Hostname: page-component-546b4f848f-hhr79 Total loading time: 0 Render date: 2023-06-01T17:07:18.103Z Has data issue: false Feature Flags: { "useRatesEcommerce": true } hasContentIssue false
  • English

A Large Outbreak of Clostridium difficile–Associated Disease with an Unexpected Proportion of Deaths and Colectomies at a Teaching Hospital Following Increased Fluoroquinolone Use

Published online by Cambridge University Press:  21 June 2016

Carlene A. Muto ,
Marian Pokrywka ,
Kathleen Shutt ,
Aaron B. Mendelsohn ,
Kathy Nouri ,
Kathy Posey ,
Terri Roberts ,
Karen Croyle ,
Sharon Krystoflak  and
Sujata Patel-Brown
...Show all authors
Carlene A. Muto*
Affiliation:
Division of Hospital Epidemiology and Infection Control, University of Pittsburgh Medical Center, Presbyterian Campus, Pittsburgh, Pennsylvania Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine, and Graduate School of Public Health, Pittsburgh, Pennsylvania
Marian Pokrywka
Affiliation:
Division of Hospital Epidemiology and Infection Control, University of Pittsburgh Medical Center, Presbyterian Campus, Pittsburgh, Pennsylvania
Kathleen Shutt
Affiliation:
Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine, and Graduate School of Public Health, Pittsburgh, Pennsylvania
Aaron B. Mendelsohn
Affiliation:
Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, Pennsylvania
Kathy Nouri
Affiliation:
Division of Hospital Epidemiology and Infection Control, University of Pittsburgh Medical Center, Presbyterian Campus, Pittsburgh, Pennsylvania
Kathy Posey
Affiliation:
Division of Hospital Epidemiology and Infection Control, University of Pittsburgh Medical Center, Presbyterian Campus, Pittsburgh, Pennsylvania
Terri Roberts
Affiliation:
Division of Hospital Epidemiology and Infection Control, University of Pittsburgh Medical Center, Presbyterian Campus, Pittsburgh, Pennsylvania
Karen Croyle
Affiliation:
Division of Hospital Epidemiology and Infection Control, University of Pittsburgh Medical Center, Presbyterian Campus, Pittsburgh, Pennsylvania
Sharon Krystoflak
Affiliation:
Division of Hospital Epidemiology and Infection Control, University of Pittsburgh Medical Center, Presbyterian Campus, Pittsburgh, Pennsylvania
Sujata Patel-Brown
Affiliation:
Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine, and Graduate School of Public Health, Pittsburgh, Pennsylvania
A. William Pasculle
Affiliation:
Division of Microbiology, University of Pittsburgh Medical Center, Presbyterian Campus, Pittsburgh, Pennsylvania Department of Pathology, Pittsburgh, Pennsylvania
David L. Paterson
Affiliation:
Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine, and Graduate School of Public Health, Pittsburgh, Pennsylvania
Melissa Saul
Affiliation:
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Lee H. Harrison
Affiliation:
Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine, and Graduate School of Public Health, Pittsburgh, Pennsylvania
*
University of Pittsburgh Medical Center (UPMC-P), 1215 Kaufmann Building, Pittsburgh, PA 15213mutoca@msx.upmc.edu
Get access Rights & Permissions[Opens in a new window]

Abstract

Background and Objective:

Fluoroquinolones have not been frequently implicated as a cause of Clostridium difficile outbreaks. Nosocomial C. difficile infections increased from 2.7 to 6.8 cases per 1,000 discharges (P < .001). During the first 2 years of the outbreak, there were 253 nosocomial C. difficile infections; of these, 26 resulted in colectomy and 18 resulted in death. We conducted an investigation of a large C. difficile outbreak in our hospital to identify risk factors and characterize the outbreak.

Methods:

A retrospective case-control study of case-patients with C. difficile infection from January 2000 through April 2001 and control-patients matched by date of hospital admission, type of medical service, and length of stay; an analysis of inpatient antibiotic use; and antibiotic susceptibility testing and molecular subtyping of isolates were performed.

