Antibacterial effect evaluation of moxalactam against extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae with in vitro pharmacokinetics/pharmacodynamics simulation
Chen Huang,1,* Beiwen Zheng,1,* Wei Yu,2 Tianshui Niu,1 Tingting Xiao,1 Jing Zhang,1 Yonghong Xiao1 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-01-01
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| Series: | Infection and Drug Resistance |
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| Online Access: | https://www.dovepress.com/antibacterial-effect-evaluation-of-moxalactam-against-extended-spectru-peer-reviewed-article-IDR |
| _version_ | 1818201655102930944 |
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| author | Huang C Zheng B Yu W Niu T Xiao T Zhang J Xiao Y |
| author_facet | Huang C Zheng B Yu W Niu T Xiao T Zhang J Xiao Y |
| author_sort | Huang C |
| collection | DOAJ |
| description | Chen Huang,1,* Beiwen Zheng,1,* Wei Yu,2 Tianshui Niu,1 Tingting Xiao,1 Jing Zhang,1 Yonghong Xiao1 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; 2Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Hangzhou, China *These authors contributed equally to this work Objectives: The aim of this study was to evaluate the bactericidal effects of moxalactam (MOX), cefotaxime (CTX), and cefoperazone/sulbactam (CFZ/SBT) against extended-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, using an in vitro pharmacokinetics (PK)/pharmacodynamics model.Methods: Two clinical ESBL-producing strains (blaCTX-M-15 positive E. coli 3376 and blaCTX-M-14 positive K. pneumoniae 2689) and E. coli American Type Culture Collection (ATCC)25922 were used in the study. The PK Auto Simulation System 400 was used to simulate the human PK procedures after intravenous administration of different doses of MOX, CTX, and CFZ/SBT. Bacterial growth recovery time (RT) and the area between the control growth curve and bactericidal curves (IE) were employed to assess the antibacterial efficacies of all the agents.Results: The minimum inhibitory concentrations of MOX, CTX, and CFZ/SBT against E. coli ATCC25922, 3376, and 2689 strains were 0.5, 0.5, 0.25; 0.06, >256, 256; and 0.5/0.5, 16/16, 32/32 mg/L. All the agents demonstrated outstanding bactericidal effects against E. coli ATCC25922 (RT >24 h and IE >120 log10 CFU/mL·h−1) with simulating PK procedures, especially in the multiple dose administration models. Against ESBL producers, CTX and CFZ/SBT displayed only weak bactericidal effects, and subsequent regrowth was evident. MOX exhibited potent antibacterial activity against all the strains tested. The values of effective parameters of MOX were much higher than those of CTX and CFZ/SBT (the bacterial RTs with the 3 agents were >24, <4, and <13 h, and the IEs were >110, <10, and <60 log10 CFU/mL·h−1, respectively).Conclusion: MOX demonstrated excellent bactericidal effect, which is worthy of further exploration to serve as an alternative therapeutic agent against ESBL-producing Enterobacteriaceae. Keywords: moxalactam, in vitro, pharmacokinetics/pharmacodynamics, extended-spectrum β-lactamases, Escherichia coli, Klebsiella pneumoniae |
| first_indexed | 2024-12-12T02:57:00Z |
| format | Article |
| id | doaj.art-cba139feaf0a4c99a06499ad2652cdde |
| institution | Directory Open Access Journal |
| issn | 1178-6973 |
| language | English |
| last_indexed | 2024-12-12T02:57:00Z |
| publishDate | 2018-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Infection and Drug Resistance |
| spelling | doaj.art-cba139feaf0a4c99a06499ad2652cdde2022-12-22T00:40:44ZengDove Medical PressInfection and Drug Resistance1178-69732018-01-01Volume 1110311236376Antibacterial effect evaluation of moxalactam against extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae with in vitro pharmacokinetics/pharmacodynamics simulationHuang CZheng BYu WNiu TXiao TZhang JXiao YChen Huang,1,* Beiwen Zheng,1,* Wei Yu,2 Tianshui Niu,1 Tingting Xiao,1 Jing Zhang,1 Yonghong Xiao1 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; 2Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Hangzhou, China *These authors contributed