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Open Wide: Big Bolus of ID 2015 Internal Medicine Board Review July 17, 2015 Ben Brock, MD Board Question Breakdown Infectious Disease (9%) 15-17 Q • • • • • • • • • • • • • • • • • • • • Skin and soft tissue infections CNS infections Upper respiratory tract infections Eye infections Lower respiratory tract infections Endocarditis and other cardiovascular infections Hepatic infections Enteric infections AIDS and HIV infection Sexually transmitted diseases Urinary tract infections Infectious arthritis Osteomyelitis Bacteremia/sepsis syndrome Rheumatic fever Procedure- and device-associated infections Nosocomial infections Immunization Prevention of infectious disease Specific causative organisms 0–2 1–2 1–2 0–1 2–4 0–1 0–1 1–4 1–2 0–2 0–1 1–2 0–1 0–2 0–1 0–2 0–1 0–1 0–1 1–3 • Miscellaneous infectious disease disorders 0–1 Antibiotic Adverse Effects • C difficile colitis and GI upset with essentially any antibiotic • Beta-lactams cause interstitial nephritis, thrombocytopenia (and leukopenia/anemia, less commonly), and immediate-type hypersensitivity • Carbapenems lower seizure threshold (ertapenem without Pseudomonas activity) • Aminoglycosides cause nephrotoxicity, ototoxicity (high frequency), and neuromuscular blockade (the latter only if bolused) • Fluoroquinolones cause tendinitis, delirium in the elderly, and prolonged QTc Antibiotic Adverse Effects • Macrolides also prolong QTc • Vancomycin red man syndrome typically spares lower extremities, blanches, occurs shortly after 1st infusion and improves with later infusions. Relieved by slowing infusion rate. • Doxycycline causes pill esophagitis • Metronidazole causes disulfiram reaction, peripheral neuropathy, metallic taste • Linezolid causes cytopenias (esp. platelets) and neuropathy. • Daptomycin causes myopathy (follow CPK) • Trimethoprim causes hyperkalemia Respiratory Infections • Bacterial Sinusitis – Acute Bacterial Sinusitis (ABS) • Often preceded by viral URTI • Suggests ABS – – – – Symptoms past 7-10 d Unilateral sinus pain/tenderness Maxillary tooth or face pain Purulent nasal discharge • No need for treatment or imaging Respiratory Infections • Bacterial Sinusitis – Chronic Sinusitis • It’s all about obstruction use nasal saline, topical corticosteroids, antihistamines, decongestants • Micro – S.aureus, S. epidermidis, anaerobes – Targeting them probably doesn’t help – If acute flare, treat same organisms as ABS – CT sinuses may be helpful (polyps), ENT should evaluate if present Respiratory Infections • Pharyngitis – Usually viral (80%) in adults; group A streptococci in kids – GABHS or Streptococcus pyogenes (5-10%) • Sore throat, exudate, adenopathy, fever+/• No cough or hoarseness • Rapid antigen detection test • Most accurate: culture • Always susceptible to penicillin (goal is to prevent rheumatic fever) HY: 1. In adults, if rapid negative, pass on culture 2. Gram stain of throat is worthless Acute Rheumatic Fever • Noninfectious sequelae 2-4 weeks after GAS infection (usually pharyngitis, not SSTI) • Most common in kids 5-15 • Clinical diagnosis • 80-85% have elevated ASO titers • Treatment: aspirin, eradicate GAS (pcn), treat heart failure if present • Strong tendency to recur after reinfection with GAS, so secondary prophylaxis to prevent (usually 10 years, or until 21, whichever is longer) Acute rheumatic fever: Jones criteria GAS & 2 major or 1 major/2 minor • Major J : Joints (migratory arthritis, usually large joints) : Pancarditis (50-60%) {aschoff bodies} N: Nodules, subcutaneous (<4%) E : Erythema marginatum (<10%) S : Sydenham chorea (20-30%) • Minor Fever, arthralgias, elevated CRP/ESR, prolonged PR Infectious mononucleosis Pharyngitis in adults -> consider other possibilities (acute HIV) IM: primary infection with EBV – Fever, sore throat, LAD – Splenomegaly (no contact sports until resolved) – Look for increased lymphocytes on differential and elevated ALT, AST or LDH – If given amoxicillin diffuse, pruritic, MP rash (not allergic rxn) – Heterophile Ab against EBV (90% +) CAP – Microbes/Associations • Pneumococcus: most common cause among all ages (urine Ag) • MRSA: cavitary infiltrates (w/o aspiration), sepsis, IVDU, recent SSTI or influenza • Legionella – can be epidemics, recent travel (hotel/cruise), summer; severe CAP, GI sx, CNS sx, hyponatremia (urine Ag) • Klebsiella: alcoholics • H. flu and Moraxella more common in patients with chronic lung disease • Pseudomonas: CF, bronchiectasis, severe COPD, chronic steroids • Adolescents and outpatients who are not that ill – consider Mycoplasma (serology, cold agglutinins) or Chlamydia pneumoniae (serology) {resp. PCR best for both} • Anaerobic bacteria – aspiration pneumonia CAP – Microbes/Associations • Coxiella burnetti (Q fever) – farm animals, parturient cats (serology) • Viral (uncommon in adults): adenovirus, parainfluenza, respiratory syncytial virus, and human metapneumovirus • Histoplasma – bat or bird droppings • Francisella tularensis – rabbits • Hantavirus - rodent excreta/urine • Coccidioides, hantavirus – Southwest US • Burkholderia pseudomallei – Southeast Asia and China • Chronic pneumonia >3 weeks-think TB or Histoplasma CAP Diagnosis in Hospitalized Patients: 2007 IDSA/ATS Guidelines – Sputum gram stain and culture (expectorated or endotracheal aspirates) recommended for the following groups of patients: • • • • • • • • Intensive care unit admission Failure of outpatient antibiotic therapy Cavitary lesions Active alcohol abuse Severe obstructive or structural lung disease Positive urine antigen test for pneumococcus Positive urine antigen test for legionella (special culture needed) Pleural effusion – Blood cultures: low yield (5-14%) but when positive, establishes the diagnosis – Urinary legionella and pneumococcal antigen tests – CXR CAP Treatment: 2007 IDSA/ATS Guidelines Outpatient General Medical Ward ICU/Severe If no significant risks for DRSP*: Macrolide or doxycycline If risks for DRSP*: Antipneumococcal fluoroquinolone OR High-dose amoxicillin (3 gm/day) or high dose amoxicillin/clavulanate (4 gm/day) plus macrolide (if amoxicillin is used and there is a concern for H. influenzae, use macrolide active for lactamase producing strains) Beta-lactam (ceftriaxone, cefotaxime, ampicillin/sulbactam, ertapenem) plus macrolide (can use doxycycline if macrolide not tolerated) OR Antipneumococcal fluoroquinolone alone Beta-lactam (ceftriaxone, cefotaxime, ampicillin/sulbactam) plus IV azithromycin or IV fluoroquinolone If concern for Pseudomonas (eg, presence of structural lung disease such as bronchiectasis): antipseudomonal agent (piperacillin/tazobactam, imipenem, meropenem, or cefepime) plus antipseudomonal fluoroquinolone (ciprofloxacin or high dose levofloxacin); If concern for MRSA: add vancomycin or linezolid *RF for DRSP: >65, exposure to children in