Clinical Trial: The Burden and Genetic Variability of Extended-Spectrum ß-Lactamase (ESBL) - Producing Pathogens in Swiss Children

Study Status: Completed
Recruit Status: Unknown status
Study Type: Observational

Official Title: Epidemiology of Extended-spectrum ß-lactamase (ESBL)-Producing Enteric Gram-negative Bacilli in Swiss Children

Brief Summary:

Objectives:

The aim of the study is to determine the molecular epidemiology and genetic variability of ESBL-producing enterobacteriaceae (E-ESBL) among children in Switzerland and to estimate the associated clinical burden of disease.

The investigators' hypotheses are:

  1. The genetic variability (and especially the distribution of strains harbouring the CTX-M genes) among children is similar to that observed in adults;
  2. The overall burden of disease is still low in Switzerland compared to neighbouring countries. However, treatment of severe E-ESBL infections is challenging;
  3. The recommended oral treatment procedure with 3rd generation cephalosporins for febrile urinary tract infection may contribute to increased prevalence of E-ESBL in the long term.

The study is scheduled to start July 1st, 2008, and end June 30th, 2010.


Detailed Summary:

Background & Rationale:

Increasing resistance to antibiotics is a growing problem in public health and is associated with treatment failures, increased health care costs, and prolonged hospital stays. Over the past years, one mechanism of resistance has been of particular concern: ESBL, which is produced mainly by Escherichia coli and Klebsiella species but also found in other gram negative bacteria. ESBLs are plasmid-encoded ß-lactamases conferring resistance to penicillins, cephalosporins and aztreonam.

ESBL-producing enterobacteria are usually susceptible to carbapenems, such as ertapenem, imipenem or meropenem. Thus, treatment with carbapenems remains safe if the presence of ESBL is recognized. However, the confirmation of ESBL is not always a routine procedure in all laboratories. Furthermore, ESBL strains with high resistance to ertapenem and decreased activity to imipenem and meropenem have already been described. The mechanism among these strains however, appears to be a combination of the expression of ESBL and impermeability or increased efflux for carbapenems. Infection with ESBL-producing E. coli or K. pneumoniae is potentially hazardous for patients. Mortality is significantly higher following a bloodstream infection caused by ESBL producing E. coli compared to non-ESBL producing strains.

ESBLs are encoded on plasmids: classically, these plasmid mediated enzymes have been of the TEM and SHV type. However, in recent years CTX-M-type ESBLs have been increasingly identified worldwide throughout the world. CTX-M enzymes predominantly hydrolyze cefotaxime, but are weakly active against ceftazidime. However, some ESBLs of the CTX-M family also display increased hydrolytic activities against ceftazidime, as is the case for CTXM-15 and CTX-M-32.

Same as current

Current Secondary Outcome: Genetic variability (and especially the distribution of strains harbouring the CTX-M genes) among Swiss children [ Time Frame: 2 years ]

Original Secondary Outcome: Same as current

Information By: University Hospital, Geneva

Dates:
Date Received: May 4, 2009
Date Started: July 2008
Date Completion: December 2010
Last Updated: September 24, 2009
Last Verified: May 2009