Optimal tigecycline dosage regimen is urgently needed: results from a pharmacokinetic/pharmacodynamic analysis of tigecycline by Monte Carlo simulation

• Published in: International journal of infectious diseases Vol. 18; pp. 62 - 67
• Main Authors: Xie, Jiao, Wang, Taotao, Sun, Jinyao, Chen, Siying, Cai, Jiangxia, Zhang, Weipeng, Dong, Haiyan, Hu, Sasa, Zhang, Di, Wang, Xue, Dong, Yalin
• Format: Journal Article
• Language: English
• Published: Canada Elsevier Ltd 01.01.2014
• Subjects: Acinetobacter baumannii - drug effects; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Dose-Response Relationship, Drug; Enterobacter - drug effects; Humans; Infectious Disease; Klebsiella pneumoniae - drug effects; Microbial Sensitivity Tests; Minocycline - administration & dosage; Minocycline - analogs & derivatives; Minocycline - pharmacokinetics; Monte Carlo Method; Monte Carlo simulation; Optimal dosage regimen; Pharmacokinetic/pharmacodynamic analysis; Pulmonary/Respiratory; Tigecycline; Optimal dosage regimen; Tigecycline; Monte Carlo simulation; Pharmacokinetic/pharmacodynamic analysis
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2013.09.008

Summary Background The number of reported cases of resistance to tigecycline is increasing. The aim of this study was to evaluate the current standard tigecycline dosage regimen from a pharmacokinetic/pharmacodynamic (PK/PD) perspective. Methods Pharmacokinetic parameters and microbiological data were analyzed by Monte Carlo simulation in an evaluation of effectiveness. Results Tigecycline exhibits excellent in vitro antimicrobial activity, however the standard tigecycline dosing regimen fails to achieve the best outcome in vivo for the common drug-resistant strains, including Acinetobacter baumannii , Enterobacter spp , and Klebsiella pneumoniae . This may result in a lack of response to tigecycline therapy or to a further increase in the resistance rate. Conclusions In the absence of new drugs on the horizon, rather than using a single fixed dosing regimen, tigecycline dosing needs to be optimized in order to achieve the desired successful clinical response and to prevent an escalation in drug resistance.