day care, alcoholism or other severe underlying disease, or recent antibiotics Healthcare-Associated Pneumonia • Risk Factors: – – – – IV therapy, wound care, or IV chemo within 30 days NH, LTAC Recent hospitalization (last 90d) for 2+ days Hospital or hemodialysis clinic last 30 days • Antibiotic choice depends on RF for multi-drug resistant organisms (MDR): – No known risk factors for MDR: ceftriaxone, ampicillinsulbactam or piperacillin-tazobactam, levofloxacin, moxifloxacin, or ertapenem – Risk factors for MDR: cefipime or ceftazidime, imipenem, meropenem, doripenem, piperacillin-tazobactam, or aztreonam PLUS levofloxacin or gentamicin PLUS linezolid or vancomycin (if MRSA suspected) HAP & VAP • Pneumonia that occurs 48 hours or more after admission and did not appear to be incubating at the time of admission • Ventilator is the number one RF • Treatment regimens similar to health-care associated pneumonia • Treat early and broadly, then de-escalate based on clinical improvement and culture results • A short duration of therapy (eg, 7-8 days) is sufficient for most patients with uncomplicated infection who have a good clinical response Hospital acquired infections • Not present on admission, develop after 48h • Hand hygiene is the most important preventative measure • CAUTI (UTI in patient w/ catheter) – – – – – Pyuria not reliable Local or systemic symptoms D/c foley if possible, or if not possible, change if in place 2+ weeks, then get culture Usually treat for 7 d, no more than 10-14d Antiseptic-coated catheters, screening cultures unnecessary • CLABSI (bloodstream infection w/central line, w/o other source) – Removal of line most important (Staph aureus, Pseudomonas, Candida) – For prevention: site selection, HH, full barrier precautions, chlorhexidine • SSI (within 30d of surgery in local manipulated) – Staph aureus most common – Prevent: follow abx prophylaxis guidelines, clipping, chlorhexidine, glucose control Device-associated infections • Includes orthopedic prostheses, implantable cardiac devices, neurosurgical shunts/implants • Removal of the prosthetic is the mantra • Treatment directed by culture • Duration depends on site (4-6 weeks for ortho, 4 weeks cardiac, 2 weeks for shunt) • Chronic oral therapy after IV if hardware not removed can be considered Urinary Tract Infections • Predisposing factors: stricture, stone, obstruction, tumor, foreign body, DM • Presentation: all can have dysuria, frequency, urgency – Cystitis: SP pain, mild/absent fever – Pyelonephritis: CVA/flank tenderness, fever – Perinephric abscess: Same as pyelo but persisting despite appropriate treatment • Diagnosis – Urinalysis • 10+ WBC or +leukocyte esterase on dipstick • if above present w/ symptoms, then UTI – Urine culture • Not needed in uncomplicated cystitis • >100,000 cfu – Only image pyleo if cont. fever or flank pain after 72h of abx treatment – If perinephric abscess, aspirate to guide therapy Urinary Tract Infections • Treatment – Uncomplicated cystitis: empiric, 3 days (TMP-SMX, nitrofurantoin, fosfomycin); 7 days if complicated – Pyelonephritis • 14 days (TMP-SMX, AG or cephalosporin) • 7 days cipro 500mg po bid • 5 days levo 750mg po daily – Perinephric abscess: need culture, antibiotic pressure usually selects for uncovered gram positive cocci • Asymptomatic bacteriuria: – Only screen and treat pregnant women and those undergoing urologic procedures expected to cause mucosal bleeding – In all other cases, treatment increases resistance and does not improve the outcome, including those with indwelling bladder catheters and no signs systemic disease – change catheter only Bloodstream infections • Usually associated with intravascular catheter/device or focal infection/abscess • Source control paramount • Exclusion of endocarditis most important for gram positive and Candida • Err on not presuming contaminant (must be ½ bottles, alternative explanation, no indwelling hardware, and a skin commensal) Bloodstream infections • Typical treatment duration of 2 weeks after negative culture, 4 weeks if endocarditis • Use beta-lactam if able • Vancomycin if MRSA or MSSA with pen allergy • Fluoroquinolones alternative in gram negatives • Single agent adequate, culture-directed Sepsis • Broad spectrum, prompt antibiotics followed by narrow, culture-directed antibiotics • Cardiopulmonary support • Source control Endocarditis Prophylaxis • • • 2007 AHA guideline for the prevention of endocarditis made major revisions, decreasing indications for prophylaxis. Procedures include major dental, GI, or pulmonary Cardiac conditions associated with the highest risk of bad outcome if IE (and thus worthy of prophylaxis): – Prosthetic cardiac valve or prosthetic material used for cardiac valve repair – Previous IE – Congenital heart disease (CHD): • Unrepaired cyanotic CHD, including palliative shunts and conduits • Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure • Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization) – Cardiac transplants who develop cardiac valvulopathy Endocarditis • Presentation: – Fever & new/changed murmur – Hands/feet • Janeway lesions: flat & painless • Osler nodes: raised & painful • Splinter hemorrhages in nail beds – Retina: Roth spots – Hematuria • Emboli to kidneys • Post-infectious glomerulonephritis with immune complexes in glomeruli – Mycotic aneurysms Endocarditis • Diagnostic tests: – Blood cultures • Best initial test: 95-99% sensitive – If positive, then echocardiogram • If both positive, you’ve got endocarditis (but organism needs to be a typical microbe for endocarditis) – TTE and TEE equally specific (95%) – Sensitivity: TTE (60%); TEE (90-95%) Endocarditis • Diagnostic tests (cont.) – Normocytic anemia in 90% – Elevated ESR (& CRP) – UA with proteinuria, hematuria, red cell casts • Culture negative endocarditis – In the 1-5% with negative blood cultures, vegetation on ECHO also needs any 3 minor criteria • • • • • Fever Risk factor (PV, IV drug use) Vascular phenomena (infarcts, hemorrhages, Janeway) Immunologic phenomena (GN, Osler, Roth) Atypical organisms Endocarditis Treatment • Best initial empiric if acutely ill: vancomycin • Strep Viridans group • Penicillin or ampicillin or ceftriaxone x 4 weeks • If partial resistance, pen or amp x 4 weeks, with gentamicin added for first 2 weeks – Enterococcus • Ampicillin and gentamicin x 6 weeks – MSSA • Oxacillin or Nafcillin x 6 weeks (+/- gent for 3-5 days) – MRSA • Vancomycin x 6 weeks – HACEK (Haemophilus,Aggregatibacter/Actinobacillus,Cardiobacterium,Eikenella,Kingella) • Ceftriaxone or ampicillin/sulbactam x 4 weeks Endocarditis: Micro Pearls • Streptococcus gallolyticus (formerly bovis): colonoscopy, r/o CA • Q fever: parturient cats, livestock, chronic fibrosis on histopath; if positive culture and serology for Coxiella burnetii = major criteria • Staphylococcus lugdunensis – coag negative staph, NVE, bad infection • Gram negative rods: healthcare associated >> IVDU • Bartonella: homeless, alcoholic, body lice, cats • Whipple’s: histopath: “foamy macrophages”; indolent infection with arthralgias, CHF, murmur, emboli; no fever; diarrhea and GI symptoms may be mild/absent • Culture negative: – prior antibiotics #1 cause (usually masking a typical strep) – also think about HACEK, Bartonella sp., Coxiella burnetii, Brucella, and Tropheryma whipplei Endocarditis • Indications for surgery – Acute rupture of valve or chordae tendinae – Acute congestive heart failure – Abscess – Fungal endocarditis – AV block – Recurrent major embolic events on antimicrobials – Highly resistant organism Miscellaneous Cardiac Infections • Myocarditis due to viruses (Enterovirus) and Trypanosoma cruzi (Chagas’) • Pericarditis due to viruses (Enterovirus), TB (calcific), and rarely bacteria Meningitis • Most commonly present with mix of fever, HA, stiff neck, photophobia • Diagnostics – Best initial test: CSF cell count (sens: 95-98%) – Most accurate test: CSF culture (spec: ~100%) – GS: if positive, specific (sens: 60-70%); narrow Rx accordingly – Protein: normal protein excludes meningitis – Glucose: poor sens/spec – Cell count: if very high neutrophil count, fairly specific – Bacterial antigen (latex agglutination) doesn’t usually add to treatment, so ACP advising not to order CSF in Meningitis Bacterial Viral TB Cryptococcus 20-50 cm H20 < 25 18-30 >20 1000-5000 wbc 50-1000 wbc 50-300 wbc 20-500 wbc Neutrophils Lymphocytes Lymphocytes Lymphocytes Glu < 40 mg/dl >45 (nl-50% of (less than 18 strongly serum glu) predictive) < 45 < 40 Protein 100-500 mg/dl (nl 20-40 1mg/1000 rbcs) < 200 (slightly elevated) 50-300 >45 Gram stain (+6090%) Stains – (add fungal, VDRL, AFB, India Ink, HSV PCR) (repeat at 3 days if suspicion remains) AFB (25%+) – (add fungal studies,VDRL, India Ink, etc.) India ink + > 60%) – (obtain crypto Ag CSF) Meningitis • CT head before LP if – – – – – Papilledema Focal neurologic deficits Seizure or severe confusion Immunocompromised H/o CNS disease • If a CT is needed, answer “antibiotics prior to CT” • Regardless, there is always time for STAT blood cultures before antibiotics and/or LP Meningitis • Etiology – Pneumococcus (GPC): common (60-70%), OM/sinusitis/pna, immunocompromised, csf leak – Neisseria meningitidis (GN diplococcus): young, healthy, military, college (young adult w/ petechial rash, 1000’s neutrophils on CSF) – Haemophilus influenzae (GN coccobacilli): rare since vaccine – Listeria monocytogenes (GP rod): immunocompromised, >50 – Staphylococcus aureus (GPC): NSG, penetrating trauma Meningitis Associations • Cranial nerve involvement • TB, sarcoid, Lyme disease (especially 7th: Bell’s palsy - also may have foot drop), carcinomatosis • Exposures • TB – prisoner, immigrant, abnormal CXR • Cryptococcus- HIV, alcoholics, chronic steroids, AIDS, ALL, Hodgkins lymphoma • Listeria – elderly, alcoholics, pregnant, immunosuppressed • Coccidioides – Southwest US • Meningococcal – crowded living conditions • Recurrent meningitis • Aseptic – NSAIDs, Mollaret’s (herpes simplex), tumor • Pneumococcal – CSF leak, asplenia • Meningococcal – properdin & C5-9 deficiency, asplenia Empiric Therapy for Meningitis Based on Age or Underlying Condition Age 2-50 S. pneumo/N.meningitidis Vanc + third generation ceph (cefotaxime, ceftriaxone) Age > 50 S. pneumo/N.meningitidis/ Listeria Vanc + 3rd ceph + Amp Basilar skull FX S. pneumo/H. flu/ gr A strep Vanc + 3rd ceph Post neurosurg/trauma S. aureus, Coag-neg staph/gram negative bacilli (including pseudomonas) Vanc + Ceftazidime or Cefepime or meropenem CSF Shunt S. Aureus, coag-neg staph/ gram negative bacilli (including pseudomonas)/diptheroids Vanc + Ceftazidime or Cefepime or meropenem Meningitis • Treatment – If positive gram stain (or culture) should narrow Rx • Meningococcus, Haemophilus – 3rd gen cephalosporin • Pneumococcus – vanco, 3rd gen cephalosporin, dexamethasone • Listeria – ampicillin or PCN G – If meningococcus • Suspected - needs droplet isolation (for 24 hours after abx) • Confirmed: close contacts – Get cipro, rifampin or ceftriaxone within 24h of ID – CC are day care, household contacts, salivary contacts, or HCW in direct contact with oral or respiratory secretions – If random HCW, classroom/office contact, “reassurance only” CSF lymphocytosis (aseptic meningitis) Tuberculosis • Immigrant, lung lesions, very high protein • high volume serial lp for AFB; also PCR • 4 drug rx + steroids RMSF • Camper/hiker w/ rash moving to trunk • Serology, biopsy • Doxycycline Lyme • Tick bite, rash, joint pain, carditis • Serology • IV ceftriaxone/cefotaxime Enteroviral • • PCR for diagnosis Treatment is supportive Drug-induced • • NSAIDs, IVIG, trim-sulfa Stop the offender Cryptococcus • • • AIDS, cd4 <50 India ink, Ag Ampho, then fluconazole Encephalitis Associations • West Nile: flu-like symptoms followed by flaccid paralysis, seizures • Rabies – presume exposure if bat in room and patient not at 100% awareness (Sx: hydrophobia, pharyngeal spasms, hyperactivity) • Mumps – parotitis present • VZV - Grouped vesicles - (but can have without vesicles) • HSV - Temporal lobe changes on imaging studies - *clinically most important to r/o since treatment changes mortality* HSV & CNS • Type I traditionally non-genital • Type II predominantly genital (see STD section) • Common infection in the general population (Type I 80%, Type II 20% adults positive) • Acute treatment reduces duration of symptoms • Chronic treatment reduces symptomatic episodes, asymptomatic shedding and transmission • Two neurological syndromes: – Aseptic meningitis – Type II, benign but may be recurrent – Encephalitis – Type I, needs IV acyclovir, high morbidity/mortality if untreated HSV Infections – Ophthalmologic & Neurologic Syndromes • Dendritic keratitis – usually caused by Type I, reactivation of the virus in the trigeminal ganglion, ulcers seen on fluorescein staining, most frequent cause of corneal blindness in US • Encephalitis – usually caused by Type I – CSF with lymphocytic pleocytosis, increased number of erythrocytes, and elevated protein • Unilateral temporal lobe lesions on imaging with associated mass effect – Diagnose with HSV PCR CSF (98% sensitive, 94-100% specific) – Treat with IV acyclovir 10 mg/kg q8h; give early if clinical picture is suspicious for this infection; early therapy prevents mortality and limits the severity of chronic post-encephalitic behavioral and cognitive impairments – 70% mortality if untreated – Duration of therapy 14-21 days • Aseptic meningitis – Type II, benign but may be recurrent (Mollaret’s) VZV Infection (shingles) • • Characteristic clinical presentation: rash in a dermatomal distribution with acute neuritis Complications in immunocompetent patients: – Post herpetic neuralgia – Bacterial skin infections – Ocular complications, including uveitis and keratitis – Motor neuropathy – Meningitis – Ramsay Hunt Syndrome (Bell's palsy, deafness, vertigo, and pain) • Cause of herpes zoster ophthalmicus: – Linked to VZV reactivation in the trigeminal ganglion; sight-threatening disease – Vesicular lesions on the nose: Hutchinson’s sign: involvement of nasociliary branch of CN V: conveys high risk of zoster opthalmicus • Cause of acute retinal necrosis (ARN) Varicella Zoster Virus • Treatment: – Acyclovir, valacyclovir, famciclovir (high dose) – Analgesia for acute neuritis – Prednisone – role uncertain – may be useful in acute neuritis that is not controlled by opioid analgesics – Immunocompromised – IV acyclovir – Varicella zoster immune globulin for high risk patients (exposed immunocompromised or seronegative pregnant) – Herpes zoster vaccine for prevention of shingles if >60; reduces incidence, decreases postherpetic neuralgia Influenza • Influenza A – Subtypes based on surface proteins (hemagglutinin, neuraminidase) – Drifts: minor mutations, local outbreaks – Shifts: major mutations, epidemics/pandemics (if human illness, efficient human to human transfer, and little preexisting immunity) • Influenza B – Less severe outbreaks, can’t differentiate clinically • • • • • • Illness in winter months, most serious <2, >65, comorbidities 1-4d incubation Symptoms: fever, HA, myalgia, nonproductive cough, sore throat, nasal d/c Rapid test helpful if positive, doesn’t exclude if negative If influenza in community, diagnose w/ signs/symptoms only Treat (oseltamivir, zanamivir) hospitalized, severely infected, severely at risk; try to start in first 2 days of illness • Vaccinate all above 6 months of age Malignant Otitis Externa • • • • Invasive infection of the external auditory canal and temporal bone Elderly patients with diabetes mellitus Pseudomonas always the responsible organism Patients present with exquisite otalgia and otorrhea, which are not responsive to topical measures used to treat simple external otitis; also can have a cranial neuropathy (usually CN 7) and intracranial complications (meningitis, brain abscess, dural sinus thrombosis) • Diagnosis: culture and sensitivity of drainage from ear, imaging studies (CT, MRI, bone scan) • Treatment: anti-pseudomonal antimicrobial; duration 6 weeks due to associated osteomyelitis • Surgery reserved for local debridement, removal of bony sequestrum, or abscess drainage Soft Tissue Infections from Cat or Dog Bites • Microbes • Pasteurella species: 50% dog wounds, 75% cat wounds • Capnocytophaga canimorsus: fastidious GNR, bacteremia and fatal sepsis, especially in asplenic, hepatic disease • Anaerobes • Staph and strep from human skin • Wound care, antibiotics, and tetanus vaccination • Amoxicillin/clavulanate, or if severe ampicillin-sulbactam IV • Antibiotic prophylaxis X 3-5 days w/ amox-clav if : – – – – – – Deep puncture wounds (especially due to cat bites) Moderate to severe wounds with associated crush injury Wounds in areas of underlying venous and/or lymphatic compromise Wounds on the hand(s) or in close proximity to a bone or joint Wounds requiring surgical repair Wounds in immunocompromised hosts Human Bites • Human mouths are nasty • Microbes – Oral flora, polymicrobial – Staph, strep, Haemophilus, Eikenella, anaerobes • Consider evaluation other potential pathogens – HIV, Hep B, Hep C, HSV • Prophylaxis for all wounds w/ amoxicillin-clavulanate for 3-5 days • Closed-fist injuries deserve radiography, hand consult, possibly admission MRSA Infections • Altered penicillin binding proteins – resistant to all beta-lactam antibiotics • Causes skin/soft tissue infections, bacteremia, and pneumonia • Hospital and community strains differ: – CA-MRSA associated with Panton-Valentine leukocidin (PVL) virulence factor – HA-MRSA strains more resistant to other antibiotics • CA-MRSA associated with crowding (prisons), athletes, hot tubs, body shaving, etc. • CA-MRSA now dominant clone of community isolates, and increasingly in hospital MRSA – Outpatient Treatment Local Drainage Most Important for Skin/Soft Tissue Infections Drug Issues Doxycycline 15% resistance Trimethoprim/sulfa Not good for group A strep Fluoroquinolone Resistance frequent HAMRSA Clindamycin 15% resistance, inducible resistance, positive D test Linezolid High cost, marrow suppression MRSA – Treatment for Pneumonia/Bacteremia Drug Issues Vancomycin Time tested, slow clearance of bacteremia, MIC creep (2+) Daptomycin Poor pulmonary activity, high cost Linezolid IV/PO, BMT, high cost Tigecycline Low blood levels / not for BSI, high cost Necrotizing fasciitis • Severe infection of SC soft tissues; erythema, swelling bullae, cutaneous gangrene (rapid). • Often LE, abdomen, perineum • Type I: polymicrobial (anaerobes/strept/enterobacter) • Type II: group A strep • Also can see w/ CA-MRSA • RF: DM, PVD, surgery, trauma • Surgical exploration stat • Empiric antibiotics (vancomycin plus clindamycin plus beta-lactam/bl-inhibitor or carbapenem) Gas Gangrene – Clostridial myonecrosis: lifethreatening muscle infection that develops from contiguous area of superficial trauma – Diagnosis: severe pain at site of injury, systemic toxicity, swelling/crepitance/gas in the soft tissues, large gram variable rods in tissue – Treat with surgical debridement, PCN + clindamycin Streptococcal Toxic Shock Syndrome • Group A streptococcal infection (usually SSTI), fever, hypotension MOF • Mediated by toxins, cause release of inflammatory cytokines capillary leak and tissue damage • Risk factors: minor trauma, liposuction, vaginal delivery or csection, minor and major surgeries, viral infections, NSAIDs • Complications include bacteremia (usually), ARDS, DIC, MSOF • Usually no rash or desquamation • Treat with IV fluids, penicillin, clindamycin Staphylococcal Toxic Shock Syndrome • Fever, sunburn rash, hypotension MOF • Associated with colonization of wound or vagina with toxinproducing S. aureus w/o invasive disease • Not usually bacteremic • Desquamation occurs late • Most commonly associated with menstruation • Support with IV fluids, removal of source (tampon, sponge) are most important treatments • ABX may help; vanco and clinda empiric; if cultured + for MSSA can do naf/ox and clinda Vibrio vulnificus • Present w/ sepsis, hemorrhagic bullae, necrotizing fasciitis • H/o exposure – Warm brackish/salt water, Gulf of Mexico, summer – Inoculation through skin trauma – (Can also see as septicemia after ingestion of raw or undercooked shellfish) • RF: hemachromatosis, liver disease • Rx: Doxycycline + ceftriaxone Infectious Arthritis • Nongonococcal arthritis – – – – – Acute onset, monoarticular joint pain, swelling Knee most common, then hip Staph aureus, Strept most common Ecoli, Pseudomonas less common RF: age >80, DM, IVDU, endocarditis, recent joint