

            Clostridium spp.                       DT (binds EF-2)

            EHEC                                      shiga-like verotoxin (O157:H7)

            ETEC                                       LT (cholera-like), ST

            S. dysenteriae                           shigatoxin (inhibits 60s ribosomes)

            Klebsiella                                 ST (like E. coli)

            B. pertussis                               PT (below) and invasive AC

            V. cholerae                               choleratoxin (like LT toxin of ETEC)

 

 

HACEK Organisms

oral colonizers

Organisms: Haemophilus (1st) >> Actinobacillus, Cardiobacterium, Eikenella, Kingella

·        clenched fist injury

·        human bite infections

·        endocarditis in previously damaged valves (can be relatively fast in forming vegetations; in spite of being thought of as fastidious)

Diagnosis: usu. take about 5 days to culture but may take up to one month

·        Echocardiography: positive vegetations in 85% of cases

Treatment: ceftriaxone

 

ADP-ribosylators

 

C. diptheriae     DT (binds EF-2)

P. aeruginosa    exo A

V. cholerae       cholera toxin (increases cAMP)

ETEC               heat labile enterotoxin LT (A-B toxin) ribosylates Gs (increased cAMP)

B. pertussis       pertussis toxin (A-B toxin) ribosylates Gs (prevents host inactivation of AC)                 

 


Encapsulated

 

quellung rxn:

-swells in antisera as IgG accumulates

 

S. pneumoniae (vaccine Ag) à 1st important for post-splenectomy

H. influenza (Hib vaccine Ag) à 2nd important for post-splenectomy

B. anthracis

N. meningitidis (vaccine Ag)

Klebsiella pneumoniae

S. pyogenes (~M protein, anti-phagocytic)

E. coli (K1, anti-phagocytic)

 

Normal Flora

 

S. epidermidis               skin

C. ulcerans                   skin

S. aureus                      nose

S. viridans                    mouth

S. mutans                     plaque

B. fragilis >> E. coli    gut

lactobacillus                  vagina

E. coli                           vagina

Group B strep              vagina

 

Nosocomial

 

staph

GNR

 

IV drugs/alcohol

 

S. pneumo

Klebsiella

Staph

neonatal

group B strep

E. coli

ureaplasma

 

Post-viral

 

Staph

H. influenza

atypical

mycoplasma

legionella

chlamydia

 

Vaccine Available (these lists need to be added to—please check back or clue me in?)

 

Bacteria

 

            H. influenza                PRP protein conjugate

            S. pneumoniae            ?

            C. diptheriae                 DPT

            B. pertussis                   DPT

            C. tetani                       DPT

            B. Anthracis                 protective antigen toxoid

            N. meningitidis  polysaccharide Ag combination (except for group B)

            F. tularemia                  only for lab workers

            Y. pestis                       formalin-killed / only high risk

 

Viruses

 

            Influenzavirus popular mix of antigens (didn’t work for me!)

            Adenovirus                   to prevent ARDS / live attenuated?

            VZV

            HAV

            HBV               

            MMR (alpha, toga)       live attenuated

            togaviruses

            -EEE, WEE                  inactivated

            flavivirus

            -Yellow fever               live attenuated

            -powasan fever live attenuated

            smallpox                       live attenuated

            rhabdovirus                  killed virus

 

Animal Bites

 

Human bite infections                       

viridans / prevotela, fusobacterium / HACEK

can get septic arthritis / endocarditis

 

Cat bites           Pasteurella

Dog bites          capnocytophagia (DF2)

 

Miscellaneous Microbiological Tidbits

 

DNA viruses all double stranded (except parvovirus)

RNA viruses all sing stranded (except reovirus, Col. Tick Fever, rotavirus)

DNA viruses all replicated in nucleus (except Poxvirus)

 

all icosohedral viruses are positive strand

all helical viruses are negative strand (except coronavirus)

 

E. coli turns pink in MacConkey (lac+) / Salmonella does not (lac-)

may refrigerate: sputum / urine / stool / blood

must process immediately: CSF / biopsy

 

things you can treat with ribavirin

paramyxoviruses RSV, parainfluenza, measles (mumps?)

arenaviruses      Lassa fever

bunyaviruses     ribavirin IV for hemorrhagic fevers (many others~)

 

only type A influenza may be treated with amantadine

-inhibits virus uncoating (also releases DA for Parkinson’s)

 

chronic fatigue syndrome is of unknown etiology

HIV has low Ab titre, high antigenic variation

HTLV-1 retrovirus is oncogenic (not HIV)

SSPE shows high Ab titres

Dengue has only 1 protein product

T. solium has hooks (others do not)

D. latum (fish) causes B12 deficiency

 

 

Disclaimer:
The information on this site is intended for educational purposes only, and its makers are not responsible for anything that happens as a result of its use.

 

 

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