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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


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 MD……

  • 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 MD……

  • 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 MD……

  • Advanced age

  • Cigarette smoking

  • Chronic lung disease

  • Immunosuppression

  • Nosocomial: transplant recipients or any surgery

33

29

24

14


Clinical manifestions legionnaires disease
CLINICAL MANIFESTIONS: MD……Legionnaires’ Disease


Legionella vs other cap
Legionella vs. other CAP MD……

  • 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 MD……

  • Bradycardia relative to temp elevation

  • Rash

  • Hypophosphatemia

  • Rhabdomyolysis

  • Thrombocytopenia

  • Leukocytosis

  • DIC


Extrapulmonary legionella

RARE! MD……

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 MD……:

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 MD……

  • 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 MD……

  • 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 MD……

  • 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 MD……

  • 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 MD……

  • 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


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