Pharmacokinetic/pharmacodynamic modelling to evaluate the efficacy of various dosing regimens of ceftazidime/avibactam in patients with pneumonia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae: a multicentre study in northern China
ABSTRACT: Objectives: The objective of this study was to evaluate the efficacy of different dosing regimens of ceftazidime/avibactam (CZA) in patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) pulmonary infections. Methods: A total of 70 KPC-Kp strains were isolated...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Journal of Global Antimicrobial Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716521001909 |
| _version_ | 1818950442956095488 |
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| author | Yixin Kang Qian Zhou Junchang Cui |
| author_facet | Yixin Kang Qian Zhou Junchang Cui |
| author_sort | Yixin Kang |
| collection | DOAJ |
| description | ABSTRACT: Objectives: The objective of this study was to evaluate the efficacy of different dosing regimens of ceftazidime/avibactam (CZA) in patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) pulmonary infections. Methods: A total of 70 KPC-Kp strains were isolated from sputum and bronchoalveolar lavage samples of patients with pulmonary infections in three hospitals in northern China from April 2015 to October 2015. Monte Carlo simulation (MCS) was performed using population pharmacokinetic parameters of CZA combined with the minimum inhibitory concentration (MIC) distributions gained from antimicrobial susceptibility testing to predict the efficacy of different dosing regimens. Various CZA dosing regimens were modelled using MCS. Results: The in vitro study showed potent activity of CZA against KPC-Kp strains with MIC50/90 values of 1/2 mg/L, with a susceptibility rate of 95.7%. The values of cumulative fraction of response (CFR) for bactericidal (50%fT>5 × MIC) target were as follows: for patients with creatinine clearance (CLCr) >51 mL/min, the CFR was 96.01% for 2.5 g CZA every 12 h (q12h) and 97.14% for 2.5 g CZA every 8 h (q8h); and for patients with moderate renal impairment (CLCr >30 to ≤50 mL/min), the CFR was 95.75% for 1.25 g CZA q12h and 97.09% for 1.25 g CZA q8h. Conclusion: This study indicated that the recommended dose of CZA can provide adequate pharmacodynamic exposure for treating KPC-Kp pneumonia. |
| first_indexed | 2024-12-20T09:18:40Z |
| format | Article |
| id | doaj.art-206f92750bb94e8b9e4edcfa31772474 |
| institution | Directory Open Access Journal |
| issn | 2213-7165 |
| language | English |
| last_indexed | 2024-12-20T09:18:40Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj.art-206f92750bb94e8b9e4edcfa317724742022-12-21T19:45:21ZengElsevierJournal of Global Antimicrobial Resistance2213-71652021-12-01276771Pharmacokinetic/pharmacodynamic modelling to evaluate the efficacy of various dosing regimens of ceftazidime/avibactam in patients with pneumonia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae: a multicentre study in northern ChinaYixin Kang0Qian Zhou1Junchang Cui2Department of Respiratory Diseases, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, ChinaDepartment of Respiratory Diseases, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China; Department of Respiratory Diseases, People's Hospital of Hainan District, Wuhai 016000, ChinaDepartment of Respiratory Diseases, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China; Corresponding author. Mailing address: The First Medical Center, Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. Tel.: +086 010 5547 3166.ABSTRACT: Objectives: The objective of this study was to evaluate the efficacy of different dosing regimens of ceftazidime/avibactam (CZA) in patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) pulmonary infections. Methods: A total of 70 KPC-Kp strains were isolated from sputum and bronchoalveolar lavage samples of patients with pulmonary infections in three hospitals in northern China from April 2015 to October 2015. Monte Carlo simulation (MCS) was performed using population pharmacokinetic parameters of CZA combined with the minimum inhibitory concentration (MIC) distributions gained from antimicrobial susceptibility testing to predict the efficacy of different dosing regimens. Various CZA dosing regimens were modelled using MCS. Results: The in vitro study showed potent activity of CZA against KPC-Kp strains with MIC50/90 values of 1/2 mg/L, with a susceptibility rate of 95.7%. The values of cumulative fraction of response (CFR) for bactericidal (50%fT>5 × MIC) target were as follows: for patients with creatinine clearance (CLCr) >51 mL/min, the CFR was 96.01% for 2.5 g CZA every 12 h (q12h) and 97.14% for 2.5 g CZA every 8 h (q8h); and for patients with moderate renal impairment (CLCr >30 to ≤50 mL/min), the CFR was 95.75% for 1.25 g CZA q12h and 97.09% for 1.25 g CZA q8h. Conclusion: This study indicated that the recommended dose of CZA can provide adequate pharmacodynamic exposure for treating KPC-Kp pneumonia.http://www.sciencedirect.com/science/article/pii/S2213716521001909Ceftazidime/avibactamPharmacokinetic/pharmacodynamicMonte Carlo simulationKlebsiella pneumoniae carbapenemaseKPCKPC-producing K. pneumoniae |
| spellingShingle | Yixin Kang Qian Zhou Junchang Cui Pharmacokinetic/pharmacodynamic modelling to evaluate the efficacy of various dosing regimens of ceftazidime/avibactam in patients with pneumonia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae: a multicentre study in northern China Journal of Global Antimicrobial Resistance Ceftazidime/avibactam Pharmacokinetic/pharmacodynamic Monte Carlo simulation Klebsiella pneumoniae carbapenemase KPC KPC-producing K. pneumoniae |
| title | Pharmacokinetic/pharmacodynamic modelling to evaluate the efficacy of various dosing regimens of ceftazidime/avibactam in patients with pneumonia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae: a multicentre study in northern China |
| title_full | Pharmacokinetic/pharmacodynamic modelling to evaluate the efficacy of various dosing regimens of ceftazidime/avibactam in patients with pneumonia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae: a multicentre study in northern China |
| title_fullStr | Pharmacokinetic/pharmacodynamic modelling to evaluate the efficacy of various dosing regimens of ceftazidime/avibactam in patients with pneumonia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae: a multicentre study in northern China |
| title_full_unstemmed | Pharmacokinetic/pharmacodynamic modelling to evaluate the efficacy of various dosing regimens of ceftazidime/avibactam in patients with pneumonia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae: a multicentre study in northern China |
| title_short | Pharmacokinetic/pharmacodynamic modelling to evaluate the efficacy of various dosing regimens of ceftazidime/avibactam in patients with pneumonia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae: a multicentre study in northern China |
| title_sort | pharmacokinetic pharmacodynamic modelling to evaluate the efficacy of various dosing regimens of ceftazidime avibactam in patients with pneumonia caused by klebsiella pneumoniae carbapenemase kpc producing k pneumoniae a multicentre study in northern china |
| topic | Ceftazidime/avibactam Pharmacokinetic/pharmacodynamic Monte Carlo simulation Klebsiella pneumoniae carbapenemase KPC KPC-producing K. pneumoniae |
| url | http://www.sciencedirect.com/science/article/pii/S2213716521001909 |
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