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PCC Conference 8-30-06

PCC Conference 8-30-06

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PCC Conference 8-30-06

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  1. PCC Conference8-30-06 Marcia Lux, MD

  2. By way of introduction… • New to the Division of GIM 7/1/06 • Harvard Medical School, 2001 • Columbia Presbyterian Internal Medicine Residency, 2001-2004 • Hospitalist CPMC, 2004-2006 • Case 1: July 2004 • Case 2: May 2006

  3. Case 1: • 86F readmitted for diarrhea • PMH: • mild dementia • HTN • DM • CAD s/p MI 1979 • ischemic CM EF 25%

  4. History of present illness: • Multiple CPMC admissions 2003-04 • 1/03 syncope PPM • 12/03 fall  UTI, CHF • 2/04 NSTEMI, MSSA bacteremia ?veg on PPM wire s/p Vanco x 6wks, UTI, CHF • 3/04 CHF, unexplained leukocytosis • 4/04 constipation • 5/04 hypoxia ?PE, CHF, contrast-induced ARF, UTI

  5. HPI Cont. • June 27, 2004-Readmitted • 10d diarrhea, abdominal pain, dizziness • Copious, foul smelling, bed bound • No f/c/n/v • WBC 14.9 • Cdif toxin positive • Rx’d Flagyl 500 po TID x 10d • d/c’d on hospital day #2

  6. HPI Cont. • Readmitted 7/7/04, cont abd pain, diarrhea, subjective fevers • 120/80, HR 75, T98, bibasilar rales o/w benign exam • WBC 14.6, Cr 1.2, stool Cdif + • CXR mild PVC, AXR normal • Rx’d Flagyl 500 TID, Vanco 750mg PO QOD (CrCl 26) approved by ID on Hosp Day #1

  7. HPI Cont. • GI Consulted, HD#1 • NPO/Bowel rest, judicious IVF • Clinically deteriorating, ongoing diarrhea, dehydration, lethargy, delerium • Sigmoidoscopy HD #6, severe pseudomembranes • Vanco dosing adjusted: 250 PO QID

  8. HPI Cont. • Labs: WBC 24.9, HCO3 13-16 • DNR • HD #13, more alert, WBC 13.8 • HD #14 PICC placed for TPN, tolerating clears

  9. HPI Cont. • HD #14, 5:30 pm- RN note: “BP 80/50, beeper 3281 paged, no answer” • 8pm-RN note: “BP 75/48, lopressor held, beeper 4778 paged, no answer” • 5:30 am- RN note: “pt.w/ agonal breathing, unresponsive, 4778 aware, will evaluate” • Pronounced by House MD at 6 AM • Family declined autopsy

  10. Historical Background • C dif first described 1935 gram-positive anaerobic bacillus • “difficult clostridium”-difficult to grow in culture • Found in stool specimens from healthy neonates leading to misclassification as a commensal organism • 1970s: “clindamycin colitis” pseudomembranous colitis in hospitalized pts • 1978: C dif recognized as causative organism

  11. Confusing terminology • Antibiotic-associated diarrhea • C. difficile is one of many causes(approx 20-30%) • Clostridium difficile-associated diarrhea • diarrhea + positive stool test • Clostridium difficile colitis • underlying pathologic process • Pseudomembranous colitis • endoscopic demonstration of exudative lesions • Toxic megacolon • radiologic and surgical diagnosis

  12. Disruption of protective colonic flora (abx/chemo) Colonization with toxigenic C. difficile by fecal-oral transmission Toxin A and B production A/B: Cytoskeletal damage, loss of tight junctions. A: Mucosal injury, inflammation, fluid secretion. Colitis and Diarrhea

  13. Epidemiology & RFs • Leading cause nosocomial enteric infection • Approx 3 million cases/yr • RISK FACTORS: • Elderly • debilitated • GI surgery • infected roommate • enteral feeding • prolonged course of abx/multi-agent tx

  14. Cdif incidence by population Adapted from Kelly CP & LaMont JT (1998). Clostridium difficile infection. Annual Review of Medicine 49, 375-390.

