Effect of cloned inhibitor-resistant TEM beta-lactamases on the susceptibility of Haemophilus influenzae to amoxicillin/clavulanate

J Antimicrob Chemother. 2007 Nov;60(5):1151-4. doi: 10.1093/jac/dkm311. Epub 2007 Sep 6.

Abstract

Objectives: To determine the effect of cloned inhibitor-resistant TEM beta-lactamases (IRTs) on the susceptibility of Haemophilus influenzae to amoxicillin/clavulanate.

Methods: IRT-2, -4 and -5 genes with various promoters were cloned into control strains of H. influenzae and the amoxicillin/clavulanate MICs were measured using Etests.

Results: IRT enzymes were able to raise the amoxicillin/clavulanate MICs to between 0.38/0.19 and 4.0/2.0 mg/L depending on the IRT and promoter genotype, compared with MICs of 0.19/0.09 to 0.5/0.25 mg/L for the corresponding strains with TEM-1. Strains with an IRT and altered penicillin-binding proteins had amoxicillin/clavulanate MICs as high as 8.0/4.0 mg/L.

Conclusions: Cloned IRT enzymes in H. influenzae raise the amoxicillin/clavulanate MICs to an extent comparable to naturally occurring strains with decreased amoxicillin/clavulanate susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amoxicillin-Potassium Clavulanate Combination / pharmacology*
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cloning, Molecular
  • Drug Resistance, Multiple, Bacterial
  • Haemophilus influenzae / drug effects
  • Haemophilus influenzae / enzymology*
  • Haemophilus influenzae / genetics*
  • Microbial Sensitivity Tests
  • Mutation
  • Promoter Regions, Genetic / genetics
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / genetics*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • beta-Lactamase Inhibitors
  • Amoxicillin-Potassium Clavulanate Combination
  • beta-Lactamases