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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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/10/1174 |
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| author | Pilar Lumbreras-Iglesias María Rosario Rodicio Pablo Valledor Tomás Suárez-Zarracina Javier Fernández |
| author_facet | Pilar Lumbreras-Iglesias María Rosario Rodicio Pablo Valledor Tomás Suárez-Zarracina Javier Fernández |
| author_sort | Pilar Lumbreras-Iglesias |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T06:46:12Z |
| format | Article |
| id | doaj.art-54448d1e8ed94fe6914dff2b9426f7ea |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T06:46:12Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-54448d1e8ed94fe6914dff2b9426f7ea2023-11-22T17:13:12ZengMDPI AGAntibiotics2079-63822021-09-011010117410.3390/antibiotics10101174High-Level Carbapenem Resistance among OXA-48-Producing <i>Klebsiella</i><i>pneumoniae</i> with Functional OmpK36 Alterations: Maintenance of Ceftazidime/Avibactam SusceptibilityPilar Lumbreras-Iglesias0María Rosario Rodicio1Pablo Valledor2Tomás Suárez-Zarracina3Javier Fernández4Department of Clinical Microbiology, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainTraslational Microbiology Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, SpainResearch & Innovation, Artificial Intelligence and Statistical Department, Pragmatech AI Solutions, 33003 Oviedo, SpainDepartment of Internal Medicine, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainDepartment of Clinical Microbiology, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainThe 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.https://www.mdpi.com/2079-6382/10/10/1174<i>K. pneumoniae</i>carbapenem resistanceOXA-48porinsceftazidime/avibactam |
| spellingShingle | Pilar Lumbreras-Iglesias María Rosario Rodicio Pablo Valledor Tomás Suárez-Zarracina Javier Fernández High-Level Carbapenem Resistance among OXA-48-Producing <i>Klebsiella</i><i>pneumoniae</i> with Functional OmpK36 Alterations: Maintenance of Ceftazidime/Avibactam Susceptibility Antibiotics <i>K. pneumoniae</i> carbapenem resistance OXA-48 porins ceftazidime/avibactam |
| title | High-Level Carbapenem Resistance among OXA-48-Producing <i>Klebsiella</i><i>pneumoniae</i> with Functional OmpK36 Alterations: Maintenance of Ceftazidime/Avibactam Susceptibility |
| title_full | High-Level Carbapenem Resistance among OXA-48-Producing <i>Klebsiella</i><i>pneumoniae</i> with Functional OmpK36 Alterations: Maintenance of Ceftazidime/Avibactam Susceptibility |
| title_fullStr | High-Level Carbapenem Resistance among OXA-48-Producing <i>Klebsiella</i><i>pneumoniae</i> with Functional OmpK36 Alterations: Maintenance of Ceftazidime/Avibactam Susceptibility |
| title_full_unstemmed | High-Level Carbapenem Resistance among OXA-48-Producing <i>Klebsiella</i><i>pneumoniae</i> with Functional OmpK36 Alterations: Maintenance of Ceftazidime/Avibactam Susceptibility |
| title_short | High-Level Carbapenem Resistance among OXA-48-Producing <i>Klebsiella</i><i>pneumoniae</i> with Functional OmpK36 Alterations: Maintenance of Ceftazidime/Avibactam Susceptibility |
| title_sort | high level carbapenem resistance among oxa 48 producing i klebsiella i i pneumoniae i with functional ompk36 alterations maintenance of ceftazidime avibactam susceptibility |
| topic | <i>K. pneumoniae</i> carbapenem resistance OXA-48 porins ceftazidime/avibactam |
| url | https://www.mdpi.com/2079-6382/10/10/1174 |
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