equally to this work Objectives: The aim of this study was to evaluate the bactericidal effects of moxalactam (MOX), cefotaxime (CTX), and cefoperazone/sulbactam (CFZ/SBT) against extended-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, using an in vitro pharmacokinetics (PK)/pharmacodynamics model.Methods: Two clinical ESBL-producing strains (blaCTX-M-15 positive E. coli 3376 and blaCTX-M-14 positive K. pneumoniae 2689) and E. coli American Type Culture Collection (ATCC)25922 were used in the study. The PK Auto Simulation System 400 was used to simulate the human PK procedures after intravenous administration of different doses of MOX, CTX, and CFZ/SBT. Bacterial growth recovery time (RT) and the area between the control growth curve and bactericidal curves (IE) were employed to assess the antibacterial efficacies of all the agents.Results: The minimum inhibitory concentrations of MOX, CTX, and CFZ/SBT against E. coli ATCC25922, 3376, and 2689 strains were 0.5, 0.5, 0.25; 0.06, >256, 256; and 0.5/0.5, 16/16, 32/32 mg/L. All the agents demonstrated outstanding bactericidal effects against E. coli ATCC25922 (RT >24 h and IE >120 log10 CFU/mL·h−1) with simulating PK procedures, especially in the multiple dose administration models. Against ESBL producers, CTX and CFZ/SBT displayed only weak bactericidal effects, and subsequent regrowth was evident. MOX exhibited potent antibacterial activity against all the strains tested. The values of effective parameters of MOX were much higher than those of CTX and CFZ/SBT (the bacterial RTs with the 3 agents were >24, <4, and <13 h, and the IEs were >110, <10, and <60 log10 CFU/mL·h−1, respectively).Conclusion: MOX demonstrated excellent bactericidal effect, which is worthy of further exploration to serve as an alternative therapeutic agent against ESBL-producing Enterobacteriaceae. Keywords: moxalactam, in vitro, pharmacokinetics/pharmacodynamics, extended-spectrum β-lactamases, Escherichia coli, Klebsiella pneumoniaehttps://www.dovepress.com/antibacterial-effect-evaluation-of-moxalactam-against-extended-spectru-peer-reviewed-article-IDRMoxalactamin vitroPharmacokinetics/PharmacodynamicsExtended-spectrum β-lactamasesEscherichia coliKlebsiella pneumoniae |
| spellingShingle | Huang C Zheng B Yu W Niu T Xiao T Zhang J Xiao Y Antibacterial effect evaluation of moxalactam against extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae with in vitro pharmacokinetics/pharmacodynamics simulation Infection and Drug Resistance Moxalactam in vitro Pharmacokinetics/Pharmacodynamics Extended-spectrum β-lactamases Escherichia coli Klebsiella pneumoniae |
| title | Antibacterial effect evaluation of moxalactam against extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae with in vitro pharmacokinetics/pharmacodynamics simulation |
| title_full | Antibacterial effect evaluation of moxalactam against extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae with in vitro pharmacokinetics/pharmacodynamics simulation |
| title_fullStr | Antibacterial effect evaluation of moxalactam against extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae with in vitro pharmacokinetics/pharmacodynamics simulation |
| title_full_unstemmed | Antibacterial effect evaluation of moxalactam against extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae with in vitro pharmacokinetics/pharmacodynamics simulation |
| title_short | Antibacterial effect evaluation of moxalactam against extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae with in vitro pharmacokinetics/pharmacodynamics simulation |
| title_sort | antibacterial effect evaluation of moxalactam against extended spectrum beta lactamase producing escherichia coli and klebsiella pneumoniae with in vitro pharmacokinetics pharmacodynamics simulation |
| topic | Moxalactam in vitro Pharmacokinetics/Pharmacodynamics Extended-spectrum β-lactamases Escherichia coli Klebsiella pneumoniae |
| url | https://www.dovepress.com/antibacterial-effect-evaluation-of-moxalactam-against-extended-spectru-peer-reviewed-article-IDR |
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