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PCC Conference 8-30-06. Marcia Lux, MD. 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. Case 1:.

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pcc conference 8 30 06

PCC Conference8-30-06

Marcia Lux, MD

by way of introduction
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
case 1
Case 1:
  • 86F readmitted for diarrhea
  • PMH:
    • mild dementia
    • HTN
    • DM
    • CAD s/p MI 1979
    • ischemic CM EF 25%
history of present illness
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
hpi cont
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
hpi cont1
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
hpi cont2
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
hpi cont3
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
hpi cont4
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
historical background
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
confusing terminology
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
slide12
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

epidemiology rfs
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
cdif incidence by population
Cdif incidence by population

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

clinical manifestations
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
clinical manifestations1
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
diagnosis
DIAGNOSIS
  • Endoscopy (pseudomembranous colitis)
  • Culture
  • Cell culture cytotoxin test
  • ELISA toxin test
  • PCR toxin gene detection
elisa toxin tests
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
treatment
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]

treatment cont
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

recurrent c dif infection
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
treatment of recurrence
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!)
resistance
Resistance?
  • Generally NOT considered a clinically significant problem
  • Flagyl resistant strains have been isolated in vitro
  • No resistance to vancomycin has been reported
case 2
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
case 2 cont
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
labs cxr
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

pneumonia severity index
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

case 2 cont1
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……….
terminology
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
epidemiology
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
risk factors
Risk Factors
  • Advanced age
  • Cigarette smoking
  • Chronic lung disease
  • Immunosuppression
  • Nosocomial: transplant recipients or any surgery

33

29

24

14

legionella vs other cap
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
pe and lab findings
PE and Lab findings
  • Bradycardia relative to temp elevation
  • Rash
  • Hypophosphatemia
  • Rhabdomyolysis
  • Thrombocytopenia
  • Leukocytosis
  • DIC
extrapulmonary legionella
RARE!

Cellulitis

Sinusitis

Septic arthritis

Perirectal abscess

Pancreatitis

Peritonitis

Pyelonephritis

Most commonly affects heart:

Pericarditis

Myocarditis

PV Endocarditis

Surgical wound infections

Extrapulmonary Legionella
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

Laboratory Diagnosis
urine antigen
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%
treatment1
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
treatment2
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
prognosis
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
summary
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
ad