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Case-Control Study of Antibiotic Use and Subsequent Clostridium difficile–Associated Diarrhea in Hospitalized Patients

Published online by Cambridge University Press:  02 January 2015

Roger Baxter ,
G. Thomas Ray  and
Bruce H. Fireman
Roger Baxter*
Affiliation:
Permanente Medical Group, Oakland, California
G. Thomas Ray
Affiliation:
Division of Research, Kaiser Permanente Medical Care Program (Northern California Region), Oakland, California
Bruce H. Fireman
Affiliation:
Permanente Medical Group, Oakland, California
*
Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, Ordway Bldg., 16th Floor, Oakland, CA 94612 ([email protected])
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Abstract

Objective.

To determine which antibiotics increase or decrease the risk of Clostridium difficile-associated diarrhea (CDAD).

Design.

Retrospective case-control study.

Setting.

Nonprofit, integrated healthcare delivery system in Northern California.

Patients.

Study participants included patients with cases of hospital-acquired CDAD that occurred during the period from 1999 through 2005 (n = 1,142) and control patients (n = 3,351) matched for facility, calendar quarter during which hospitalization occurred, diagnosis related group for the index hospitalization, and length of hospital stay. All case and control patients had received antibiotics in the 60 days before the index date. For each antibiotic, the risk of CDAD was examined in relation to whether the patient received the antibiotic, after adjustment for use of other antibiotics, demographic characteristics, selected health conditions, and use of healthcare services.

Results.

The following antibiotics were associated with a significantly increased risk of acquiring CDAD: imipenem-cilastin (odds ratio [OR], 2.77), clindamycin (OR, 2.31), cefuroxime (OR, 2.16), moxifloxacin (OR, 1.88), ceftazidime (OR, 1.82), cefpodoxime (OR, 1.58), ceftizoxime (OR, 1.57), and ceftriaxone (OR, 1.49). Metronidazole and doxycycline were associated with a significantly reduced risk of CDAD (OR for metronidazole, 0.67; OR for doxycycline, 0.41). Other factors associated with an increased risk of CDAD were older age, longer hospital stays, use of proton pump inhibitors, prior gastrointestinal disease, and prior infection (not including C. difficile infection.)

Conclusions.

Some antibiotics appear to increase the risk of acquiring CDAD, notably clindamycin, third-generation cephalosporins, and carbapenems, whereas metronidazole and doxycycline appear to be protective, compared with other antibiotics.

Type
Original Articles
Information
Infection Control & Hospital Epidemiology , Volume 29 , Issue 1 , January 2008 , pp. 44 - 50
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2008

