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IIR 04-235 – HSR&D Study

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IIR 04-235
Antibiotic Use, Resistance and Clostridium Difficile-Associated Diarrhea
Stuart B. Johnson MD BA
Edward Hines Jr. VA Hospital, Hines, IL
Hines, IL
Funding Period: September 2005 - August 2007

BACKGROUND/RATIONALE:
Clostridium difficile-associated diarrhea (CDAD), is strongly associated with health care facilities and previous antimicrobial treatment, as well as with increased hospital costs and increased length of stay. The estimated annual cost of CDAD in the US is likely to exceed $1.1 billion. Severe pseudomembranous colitis, toxic megacolon and fulminant CDAD are life-threatening complications of C. difficile.
Antibiotics (AB) are not equal in terms of CDAD risk. CDAD rates significantly decrease when clindamycin or third-generation cephalosporin use is reduced. Increased CDAD risk has been associated with fluoroquinolone (FQ) use. Large quantities of FQs used at hospitals contribute to high CDAD attributable risk. The risk of AB-associated CDAD increases when C. difficile is resistant to the AB. High-level FQ resistance isolates have been identified. The recent VISN 12 formulary change from levofloxacin to gatifloxacin to moxifloxacin afforded the opportunity to measure the impact of AB use on the emergence of nosocomial infections C. difficile. The VA is particularly well suited to study these issues because of its electronic medical records and extensive databases.

OBJECTIVE(S):
This study aimed to: (1) Determine the impact of AB formulary changes on CDAD rates, (2) Link CDAD-incidence to AB therapy using local and national VA databases to identify relative risk and attributable risk of specific ABs with the development of CDAD, (3) Show CDAD rates differ between levofloxacin period and gatifloxacin period and moxifloxacin period. HYPOTHESIS: Changes in medication formulary (levofloxacin to gatifloxacin and moxifloxacin) will be associated with increased CDAD rates at affected VA hospitals.

METHODS:
This is an observational study of the effects of an AB formulary change on rates of an unanticipated complication, CDAD. It is a retrospective review of inpatients receiving levofloxacin from Oct 01-March 04 to those who receiving gatifloxacin March 04 to Feb 06, and Moxifloxacin from March 06-Sept 06. We conducted a matched control cohort study, and performed tests for trends and multivariate logistic regression modeling, as well as calculation of antibiotic specific attack rates, to detect meaningful changes in rates in CDAD over the study period. The study was conducted at Hines VA, Jesse Brown VA and North Chicago VA.
Data sources included the VA National Patient Care Databases (NPCD), VA BIRLS Death file, VA Decision Support System (DSS) National Extracts. Microbiology data was obtained from each facility’s local medical record database - Veterans Health Information Systems Technology Architecture (VISTA).

FINDINGS/RESULTS:
CDAD infections increased markedly after the levofloxacin to gatifloxacin formulary change, and continued high during the moxifloxacin period, suggesting greater potentials of the two broader-spectrum FQs to induce CDAD. This was borne out both in analysis focused on pre-post trends as well as case-control. Thus, CDAD may be one unanticipated consequence of AB formulary changes. Presence of the new epidemic strain may have partially contributed to the increased CDAD rates.

IMPACT:
Study findings have: (1) increased knowledge about FQ potential to induce CDAD, (2) Support the need for including adverse reactions into formulary calculations, (3) Developed novel methods for merging VA databases to obtain meaningful patient-level data without the need for individual patient chart reviews.

PUBLICATIONS:

Journal Articles

  1. Belmares J, Gerding DN, Parada JP, Miskevics S, Weaver F, Johnson S. Outcome of metronidazole therapy for Clostridium difficile disease and correlation with a scoring system. The Journal of Infection. 2007 Dec 1; 55(6):495-501.
  2. Chang HT, Krezolek D, Johnson S, Parada JP, Evans CT, Gerding DN. Onset of symptoms and time to diagnosis of Clostridium difficile-associated disease following discharge from an acute care hospital. Infection control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America. 2007 Aug 1; 28(8):926-31.
Conference Presentations

  1. Parada JP, Conway W, Johnson S, Hur K, Evans CT, Weaver FM, Gerding DN. All Antibiotics Are Not Created Equal - Lessons Not Learned and Unintended Consequences of an Antibiotic Formulary Change. Poster session presented at: Society for Healthcare Epidemiology of America Scientific Annual Meeting; 2009 Mar 20; San Diego, CA.
  2. Parada JP, Conway W, Gerding DN, Evans CT, Weaver FM, Johnson S. Seasonal Variation of Clostridium difficile-associated Disease. Presented at: Society for Healthcare Epidemiology of America Scientific Annual Meeting; 2008 Apr 6; Orlando, FL.
  3. Parada JP, Conway W, Evans CT, Miskevics SA, Weaver FM, Gerding DN, Johnson S. Speed to Diarrhea – Fast and Slow Inducers of Clostridium difficile-associated diarrhea. Presented at: Infectious Diseases Society of America Annual Meeting; 2007 Oct 4; San Diego, CA.
  4. Parada JP, Conway W, Evans CT, Miskevics SA, Weaver FM, Johnson S, Gerding DN. Attack Rates and Relative Risk in Clostridium difficile-associated Diarrhea: Not All Meds are Created Equal. Presented at: Infectious Diseases Society of America Annual Meeting; 2007 Oct 4; San Diego, CA.
  5. Parada JP, Conway W, Miskevics SA, Evans CT, Weaver FM, Johnson S, Gerding DN. Out of the Pan and into the Fire? Lessons Not Learned From Unanticipated Consequences of an Antibiotic Formulary Change. Presented at: Infectious Diseases Society of America Annual Meeting; 2007 Oct 4; San Diego, CA.
  6. Belmares J, Parada JP, Miskevics SA, Weaver FM, Gerding DN, Johnson SB. A Severity of C. difficile-Associated Disease (CDAD) Index Predicts Treatment Outcomes with Metronidazole. Paper presented at: Infectious Diseases Society of America Annual Meeting; 2006 Oct 13; Toronto, Canada.
  7. Parada JP, Conway WP, Miskevics SA, Evans CT, Johnson SB, Lavela SL, Santhiraj M, Sullivan D, Weaver FM, Gerding DN. Impact of Formulary Fluoroquinolone Change on Inpatient Clostridium difficile-Associated Diarrhea. Poster session presented at: Infectious Diseases Society of America Annual Meeting; 2006 Oct 13; Toronto, Canada.


DRA: Health Systems
DRE: Epidemiology
Keywords: Patient outcomes, Pharmaceuticals, Quality assessment
MeSH Terms: none

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