Results:

On logistic regression analysis, clindamycin (odds ratio [OR], 4.8; 95% confidence interval [CI95], 1.9-12.0), ceftriaxone (OR, 5.4; CI95, 1.8-15.8), and levofloxacin (OR, 2.0; CI95, 1.2-3.3) were independently associated with infection. The etiologic fractions for these three agents were 10.0%, 6.7%, and 30.8%, respectively. Fluoroquinolone use increased before the onset of the outbreak (P < .001); 59% of case-patients and 41% of control-patients had received this antibiotic class. The outbreak was polyclonal, although 52% of isolates belonged to two highly related molecular subtypes.

Conclusions:

Exposure to levofloxacin was an independent risk factor for C. difficile-associated diarrhea and appeared to contribute substantially to the outbreak. Restricted use of levofloxacin and the other implicated antibiotics may be required to control the outbreak.

Type
Original Articles
Information
Infection Control & Hospital Epidemiology , Volume 26 , Issue 3 , March 2005 , pp. 273 - 280
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Gerding, DN, Olson, MM, Peterson, LR, et al.Clostridium difficile-associated diarrhea and colitis in adults: a prospective case-controlled epidemiologic study. Arch Intern Med 1986;146:95–100.CrossRefGoogle ScholarPubMed
2.Bartlett, JG. Antibiotic-associated diarrhea. Clin Infect Dis 1992;15:573–581.CrossRefGoogle ScholarPubMed
3.Fekety, R, Shah, AB. Diagnosis and treatment of Clostridium difficile colitis. JAMA 1993;269:71–75.CrossRefGoogle ScholarPubMed
4.McFarland, LV, Mulligan, ME, Kwok, RY, Stamm, WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989;320:204–210.CrossRefGoogle ScholarPubMed
5.Johnson, S, Clabots, CR, Linn, FV, Olson, MM, Peterson, LR, Gerding, DN. Nosocomial Clostridium difficile colonisation and disease. Lancet 1990;336:97–100.CrossRefGoogle ScholarPubMed
6.Brown, E, Talbot, GH, Axelrod, P, Provencher, M, Hoegg, C. Risk factors for Clostridium difficile toxin-associated diarrhea. Infect Control Hosp Epidemiol 1990;11:283–290.CrossRefGoogle ScholarPubMed
7.Lai, K, Melvin, ZS, Menard, MJ, et al.Clostridium difficile-associated diarrhea: epidemiology, risk factors, and infection control. Infect Control Hosp Epidemiol 1997;18:628–632.CrossRefGoogle ScholarPubMed
8.Pear, SM, Williamson, TH, Bettin, KM, Gerding, DN, Galgiani, JN. Decrease in nosocomial Clostridium difficile-associated diarrhea by restricting clindamycin use. Ann Intern Med 1994;120:272–277.CrossRefGoogle ScholarPubMed
9.Drapin, MS, Worthington, MG, Chang, TW, Razvi, SA. Clostridium difficile colitis mimicking acute peritonitis. Arch Surg 1985;120:1321–1322.CrossRefGoogle Scholar
10.Rubin, MS, Bodenstein, LE, Kent, KC. Severe Clostridium difficile colitis. Dis Colon Rectum 1995;38:350–354.CrossRefGoogle ScholarPubMed
11.Kyne, L, Hamel, MB, Polavaram, R, Kelly, CP. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clin Infect Dis 2002;34:346–353.CrossRefGoogle ScholarPubMed
12.Bartlett, JG. Antimicrobial agents implicated in Clostridium difficile toxin-associated diarrhea or colitis. Johns Hopkins Med J 1981;149:6–9.Google ScholarPubMed
13.Gerding, DN. Disease associated with Clostridium difficile infection. Ann Intern Med 1989;110:255–257.CrossRefGoogle ScholarPubMed
14.Thibault, A, Miller, MA, Gaese, C. Risk factors for the developmenl of Clostridium difficile-associatei diarrhea during hospital outbreak. Infect Control Hosp Epidemiol 1991;12:345–348.CrossRefGoogle ScholarPubMed
