Effect of cloned inhibitor-resistant TEM beta-lactamases on the susceptibility of Haemophilus influenzae to amoxicillin/clavulanate.
OBJECTIVE
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.
Tristram
Stephen G
SG
School of Human Life Sciences, University of Tasmania, Launceston, Tasmania 7250, Australia. stephen.tristram@utas.edu.au
Burdach
Jonathan G
JG
D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D024901:Drug Resistance, Multiple, Bacterial; D006193:Haemophilus influenzae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics*