The in vitro Activity of Omadacycline Alone and in Combination Against Carbapenem-Resistant Klebsiella pneumoniae
Yingying Du,1– 3,* Yan Liu,4,* Tong Liu,1 Fen Pan,5 Shikui Mu,2 Yunlou Zhu,2 Hanlu Gao,2 Xin Jing,2 Xing Wang,6 Yuhao Liu,2 Sheng Wang1– 3 1Intensive Care Medical Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China; 2Department...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2024-12-01
|
| Series: | Infection and Drug Resistance |
| Subjects: | |
| Online Access: | https://www.dovepress.com/the-in-vitro-activity-of-omadacycline-alone-and-in-combination-against-peer-reviewed-fulltext-article-IDR |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850051084661293056 |
|---|---|
| author | Du Y Liu Y Liu T Pan F Mu S Zhu Y Gao H Jing X Wang X Liu Y Wang S |
| author_facet | Du Y Liu Y Liu T Pan F Mu S Zhu Y Gao H Jing X Wang X Liu Y Wang S |
| author_sort | Du Y |
| collection | DOAJ |
| description | Yingying Du,1– 3,* Yan Liu,4,* Tong Liu,1 Fen Pan,5 Shikui Mu,2 Yunlou Zhu,2 Hanlu Gao,2 Xin Jing,2 Xing Wang,6 Yuhao Liu,2 Sheng Wang1– 3 1Intensive Care Medical Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China; 2Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 3Key Laboratory of Pathogen-Host Interaction, Ministry of Education, Shanghai, 200092, People’s Republic of China; 4Department of Clinical Microbiology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 5Department of Laboratory Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 200032, People’s Republic of China; 6Department of Laboratory Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuhao Liu; Sheng Wang, Email lyh-7906@163.com; wangsheng@tongji.edu.cnObjective: This study aimed to evaluate the in vitro activity of omadacycline (OMC) and OMC-based combination therapy against carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods: The broth microdilution assay assessed the in vitro susceptibility of CRKP to OMC. The checkerboard assay was performed to evaluate the activity of OMC combined with polymyxin B (PB), amikacin (AN), or meropenem (MEM) against KPC-producing (class A) CRKP strains, and OMC combined with PB, aztreonam (ATM), MEM, or AN against class B and class A plus class B CRKP strains. Synergistic effects of OMC and PB were further evaluated by time-kill assays in the KPC-producing CRKP strains.Results: Broth microdilution assays revealed a notable variation in susceptibility between KPC-producing and class B CRKP strains, with MIC50/90 of 32/32 mg/L and 0.5/8 mg/L, respectively. Although KPC-producing CRKP strains were resistant to OMC, a synergistic effect was observed in 37.5% of KPC-producing CRKP strains when OMC was combined with PB. In the nine KPC-producing CRKP strains, time-kill assays found that cell densities of six strains (66.7%) decreased by 3.61 ± 0.23 log10 CFU/mL compared to the initial inoculum after 2 hours of PB exposure. The cell densities further decreased by an average of 2.38 ± 0.23 log10 CFU/mL when the six strains were exposed to OMC plus PB, confirming their potent synergism.Conclusion: OMC monotherapy is ineffective against KPC-producing CRKP strains, but OMC plus PB has a potent synergistic effect on them, suggesting that OMC plus PB is the preferred combination therapy against KPC-producing CRKP in vitro.Keywords: Klebsiella pneumoniae, carbapenem resistance, omadacycline, polymyxin B, antibiotic combination treatment, time-kill test |
| format | Article |
| id | doaj-art-8529e7160d8546eb8f63a9d348cbad59 |
| institution | DOAJ |
| issn | 1178-6973 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Infection and Drug Resistance |
| spelling | doaj-art-8529e7160d8546eb8f63a9d348cbad592025-08-20T02:53:16ZengDove Medical PressInfection and Drug Resistance1178-69732024-12-01Volume 175785579498660The in vitro Activity of Omadacycline Alone and in Combination Against Carbapenem-Resistant Klebsiella pneumoniaeDu YLiu YLiu TPan FMu SZhu YGao HJing XWang XLiu YWang SYingying Du,1– 3,* Yan Liu,4,* Tong Liu,1 Fen Pan,5 Shikui Mu,2 Yunlou Zhu,2 Hanlu Gao,2 Xin Jing,2 Xing Wang,6 Yuhao Liu,2 Sheng Wang1– 3 1Intensive Care Medical Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China; 2Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 3Key Laboratory of Pathogen-Host Interaction, Ministry of Education, Shanghai, 200092, People’s Republic of China; 4Department of Clinical Microbiology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 5Department of Laboratory Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 200032, People’s Republic of China; 6Department of Laboratory Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuhao Liu; Sheng Wang, Email lyh-7906@163.com; wangsheng@tongji.edu.cnObjective: This study aimed to evaluate the in vitro activity of omadacycline (OMC) and OMC-based combination