Research Article| Volume 22, ISSUE 1, P91-102, January 2000

Antibiotics and Clostridium difficile diarrhea in the ambulatory care setting

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      The goal of this study was to determine the prevalence of Clostridium difficile diarrhea (CDD) and the risk for CDD associated with different oral antibiotics commonly used in the ambulatory care setting.


      The prevalence of CDD was determined for enrollees in 4 UnitedHealth Group-affiliated health plans between January 1, 1992, and December 31, 1994. Cases were identified based on the presence of an inpatient or outpatient claim with a primary diagnosis of diarrhea, a pharmacy claim for a prescription drug used to treat CDD, or a physician or facility claim for the C difficile toxin test, and were confirmed using full-text medical records. Within a retrospective cohort design, periods of risk for CDD were defined on the basis of duration of antibiotic therapy. To control for potential selection bias created by heterogeneous rates of C difficile testing and to limit confounding due to multiple antibiotic exposures, we used a nested case-control design, restricting eligibility to subjects who underwent screening for C difficile and who had been exposed to only 1 antibiotic risk period with a single antibiotic.


      The global prevalence of CDD in 358,389 ambulatory care enrollees was 12 per 100,000 person-years. In the nested case-control study, after controlling for other risk factors, 2 antibiotics demonstrated an increased association with CDD: cephalexin (odds ratio [OR] = 7.5, 95% CI = 1.8 to 34.7) and cefixime (OR = 6.4, 95% CI = 1.2 to 39.0).


      Although CDD is thought to occur primarily in hospitalized patients, it was found to be present in an ambulatory care population, but at a low frequency. In this population, it appeared to be associated with 2 cephalosporins but not with other types of antibiotics usually linked with nosocomial CDD. Because the frequency of C difficile testing was shown to be more common with high-risk antibiotics, CDD may be underdiagnosed in the ambulatory care setting.

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        • Fekety R
        • Shah AB
        Diagnosis and treatment of Clostridium difficile colitis.
        JAMA. 1993; 269: 71-75
        • Kelly CP
        • Pothoulakis C
        • LaMont JT
        Clostridium difficile colitis.
        N Engl J Med. 1994; 330: 257-262
        • Bartlett JG
        Antibiotic-associated diarrhea.
        Clin Infect Dis. 1992; 15: 573-581
        • Fekety R
        Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis.
        Am J Gastroenterol. 1997; 92: 739-750
        • Bartlett JG
        Clostridium difficile: Clinical considerations.
        Rev Infect Dis. 1990; 12: 5235-5251
        • McFarland LV
        • Mulligan ME
        • Kwok RY
        • Stamm WE
        Nosocomial acquisition of Clostridium difficile-associated infection.
        N EnglJ Med. 1989; 320: 204-210
        • Clabots CR
        • Johnson S
        • Olson MM
        • et al.
        Acquisition of Clostridium difficile by hospitalized patients: Evidence for colonized new admissions as a source of infection.
        J Infect Dis. 1992; 166: 561-567
        • Kofsky P
        • Rosen L
        • Reed J
        • et al.
        Clostridium difficile—a common and costly colitis.
        Dis Colon Rectum. 1991; 34: 244-248
        • Alfa MJ
        • Du T
        • Beda G
        Survey of incidence of Clostridium difficile infection in Canadian hospitals and diagnostic approaches.
        J Clin Microbiol. 1998; 36: 2076-2080
        • Samore MH
        • Bettin KM
        • DeGirolami PC
        • et al.
        Wide diversity of Clostridium difficile types at a tertiary referral hospital.
        J Infect Dis. 1994; 170: 615-621
        • Simor AE
        • Yake SL
        • Tsimidis K
        Infection due to Clostridium difficile among elderly residents of a long-term-care facility.
        Clin Infect Dis. 1993; 17: 672-678
        • McFarland LV
        Diarrhea acquired in the hospital.
        in: Giannella RA Gastroenterology Clinics of North America. Acute Infectious Diarrhea. Vol 22. W.B. Saunders, Philadelphia1993: 563-577
        • Riley TV
        • Wetherall F
        • Bowman J
        • et al.
        Diarrheal disease due to Clostridium difficile in general practice.
        Pathology. 1991; 23: 346-349
        • Stergachis A
        • Perera DR
        • Schnell MM
        • Jick H
        Antibiotic-associated colitis.
        West J Med. 1984; 140: 217-219
        • Hirschhorn LR
        • Trnka U
        • Onderdonk A
        • et al.
        Epidemiology of community-acquired Clostridium difficile-associated diarrhea.
        J Infect Dis. 1994; 169: 127-133
        • Quam L
        • Ellis LB
        • Venus P
        • et al.
        Using claims data for epidemiologic research.
        Med Care. 1993; 31: 498-507
        • Peterson E
        • Shatin D
        • McCarty D
        Health services research at United HealthCare Corporation: The role of the Center for Health Care Policy and Evaluation.
        Med Care Res Rev. 1996; 53 (Suppl): S65-S76
        • US Department of Health and Human Services
        International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). 2nd ed. US Government Printing Office, Washington, DC1980
        • Kirshner CG
        • Burkett RC
        • Coy JA
        • et al.
        4th ed. Physicians' Current Procedural Terminology. American Medical Association, Chicago, Ill1993
        • Kyne L
        • Merry C
        • O'Connell B
        • et al.
        Community-acquired Clostridium difficile infection.
        J Infect. 1998; 36: 287-288
        • Fekety R
        • McFarland LV
        • Surawicz CM
        • et al.
        Recurrent Clostridium difficile diarrhea: Characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial.
        Clin Infect Dis. 1997; 24: 324-333
        • Wiley SH
        • Bartlett JG
        Cultures for C difficile in stools containing a cytotoxin neutralized by Clostridium sordellii antitoxin.
        J Clin Microbiol. 1979; 10: 880-884
        • Brewlow NE
        • Day NE
        Statistical Methods in Cancer Research. Volume I—The Analysis of Case-Control Studies.
        in: International Agency for Research on Cancer, Lyon, France1980
        • Brown E
        • Talbot GH
        • Axelrod P
        • et al.
        Risk factors for Clostridium difficile toxin-associated diarrhea.
        Infect Control Hosp Epidemiol. 1990; 11: 283-290
        • Zakik PM
        • Moore AP
        Antimicrobial associations of an outbreak of diarrhoea due to Clostridium difficile.
        J Hosp Infect. 1998; 39: 189-193
        • Nelson DE
        • Auerbach SB
        • Baltch AL
        • et al.
        Epidemic of Clostridium difficile-associated diarrhea: Role of second-and third-generation cephalosporins.
        Infect Control Hosp Epidemiol. 1994; 15: 88-94
        • McFarland LV
        • Surawicz CM
        • Stamm WE
        Risk factors for Clostridium difficile carriage and C difficile-assoctated diarrhea in a cohort of hospitalized patients.
        J Infect Dis. 1990; 162: 678-684
        • Esposito AL
        • Agraharkar ML
        • Pitts WC
        Community acquired, antibiotic unassociated Clostridium difficile colitis: Report of four patients.
        Infect Dis Clin Pract. 1997; 6: 385-390
        • McFarland LV
        • Surawicz CM
        • Rubin M
        • et al.
        Recurrent Clostridium difficile disease: Epidemiology and clinical characteristics.
        Infect Control Hosp Epidemiol. 1999; 20: 43-50