What Contributes to the Minimum Inhibitory Concentration? Beyond β-Lactamase Gene Detection in Klebsiella pneumoniae
Abstract Background Klebsiella pneumoniae is capable of resistance to β-lactam antibiotics through expression of β-lactamases (both chromosomal and plasmid-encoded) and downregulation of outer membrane porins. However, the extent to which these mechanisms interplay in a resistant phenotype is not we...
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Veröffentlicht in: | The Journal of infectious diseases 2024-10, Vol.230 (4), p.e777-e788 |
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Zusammenfassung: | Abstract
Background
Klebsiella pneumoniae is capable of resistance to β-lactam antibiotics through expression of β-lactamases (both chromosomal and plasmid-encoded) and downregulation of outer membrane porins. However, the extent to which these mechanisms interplay in a resistant phenotype is not well understood. The purpose of this study was to determine the extent to which β-lactamases and outer membrane porins affected β-lactam resistance.
Methods
Minimum inhibitory concentrations (MICs) to β-lactams and inhibitor combinations were determined by agar dilution or Etest. Outer membrane porin production was evaluated by Western blot of outer membrane fractions. β-lactamase carriage was determined by whole genome sequencing and expression evaluated by real-time reverse-transcription polymerase chain reaction.
Results
Plasmid-encoded β-lactamases were important for cefotaxime and ceftazidime resistance. Elevated expression of chromosomal SHV was important for ceftolozane-tazobactam resistance. Loss of outer membrane porins was predictive of meropenem resistance. Extended-spectrum β-lactamases and plasmid-encoded AmpCs (pAmpCs) in addition to porin loss were sufficient to confer resistance to the third-generation cephalosporins, piperacillin-tazobactam, ceftolozane-tazobactam, and meropenem. pAmpCs (CMY-2 and DHA) alone conferred resistance to piperacillin-tazobactam.
Conclusions
Detection of a resistance gene by whole genome sequencing was not sufficient to predict resistance to all antibiotics tested. Some β-lactam resistance was dependent on the expression of both plasmid-encoded and chromosomal β-lactamases and loss of porins.
β-lactamases are the major resistance mechanism associated with β-lactam resistance. However, chromosomal β-lactamases and porins are important resistance mechanisms that contribute to the minimum inhibitory concentration (MIC). This article identifies the interplay among chromosomal and plasmid-encoded mechanisms and their contribution to the MIC.
Graphical Abstract
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ISSN: | 0022-1899 1537-6613 1537-6613 |
DOI: | 10.1093/infdis/jiae204 |