surgery, joint prosthesis, skin infection, RA – Fever, chills, NWB, pain w/ motion, large effusion, hot and tender joint – Diagnosis: • Blood cultures + in <50% • Typical arthrocentesis: >50k wbc, >90% neutrophils Osteomyelitis Osteomyelitis • Contiguous or hematogenous • Predisposing conditions: PAD, DM, Skin ulcer with local infection • Presents with – pain, tenderness, erythema, warmth – severe osteomyelitis can lead to sinus tract – fever and systemic signs rare (10%) • Staphylococcus aureus most common, but many others • Diagnostic tests Osteomyelitis – X-ray best initial • If positive no need for further imaging • 2-3 weeks to see changes (periosteal elevation, destroyed bone) – MRI if X-ray negative; don’t f/u MRI for resolution – Nuclear bone scan: only if MRI contraindicated (PM) – To guide therapy you need: • Most accurate: bone biopsy with culture • Positive blood cultures (10%) – Sterile metal probe to bone gives diagnosis, but biopsy for culture needed to get organism • Treatment – – – – Empiric therapy shouldn’t be an answer MSSA: ox/naf/cefaz MRSA: vanco GNR: oral FQ Anyone out there still awake? Sexually Transmitted Diseases • • • • • Gonorrhea Chlamydia PID Trichomonas Genital Ulcerative Disease – – – – Syphilis Herpes Chancroid LGV • Genital Warts /HPV Gonorrhea • Urethritis in males; cervicitis and PID in females • GS of urethral discharge showing PMNs with intracellular gram-negative diplococci, but not sensitive enough to exclude, so NAAT • Treatment options: – Ceftriaxone 250 mg IM X 1 – Cefixime 400 mg po X 1 – Alternatives: • Spectinomycin (not readily available) • Azithromycin (GI tract symptoms in 35% patients, expensive) – Pregnant: • Either of the above cephalosporins or spectinomycin or azithromycin – Note: Fluoroquinolones not recommended anymore – Always treat for Chlamydia infection as well as co-infection rates are high – Always treat partners Disseminated Gonococcal Infection • Fever, migratory polyarthralgias, tenosynovitis, and skin lesions (maculopapular, vesicular, or necrotic) • Asymmetric joint involvement common • If untreated, patient can later present with a monoarticular septic arthritis • Diagnosis: send specimen to be plated on Thayer-Martin media: – Arthrocentesis diagnostic procedure of choice: • Synovial fluid cultures positive in only 25-30% patients – 80% patients have a positive test for gonorrhea from cervix, urethra, rectum, blood, or pharynx • Treatment options: – Ceftriaxone 1 g IV qd – Cefotaxime 1 g IV q8 Infectious Arthritis • Gonococcal arthritis • Most common < 40 yo – Women > men – Monoarticular arthritis (knee) – Arthrocentesis • Can see >50k wbc • 10% w/ positive gram stain • <50% are culture positive – Treat with ceftriaxone, include doxy or azithro to cover chlamydia Chlamydia • Non-gonococcal urethritis (NGU) in males; cervicitis and PID in females • Intracellular organism • Diagnosed with NAAT • Treatment options: – Azithromycin po X 1 – Doxycycline po bid X 7 days – Pregnant women: • Amoxicillin po tid X 7 days • Azithromycin po X 1 • Need test for cure in 3-4 weeks – Treat all partners of infected patients Pelvic Inflammatory Disease • PID is considered polymicrobial, GC and CT cause most of it • Highest risk in young, sexually active females • Can be mild, have to have high index of suspicion due to complications (FT scarring, TOA, infertility) • Consider if sexually active woman w/ low abd or pelvic pain, plus cervical motion, uterine or adnexal tenderness • Mucopurulent cervicitis increases likelihood • Can also see fever, +GC/CT on NAAT • Rx – Parenteral: cefotetan/cefoxitin + doxycycline – Outpatient (PO + IM) ceftriaxone + doxy, +/-metronidazole Trichomoniasis • Intense pruritis with a malodorous, frothy, yellow discharge • Pelvic exam demonstrates diffuse erythema of vaginal walls and cervical inflammation (strawberry cervix) • Typically asymptomatic in men • Diagnosis made by observing motile trichomonads on wet prep; vaginal pH > 4.5 • Treatment options: – Metronidazole po X 1 – Tinidazole po X 1 – Failure: Metronidazole bid X 7 days – Pregnant: 100 mg vaginal suppository or cream qd for 7 days: may relieve symptoms – Treat all partners of infected patients Genital Ulcer Diseases • • • • Syphilis – painless ulcer Genital herpes – painful ulcer Chancroid – painful ulcer, tender nodes Lymphogranuloma venereum – painless ulcer, tender nodes Syphilis • Primary syphilis – Painless chancre; resolves in 3-6 weeks – Regional LAD • Secondary syphilis – MP rash, condylomata lata, alopecia, mucous patch – LG fever, malaise, pharyngitis, laryngitis, LAD, anorexia, weight loss, arthralgias, HA, meningismus – Usually 2-8 weeks after chancre • Latent syphilis – Positive serology, no symptoms – Early latent: less than a year – Late latent: > 1 year or unknown Syphilis • Tertiary syphilis – Can have aortitis, gummas – Neurosyphilis • CSF: wbc>5, increased protein, low glucose, positive VDRL • Usually asymptomatic • Some signs Tabes dorsalis – wide-base gait, foot slap Argyll Robertson pupil (small, does not react to light, contracts normally to accommodation) Meningovascular disease Syphilis serology • Non-treponemal tests (Screening test) – Relies on reactivity of serum antibodies against a cardiolipin-lecithincholesterol antigen (RPR, VDRL) – Not highly specific; can have false positives – Insensitive in primary and late syphilis: check a treponemal test – Titers of 1:8 or higher are unusual for false positives – 4-fold decline in titer is considered an adequate response • Treponemal tests: antibody to T. pallidum (TPPA, FTA-Abs) – Confirmatory test – May remain positive for extended periods, possibly for life, even after adequate treatment of syphilis – A persistently reactive treponemal test does NOT indicate inadequate treatment, relapse, or re-infection Syphilis Treatment • Primary, secondary, early latent (test and treat contacts): – Benzathine penicillin G IM X 1 – Alternative: • Doxycycline PO X 14 days • Tertiary (not neurosyphilis) and late latent: – Benzathine penicillin G IM q week X 3 weeks – Alternative: • Doxycycline PO X 28 days • Neurosyphilis: – Penicillin G IV x 10-14 days – Alternative: • Ceftriaxone IV x 10-14 days • If pregnant + penicillin allergic: desensitize to penicillin • If neurosyphilis + penicillin allergic: desensitize to penicillin Genital Herpes • Caused by HSV-1 or HSV-2 infection • 45 million Americans with positive HSV-2 serology • Spread by direct contact – abraded skin or mucous membranes are more susceptible than intact skin • Characterized by small, painful, grouped vesicles in the anogenital region that rapidly ulcerate and form shallow, tender lesions: – Initial episode most severe and may present with fever, myalgias, inguinal adenopathy, headache, and aseptic meningitis – Recurrent episodes may be proceeded by a prodromal period associated with pain – Diagnosis