  15. Clinical Manifestations • Carrier State: “fecal excretors” asymptomatic-->majority of patients • Diarrhea without colitis: mild, 3-4 loose BM/d +/- cramps • Colitis w/o pseudomembranes: more severe systemic c/o, n/v, profuse diarrhea, fever, leukocytosis, abd pain • Pseudomembranous colitis

  16. Clinical Manifestations • Fulminant colitis: • Rare, 2-3% of patients, esp elderly • Serious: ileus, perforation, megacolon, death • High fever, chills, marked leukocytosis (>40K) • May not have diarrhea if ileus or megacolon • Risk of perforation w/ sigmoid/colonoscopy • Tx surgical • Unusual presentations: • Long latency period (1-2months) • Absence of antibiotic exposure

  17. Antibiotics associated with C Dif diarrhea and colitis

  18. Radiographic Findings

  19. Endoscopic findings

  20. DIAGNOSIS • Endoscopy (pseudomembranous colitis) • Culture • Cell culture cytotoxin test • ELISA toxin test • PCR toxin gene detection

  21. ELISA toxin tests • Can detect toxin A, toxin B, or both • Rapid, cheap, and specific • Less sensitive, depends on rapid processing by lab • Toxin A tests will miss rare C. difficile isolates that produce toxin B only

  22. TREATMENT 1. Discontinue offending agent or modify to less offensive agent (successful in 20% to 25%) 2. Replace fluids and electrolytes 3. Avoid antiperistaltic agents: may worsen diarrhea or precipitate toxic megacolon 4. If conservative measures not effective or practical, rx metronidazole 500 mg TID X 10d [ can also use IV flagyl as good excretion into GI tract via bile and exudation from inflamed colon]

  23. Treatment cont. 5. Re-treat first-time recurrences with the same regimen used to treat the initial episode 6. Avoid vancomycin if possible: equal efficacy but can lead to VREF. Cannot use IV vanco. Can use vancomycin enemas if NPO 7. Do not treat nosocomial diarrhea empirically without testing, <30% have C. dif infection

  24. Recurrent C. dif Infection • 10-25% of patients will relapse • Si/sx similar to initial attack • Most often occurs w/i 1-2 wks but can be up to 2 months later • Pathogenesis unclear: reinfection vs. failure to mount adequate immune response vs. survival in diverticula

  25. Treatment of Recurrence • First relapse: treat conservatively if mild sx otherwise repeat Flagyl x 10-14d • Other therapies with some potential efficacy • Pulsed vancomycin taper (4+weeks) • Cholestyramine • Fecal enema (yuck!)

  26. Resistance? • Generally NOT considered a clinically significant problem • Flagyl resistant strains have been isolated in vitro • No resistance to vancomycin has been reported

  27. Case 2 • 54F, no prior hospitalizations • CC: fever, malaise, HA, dry cough x2d • HPI:denied SOB or pleurisy, +sweats, no chills/rigors, no sick contacts, no prior respiratory illness, no flu shot • ROS: +4-5/d watery diarrhea and diffuse arthralgias

  28. Case 2, cont • PMHx: • HTN- well controlled on monotherapy • Morbid obesity • SHx: telephone operator for Verizon, lived alone, never married, non-smoker • In ER: T 103.8, 130/80, HR 125, RR 24, O2 94% RA • PE: mild distress, area of crackles in left lower lung field, benign abdomen

  29. LABS & CXR • WBC 18K • 73% PMN, 0 bnd • Na 134 • Cr 1.1 • AST 244 • ALT 187 • CK 2200 ER Dx: CAP; Rx: CTX/Azithro and admit

  30. Age 54 44 Temp > 40F 15 Pulse > 125 10 ____ Total 69 Class I (age < 50) Class II <70 Class III 71-90 Class IV 91-130 Class V >130 Pneumonia Severity Index ClassMortality (%) I 0.1 II 0.6 III 2.8 IV 8.2 V 29.2

  31. Case 2, cont • Admit Hospitalist service • Continue CTX/Azithro • Supportive care, IVFs • CK peaked 3400 without renal compromise • AST/ALT normalized by HD 1 • Pt stable for discharge on Friday but uncomfortable with the plan……….