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References

1.Yassin, SF, Young-Fadok, TM, Zein, NN, Pardi, DS. Clostridium difficile-associated diarrhea and colitis. Mayo Clin Proc 2001;76:725–730.CrossRefGoogle ScholarPubMed
2.Archibald, LK, Banerjee, SN, Jarvis, WR. Secular trends in hospital-acquired Clostridium difficile disease in the United States, 1987-2001. J Infect Dis 2004;189:1585–1589.CrossRefGoogle ScholarPubMed
3.Thomas, C, Stevenson, M, Williamson, DJ, Riley, TV. Clostridium difficile-associated diarrhea: epidemiological data from Western Australia associated with a modified antibiotic policy. Clin Infect Dis 2002;35:1457–1462.CrossRefGoogle ScholarPubMed
4.McDonald, LC, Killgore, GE, Thompson, A, et al.An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005;353:2433–2441.CrossRefGoogle ScholarPubMed
5.Kazakova, SV, Ware, K, Baughman, B, et al.A hospital outbreak of diarrhea due to an emerging epidemic strain of Clostridium difficile. Arch Intern Med 2006;166:2518–2524.CrossRefGoogle Scholar
6.Hubert, B, Loo, VG, Bourgault, AM, et al.A portrait of the geographic dissemination of the Clostridium difficile North American pulsed-field type 1 strain and the epidemiology of C. difficile-associated disease in Quebec. Clin Infect Dis 2007;44:238–244.CrossRefGoogle ScholarPubMed
7.Gerding, DN, Johnson, S, Peterson, LR, Mulligan, ME, Silva, J Jr.Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol 1995;16:459–477.CrossRefGoogle ScholarPubMed
8.Bignardi, GE. Risk factors for Clostridium difficile infection. J Hosp Infect 1998;40:1–15.CrossRefGoogle ScholarPubMed
9.Kyne, L, Sougioultzis, S, McFarland, LV, Kelly, CP. Underlying disease severity as a major risk factor for nosocomial Clostridium difficile diarrhea. Infect Control Hosp Epidemiol 2002;23:653–659.CrossRefGoogle Scholar
10.McFarland, LV. Epidemiology, risk factors and treatments for antibiotic-associated diarrhea. Dig Dis 1998;16:292–307.Google Scholar
11.Thomas, C, Stevenson, M, Riley, TV. Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review. J Antimicrob Chemother 2003;51:1339–1350.Google Scholar
12.McFarland, LV, Surawicz, CM, Stamm, WE. Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized Patients. J Infect Dis 1990;162:678–684.Google Scholar
13.Dial, S, Delaney, JA, Barkun, AN, Suissa, S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA 2005;294:2989–2995.CrossRefGoogle ScholarPubMed
14.Bartlett, JG. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med 2006;145:758–764.CrossRefGoogle ScholarPubMed
15.Climo, MW, Israel, DS, Wong, ES, Williams, D, Coudron, P, Markowitz, SM. Hospital-wide restriction of clindamycin: effect on the incidence of Clostridium difficile-associated diarrhea and cost. Ann Intern Med 1998;128:989–995.Google Scholar
16.Pepin, J, Saheb, N, Coulombe, MA, et al.Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrheas cohort study during an epidemic in Quebec. Clin Infect Dis 2005;41:1254–1260.Google Scholar
17.Modena, S, Bearelly, D, Swartz, K, Friedenberg, FK. Clostridium difficile among hospitalized patients receiving antibiotics: a case-control study. Infect Control Hosp Epidemiol 2005;26:685–690.CrossRefGoogle ScholarPubMed
18.Palmore, TN, Sohn, S, Malak, SE, Eagan, J, Sepkowitz, KA. Risk factors for acquisition of Clostridium difficile-associated diarrhea among outpatients at a cancer hospital. Infect Control Hosp Epidemiol 2005;26:680–684.Google Scholar
19.McCusker, ME, Harris, AD, Perencevich, E, Roghmann, MC. Fluoroquinolone use and Clostridium difficile-associated diarrhea. Emerg Infect Dis 2003;9:730–733.Google Scholar
20.Anand, A, Bashey, B, Mir, T, Glatt, AE. Epidemiology, clinical manifestations, and outcome of Clostridium difficile-associated diarrhea. Am J Gastroenterol 1994;89:519–523.Google Scholar
21.Gaynes, R, Rimland, D, Killum, E, et al.Outbreak of Clostridium difficile infection in a long-term care facility: association with gatifloxacin use. Clin Infect Dis 2004;38:640–645.CrossRefGoogle Scholar
22.Zimmerman, RK. Risk factors for Clostridium difficile cytotoxin-positive diarrhea after control for horizontal transmission. Infect Control Hosp Epidemiol 1991;12:96–100.Google Scholar
23.Dhalla, IA, Mamdani, MM, Simor, AE, Kopp, A, Rochon, PA, Juurlink, DN. Are broad-spectrum fluoroquinolones more likely to cause Clostridium difficile-associated disease? Antimicrob Agents Chemother 2006;50:3216–3219.Google Scholar
24.Raveh, D, Rabinowitz, B, Breuer, GS, Rudensky, B, Yinnon, AM. Risk factors for Clostridium difficile toxin-positive nosocomial diarrhoea. Int J Antimicrob Agents 2006;28:231–237.Google Scholar
25.Wistrom, J, Norrby, SR, Myhre, EB, et al.Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother 2001;47:43–50.Google Scholar
26.Chang, VT, Nelson, K. The role of physical proximity in nosocomial diarrhea. Clin Infect Dis 2000;31:717–722.CrossRefGoogle ScholarPubMed
27.Starr, JM, Martin, H, McCoubrey, J, Gibson, G, Poxton, IR. Risk factors for Clostridium difficile colonisation and toxin production. Age Ageing 2003;32:657–660.CrossRefGoogle ScholarPubMed
28.Muto, CA, Pokrywka, M, Shutt, K, et al.A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol 2005;26:273–280.CrossRefGoogle Scholar
29.Ray, GT, Levine, P, Croen, LA, Bokhari, FA, Hu, TW, Habel, LA. Attention-deficit/hyperactivity disorder in children: excess costs before and after initial diagnosis and treatment cost differences by ethnicity. Arch Pediatr Adolesc Med 2006;160:1063–1069.Google Scholar
30.Ray, GT, Mertens, JR, Weisner, C. The excess medical cost and health problems of family members of persons diagnosed with alcohol or drug problems. Med Care 2007;45:116–122.CrossRefGoogle ScholarPubMed
31.Vesta, KS, Wells, PG, Gentry, CA, Stipek, WJ. Specific risk factors for Clostridium difficile-associated diarrhea: A prospective, multicenter, case control evaluation. Am J Infect Control 2005;33:469–472.Google Scholar
32.Changela, U, Cannon, JP, Aneziokoro, C, Shah, PS, Thottapurathu, L, Len-tino, J. Risk factors and mortality associated with Clostridium difficile-associated diarrhoea at a VA hospital. Int J Antimicrob Agents 2004;24:562–566.CrossRefGoogle Scholar
33.Loo, VG, Poirier, L, Miller, MA, et al.A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005;353:2442–2449.Google Scholar
34.Gerding, DN. Clindamycin, cephalosporins, fluoroquinolones, and Clostridium difficile-associated diarrhea: this is an antimicrobial resistance problem. Clin Infect Dis 2004;38:646–648.Google Scholar
35.Johnson, S, Samore, MH, Farrow, KA, et al.Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals. N Engl J Med 1999;341:1645–1651.Google Scholar