by viral culture or PCR (more sensitive) – Serologic studies useful for counseling couples – Serodiscordant considerations: avoid sex during prodrome/outbreak, condoms, daily suppressive medication Genital Herpes Anogenital Herpes Treatment of Genital Herpes • Initial episode – Acyclovir PO tid x 7-10 days – Famciclovir PO tid x 7-10 days – Valacyclovir PO bid x 7-10 days • Recurrent episode – Same meds, slight changes in dosing – Most effective if initiated during the prodrome or within one day of recurrence of vesicles • Daily suppressive therapy – If the patient is having 6 or more episodes per year, or serodiscordant couple – Asymptomatic viral shedding can still occur on treatment Chancroid • Common worldwide, uncommon in U.S., usually related to sex for drugs • Caused by Haemophilus ducreyi • Painful genital ulcers with tender suppurative inguinal lymphadenopathy • Consider only after syphilis and HSV excluded • Diagnosis made by inguinal LN biopsy • Re-examine in one week to evaluate for ulcer improvement • Treatment options: – – – – Azithromycin PO X 1 Ceftriaxone IM X 1 Ciprofloxacin PO X 3 days Erythromycin PO X 7 days Chancroid Lymphogranuloma Venereum (LGV) • Caused by Chlamydia trachomatis serovars L1-L3 • Painless ulcer at inoculation, resolves, followed by unilateral tender inguinal lymphadenopathy which may suppurate, drain • Diagnosis made by type-specific Chlamydia serology • Treatment of choice: – Doxycycline PO X 21 days • Alternative treatments: – Azithromycin X 3 weeks – Ciprofloxacin X 3 weeks – Erythromycin X 3 weeks – Bactrim X 3 weeks LGV Genital Warts • Usually due to HPV serotypes 6 and 11 (16 and 18 associated with cervical CA) • Perianal warts common in MSM, associated w/ CA • Usually asymptomatic • Clinical diagnosis • Treatment only if symptomatic, or cosmetic concerns • HPV vaccine recommended for 11-12 yo males x 3 doses; protects against HPV, related CA, and likely will protect females by reducing transmission of cervical CA causing serotypes Antifungals • Azoles, amphotericin, echinocandins • Fluconazole active against Candida (other than glabrata/krusei), Cryptococcus • Itraconazole for Sporothrix, Histoplasma, Blastomyces • Voriconazole for Aspergillus • Azoles CYP inhibitors Antifungals • Lipid formulations of amphotericin preferred • LA-AmB preferred agent for severe fungal infections (Cryptococcal meningitis, acute disseminated Histoplasmosis, mucormycosis) • Nephrotoxicicty (electrolyte wasting, decreased GFR) major toxicity • Echinocandins drug of choice for C krusei and glabrata, minimal toxicities (hepatic) Invasive Fungal Infections • Dimorphic fungi – – – – – Histoplasma capsulatum Blastomyces dermatitidis Coccidioides immitis Penicillium marneffei Sporothrix schenckii • Opportunistic Yeasts and Molds – – – – – Candida Cryptococcus Aspergillus Pneumocystis Zygomycetes Candidemia • Candida in blood is not a contaminant, it’s an emergency • Start empiric antifungal therapy – Echinocandin • If previous exposure to fluconazole • If institution has high % of resistant species (C. glabrata & krusei) • If severe sepsis – After speciation, change to fluconazole if possible • Cheaper • Oral fine if stable • Remove lines • Dilated ophthalmologic exam to r/o candidal endophthalmitis • Treat at least 2 weeks after clearance of blood cultures Histoplasmosis • Acute disseminated in AIDS patients (fevers, weight loss, LAD) • Acute pulmonary Histo similar to influenza, prominent hilar LAD • Chronic cavitary Histo rare, presents similar to cavitary TB • Mediastinal fibrosis rare hypersensitivity reaction causing compression of mediastinal structures, no response to antifungals • Amphotericin for severe disease, itraconazole for mild/moderate • Can be grown in fungal culture but slow, urine antigen Blastomycosis • Dimorphic fungus, broad based budding • Pulmonary route of entry, disseminates to skin, bone, CNS • Skin lesions nodular or verrucous • Similar diagnosis and treatment as for Histoplasmosis Coccicioidomycosis • Dimorphic fungus endemic to northern Mexico and southwestern US • Usually causes an acute pulmonary infection similar to influenza, self-limited (valley fever) • Disseminated infection (even from remote prior infection) in immunocompromised (TNFalpha inhibitors, steroids) Sporotrichosis • • • • • • Soil fungus that causes a subacute to chronic infections (Sporothrix schenckii) Suppurating multiple subcutaneous nodules that progress proximally along lymphatic channels (lymphocutaneous sporotrichosis) Initial reddish, necrotic, nodular papule of cutaneous sporotrichosis generally appears 1-10 weeks after a penetrating skin injury: usually from a splinter, thorn, or woody fragments of plants Associated with: gardening, landscaping, farming, berry-picking, horticulture, and carpentry Definitive diagnosis requires isolation of the organism in a specimen culture or visualization (cigar-shaped yeast) in a tissue biopsy Itraconazole is the drug of choice for treatment, continue until 2-4 weeks after all lesions have resolved Aspergillosis • Several pulmonary manifestations (ABPA, Aspergilloma, IPA) • Aspergilloma with fungus ball on imaging and no treatment indicated Allergic Bronchopulmonary Aspergillosis • • • • • • A history of asthma Immediate skin test reactivity to Aspergillus antigens Precipitating serum antibodies to A. fumigatus Serum total IgE concentration >417 IU/mL (>1000 ng/mL) Peripheral blood eosinophilia >500/mm3 Lung infiltrates on chest radiograph or chest high-resolution computed tomography (HRCT) • Central bronchiectasis on chest computed tomography (CT) • Elevated specific serum IgE and IgG to A. fumigatus Invasive Pulmonary Aspergillosis • Classically in neutropenic patients • Suspected by imaging (halo sign-infarction of lung tissue, air crescent), positive galactomannan, high risk patient, prolonged fever • Confirmed by biopsy demonstrating vascular invasion by acute angle branching mold • Voriconazole DOC Mucormycosis – Rare OI (rhino-orbital-cerebral most common, rapidly fatal) – RF: diabetes, iron overload, burn patients, immunocompromised state – HA, fever, visual changes, sinusitis, & eventually proptosis – Black necrotic tissue on nose or palate is pathognomonic – Diagnose with imaging studies, FNA of material in sinuses with histopathology: non-septate hyphae with broad right angle branching – Treat with Amphotericin B, aggressive, surgical excision Tuberculosis Skin Testing (TST) > 5 mm – HIV positive – Persons on steroids (15mg/day)/immunosuppressive drugs – Transplant patients – Close contact of an active case – Fibrotic CXR lesions c/w prior TB > 10 mm – Healthcare workers – Recent immigrants – IVDU – Homeless, prisoners, longterm care facilities – Some chronic health conditions > 15 mm – No increased risk TB screening: IGRA vs. TST • IGRA • • • • as sensitive but more specific BCG vaccine