Novel mechanisms of resistance to β-lactam antibiotics in Haemophilus parainfluenzae: β-lactamase-negative ampicillin resistance and inhibitor-resistant TEM β-lactamases

To determine the mechanisms of resistance to β-lactam antibiotics in clinical isolates of Haemophilus parainfluenzae. Twenty clinical isolates of H. parainfluenzae with decreased susceptibility to aminopenicillins were examined and compared with a control group of 20 fully susceptible isolates. In t...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2013-05, Vol.68 (5), p.1054-1059
Main Authors: García-Cobos, S, Arroyo, M, Campos, J, Pérez-Vázquez, M, Aracil, B, Cercenado, E, Orden, B, Lara, N, Oteo, J
Format: Article
Language:English
Subjects:
Ampicillin - pharmacology
Ampicillin Resistance
Anti-Bacterial Agents - pharmacology
beta-Lactamases - genetics
beta-Lactamases - secretion
DNA, Bacterial - chemistry
DNA, Bacterial - genetics
Genotype
Haemophilus Infections - microbiology
Haemophilus influenzae - drug effects
Haemophilus influenzae - enzymology
Haemophilus influenzae - isolation & purification
Humans
Microbial Sensitivity Tests
Penicillin-Binding Proteins - genetics
Polymerase Chain Reaction
Sequence Analysis, DNA
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Summary:To determine the mechanisms of resistance to β-lactam antibiotics in clinical isolates of Haemophilus parainfluenzae. Twenty clinical isolates of H. parainfluenzae with decreased susceptibility to aminopenicillins were examined and compared with a control group of 20 fully susceptible isolates. In this collection, the presence of amino acid substitutions in the transpeptidase domain of penicillin-binding protein 3 (PBP3), β-lactamase production and the surrounding genetic regions of blaTEM genes in selected isolates were analysed. Of the 20 non-susceptible isolates, 8 produced TEM β-lactamase (gBLPAR), 7 had mutations in the transpeptidase domain of the ftsI gene related to decreased susceptibility to β-lactams (gBLNAR) and 5 had both resistance mechanisms (gBLPACR). No resistance mechanisms were identified in the susceptible control group (gBLNAS). gBLNAR isolates had MIC90 values 4- to 16-fold higher than gBLNAS isolates for ampicillin, amoxicillin/clavulanic acid, cefuroxime, cefotaxime and cefixime, and the most common PBP3 mutation was Asn526Ser. The additional Ser385Thr substitution (III-like group) may confer decreased susceptibility to cefotaxime, cefixime and aztreonam, as in Haemophilus influenzae. In two β-lactamase-positive isolates without PBP3 mutations, the inhibitor-resistant TEM (IRT) β-lactamases TEM-34 and the novel TEM-182 were detected and carried by a TnA transposon of the Tn2 type; both isolates had an amoxicillin/clavulanic acid MIC of ≥8 mg/L. The TnA transposons of two β-lactamase-positive isolates (TEM-1 and TEM-182) were inserted between the tfc20 and tfc21 genes, typically associated with integrative and conjugative elements in Haemophilus spp.; the TEM-34 IRT β-lactamase was harboured in a ∼5.5 kb plasmid. Clinical isolates of H. parainfluenzae express a variety of aminopenicillin resistance mechanisms, either alone or in combination, including PBP3 modifications, blaTEM-1 and IRT β-lactamase production.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dks525