Loss of OmpK35 and Glycine-aspartic acid Duplication in ompK36 Negatively Affect the in vitro Synergy of Meropenem in Combination with Piperacillin/tazobactam or Imipenem Against OXA-48-like Carbapenemase-producing Klebsiella pneumoniae
BACKGROUND-AIM: Although ceftazidime/avibactam is the agent of choice in OXA-48-producing Klebsiella pneumoniae infections, it is not readily available or prohibitively expensive in many countries. Since piperacillin/tazobactam plus meropenem combination was recently reported as highly synergistic a...
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Elsevier
2024-12-01
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| Series: | Journal of Global Antimicrobial Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716524001966 |
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| author | Abdullah Tarik Aslan Mervenur Demir Elif Seren Tanriverdi Budi Permana Rhys Izuagbe Kay A. Ramsay Brian Forde Baris Otlu David L. Paterson Patrick Harris Murat Akova Gulsen Hazirolan |
| author_facet | Abdullah Tarik Aslan Mervenur Demir Elif Seren Tanriverdi Budi Permana Rhys Izuagbe Kay A. Ramsay Brian Forde Baris Otlu David L. Paterson Patrick Harris Murat Akova Gulsen Hazirolan |
| author_sort | Abdullah Tarik Aslan |
| collection | DOAJ |
| description | BACKGROUND-AIM: Although ceftazidime/avibactam is the agent of choice in OXA-48-producing Klebsiella pneumoniae infections, it is not readily available or prohibitively expensive in many countries. Since piperacillin/tazobactam plus meropenem combination was recently reported as highly synergistic against OXA-48-producing K. pneumoniae, we aimed to test in vitro synergy between piperacillin/tazobactam and meropenem against these isolates having a range of meropenem minimum inhibitory concentration (MIC) values. METHODS: Time-kill assays were performed in duplicate against 17 carbapenemase-producing K. pneumoniae isolates (OXA-48, n= 7; OXA-232, n= 6; NDM-1, n= 3; OXA-48 + NDM-1, n= 1) and 2 non-carbapenemase-producing K. pneumoniae isolates with a glycine-aspartic acid (GD) duplication in ompK36. Antibiotic concentrations simulated the clinically attainable concentrations in critically ill patients. RESULTS: The piperacillin/tazobactam plus meropenem and imipenem plus meropenem combinations were synergistic against 30.8% (4/13) and 46.2% (6/13) of OXA-48-like carbapenemase producers, respectively (P= 0.5). Among isolates with low meropenem MIC (1-2 mg/L), the synergy rate between piperacillin/tazobactam and meropenem was significantly higher than in those with meropenem MIC ≥16 mg/L (75% vs 11%; P= 0.05). Such a significant interaction was not observed between meropenem and imipenem (75% vs 33%, P= 0.26). The in vitro synergy in both combinations were negatively impacted by mutations in either or both ompK35 and ompK36 genes (piperacillin/tazobactam plus meropenem: 1/10 [10%] vs 3/3 [100%]; P= 0.014; imipenem plus meropenem: 3/10 [30%] vs 3/3 [100%] P= 0.070). CONCLUSIONS: The absence of OmpK35 and GD duplication in ompK36 hamper the synergy between piperacillin/tazobactam and meropenem against OXA-48-like carbapenemase-producing K. pneumoniae. |
| format | Article |
| id | doaj-art-e78aacbe91d747ac8dfdd12dca5ee0f6 |
| institution | DOAJ |
| issn | 2213-7165 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj-art-e78aacbe91d747ac8dfdd12dca5ee0f62025-08-20T02:55:57ZengElsevierJournal of Global Antimicrobial Resistance2213-71652024-12-0139710.1016/j.jgar.2024.10.019Loss of OmpK35 and Glycine-aspartic acid Duplication in ompK36 Negatively Affect the in vitro Synergy of Meropenem in Combination with Piperacillin/tazobactam or Imipenem Against OXA-48-like Carbapenemase-producing Klebsiella pneumoniaeAbdullah Tarik Aslan0Mervenur Demir1Elif Seren Tanriverdi2Budi Permana3Rhys Izuagbe4Kay A. Ramsay5Brian Forde6Baris Otlu7David L. Paterson8Patrick Harris9Murat Akova10Gulsen Hazirolan11The University of Queensland, Faculty of Medicine, UQ Centre for Clinical Research, Brisbane, AustraliaHacettepe University, Faculty of Medicine, Medical Microbiology, Ankara, TürkiyeInonu University, Faculty of Medicine, Medical Microbiology, Malatya, TürkiyeThe University of Queensland, Faculty of Medicine, UQ Centre for Clinical Research, Brisbane, AustraliaThe University of Queensland, Faculty of Medicine, UQ Centre for Clinical Research, Brisbane, AustraliaThe University of Queensland, Faculty of Medicine, UQ Centre for Clinical Research, Brisbane, AustraliaThe University of Queensland, Faculty of Medicine, UQ Centre for Clinical Research, Brisbane, AustraliaInonu University, Faculty of Medicine, Medical