or chemotherapy does not cross-react one blood draw, no need for return, multi-step used in place of (and not in addition to) the TST • TST • preferred in children < 5 • cheaper • reaction influenced by BCG, atypical mycobacteria Latent Tuberculosis Infection (LTBI) • Treatment • Isoniazid (INH) x 9 months (remember to add pyridoxine [B6]) or • Rifampin x 4 months • TB Natural History – In Normal Host: • If TB infected: 5% risk of disease in first 2 years + 5% risk of disease throughout life = 10% overall risk of active disease – In HIV infected: • 5-10% risk/year of active disease Tuberculosis • Extremely rare in U.S. outside certain groups – Recent immigrants, homeless alcoholics, prisoners, HIV/AIDS, HCW, transplant recipients, folks on dialysis or w/ silicosis, close contacts of TB infected • Presents like other chronic lung infections – Fever, cough, sputum, weight loss, signs of consolidation on exam • Diagnostics – – – – CXR can show apical infiltrates, cavity formation Acid-fast stain, mycobacterial culture Pleural biopsy in presence of effusion is single most accurate test Direct probes are help in smear positive patients Treatment summary: >Start 4 drug therapy w/ isoniazid, rifampin, pyrazinamide and ethambutol (+B6) >At 2 months, sensitivities known, can usually drop to INH and rifampin >Treat for 6 months total if no cavitation >Add steroids for TB pericarditis, meningitis (9-12m) >Cavitation calls for 9m total >Pregnant? Can’t take PZA, therefore 9 m total >SE: all hepatotoxic; also PZA=>hyperuricemia EMB=>optic neuritis INH=>neurotoxicity MMWR 2003 Nocardia vs. Actinomyces • Both are gram positive branching rods • Nocardia is acid fast (weak); Actino is not • Nocardia: abscesses; Actino: sulfur granules, sinus tracts • Nocardia:immunocompromised; Actino: normal, or maybe poor dentition, IVDU • Both get lung, but Nocardia CNS; Actino mandible • Nocardia treat with TMP-SMX; Actino with PCN Tick Borne Diseases • • • • • • • RMSF Lyme Ehrlichiosis Southern Tick Associated Rash Illness Babesiosis Tularemia Relapsing Fever Rocky Mountain Spotted Fever • • • • • Caused by Rickettsia rickettsii Dermacentor variabilis Ticks need to attach for 6-10 hours Seasonal variation: spring and early summer most likely times Incubation period ~ 7 days (3-12 days), followed by fever (94%), headache (88%), myalgia (85%), and vomiting (60%) • 2-6 days later: petechial rash (83%), cough, electrolyte abnormalities, thrombocytopenia, elevated transaminases • Initial diagnosis clinical (+/- skin biopsy – not useful after 48 hrs doxycycline); confirmed by convalescent antibody titer at 14-21 days • Treatment: doxycycline – Death in 1-3% of those treated compared with 30% in untreated patients (death due to ARDS, mycocarditis, ARF, encephalopathy) Lyme Disease • Borrelia burgdorferi transmitted by nymph of deer tick (Ixodes sp.) • Tick has to feed for 1-2 days for transmission • Reservoir: white-footed mouse • Most common in Northeast, MN, WI • Stage I: erythema migrans (target rash) – occurs in 80% patients – erythematous rash with central clearing (bull’s eye appearance), myalgias, arthralgias, headaches, lymphadenopathy • Stage II: early disseminated disease: neurologic disease including meningitis and cranial nerve palsies, myocarditis (heart block) • Stage III: late or chronic disease: arthritis (large joints), chronic subtle neurologic manifestations (encephalopathy, peripheral neuropathy) Lyme Disease – Diagnosis and Treatment • Diagnosis: – Stage I: clinical – based on characteristic rash and compatible history; serology usually NEGATIVE at this time – Stage II, III: ELISA, Western blot • High false positive rate • Treatment: – Stage I, Bell’s palsy: amoxicillin or doxycycline for 14-21 days – Arthritis: amoxicillin or doxycycline for 28 days – Cardiac, neurological manifestations: ceftriaxone IV for 21 days Ehrlichiosis • Due to rickettsia-like bacteria • Two forms: – Monocytic – South Central USA (HME) – Granulocytic – Upper Midwest, Northeast (HGE) • S&S: fever, HA, cytopenias, elevated AST, +/- rash in HME • Diagnosis: – Serology, PCR – Inclusions in WBC (morula) – low sensitivity • Treatment: doxycycline • Has been called “spotless RMSF” Other Zoonoses • • • • • • Q Fever Brucellosis Leptospirosis Malaria Leishmaniasis Cysticercosis Q Fever – Coxiella burnetii • Reservoir: livestock • Exposures: aerosols from infected animals, esp. slaughter house, after birthing; drinking contaminated birthing products • S&S: fever, headache, myalgia, cough, N/V, abdominal pain • Clinical manifestations: granulomatous hepatitis, culture negative endocarditis, pneumonia • Diagnosis: serology: seroconversion usually detected 7-15 days after onset of illness • Treatment: doxycycline, long duration for endocarditis: minimum of 18 months! Brucellosis – Brucella sp. • Brucella sp.: B. abortus (cow), B. suis (pig), B. melitensis (goat), B. canis (dog) • Risk factor: consumption of unpasteurized dairy products, especially Mexican goat cheese • Clinical manifestations: non-specific febrile illness; enteric fever (fever + abdominal pain), septic arthritis, sacroiliitis, hepatitis, splenitis, meningitis, endocarditis, orchitis, hematologic disorders • Diagnosis: blood/marrow cultures (slow-growing); serology • Treatment: doxycycline + (rifampin or streptomycin) Leptospirosis – Leptospira interrogans • Infects many domestic and wild animals • Human infection after exposure to environmental sources, such as animal urine, contaminated water or soil, or infected animal tissue. Portals of entry include cuts or abraded skin, mucous membranes or conjunctiva. • Think of if flu-like illness and environmental exposure (eco-challenge, adventure racing, triathalon, whitewater rafting) • Usually contamination arises from infected rat and dog urine • S&S: fever, myalgias, headache, N/V, conjunctival suffusion, meningitis, nephritis/ATN, hepatitis (high bilirubin, minimal increase in transaminases); pneumonia • **Weil’s syndrome: more severe hepatitis, renal involvement • Diagnosis: clinical, serology (IgG ELISA, MAT: microscopic agglutination), blood, urine, and CSF cultures • Treatment: PCN G, doxycycline Malaria • • • • Common cause of fever in returned travelers Presents w/ fever, chills, malaise, HA, myalgias, GI symptoms Symptoms cyclical, due to w/ rupture of parasitized RBC (48-72h) Signs: hemolytic anemia, splenomegaly, hypoglycemia, thrombocytopenia, transaminitis, indirect hyperbilirubinemia, hemoglobinuria • For P. falciparum, 1-2 weeks after infection; longer for others • Order thick and thin blood smears on all febrile travelers from endemic areas Malaria • P. falciparum – widespread, drug-resistant, lethal – high parasitemia (>1%), can have >1 parasite per RBC, banana-shaped gametocytes, paucity of mature schizonts • P. vivax – widespread, less virulent – often see gametocytes and schizonts • P. ovale – much less common – often see gametocytes and schizonts • P. malariae – much less common – often see gametocytes and schizonts • P. vivax and ovale can relapse (dormant liver stages/hypnozoites) Malaria - Treatment • P. falciparum – Preferred -Quinine + doxycycline -Quinine + suladoxinepyrimethamine – Alternative -Quinine + clindamycin -Mefloquine -Atovaquone/proguanil • P. vivax, ovale – Blood stage treatment • Chloroquine – Eradication of the hypnozoite stage is necessary to prevent relapses • Primaquine Bioterrorism Agents: Anthrax • Other forms, but pneumonic/inhalational for BT • Fever, chills, malaise, fatigue, N/V, cough, respiratory disease, shock, and death within 24-36 hours of severe symptoms • Inhalational mediastinal widening • Incubation period: range 2-50 days; 4-6 days if inhaled • Diagnosis: gram stain, culture, ELISA, blood, skin, pleural fluid, CSF • Standard isolation precautions • Chemoprophylaxis: cipro 500 bid x 60d; alt: doxy, amoxicillin Anthrax: Cutaneous and Inhalational Boxcar-shaped gram positive rod Mediastinal widening Bioterrorism: Botulism – Clostridium botulinum • Neurotoxin of spore-forming Clostridium botulinum • Inhalational: Incubation period 12 hours to several days • Key clinical features: – cranial nerve palsies (ptosis, diplopia, dysphagia) – followed by symmetrical descending flaccid paralysis – patients are afebrile, alert, and oriented • Death usually due to respiratory failure • Standard isolation precautions Bioterrorism: Plague – Yersinia pestis • Primary pneumonic plague – rare, think aerosolized, BT – Incubation 1-3 days – Fulminant pneumonia- watery, bloody sputum in previously healthy persons – Septic shock, DIC – Diagnosis: gram stain of blood or sputum (small gram negative coccobacillus) – bipolar staining (“safety-pin”); DFA at Public Health lab – Infection control: transmissible person-to-person by respiratory droplets – gown, glove, and droplet precautions (also need eye protection if aerosols anticipated) Bioterrorism: Tularemia – Francisella tularensis • Humans are accidental hosts, following contact with infected animals (especially rabbits and other rodents) • Some occupations confer risk for tularemia; they include laboratory workers, landscapers, farmers, veterinarians, hunters, trappers, cooks, and meat handlers. • If bioterrorism event, probably airborne delivery • Symptoms after 3-5 days or as long as 2 weeks – Fever, chills, HA, myalgias, arthralgias, diarrhea, dry cough – Can progress to pneumonia w/ pleuritic CP, hemoptysis, respiratory failure • Not spread person to person, so no need for isolation Bioterrorism: Smallpox Contact and Airborne Precautions Necessary CDC Major Criteria • Febrile prodrome occurring 1-4 days before rash onset: fever and at least one of the following: prostration, HA, backache, chills, vomiting, or severe abdominal pain • Classic smallpox lesions: deep, firm/hard, round, wellcircumscribed; may be umbilicated or confluent • Lesions are in the same stage of development on any one part of the body (i.e. face or arm) CDC Minor Criteria • Centrifugal distribution: greatest concentration of lesions on face and distal extremities • First lesions on oral mucosa or palate, face, forearms • Patient appears toxic • Slow evolution: lesions evolve from macules to papules to pustules over days • Lesions on palms and soles (majority of cases) Appearance of Smallpox Lesions Hemorrhagic-type variola major lesions. Death usually ensued before typical pustules developed. Food-borne Illness • • • • Secondary to bacteria, viruses, parasites or ingestion of bacterial toxins Remember to report to Department of Health Often nausea, vomiting, diarrhea and/or abdominal pain Timing can be helpful – 1-6 hours: Staph aureus, Bacillus cereus (preformed enterotoxins) – 8-16 hours: Clostridium perfringens, B. cereus – 16-72 hours: Campylobacter, Salmonella, Shigella, E. coli, Yersinia, Vibrio • Associations • Rice – Bacillus cereus • Potato salad, cream pastries, poultry – Staph • Home-canned foods – Clostridium perfringens • Honey – Clostridium botulinum • Apple cider, undercooked hamburgers - STEC Infectious Diarrhea • Classified – Community-acquired – Healthcare-associated – Persistent (>7d) • If healthy – Bacteria/viral infection self-limited regardless of treatment – Greater than 7 days duration suggestive of parasitic infection or noninfectious etiology • Who gets stool culture? – Yes, if diarrhea present for >72h (esp. if fever, bloody or mucoid stools) – No, if present > 1 week, or if starts more than 3d after admission • What grows? – Salmonella, Shigella, Campylobacter, (EHEC if ordered) Infectious Diarrhea Associations • • • • • • • • • • • • Bloody stools (EHEC, Shigella, Salmonella, Campylobacter, Entamoeba) Raw eggs and reptiles (Salmonella) Recent abx or hospitalization (C diff) Seafood/seawater (Vibrio) Travel (ETEC, EAEC, parasites) Cruise ship (norovirus) Hikers (Giardia) Freshwater (Aeromonas, Plesiomonas) Pork chitterlings or pseudoappendicitis (Yersinia) Puppy/kitten w/ diarrhea, chicken salad (Campylobacter) Daycare centers (Shigella, Giardia, rotavirus, norovirus) Guillain-Barre Syndrome (Campylobacter) Pathogens Treatment S. Aureus, B. Cereus None Non-typhoid Salmonella spp. None (Treat if severe illness, elderly, bacteremic, prosthetics, valvular disease, atherosclerotic disease, IC, malignancy) Shigella Oral quinolone (Always treat, 3 days, or 7 days if IC) Campylobacter Azithromycin X 1-3 days (Treat only if severe illness, high fever, gross blood, elderly, pregnant or IC) Yersinia Oral quinolone X 3 days (Treat only if IC, bacteremic or pseudoappendicitis syndrome) ETEC (traveler’s diarrhea) Oral quinolone X 1-3 days EHEC: Shiga toxin-producing E. coli (including O157:H7) None – avoid, as can precipitate HUS Entamoeba histolytica Metronidazole X 7-10 d Then paromomycin X 7 d Giardia spp. Metronidazole X 7-10 d Clostridium difficile infection • Most commonly presents after extended antibiotic use (any kind) – Clindamycin, FQ, cephalosporins most common offenders • Increasingly severe secondary to more virulent strain (NAP1/BI/O27) • Signs and symptoms include – Foul-smelling, watery diarrhea w/ mucous, cramping, tenesmus, abd. tenderness – Fever in 15%; if present, severe • Complications: toxic megacolon, perforation, sepsis Clostridium difficile infection • Diagnosis toxins in stool – EIA up to 30% false negative (so x3); PCR more sensitive and specific (x1) – Don’t test formed stools, don’t test for clearance • Treatment – – – – – Wash hands with soap and water (not ETOH) Stop inciting antibiotics if possible Oral metronidazole for mild-mod disease, repeat same if relapse (20%) Severe (wbc>15, colitis on CT, low albumin, fever) =>PO vancomycin Severe w/ MOF, ileus or toxic megacolon =>PO vanco, IV metro, surgery consult Have you had more than enough? The End.