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Activity of faropenem against cephalosporin-resistant Enterobacteriaceae
Shazad Mushtaq1, Russell Hope, Marina Warner
1Antibiotic Resistance Monitoring and Reference Laboratory, Health Protection Agency Centre for Infections, London NW9 5EQ, UK.
Background:
There is a need for new oral agents active against extended-spectrum beta-lactamase (ESBL) producers, as these increasingly cause community-onset infections. We therefore evaluated faropenem, a penem in Phase III development, against recently collected oxyimino-cephalosporin-resistant bacteria.
Methods:
We tested 847 consecutive cephalosporin-resistant Enterobacteriaceae collected at 16 centres in South-East England in 2004, 501 of them with CTX-M enzymes; we also tested reference strains and transconjugants with acquired beta-lactamases and various modes of AmpC expression. MICs were determined by the BSAC agar dilution method.
Results:
Modal MICs of faropenem for Escherichia coli or Klebsiella spp. with CTX-M or non-CTX-M ESBLs or high-level AmpC enzyme were 0.5-1 mg/L, with over 95% of producers susceptible to
Conclusions:
Faropenem has good activity against E. coli and Klebsiella spp. with ESBLs, including the CTX-M types now proliferating in Europe, but was less active against AmpC-derepressed and ESBL-producing Enterobacter spp. Its clinical utility will depend on levels achieved in the urinary tract, the site of most of the community infections caused by ESBL producers, and more work is needed in this area.
Insights
Faropenem shows good activity against common extended-spectrum beta-lactamase (ESBL) producing E. coli and Klebsiella, but less so against Enterobacter spp. Further research is needed to determine its clinical utility, especially for urinary tract infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Rising prevalence of community-onset infections caused by extended-spectrum beta-lactamase (ESBL) producers necessitates novel oral antimicrobial agents.
- Faropenem, a penem antibiotic in Phase III development, is being evaluated for its efficacy against resistant bacteria.
Purpose of the Study:
- To assess the in vitro activity of faropenem against a collection of recently isolated oxyimino-cephalosporin-resistant Enterobacteriaceae.
- To evaluate faropenem's effectiveness against various beta-lactamase expression mechanisms, including CTX-M enzymes and AmpC hyperproduction.
Main Methods:
- Testing of 847 consecutive cephalosporin-resistant Enterobacteriaceae isolates from South-East England (2004).
- Inclusion of strains with specific beta-lactamases (CTX-M, AmpC) and reference strains.
- Determination of Minimum Inhibitory Concentrations (MICs) using the BSAC agar dilution method.
Main Results:
- Faropenem exhibited modal MICs of 0.5-1 mg/L against Escherichia coli and Klebsiella spp. producing CTX-M or non-CTX-M ESBLs, with >95% susceptibility at ≤2 mg/L.
- Against ESBL-producing or AmpC-derepressed Enterobacter and Citrobacter spp., modal MICs were 2-4 mg/L, with a small percentage requiring higher concentrations (up to 16 mg/L).
- NMC-A and IMP carbapenemases were the only beta-lactamases tested that significantly increased faropenem MICs.
Conclusions:
- Faropenem demonstrates promising activity against ESBL-producing E. coli and Klebsiella spp., including prevalent CTX-M types.
- Activity was reduced against AmpC-derepressed and ESBL-producing Enterobacter spp.
- Clinical utility, particularly for urinary tract infections, requires further investigation regarding achievable drug levels.
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