Open Wide: Big Bolus of ID 2014 Internal Medicine Board Review

1. Open Wide: Big Bolus of ID2014 Internal Medicine Board Review Friday, July 18th Jason Parham, MD, MPH

2. Board Question Breakdown Infectious Disease (9%) 19–21 Q • AIDS and HIV infection 2–4 • Lower respiratory tract infections 1–5 • Enteric infections 1–4 • CNS infections 1–3 • Infectious arthritis 1–2 • Procedure- and device-associated infections 1–2 • Specific causative organisms 0–5 • Skin and soft tissue infections 0–3 • STD, genital tract infections 0–2 • Endocarditis and other cardiovascular infections 0–2 • Upper respiratory tract infections 0–2 • Hepatic infections 0–2 • Bacteremia/sepsis syndrome 0–2 • Urinary tract infections 0–1 • Osteomyelitis 0–1 • Rheumatic fever 0–1 • Nosocomial infections 0–1 • Immunization 0–1 • Prevention of infectious disease 0–1 • Miscellaneous infectious disease disorders 0–1

3. Antibiotic Questions • Options for treating Pseudomonas infection in a patient with a serious PCN allergy: name 3 classes of antibiotics. • Antibiotic which can precipitate with calcium and form biliary stones? • Class of antibiotics that can precipitate tendinitis and tendon rupture in adults? • Name 3 antibiotics used to treat Listeria infections. • What lab do you need to monitor in patients on daptomycin?

4. More Antibiotic Questions • Main side effect of metronidazole? • Most common side effect of rifampin? • What two antibiotics (in different classes) that can prolong the QT interval? • Adverse events with linezolid? • Long-term use of this antibiotic can result in peripheral neuropathy, hepatotoxicity and pulmonary toxicity, most often seen in the elderly?

5. 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 • Diagnosis: ultimately clinical and unsatisfying • Gold: culture of sinus aspirate (not often done) • Imaging for uncomplicated ABS not recommended

6. Respiratory Infections • Bacterial Sinusitis • Acute Bacterial Sinusitis (ABS) • Micro: S.pneumonia, H. influenzae, M. catarrhalis • Treatment • Most will get better without abx • If treating, prefer amox-clav • Complications are rare but include meningitis, brain abscess, osteomyelitis HY: 1. Sounds viral/allergic/recent/stable – don’t give abx 2. In acute sinusitis, give abx or don’t– imaging isn’t the answer

7. 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

8. Respiratory Infections • Otitis Media • Starts with URI or allergies • Uncommon in adults • Most common symptoms: otalgia, fever • Bulging red TM (insufflation) • S. pneumonia, H. influenzae common • Amoxicillin/clavulanate, cefuroxime, azithromycin (w/ questionable utility) • Meningitis, mastoiditis, osteomyelitis - rare

9. 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

10. 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)

11. 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

12. Infectious mononucleosis Pharyngitis in adults -> consider other possibilities 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% +)

13. Back to Respiratory Infections • Acute Bronchitis • Most common cause of acute cough in outpatients • In healthy, nonsmokers: 90% viral • Purulent sputum doesn’t mean bacteria • In 50%, cough resolves by 2 weeks; 90% by 3 weeks • If cough is severe, >3 weeks: consider pertussis • No need for cultures if VS normal, chest exam normal • No chest x-ray • No antibiotics needed in healthy patients; self-limited • Symptomatic support

14. Acute Exacerbation of Chronic Bronchitis • COPD associated • Can be viral or bacterial • Bacterial • Haemophilus influenzae (22%), especially smokers • Moraxella catarrhalis (9-15%) • Streptococcus pneumoniae (10-12%) • Pseudomonas and other GNR (up to 15%), prior abx use, hospitalization, frequent flares • Bronchodilators, corticosteroids helpful • Antibiotics commonly used, not great data

15. Question An 18 year old male presents to your office with mild fever and cough of several days duration. Negative PMH. No h/o recent antibiotic use. PE: O2 sat 99%, crackles left mid-lung. CXR: infiltrate in the mid-left lung. What is the most appropriate treatment? • Amoxicillin • Bactrim • Ceftriaxone • Doxycycline • Levofloxacin

16. 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

17. 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 poop/piss Coccidioides, hantavirus – Southwest US Burkholderia pseudomallei – Southeast Asia and China

18. 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

19. CAP Treatment: 2007 IDSA/ATS Guidelines *RF for DRSP: >65, exposure to children in day care, alcoholism or other severe underlying disease, or recent antibiotics

20. Community Acquired Pneumonia • A few last thoughts • Elderly • Present atypically (tachypnea best marker) • Account for 60% of pneumonia admissions • F/u CXR unnecessary except in >40, or in smokers • Smoking cessation, flu and pneumococcal vaccines are always good answers • Will likely still have respiratory symptoms 14d out, 1/3 for as long as 28d

21. 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 2 g IV daily, ampicillin-sulbactam 3 g IV q6h or piperacillin-tazobactam 4.5 g IV q6h, levofloxacin 750 mg IV daily, moxifloxacin 400 mg IV daily, or ertapenem 1 g IV qd • Risk factors for MDR: cefipime 2 g IV q8h or ceftazidime 2 g IV q8h, imipenem 500 g IV q6h, meropenem/doripenem, piperacillin-tazobactam 4.5 g IV q6hr, or aztreonam 2 g IV q6-8hr PLUS levofloxacin 750 mg IV qd or gentamicin 7 mg/kg IV daily PLUS linezolid or vancomycin (if MRSA suspected)

22. 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

23. 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

24. Hospital acquired infections: Multidrug-resistant organisms • Risk factors: ICU, transfer from OSH, HD, surgery, indwelling devices, malignancy, multiple prior abx • MRSA: vancomycin (unless MIC>=2 and failing therapy) • Pneumonia : linezolid, clindamycin • Bloodstream: daptomycin • VRE: if ampicillin sensitive, use it (alt:linezolid, dapto) • ESBL: carbapenem; once susceptibilities back, may have other options (but never pcn or cephalosporins)

25. 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

26. 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

27. Endocarditis Prophylaxis • 2007 AHA guideline for the prevention of endocarditis made major revisions, decreasing indications for prophylaxis. • 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

28. Endocarditis Prophylaxis – Dental Procedures • Prophylaxis is reasonable for patients with high risk cardiac conditions AND undergoing dental procedures involving manipulation of gingival tissues/periapical region of teeth or perforation of oral mucosa • Antibiotic regimens: • Oral: • Amoxicillin 2 grams • Clindamycin 600 mg • Cephalexin 2 grams • Clarithromycin 500 mg or azithromycin 500 mg • IV/IM (cannot take po): • Ampicillin 2 grams IM or IV • Cefazolin 1 gram IM or IV • Clindamycin 600 mg IV

29. Endocarditis Prophylaxis – Respiratory Tract Procedures • Antibiotic prophylaxis is reasonable only for patients with high risk cardiac conditions who undergo an invasive procedure of the respiratory tract that involves incision and biopsy of the respiratory mucosa • ABX prophylaxis is NOT recommended for bronchoscopy unless the procedure involves incision of the respiratory tract mucosa • ABX Regimens: • Amoxicillin 2 g PO • Ampicillin 2 g IV • Vancomycin 1 g IV (PCN allergic)

30. Endocarditis Prophylaxis –GI, Biliary, and GU Procedures • Antibiotic prophylaxis is reasonable only for patients with high risk cardiac conditions AND ongoing active infections in the procedure area • If they meet that criteria, and aren’t on appropriate coverage for their existing infection then, ABX regimens: • Amoxicillin 2 g PO • Ampicillin 2 g IV • Vancomycin 1 g IV (PCN allergic)

31. Endocarditis Prophylaxis Q&A • Patient with h/o IE undergoing root canal: • Prophylaxis or no? • What if he’s allergic to penicillin? • Patient with prosthetic AV • Undergoing screening colonoscopy with expected biopsy of polyp? • Getting transbronchial biopsy of mediastinal node? • Patient with mitral valve prolapse with regurgitation getting cystoscopy? • Given the dramatic reduction in indications for prophylaxis, if you have to guess, “no prophylaxis indicated”

32. 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

33. Endocarditis • Diagnostic tests: • Blood cultures • Best initial test: 95-99% sensitive • If positive, then transthoracic echo • If both positive, you’ve got endocarditis (but organism needs to be a typical microbe for endocarditis) • If negative transthoracic echo, then TEE • TTE and TEE equally specific (95%) • Sensitivity: TTE (60%); TEE (90-95%)

34. 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

35. 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

36. 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 aboutHACEK, Bartonella sp., Coxiella burnetii, Brucella, and Tropheryma whipplei

37. 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

38. Endocarditis Treatment Questions • Right-sided due to MSSA (IVDU)? Nafcillin/Oxacillin (x4w) + Gent (x2w) • Prosthetic valve due to MSSA? Nafcillin/Oxacillin + Rifampin (x6w), + Gent (x2w) • Prosthetic valve due to MRSA? Vanco + Rifampin (x6w), + Gent (x2w)

39. Central Nervous System Infections • “Most likely diagnosis” • All present with fever and headache • Also could see N/V, seizures • Some overlap sx, but if alone • Focal neurologic findings (abscess) • Altered mental status and confusion (encephalitis) • Neck stiffness (meningitis) • If multiple overlap sx, then you need CT or LP for diagnosis

40. 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

41. CSF in Meningitis

42. 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

43. 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

44. 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

45. Empiric Therapy for Meningitis Based on Age or Underlying Condition

46. 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”

47. CSF lymphocytosis (aseptic meningitis) • 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 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

48. 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*

49. 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

50. 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)