Management of Clostridium difficile infections...• NAP1/BI/027 strain – fluoroquinolone...

Management of Clostridium

difficile infections

Aurora Pop-Vicas MD MPH

Infectious Diseases Division

Memorial Hospital of Rhode Island

Brown University

Cdifficile

bull Anaerobic gram-positive spore-forming bacillus

bull Initially recognized as normal intestinal flora in

newborns (1935) recognized as the cause of

antibiotic-associated diarrhea and

pseudomembranous colitis in 1978

bull Transmitted by fecal-oral route (ingestion of spores)

bull Toxin A (enterotoxin) and Toxin B (cytotoxin)

Clostridium difficile

bull J strain ndash clindamycin resistant

bull 1989 ndash 92

bull NAP1BI027 strain ndash fluoroquinolone resistant

bull 2003 ndash 06

bull Hypervirulent increased toxin production

bull Ribotype 078 ndash Netherlands

bull 2005

bull Younger patients community-acquired genetically

similar to porcine isolates

Pathogenesis of C difficile

CMAJ 2004 July 6 2004 171

CMAJ 2004 July 6 171

J Clin Microbiol 2002 40 3470

The Canadian

NAP-1 strain

Experience

Increased disease severity

New risk factor - fluoroquinolones

States with BINAP1027 strain of C difficile

(N=38) November 2007

DC

PR

AK

HI

Disease incidence in United States

Risk factors for infection

bull Hospitalization

bull Older age (ge 65 years)

bull Antibiotic exposure

bull Antineoplastic agents

bull Host immune response

bull Proton pump inhibitors

Clinical manifestations

bull Diarrhea with a history of antibiotic use

bull Colitis bull Abdominal cramps

bull Fever

bull Leukocytosis

bull Hypoalbuminemia

bull Fecal leukocytes

bull Colonic inflammation (by colonoscopy or CT)

bull Fulminant disease bull Paralytic ileus toxic megacolon

bull Nausea vomiting dehydration lethargy tachycardia

bull Leukomoid reaction (WBC gt 100000 cellsmm3)

bull Shock

bull Renal failure

Copyright copyRadiological Society of North America 1999

Kawamoto S et al Radiographics 199919887-897

Pseudomembranous colitis ndash the accordion sign

Clostridium difficile diagnosis

CDI Prevention

CDI surveillance

Symptom onset

Hospital-onset Community-onset

Health-care facility associated Community-associated

Contact precautions

bull For suspected or proven CDI

bull Duration of precautions bull At least for duration of diarrhea

bull Until hospital discharge

CDIFF IDSA guidelines Infect Control Hosp Epidemiol 201031(5)431

Nosocomial C difficile transmission

7 21

72

Remained negative

Positive at

admission Acquired in hospital

N = 428 patients

1 general ward

11 months follow-up

Asymptomatic 63

Symptomatic 37

Patient-to-patient transmission

Hands of hospital personnel 59 Contaminated rooms

Positive cultures at discharge 82

N Engl J Med 1989 Jan 26320(4)204-10

Environmental cleaning with bleach-containing solutions

Bleach

Effect of minimizing cephalosporin use

Treatment

Stop the offending antibiotic

Vancomycin 125 mg po four times daily x 7-14 days

Vancomycin 125 mg po twice daily x 7 days

Vancomycin 125 mg po daily x 7 days

Vancomycin 125 mg every other day x 7 days

Vancomycin 125 mg every third day x 14 days

Recurrent CDI

bull Due to re-infection or relapse

bull In 25 of patients treated with metronidazole or

vancomycin patients with one recurrence are at

higher risk of multiple recurrences

bull Usually within 1-3 weeks of therapy cessation

but can occur later

bull Risk factors bull Age gt 65

bull Need for ongoing concomitant antibiotics

bull Lack of CDI immunity

Initial infection

American Journal of Infection Control 2007 Mar35(2)131-7

BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80

Cdifficile

bull Anaerobic gram-positive spore-forming bacillus

bull Initially recognized as normal intestinal flora in

newborns (1935) recognized as the cause of

antibiotic-associated diarrhea and

pseudomembranous colitis in 1978

bull Transmitted by fecal-oral route (ingestion of spores)

bull Toxin A (enterotoxin) and Toxin B (cytotoxin)