therapy against carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods: The broth microdilution assay assessed the in vitro susceptibility of CRKP to OMC. The checkerboard assay was performed to evaluate the activity of OMC combined with polymyxin B (PB), amikacin (AN), or meropenem (MEM) against KPC-producing (class A) CRKP strains, and OMC combined with PB, aztreonam (ATM), MEM, or AN against class B and class A plus class B CRKP strains. Synergistic effects of OMC and PB were further evaluated by time-kill assays in the KPC-producing CRKP strains.Results: Broth microdilution assays revealed a notable variation in susceptibility between KPC-producing and class B CRKP strains, with MIC50/90 of 32/32 mg/L and 0.5/8 mg/L, respectively. Although KPC-producing CRKP strains were resistant to OMC, a synergistic effect was observed in 37.5% of KPC-producing CRKP strains when OMC was combined with PB. In the nine KPC-producing CRKP strains, time-kill assays found that cell densities of six strains (66.7%) decreased by 3.61 ± 0.23 log10 CFU/mL compared to the initial inoculum after 2 hours of PB exposure. The cell densities further decreased by an average of 2.38 ± 0.23 log10 CFU/mL when the six strains were exposed to OMC plus PB, confirming their potent synergism.Conclusion: OMC monotherapy is ineffective against KPC-producing CRKP strains, but OMC plus PB has a potent synergistic effect on them, suggesting that OMC plus PB is the preferred combination therapy against KPC-producing CRKP in vitro.Keywords: Klebsiella pneumoniae, carbapenem resistance, omadacycline, polymyxin B, antibiotic combination treatment, time-kill testhttps://www.dovepress.com/the-in-vitro-activity-of-omadacycline-alone-and-in-combination-against-peer-reviewed-fulltext-article-IDRklebsiella pneumoniaecarbapenem resistanceomadacyclinepolymyxin bantibiotic combination treatmenttime-kill test. |
| spellingShingle | Du Y Liu Y Liu T Pan F Mu S Zhu Y Gao H Jing X Wang X Liu Y Wang S The in vitro Activity of Omadacycline Alone and in Combination Against Carbapenem-Resistant Klebsiella pneumoniae Infection and Drug Resistance klebsiella pneumoniae carbapenem resistance omadacycline polymyxin b antibiotic combination treatment time-kill test. |
| title | The in vitro Activity of Omadacycline Alone and in Combination Against Carbapenem-Resistant Klebsiella pneumoniae |
| title_full | The in vitro Activity of Omadacycline Alone and in Combination Against Carbapenem-Resistant Klebsiella pneumoniae |
| title_fullStr | The in vitro Activity of Omadacycline Alone and in Combination Against Carbapenem-Resistant Klebsiella pneumoniae |
| title_full_unstemmed | The in vitro Activity of Omadacycline Alone and in Combination Against Carbapenem-Resistant Klebsiella pneumoniae |
| title_short | The in vitro Activity of Omadacycline Alone and in Combination Against Carbapenem-Resistant Klebsiella pneumoniae |
| title_sort | in vitro activity of omadacycline alone and in combination against carbapenem resistant klebsiella pneumoniae |
| topic | klebsiella pneumoniae carbapenem resistance omadacycline polymyxin b antibiotic combination treatment time-kill test. |
| url | https://www.dovepress.com/the-in-vitro-activity-of-omadacycline-alone-and-in-combination-against-peer-reviewed-fulltext-article-IDR |
| work_keys_str_mv | AT duy theinvitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT liuy theinvitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT liut theinvitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT panf theinvitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT mus theinvitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT zhuy theinvitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT gaoh theinvitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT jingx theinvitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT wangx theinvitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT liuy theinvitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT wangs theinvitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT duy invitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT liuy invitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT liut invitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT panf invitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT mus invitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT zhuy invitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT gaoh invitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT jingx invitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT wangx invitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT liuy invitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae AT wangs invitroactivityofomadacyclinealoneandincombinationagainstcarbapenemresistantklebsiellapneumoniae |