15.Zimmerman, RKRisk factors for Clostridium difficile cytotoxin-positive diarrhea after control for horizontal transmission. Infect Control Hosp Epidemiol 1991;12:96–100.CrossRefGoogle ScholarPubMed
16.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.CrossRefGoogle Scholar
17.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 ScholarPubMed
18.Cartonili, TD, Panigrahi, H, Worsley, MA, et al.Management and control of a large outbreak of diarrhea due to Clostridium difficile. J Hosp Infect 1994;27:1–15.Google Scholar
19.Watanakunakorn, PW, Watanakunakorn, C, Hazy, J. Risk factors associated with Clostridium difficile diarrhea in hospitalized adult patients: a case-control study—sucralfate ingestion is not a negative risk factor. Infect Control Hosp Epidemiol 1996;17:232–235.CrossRefGoogle Scholar
20.Yip, C, Loeb, M, Salama, S, Moss, L, Olde, J. Quinolone use as a risk factor for nosocomial Clostridium difficile-associateá diarrhea. Infect Control Hosp Epidemiol 2001;22:572–575.CrossRefGoogle ScholarPubMed
21.Tedesco, FJ. Ampicillin-associated diarrhea: a prospective study. American Journal of Digestive Diseases 1975;20:295–297.CrossRefGoogle ScholarPubMed
22.Gurwith, MJ, Rabin, HR, Love, K. Diarrhea associated with clindamycin and ampicillin therapy: preliminary results of a cooperative study. J Infect Dis 1977;135(suppl):S104–S110.CrossRefGoogle Scholar
23.Wiström, J, Norrby, SR, Myhre, EB, et al.Frequency of antibiotic-associated diarrhoea in 2,462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother 2001;47:43–50.CrossRefGoogle Scholar
24.Crabtree, T, Pelletier, S, Gleason, T, Pruett, T, Sawyer, R. Clinical characteristics and antibiotic utilization in surgical patients with Clostridium difficile-associateá diarrhea. Am Surg 1999;65:507–511.Google ScholarPubMed
25.Bauwens, JE, McFarland, LV, Melcher, AS. Recurrent Clostridium difficile disease following ciprofloxacin use. Ann Pharmacother 1997;31:1090.CrossRefGoogle ScholarPubMed
26.Low, N, Harries, A. Ciprofloxacin and pseudomembranous colitis. Lancet 1990;336:1510.Google Scholar
27.Hillman, RJ, Gopal, R, Harris, RJ. Ciprofloxacin as a cause of Clostridium difficile-associated diarrhea in an HIV antibody positive patient. J Infect 1990;21:205–207.CrossRefGoogle Scholar
28.Cain, DB, O'Conner, ME. Pseudomembranous colitis associated with ciprofloxacin. Lancet 1990;336:946.CrossRefGoogle ScholarPubMed
29.Bates, CJ, Wilcox, MH, Spencer, RC. Ciprofloxacin and Clostridium difficile infection. Lancet 1990;336:1193.CrossRefGoogle ScholarPubMed
30.Loge, RV. Oral fluoroquinolone therapy for Clostridium difficile enterocolitis. JAMA 1989;261:2063–2064.CrossRefGoogle ScholarPubMed
31.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
32.McCusker, ME, Harris, AD, Perencevich, E, Roghmann, M-C. Fluoroquinolone use and Clostridium difficile-associatei diarrhea. Emerg Infect Dis 2003;9:730–733.CrossRefGoogle ScholarPubMed
33.Dallai, RM, Harbrecht, BG, Boujoukas, AJ, et al.Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications. Ann Surg 2002;235:363–372.CrossRefGoogle Scholar
34.Pokrywka, M, Croyle, K, Pasculle, AW, Muto, CA. Clostridium difficile colitis resulting in colectomies: case-control study. Presented at the 11th Annual Meeting of the Society for Healthcare Epidemiology of America; April 1-3, 2001; Toronto, Ontario, Canada.Google Scholar
35.Garner, JS, Hospital Infection Control Practices Advisory Committee. Guideline for isolation precautions in hospitals. Infect Control Hosp Epidemiol 1996;17:53–80.CrossRefGoogle ScholarPubMed
36.Yount, RJ, Vries, JK, Councill, CD. The Medical Archival Retrieval system: an information retrieval system based on distributed parallel processing. Information Processing and Management 1991;27:1–11.CrossRefGoogle Scholar
37.World Health Organization. Anatomical Therapeutic Chemical (ATC) Classification Index With Defined Daily Doses (DDDs). Oslo, Norway: WHO Collaborating Centre for Drug Statistics Methodology; 2000:94–100. Available at www.whocc.no/atcddd.Google Scholar
38.Mundy, LS, Shanholtzer, CJ, Willard, KE, Gerding, DE, Peterson, LR. Laboratory detection of Clostridium difficile: a comparison of media and incubation systems. Am J Clin Pathol 1995;103:52–56.CrossRefGoogle ScholarPubMed
39.National Committee for Clinical Laboratory Standards. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria, ed. 5. Wayne, PA: National Committee for Clinical Laboratory Standards; 2001. Approved standard. Document M11-A5.Google ScholarPubMed
40.Clabots, CR, Johnson, S, Bettin, KM, et al.Development of a rapid and efficient restriction endonuclease analysis typing system for Clostridium difficile and correlation with other typing systems. J Clin Microbiol 1993;31:1870–1875.Google ScholarPubMed
41.Rothman, KJ, Greenland, S. Modern Epidemiology. Philadelphia: Lippincott Williams & Wilkins; 1998:286, 737.Google Scholar
42.Schlesselman, JJ. Basic concepts in the assessment of risk. In: Lilienfeld, AM, ed. Case-Control Studies: Design, Conduct, Analysis. New York: Oxford University Press; 1982:27–68.Google Scholar
43.Clabots, CR, Peterson, LR, Gerding, DN. Characterization of a nosocomial Clostridium difficile outbreak by using plasmid profile typing and clindamycin susceptibility testing. J Infect Dis 1988;158:731–736.CrossRefGoogle ScholarPubMed
44.Wilcox, MH, Fawley, W, Freeman, J, Brayson, J. In vitro activity of new generation fluoroquinolones against genotypically distinct and indistinguishable Clostridium difficile isolates. J Antimicrob Chemother 2000;46:551–556.CrossRefGoogle ScholarPubMed
45.Gerding, DN. Clindamycin, cephalosporins, fluoroquinolones, and Clostridium difficile associated diarrhea: this is an antimicrobial resistance problem. Clin Infect Dis 2004;38:646–648.CrossRefGoogle ScholarPubMed
46.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.CrossRefGoogle ScholarPubMed
47.Kristiansson, M, Samore, MH, Gerding, DN, et al.Molecular differentiation of Clostridium difficile: a comparison of restriction endonuclease analyses, ribotyping, and pulsed field gel electrophoresis. J Clin Microbiol 1994;32:1963–1969.Google Scholar
48.Rafferty, ME, Baltch, AL, Smith, RP, et al.Comparison of restriction enzyme analysis, arbitrarily primed PCR, and protein profile analysis typing for epidemiologic investigation of an ongoing Clostridium difficile outbreak. J Clin Microbiol 1998;36:2957–2963.Google ScholarPubMed
49.Klaassen, CHW, van Haren, HA, Horrevorts, AM. Molecular fingerprinting of Clostridium difficile isolates: pulsed-field gel electrophoresis versus amplified fragment length polymorphism. J Clin Microbiol 2002; 40:101–104.CrossRefGoogle ScholarPubMed