Microbiology, Malatya, TürkiyeADVANCE-ID, Saw Swee Hock School of Public Health, National University of Singapore, SingaporeThe University of Queensland, Faculty of Medicine, UQ Centre for Clinical Research, Brisbane, AustraliaHacettepe University, Faculty of Medicine, Infectious Diseases and Clinical Microbiology, Ankara, TürkiyeHacettepe University, Faculty of Medicine, Medical Microbiology, Ankara, TürkiyeBACKGROUND-AIM: Although ceftazidime/avibactam is the agent of choice in OXA-48-producing Klebsiella pneumoniae infections, it is not readily available or prohibitively expensive in many countries. Since piperacillin/tazobactam plus meropenem combination was recently reported as highly synergistic against OXA-48-producing K. pneumoniae, we aimed to test in vitro synergy between piperacillin/tazobactam and meropenem against these isolates having a range of meropenem minimum inhibitory concentration (MIC) values. METHODS: Time-kill assays were performed in duplicate against 17 carbapenemase-producing K. pneumoniae isolates (OXA-48, n= 7; OXA-232, n= 6; NDM-1, n= 3; OXA-48 + NDM-1, n= 1) and 2 non-carbapenemase-producing K. pneumoniae isolates with a glycine-aspartic acid (GD) duplication in ompK36. Antibiotic concentrations simulated the clinically attainable concentrations in critically ill patients. RESULTS: The piperacillin/tazobactam plus meropenem and imipenem plus meropenem combinations were synergistic against 30.8% (4/13) and 46.2% (6/13) of OXA-48-like carbapenemase producers, respectively (P= 0.5). Among isolates with low meropenem MIC (1-2 mg/L), the synergy rate between piperacillin/tazobactam and meropenem was significantly higher than in those with meropenem MIC ≥16 mg/L (75% vs 11%; P= 0.05). Such a significant interaction was not observed between meropenem and imipenem (75% vs 33%, P= 0.26). The in vitro synergy in both combinations were negatively impacted by mutations in either or both ompK35 and ompK36 genes (piperacillin/tazobactam plus meropenem: 1/10 [10%] vs 3/3 [100%]; P= 0.014; imipenem plus meropenem: 3/10 [30%] vs 3/3 [100%] P= 0.070). CONCLUSIONS: The absence of OmpK35 and GD duplication in ompK36 hamper the synergy between piperacillin/tazobactam and meropenem against OXA-48-like carbapenemase-producing K. pneumoniae.http://www.sciencedirect.com/science/article/pii/S2213716524001966Synergyin vitroOXA-48Klebsiella pneumoniae |
| spellingShingle | Abdullah Tarik Aslan Mervenur Demir Elif Seren Tanriverdi Budi Permana Rhys Izuagbe Kay A. Ramsay Brian Forde Baris Otlu David L. Paterson Patrick Harris Murat Akova Gulsen Hazirolan Loss of OmpK35 and Glycine-aspartic acid Duplication in ompK36 Negatively Affect the in vitro Synergy of Meropenem in Combination with Piperacillin/tazobactam or Imipenem Against OXA-48-like Carbapenemase-producing Klebsiella pneumoniae Journal of Global Antimicrobial Resistance Synergy in vitro OXA-48 Klebsiella pneumoniae |
| title | Loss of OmpK35 and Glycine-aspartic acid Duplication in ompK36 Negatively Affect the in vitro Synergy of Meropenem in Combination with Piperacillin/tazobactam or Imipenem Against OXA-48-like Carbapenemase-producing Klebsiella pneumoniae |
| title_full | Loss of OmpK35 and Glycine-aspartic acid Duplication in ompK36 Negatively Affect the in vitro Synergy of Meropenem in Combination with Piperacillin/tazobactam or Imipenem Against OXA-48-like Carbapenemase-producing Klebsiella pneumoniae |
| title_fullStr | Loss of OmpK35 and Glycine-aspartic acid Duplication in ompK36 Negatively Affect the in vitro Synergy of Meropenem in Combination with Piperacillin/tazobactam or Imipenem Against OXA-48-like Carbapenemase-producing Klebsiella pneumoniae |
| title_full_unstemmed | Loss of OmpK35 and Glycine-aspartic acid Duplication in ompK36 Negatively Affect the in vitro Synergy of Meropenem in Combination with Piperacillin/tazobactam or Imipenem Against OXA-48-like Carbapenemase-producing Klebsiella pneumoniae |
| title_short | Loss of OmpK35 and Glycine-aspartic acid Duplication in ompK36 Negatively Affect the in vitro Synergy of Meropenem in Combination with Piperacillin/tazobactam or Imipenem Against OXA-48-like Carbapenemase-producing Klebsiella pneumoniae |
| title_sort | loss of ompk35 and glycine aspartic acid duplication in ompk36 negatively affect the in vitro synergy of meropenem in combination with piperacillin tazobactam or imipenem against oxa 48 like carbapenemase producing klebsiella pneumoniae |
| topic | Synergy in vitro OXA-48 Klebsiella pneumoniae |
| url | http://www.sciencedirect.com/science/article/pii/S2213716524001966 |
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