Optimal tigecycline dosage regimen is urgently needed: results from a pharmacokinetic/pharmacodynamic analysis of tigecycline by Monte Carlo simulation.
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.
Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
Jiao
J
Xie
Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
Taotao
T
Wang
Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
Jinyao
J
Sun
Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
Siying
S
Chen
Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
Jiangxia
J
Cai
Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
Weipeng
W
Zhang
Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
Haiyan
H
Dong
Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
Sasa
S
Hu
Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
Di
D
Zhang
Central Intensive Care Unit, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.
Xue
X
Wang
Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: dongyalin@mail.xjtu.edu.cn.
Yalin
Y
Dong
D040981:Acinetobacter baumannii / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004754:Enterobacter / Q000187:drug effects; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009010:Monte Carlo Method; D000078304:Tigecycline
D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline
Monte Carlo simulation; Optimal dosage regimen; Pharmacokinetic/pharmacodynamic analysis; Tigecycline