  32. After 3days of hospitalization without being seen by an MD…… • Urine Legionella: positive

  33. Terminology • Legionellosis: infectious process caused by Legionella spp.. • 1) Legionnaires’ disease: PNA caused by Legionella species (1976 Philadelphia American Legion Conference) • 2) Pontiac Fever: acute febrile, self-limited illness linked to Legionella (Pontiac, MI) • 3) Extrapulmonary Legionella infxn

  34. Epidemiology • Incidence linked to degree of water contamination • Accounts for 2-10% of CAP • Lower incidence for outpatients vs. inpatients • Nosocomial: 12-70% of hospital water supplies contaminated, also reported outbreaks in NH and LTAC facilities

  35. Risk Factors • Advanced age • Cigarette smoking • Chronic lung disease • Immunosuppression • Nosocomial: transplant recipients or any surgery 33 29 24 14

  36. CLINICAL MANIFESTIONS:Legionnaires’ Disease

  37. Legionella vs. other CAP • GI symptoms, esp. diarrhea • Neurologic findings, esp. confusion • Fever > 39 F • Sputum w/ many PMNs but no organisms • Hyponatremia • Hepatic dysfunction • Hematuria • No response to B-Lactam or aminoglycoside abx

  38. PE and Lab findings • Bradycardia relative to temp elevation • Rash • Hypophosphatemia • Rhabdomyolysis • Thrombocytopenia • Leukocytosis • DIC

  39. RARE! Cellulitis Sinusitis Septic arthritis Perirectal abscess Pancreatitis Peritonitis Pyelonephritis Most commonly affects heart: Pericarditis Myocarditis PV Endocarditis Surgical wound infections Extrapulmonary Legionella

  40. Culture: 3 different media, 3-5 days DFA staining: low Se, high Sp Serology: 4-fold rise in antibody titer URINE ANTIGEN  Culture is the Gold Standard Culture + antigen testing recommended if legionella is suspected on ddx Laboratory Diagnosis

  41. Urine Antigen • Detects L. pneumonophila serogroup 1(90% of community acq’d Legionella PNA) • Sensitivity correlates with disease severity, may miss mild cases • Enzyme immunoassay • Remains positive for days, even after initiation of treatment • Rapid urinary antigen test: results in 15 min with se/sp 80%/97%

  42. Treatment • Mortality: 16-30% if untreated or treated with wrong antibiotics • Susceptibility testing not routinely available but significant resistance has not been demonstrated • Antibiotic choice requires high intracellular penetration • Macrolides, Quinolones, Tetracycline, Rifampin • ATS recommendations for tx of CAP incorporate either a respiratory quinolone or Azithromycin as standard therapy

  43. Treatment • New macrolides (Azithromycin) or respiratory quinolones (Levaquin) are tx of choice • No head to head RCT, retrospective studies suggest Levaquin better for severe illness • Duration of tx: 10-14d • Azithromycin duration 7-10d • Use IV abx if prominent GI symptoms

  44. Prognosis • Mortality <5% if early initiation of appropriate antibiotics • Defervescence and symptomatic improvement within 3-5d • Some pts will report prolonged symptoms, usu dyspnea and fatigue for many months following resolution of acute infection

  45. SUMMARY • Legionella and C. dif are common problems whose disease spectrum bridges primary care and hospital medicine • C. dif is an extremely common nosocomial infection which can be severe • Legionella is a frequent cause of CAP that also tends to have a more severe acute presentation