Hostname: page-component-848d4c4894-75dct Total loading time: 0 Render date: 2024-05-08T21:24:11.925Z Has data issue: false hasContentIssue false
  • English
  • Français

Clinical Features of Clostridium difficile–Associated Infections and Molecular Characterization of Strains: Results of a Retrospective Study, 2000-2004

Published online by Cambridge University Press:  02 January 2015

Frédéric Barbut ,
Béatrice Gariazzo ,
Laetitia Bonné ,
Valérie Lalande ,
Béatrice Burghoffer ,
Ralucca Luiuz  and
Jean-Claude Petit
Frédéric Barbut*
Affiliation:
Service de Microbiologie, Paris, France Unité d'Hygiène et de Lutte contre les Infections Nosocomiales, Paris, France Hôpital Saint-Antoine, and the UPRES no. EA2392, Université Pierre et Marie Curie, Paris, France
Béatrice Gariazzo
Affiliation:
Service de Microbiologie, Paris, France
Laetitia Bonné
Affiliation:
Hôpital Saint-Antoine, and the UPRES no. EA2392, Université Pierre et Marie Curie, Paris, France
Valérie Lalande
Affiliation:
Service de Microbiologie, Paris, France Hôpital Saint-Antoine, and the UPRES no. EA2392, Université Pierre et Marie Curie, Paris, France
Béatrice Burghoffer
Affiliation:
Hôpital Saint-Antoine, and the UPRES no. EA2392, Université Pierre et Marie Curie, Paris, France
Ralucca Luiuz
Affiliation:
Service de Microbiologie, Paris, France
Jean-Claude Petit
Affiliation:
Service de Microbiologie, Paris, France Hôpital Saint-Antoine, and the UPRES no. EA2392, Université Pierre et Marie Curie, Paris, France
*
Hôpital Saint-Antoine, UHLIN, 184 Rue de Faubourg Saint-Antoine, Paris 75012, France (frederic.barbut@sat.ap-hop-paris.fr)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background.

Recent outbreaks of severe cases of Clostridium difficile-associated diarrhea (CDAD) reported in North America, the United Kingdom, and The Netherlands have emphasized the importance of an ongoing epidemiological surveillance of CDAD.

Objective.

To determine the epidemiology of CDAD over the years 2000-2004 and the rate of nosocomial transmission of C. difficile.

Design.

Retrospective survey of inpatients with CDAD and molecular characterization of the strains isolated.

Setting.

A 760-bed teaching hospital.

Methods.

All CDAD cases diagnosed from January 1, 2000, to December 31, 2004, were reviewed. A CDAD case was defined as diarrhea in a hospitalized patient who had a stool specimen that tested positive for C. difficile cytotoxin or had a positive toxigenic culture result. CDAD was considered to be severe if a patient fulfilled at least 1 of the following 3 criteria: (1) presence of a fever (defined as temperature higher than 38.5°C), abdominal pain, and leukocyte count greater than 10,000 cells/mm3; (2) endoscopically or histologically proven pseudomembranous colitis; or (3) complications (defined as death with C. difficile infection as the primary or a contributing cause, toxic megacolon, perforation, toxic shock, and/or colectomy). CDAD was considered community-acquired if the diarrhea occurred in the patient within 72 hours after admission and if the patient had no history of hospitalization in the previous month; otherwise, CDAD was considered healthcare-associated. All the strains isolated were serogrouped and were characterized by toxinotyping and PCR ribotyping. Detection of toxin A, toxin B, and binary toxin was performed by PCR.

Results.

One hundred fifty-one cases of CDAD were diagnosed; 147 clinical records could be reviewed, and 131 strains were studied. The overall incidence of CDAD was 1.1 cases per 1,000 patients admitted, but incidence rates were higher in 2003-2004, compared with 2000-2002 (P = .017). Diarrhea was community acquired in 28 patients (19%). For patients with healthcare-associated CDAD, transmission of the strain from patient to patient (ie, infection with a strain of the same serogroup and PCR ribotype as the strain isolated from another patient hospitalized in the same ward or in a linked ward in the previous 2 months) was demonstrated in 12 cases (10.1%). Eleven percent of strains were positive for binary toxin. Binary toxin-positive strains were associated with more-severe diarrhea (P = .01 ) and with a higher case-fatality rate (P = .03). A specific clone of C. difficile (serogroup H, PCR ribotype sa026) accounted for 35 (26.7%) of all the strains isolated, but this clone was found both in healthcare-associated and community-acquired cases. Three strains belonged to toxinotype III, but only 1 was related to the hypervirulent clone involved in recent outbreaks.

Conclusion.

The incidence of CDAD is low in our hospital, and cross-infection is limited. These results also suggest that strains with binary toxin might be more virulent.

