In Vitro Selection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases
- 1 May 2017
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 61 (5)
- https://doi.org/10.1128/aac.00079-17
Abstract
Ceftazidime-avibactam resistance is mediated by bla KPC-3 mutations, which restore carbapenem susceptibility. We subjected Klebsiella pneumoniae isolates with different bla KPC-3 mutations ( n = 5) or wild-type bla KPC-3 ( n = 2) to serial passages with meropenem. The meropenem MIC against each isolate increased. Mutations in the ompK36 porin gene evolved in 5 isolates. Among isolates with D179Y substitutions in KPC-3, bla KPC-3 mutations reverted to wild type, were replaced by new mutations, or were retained. Carbapenem treatment of ceftazidime-avibactam-resistant K. pneumoniae infections may select for carbapenem resistance.Keywords
Funding Information
- HHS | NIH | NIH Clinical Center (K08AI114883)
- HHS | NIH | NIH Clinical Center (R21AI117338)
- HHS | NIH | NIH Clinical Center (R01AI090155)
- HHS | NIH | NIH Clinical Center (R21AI128338)
- HHS | NIH | NIH Clinical Center (R21AI111037)
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