bull 1989 ndash 92


bull 2003 ndash 06



bull 2005




CMAJ 2004 July 6 2004 171



The Canadian

NAP-1 strain

Experience





DC

PR

AK

HI












bull Fever

bull Leukocytosis







bull Shock

bull Renal failure





CDI Prevention

CDI surveillance

Symptom onset



Contact precautions






7 21

72

Remained negative

Positive at


N = 428 patients

1 general ward

11 months follow-up

Asymptomatic 63

Symptomatic 37




N Engl J Med 1989 Jan 26320(4)204-10


Bleach


Treatment







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80



bull 1989 ndash 92


bull 2003 ndash 06



bull 2005




CMAJ 2004 July 6 2004 171



The Canadian

NAP-1 strain

Experience





DC

PR

AK

HI












bull Fever

bull Leukocytosis







bull Shock

bull Renal failure





CDI Prevention

CDI surveillance

Symptom onset



Contact precautions






7 21

72

Remained negative

Positive at


N = 428 patients

1 general ward

11 months follow-up

Asymptomatic 63

Symptomatic 37




N Engl J Med 1989 Jan 26320(4)204-10


Bleach


Treatment







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80


CMAJ 2004 July 6 2004 171



The Canadian

NAP-1 strain

Experience





DC

PR

AK

HI












bull Fever

bull Leukocytosis







bull Shock

bull Renal failure





CDI Prevention

CDI surveillance

Symptom onset



Contact precautions






7 21

72

Remained negative

Positive at


N = 428 patients

1 general ward

11 months follow-up

Asymptomatic 63

Symptomatic 37




N Engl J Med 1989 Jan 26320(4)204-10


Bleach


Treatment







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80



The Canadian

NAP-1 strain

Experience





DC

PR

AK

HI












bull Fever

bull Leukocytosis







bull Shock

bull Renal failure





CDI Prevention

CDI surveillance

Symptom onset



Contact precautions






7 21

72

Remained negative

Positive at


N = 428 patients

1 general ward

11 months follow-up

Asymptomatic 63

Symptomatic 37




N Engl J Med 1989 Jan 26320(4)204-10


Bleach


Treatment







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80





DC

PR

AK

HI












bull Fever

bull Leukocytosis







bull Shock

bull Renal failure





CDI Prevention

CDI surveillance

Symptom onset



Contact precautions






7 21

72

Remained negative

Positive at


N = 428 patients

1 general ward

11 months follow-up

Asymptomatic 63

Symptomatic 37




N Engl J Med 1989 Jan 26320(4)204-10


Bleach


Treatment







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80












bull Fever

bull Leukocytosis







bull Shock

bull Renal failure





CDI Prevention

CDI surveillance

Symptom onset



Contact precautions






7 21

72

Remained negative

Positive at


N = 428 patients

1 general ward

11 months follow-up

Asymptomatic 63

Symptomatic 37




N Engl J Med 1989 Jan 26320(4)204-10


Bleach


Treatment







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80





CDI Prevention

CDI surveillance

Symptom onset



Contact precautions






7 21

72

Remained negative

Positive at


N = 428 patients

1 general ward

11 months follow-up

Asymptomatic 63

Symptomatic 37




N Engl J Med 1989 Jan 26320(4)204-10


Bleach


Treatment







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80

CDI surveillance

Symptom onset



Contact precautions






7 21

72

Remained negative

Positive at


N = 428 patients

1 general ward

11 months follow-up

Asymptomatic 63

Symptomatic 37




N Engl J Med 1989 Jan 26320(4)204-10


Bleach


Treatment







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80

Contact precautions






7 21

72

Remained negative

Positive at


N = 428 patients

1 general ward

11 months follow-up

Asymptomatic 63

Symptomatic 37




N Engl J Med 1989 Jan 26320(4)204-10


Bleach


Treatment







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80


7 21

72

Remained negative

Positive at


N = 428 patients

1 general ward

11 months follow-up

Asymptomatic 63

Symptomatic 37




N Engl J Med 1989 Jan 26320(4)204-10


Bleach


Treatment







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80


Bleach


Treatment







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80


Treatment







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80







Recurrent CDI






but can occur later




Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80

Initial infection


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80


BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80

BMJ 2007 July 14 335(7610) 80

Management of Clostridium difficile infections...• NAP1/BI/027 strain – fluoroquinolone...

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