Journal Article

Contribution of β-lactamase and PBP amino acid substitutions to amoxicillin/clavulanate resistance in β-lactamase-positive, amoxicillin/clavulanate-resistant <i>Haemophilus influenzae</i>

Vlatka Matic, Bülent Bozdogan, Michael R. Jacobs, Kimiko Ubukata and Peter C. Appelbaum

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 52, issue 6, pages 1018-1021
Published in print December 2003 | ISSN: 0305-7453
Published online December 2003 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkg474
Contribution of β-lactamase and PBP amino acid substitutions to amoxicillin/clavulanate resistance in β-lactamase-positive,  amoxicillin/clavulanate-resistant Haemophilus influenzae

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The roles of β-lactamase and alterations in penicillin-binding protein in the development of amoxicillin and amoxicillin/clavulanate resistance in two β-lactamase-positive, amoxicillin/clavulanate-resistant (BLPACR) strains of Haemophilus influenzae were investigated. Seven β-lactamase-negative, ampicillin-resistant (BLNAR) strains were also studied for comparison of their resistance mechanisms. All strains had been recovered from patients in Japan. The TEM type β-lactamase of the two BLPACR strains had 100% homology with the amino acid sequences of published TEM-1 β-lactamase, showing that amoxicillin/clavulanate resistance was not associated with mutations in this β-lactamase. However, these strains, as well as the seven BLNAR strains, had multiple mutations in ftsI, which encodes penicillin binding protein 3 (PBP3). The transformation of H. influenzae Rd strain with amplified ftsI genes from two BLPACR and two BLNAR strains enabled the selection of amoxicillin/clavulanate-resistant transformants with the same mutations as their parent strains. We concluded that amoxicillin/clavulanate resistance in the two BLPACR strains was due to changes in PBP3. The possibility of the presence of an extended spectrum β-lactamase was excluded in the BLPACR strains studied.

Keywords: Keywords: H. influenzae, penicillin-binding proteins, β-lactamases, mutations

Journal Article.  1756 words. 

Subjects: Medical Oncology ; Critical Care

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