Type
Original Articles
Information
Infection Control & Hospital Epidemiology , Volume 28 , Issue 2 , February 2007 , pp. 131 - 139
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2007

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.Barbut, F, Petit, JC. Epidemiology of Clostridium difficile-associated infections. Clin Microbiol Infect 2001;7:405–410.Google Scholar
2.Kelly, CP, Pothoulakis, C, LaMont, JT. Clostridium difficile colitis. N Engl J Med 1994;330:257–262.Google Scholar
3.Cartmill, TD, Shrimpton, SB, Panigrahi, H, Khanna, V, Brown, R, Poxton, IR. Nosocomial diarrhoea due to a single strain of Clostridium difficile: a prolonged outbreak in elderly patients. Age Ageing 1992;21:245–249.CrossRefGoogle ScholarPubMed
4.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
5.McFarland, LV, Mulligan, ME, Kwok, RY, Stamm, WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989;320: 204-210.Google Scholar
6.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
7.Voth, DE, Ballard, JD. Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 2005;18:247–263.Google Scholar
8.Popoff, MR, Rubin, EJ, Gill, DM, Boquet, P. Actin-specific ADP-ribosyl-transferase produced by a Clostridium difficile strain. Infect Immun 1988;56:2299–2306.Google Scholar
9.Perelle, S, Gibert, M, Bourlioux, P, Corthier, G, Popoff, MR. Production of a complete binary toxin (actin-specific ADP-ribosyltransferase) by Clostridium difficile CD196. Infect Immun 1997;65:1402–1407.Google Scholar
10.Geric, B, Rupnik, M, Gerding, DN, Grabnar, M, Johnson, S. Distribution of Clostridium difficile variant toxinotypes and strains with binary toxin genes among clinical isolates in an American hospital. J Med Microbiol 2004;53:887–894.Google Scholar
11.Goncalves, C, Deere, D, Barbut, F, Burghoffer, B, Petit, JC. Prevalence and characterization of a binary toxin (actin-specific ADP-ribosyltransferase) from Clostridium difficile. J Clin Microbiol 2004;42:1933–1939.Google Scholar
12.Pituch, H, Rupnik, M, Obuch-Woszczatynski, P, Grubesic, A, Meisel-Mi-kolajczyk, F, Luczak, M. Detection of binary-toxin genes (cdtA and cdtB) among Clostridium difficile strains isolated from patients with C. difficile-associated diarrhoea (CDAD) in Poland. J Med Microbiol 2005;54:143–147.Google Scholar
13.Rupnik, M, Karo, N, Grabnar, M, Kato, H. New types of toxin A-negative, toxin B-positive strains among Clostridium difficile isolates from Asia. J Clin Microbiol 2003;41:1118–1125.CrossRefGoogle ScholarPubMed
14.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
15.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
16.Pepin, J, Valiquette, L, Alary, ME, et al. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. Cmaj 2004;171:466–472.CrossRefGoogle Scholar
17.Pepin, J, Valiquette, L, Cossette, B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. Cmaj 2005;173:1037–1042.Google Scholar
18.Warny, M, Pepin, J, Fang, A, et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 2005;366:1079–1084.CrossRefGoogle ScholarPubMed
19.Kuijper, EJ, Van den Berg, RJ, Debast, S, et al. Clostridium difficile ribotype 027, toxinotype III, The Netherlands. Emerg Infect Dis 2006;12:827–830.Google Scholar
20.Barbut, F, Depitre, C, Delmee, M, Corthier, G, Petit, JC. Comparison of enterotoxin production, cytotoxin production, serogrouping, and antimicrobial susceptibilities of Clostridium difficile strains isolated from AIDS and human immunodeficiency virus-negative patients. J Clin Microbiol 1993;31:740–742.Google Scholar
21.Delmee, M, Depitre, C, Corthier, G, Ahoyo, A, Avesani, V. Use of an enzyme-linked immunoassay for Clostridium difficile serogrouping. J Clin Microbiol 1993;31:2526–2528.Google Scholar
22.Stubbs, S, Rupnik, M, Gibert, M, Brazier, J, Duerden, B, Popoff, M. Production of actin-specific ADP-ribosyltransferase (binary toxin) by strains of Clostridium difficile. FEMS Microbiol Lett 2000;186:307–312.Google Scholar
23.Rupnik, M, Avesani, V, Jane, M, von Eichel-Streiber, C, Delmee, M. A novel toxinotyping scheme and correlation of toxinotypes with serogroups of Clostridium difficile isolates. J Clin Microbiol 1998;36:2240–2247.Google Scholar
24.Rupnik, M. How to detect Clostridium difficile variant strains in a routine laboratory. Clin Microbiol Infect 2001;7:417–420.CrossRefGoogle Scholar
25.Clostridium difficile toxinotypes. Available at: http://www.mf.uni-mb.si/mikro/tox/. Accessed December 14, 2006.Google Scholar
26.Spigaglia, P, Mastrantonio, P. Molecular analysis of the pathogenicity locus and polymorphism in the putative negative regulator of toxin production (TcdC) among Clostridium difficile clinical isolates. J Clin Microbiol 2002;40:3470–3475.CrossRefGoogle ScholarPubMed
