Dramatischer Anstieg von Clostridium-difficile-assoziierter Diarrhoe in Deutschland: Ist der neue Stamm PCR-Ribotyp 027 bereits angekommen?

 

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Zusammenfassung

In den letzten Jahren wurde in Nordamerika und Großbritannien ein drastischer Anstieg von Fällen nosokomialer Clostridium difficile-assoziierter Diarrhoe (CDAD) verzeichnet. Ebenso ist in Deutschland ein Anstieg der Patienten mit der Diagnose CDAD von 7,4 pro 100 000 stationärer Aufnahmen im Jahre 2000 auf 39,3 im Jahre 2004 festzustellen.

In Pittsburgh, USA wurde ein Anstieg der Inzidenz von CDAD-Fällen von 0,74 % im Jahre 1999 auf 1,2 % im Jahre 2000 beobachtet. Im gleichen Zeitraum stieg die Clostridium difficile (CD)-assoziierte Letalität von 0,5 % auf 2,0 %. Während eines Ausbruches (04/2001 - 03/2002) wurde ein neuer CD-Stamm für 87,5 % der schweren CDAD-Fälle verantwortlich gemacht. Seit März 2003 wurden in Kanada und in den USA gehäuft Ausbrüche durch diesen neuen CD-Stamm beobachtet, welcher mit einer besonders hohen Erkrankungsschwere und Letalität einhergeht. Darüber hinaus hat der Stamm auch bei jüngeren, ambulanten Patienten ohne Risikofaktoren zu Erkrankungen mit zum Teil sehr schweren Verläufen geführt.

Zeitgleich kam es auch in Großbritannien, den Niederlanden, Belgien und Frankreich zu mehreren Ausbrüchen, in denen dieser neue CD-Stamm nachgewiesen werden konnte.

In der Restriktions-Endonukleasen-Analyse wird er als Typ B1, in der PCR als Ribotyp 027, Toxintyp III und in der Pulsfeld-Gel-Elektrophorese als North American Profile 1 (NAP1) charakterisiert. Der Stamm besitzt durch ein zusätzliches binäres Toxin und durch auf ein Vielfaches erhöhte Spiegel der Toxine A und B eine erhöhte Virulenz. In Deutschland ist dieser Stamm bisher noch nicht nachgewiesen worden.

Diese Arbeit gibt einen Überblick über die bisherige Verbreitung des Erregers sowie Hinweise für die Diagnostik und Prävention.

Summary

There has been a dramatic increase of Clostridium difficile-associated diarrhea (CDAD) in North America and the UK over the last few years. A similar change in the epidemiology of CDAD has been noted in Germany where in 2004, of 100000 patients hospitalized in Germany, 39.3 were found to have CDAD, compared to 7,4 per 100 000 in 2000.

An increased incidence of CDAD was also observed in Pittsburgh, USA, from 0.74% in 1999 to 1,2% in 2000. At the same time, the mortality from CDAD rose from 0.48% to 2%. A new Clostridum difficile strain was responsible for 87.5% of severe CDAD cases during an outbreak in Pittsburgh between April 2001 and March 2002. Since March 2003 there has been an increasing number of nosocomial outbreaks due to a new Clostridium difficile strain in Canada and USA, a high proportion being severe and fatal cases of CDAD. Moreover, there have been community-acquired cases of severe CDAD in young patients without any specific risk factors for developing CDAD.

At the same time, outbreaks of CDAD involving the new Clostridium difficile strain have been reported from the UK, the Netherlands, Belgium and France. The new strain is characterized as type B1 by restriction enzyme analysis, as ribotype 027 and toxinotype III by PCR, and as North Amerikan Profile 1 (NAP 1) by pulsed-field gel electrophoresis. The extraordinary virulence of this strain is thought to be associated with an additional binary toxin and increased levels of toxins A and B.

This report provides information on the current epidemiological situation as well as recommendations for diagnosis and prevention.

