High-Level Carbapenem Resistance among OXA-48-Producing <i>Klebsiella</i><i>pneumoniae</i> with Functional OmpK36 Alterations: Maintenance of Ceftazidime/Avibactam Susceptibility
The aim of this work was to analyze outer membrane porin-encoding genes (<i>ompK35</i> and <i>ompK36</i>) in a collection of OXA-48 producing <i>Klebsiella pneumoniae</i>, to assess the effect of porin alterations on the susceptibility to ceftazidime/avibactam, an...
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| Main Authors: | , , , , |
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| Format: | Book |
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MDPI AG,
2021-09-01T00:00:00Z.
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| Summary: | The aim of this work was to analyze outer membrane porin-encoding genes (<i>ompK35</i> and <i>ompK36</i>) in a collection of OXA-48 producing <i>Klebsiella pneumoniae</i>, to assess the effect of porin alterations on the susceptibility to ceftazidime/avibactam, and to describe a screening methodology for phenotypic detection of OXA-48-producing <i>K. pneumoniae</i> with disrupted porins. Antimicrobial susceptibility was tested by Microscan and Etest. The genomes of 81 OXA-48-producing <i>K. pneumoniae</i> were sequenced. MLST, detection of antimicrobial resistance genes, and analysis of <i>ompK35</i> and <i>ompK36</i> were performed <i>in silico</i>. Tridimensional structures of the OmpK36 variants were assessed. Receiver operating characteristics curves were built to visualize the performance ability of a disk diffusion assay using carbapenems and cefoxitin to detect OmpK36 functional alterations. A wide variety of OmpK36 alterations were detected in 17 OXA-48-producing <i>K. pneumoniae</i> isolates. All displayed a high-level meropenem resistance (MIC ≥ 8 mg/L), and some belonged to high-risk clones, such as ST15 and ST147. Alterations in <i>ompK35</i> were also observed, but they did not correlate with high-level meropenem resistance. All isolates were susceptible to ceftazidime/avibactam and porin alterations did not affect the MICs of the latter combination. Cefoxitin together with ertapenem/meropenem low inhibition zone diameters (equal or lower than 16 mm) could strongly suggest alterations affecting OmpK36 in OXA-48-producing <i>K. pneumoniae</i>. OXA-48-producing <i>K. pneumoniae</i> with porin disruptions are a cause of concern; ceftazidime/avibactam showed good <i>in vitro</i> activity against them, so this combination could be positioned as the choice therapy to combat the infections caused by this difficult-to-treat isolates. |
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| Item Description: | 10.3390/antibiotics10101174 2079-6382 |