27.Bidet, P, Lalande, V, Salauze, B, et al. Comparison of PCR-ribotyping, arbitrarily primed PCR, and pulsed-field gel electrophoresis for typing Clostridium difficile. J Clin Microbiol 2000;38:2484–2487.Google Scholar
28.Barbut, F, Leluan, P, Antoniotti, G, Collignon, A, Sedallian, A, Petit, JC. Value of routine stool cultures in hospitalized patients with diarrhea. Eur J Clin Microbiol Infect Dis 1995;14:346–349.CrossRefGoogle ScholarPubMed
29.Siegel, DL, Edelstein, PH, Nachamkin, I. Inappropriate testing for diarrheal diseases in the hospital. Jama 1990;263:979–982.Google Scholar
30.Rohner, P, Pittet, D, Pepey, B, Nije-Kinge, T, Auckenthaler, R. Etiological agents of infectious diarrhea: implications for requests for microbial culture. J Clin Microbiol 1997;35:1427–1432.CrossRefGoogle ScholarPubMed
31.Barbut, F, Delmee, M, Brazier, JS, et al. A European survey of diagnostic methods and testing protocols for Clostridium difficile. Clin Microbiol Infect 2003;9:989–996.CrossRefGoogle ScholarPubMed
32.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.Google Scholar
33.Olson, MM, Shanholtzer, CJ, Lee, JT Jr, Gerding, DN. Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982-1991. Infect Control Hosp Epidemiol 1994;15:371–381.Google Scholar
34.Delmee, M, Van Broeck, J, Simon, A, Janssens, M, Avesani, V. Laboratory diagnosis of Clostridium difficile-associated diarrhoea: a plea for culture. J Med Microbiol 2005;54:187–191.CrossRefGoogle ScholarPubMed
35.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.Google Scholar
36.Barbut, F, Lalande, V, Burghoffer, B, Thien, HV, Grimprel, E, Petit, JC. Prevalence and genetic characterization of toxin A variant strains of Clostridium difficile among adults and children with diarrhea in France. J Clin Microbiol 2002;40:2079–2083.CrossRefGoogle ScholarPubMed
37.Brazier, JS, Stubbs, SL, Duerden, BI. Prevalence of toxin A negative/B positive Clostridium difficile strains. J Hosp Infect 1999;42:248–249.Google Scholar
38.Kato, H, Kato, N, Watanabe, K, et al. Identification of toxin A-negative, toxin B-positive Clostridium difficile by PCR. J Clin Microbiol 1998;36:2178–2182.Google Scholar
39.Drudy, D, Harnedy, N, Fanning, S, O'Mahoney, R, Baird, A, Kyne, L. Endemic toxin variant in a Irish teaching hospital. In: Program and Abstracts of the 1st International Clostridium difficile Symposium (Kranjska-Gora, Slovenia). Lubljana, Slovenia: M. Rupnik, 2004:44. Abstract 2.Google Scholar
40.Miller, MA, Hyland, M, Ofner-Agostini, M, Gourdeau, M, Ishak, M. Morbidity, mortality, and healthcare burden of nosocomial Clostridium difficile-associated diarrhea in Canadian hospitals. Infect Control Hosp Epidemiol 2002;23:137–140.Google Scholar
41.Barbut, F, Richard, A, Hamadi, K, Chomette, V, Burghoffer, B, Petit, JC. Epidemiology of recurrences or reinfections of Clostridium difficile-associated diarrhea. J Clin Microbiol 2000;38:2386–2388.Google Scholar
42.Svenungsson, B, Burman, LG, Jalakas-Pornull, K, Lagergren, A, Struwe, J, Akerlund, T. Epidemiology and molecular characterization of Clostridium difficile strains from patients with diarrhea: low disease incidence and evidence of limited cross-infection in a Swedish teaching hospital. Clin Microbiol 2003;41:4031–4037.CrossRefGoogle Scholar
43.Clabots, CR, Johnson, S, Olson, MM, Peterson, LR, Gerding, DN. Acquisition of Clostridium difficile by hospitalized patients: evidence for colonized new admissions as a source of infection. J Infect Dis 1992;166:561–567.CrossRefGoogle ScholarPubMed
44.Stubbs, SL, Brazier, JS, O'Neill, GL, Duerden, BI. PCR targeted to the 16S-23S rRNA gene intergenic spacer region of Clostridium difficile and construction of a library consisting of 116 different PCR ribotypes. J Clin Microbiol 1999;37:461–463.CrossRefGoogle Scholar
45.Pituch, H, Kreft, D, Obuch-Woszczatynski, P, et al. Clonal spread of a Clostridium difficile strain with a complete set of toxin A, toxin B, and binary toxin genes among Polish patients with Clostridium difficile-associated diarrhea. J Clin Microbiol 2005;43:472–475.Google Scholar
46.Barbut, F, Deere, D, Lalande, V, et al. Clinical features of Clostridium difficile-associated diarrhoea due to binary toxin (actin-specific ADP-ribosyltransferase)–producing strains. J Med Microbiol 2005;54:181–185.Google Scholar
47.Geric, B, Carman, RJ, Rupnik, M, et al. Binary toxin-producing, large clostridial toxin-negative Clostridium difficile strains are enterotoxic but do not cause disease in hamsters. J Infect Dis 2006;193:1143–1150.Google Scholar