Literatur

• 1 Anonymous. Severe Clostridium difficile-associated disease in populations previously at low risk-four states, 2005.  MMWR Morb Mortal Wkly Rep. 2005;  54 1201-1205
  Google Scholar
• 2 Anonymous. Clostridium difficile in England and Wales.  Comm Dis Rep Weekly. 2000;  10 135
  Google Scholar
• 3 Anonymus. Outbreak of Clostridium difficile infection in a hospital in south east England.  CDR weekly. 2005;  15
  Google Scholar
• 4 Bentley A H, Patel N B, Sidorczuk M. et al . Multicentre evaluation of a commercial test for the rapid diagnosis of Clostridium difficile-mediated antibiotic-associated diarrhoea.  Eur J Clin Microbiol Infect Dis. 1998;  17 788-790
  Google Scholar
• 5 Block C. The effect of Perasafe and sodium dichloroisocyanurate (NaDCC) against spores of Clostridium difficile and Bacillus atrophaeus on stainless steel and polyvinyl chloride surfaces.  J Hosp Infect. 2004;  57 144-148
  Google Scholar
• 6 Boyce J M. Using alcohol for hand antisepsis: dispelling old myths.  Infect Control Hosp Epidemiol. 2000;  21 438-441
  Google Scholar
• 7 Cohen S H, Tang Y J, Silva J. Analysis of the pathogenicity locus in Clostridium difficile strains.  J Infect Dis. 2000;  181 659-663
  Google Scholar
• 8 Dallal R M, Harbrecht B G, Boujoukas A J. et al . Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications.  Ann Surg. 2002;  235 363-372
  Google Scholar
• 9 Delmee M. Laboratory diagnosis of Clostridium difficile disease.  Clin Microbiol Infect. 2001;  7 411-416
  Google Scholar
• 10 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
  Google Scholar
• 11 George W L, Sutter V L, Citron D, Finegold S M. Selective and differential medium for isolation of Clostridium difficile.  J Clin Microbiol. 1979;  9 214-219
  Google Scholar
• 12 Geric B, Rupnik M, Gerding D N, 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
• 13 Goncalves C, Decre D, Barbut F, Burghoffer B, Petit J C. Prevalence and characterization of a binary toxin (actin-specific ADP-ribosyltransferase) from Clostridium difficile.  J Clin Microbiol. 2004;  42 1933-1939
  Google Scholar
• 14 Indra A, Huhulescu S, Hasenberger P. et al . First isolation of Clostridium difficile PCR ribotype 027 in Austria.  Euro Surveill. 2006;  11 (9) E060914.3
  Google Scholar
• 15 Joseph R, Demeyer D, Vanrenterghem D. et al . First isolation of Clostridium difficile PCR ribotype027, toxinotype III in Belgium.  Eurosurveillance weekly. 2005;  10 (10) E051020.4
  Google Scholar
• 16 Kuijper E J, Coignard B, Tull P. Emergence of Clostridium difficile-associated disease in North America and Europe.  Clin Microbiol Infect. 2006;  (Suppl 6) 12 2-18
  Google Scholar
• 17 Lai K K, Melvin Z S, Menard M J, Kotilainen H R, Baker S. Clostridium difficile-associated diarrhea: epidemiology, risk factors, and infection control.  Infect Control Hosp Epidemiol. 1997;  18 628-632
  Google Scholar
• 18 Larson E, Bobo L, Bennett R. et al . Lack of care giver hand contamination with endemic bacterial pathogens in a nursing home.  Am J Infect Control. 1992;  20 11-15
  Google Scholar
• 19 Loo V G, Poirier L, Miller M A. 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
• 20 McDonald L C, Brazier J. Oral presentations at the Clostridium difficile workshop at ECDC,. Stockholm, Sweden, January 24th 2006
  Google Scholar
• 21 McDonald L C, Killgore G E, Thompson A. et al . An epidemic, toxin gene-variant strain of Clostridium difficile.  N Engl J Med. 2005;  353 2433-2441
  Google Scholar
• 22 McDonald L C, Owings M, Jernigan D B. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996 - 2003.  Emerg Infect Dis. 2006;  12 409-415
  Google Scholar
• 23 McEllistrem M C, Carman R J, Gerding D N, Genheimer C W, Zheng L. A hospital outbreak of Clostridium difficile disease associated with isolates carrying binary toxin genes.  Clin Infect Dis. 2005;  40 265-272
  Google Scholar
• 24 McFarland L V, Mulligan M E, Kwok R Y, Stamm W E. Nosocomial acquisition of Clostridium difficile infection.  N Engl J Med. 1989;  320 204-210
  Google Scholar
• 25 Muto C A, 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
  Google Scholar
• 26 Noren T. Outbreak from a high-toxin intruder: Clostridium difficile.  Lancet. 2005;  366 1053-1054
  Google Scholar
• 27 Pear S M, Williamson T H, Bettin K M, Gerding D N, Galgiani J N. Decrease in nosocomial Clostridium difficile-associated diarrhea by restricting clindamycin use.  Ann Intern Med. 1994;  120 272-277
  Google Scholar
• 28 Pepin J, Saheb N, Coulombe M A. et al . Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec.  Clin Infect Dis. 2005;  41 1254-1260
  Google Scholar
• 29 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
• 30 Perez J, Springthorpe V S, Sattar S A. Activity of selected oxidizing microbicides against the spores of Clostridium difficile: relevance to environmental control.  Am J Infect Control. 2005;  33 320-325
  Google Scholar
• 31 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
  Google Scholar
• 32 Tachon M, Cattoen C, Blanckaert K. et al . First cluster of C. difficile toxinotype III, PCR-ribotype 027 associated disease in France: preliminary report.  Euro Surveill. 2006;  11 (5) E060504.1
  Google Scholar
• 33 Thomas C, Stevenson M, Riley T V. Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review.  J Antimicrob Chemother. 2003;  51 1339-1350
  Google Scholar
• 34 van Steenbergen J, Debast S B, Van Kregten E. et al . Isolation of Clostridium difficile ribotype 027, toxinotype III in the Netherlands after increase in C. difficile-associated diarrhoea.  Eurosurveillance weekly. 2005;  10 (7) E05714.1
  Google Scholar
• 35 Vonberg R, Schwab F, Gastmeier P. Clostridium difficile in discharged inpatients, Germany.  Emerg Infect Dis. 2007;  13 179-180
  Google Scholar
• 36 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
  Google Scholar
• 37 Wilcox M H, Fawley W N, Wigglesworth N. et al . Comparison of the effect of detergent versus hypochlorite cleaning on environmental contamination and incidence of Clostridium difficile infection.  J Hosp Infect. 2003;  54 109-114
  Google Scholar
• 38 Wistrom J, Norrby S R, Myhre E B. 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

Dr. med. Christiane Reichardt

Institut für Mirkobiologie, Arbeitsgruppe Krankenhaushygiene, Medizinische Hochschule Hannover

Carl-Neuberg-Straße 1

30625 Hannover

Phone: 0511/5329280

Fax: 0511/5328174

Email: reichardt.christiane@mh-hannover.de