PCC Conference 8-30-06

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PCC Conference8-30-06

• Marcia Lux, MD

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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

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Case 1

• 86F readmitted for diarrhea
• PMH
• mild dementia
• HTN
• DM
• CAD s/p MI 1979
• ischemic CM EF 25

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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

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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
• Rxd Flagyl 500 po TID x 10d
• d/cd on hospital day 2

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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
• Rxd Flagyl 500 TID, Vanco 750mg PO QOD (CrCl 26)
  approved by ID on Hosp Day 1

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HPI Cont.

• GI Consulted, HD1
• NPO/Bowel rest, judicious IVF
• Clinically deteriorating, ongoing diarrhea,
  dehydration, lethargy, delerium
• Sigmoidoscopy HD 6, severe pseudomembranes
• Vanco dosing adjusted 250 PO QID

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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

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HPI Cont.

• HD 14, 530 pm- RN note BP 80/50, beeper 3281
  paged, no answer
• 8pm-RN note BP 75/48, lopressor held, beeper
  4778 paged, no answer
• 530 am- RN note pt.w/ agonal breathing,
  unresponsive, 4778 aware, will evaluate
• Pronounced by House MD at 6 AM
• Family declined autopsy

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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

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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

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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
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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

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

• Carrier State fecal excretors
  asymptomatic--gtmajority 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

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Clinical Manifestations

• Fulminant colitis
• Rare, 2-3 of patients, esp elderly
• Serious ileus, perforation, megacolon, death
• High fever, chills, marked leukocytosis (gt40K)
• 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

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Antibiotics associated with C Dif diarrhea and
colitis
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Radiographic Findings
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Endoscopic findings
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DIAGNOSIS

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

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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

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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

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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, lt30 have C. dif infection

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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

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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 (4weeks)
• Cholestyramine
• Fecal enema (yuck!)

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Resistance?

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

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Case 2

• 54F, no prior hospitalizations
• CC fever, malaise, HA, dry cough x2d
• HPIdenied 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

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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

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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
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Pneumonia Severity Index

• Age 54 44
• Temp gt 40F 15
• Pulse gt 125 10
• ____
• Total 69

• Class I (age lt 50)
• Class II lt70
• Class III 71-90
• Class IV 91-130
• Class V gt130

Class Mortality () I
0.1 II 0.6 III 2.8 IV 8.2 V 29.2
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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.

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After 3days of hospitalization without being
seen by an MD

• Urine Legionella positive

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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

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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

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Risk Factors
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• Advanced age
• Cigarette smoking
• Chronic lung disease
• Immunosuppression
• Nosocomial transplant recipients or any surgery

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CLINICAL MANIFESTIONSLegionnaires Disease
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Legionella vs. other CAP

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

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PE and Lab findings

• Bradycardia relative to temp elevation
• Rash
• Hypophosphatemia
• Rhabdomyolysis
• Thrombocytopenia
• Leukocytosis
• DIC

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Extrapulmonary Legionella

• RARE!
• Cellulitis
• Sinusitis
• Septic arthritis
• Perirectal abscess
• Pancreatitis
• Peritonitis
• Pyelonephritis

• Most commonly affects heart
• Pericarditis
• Myocarditis
• PV Endocarditis
• Surgical wound infections

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Laboratory Diagnosis

• 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

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Urine Antigen

• Detects L. pneumonophila serogroup 1(90 of
  community acqd 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

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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

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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

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Prognosis

• Mortality lt5 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

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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