title: A pharmacodynamic simulation to evaluate tigecycline in treatment of nosocomial pneumonia caused by multidrug-resistant Acinetobacter baumannii.
abstract: The shortage of effective antibiotics against multidrug-resistant Acinetobacter baumannii (MDR-Ab) has posed great threat to the public health. But the advent of tigecycline gives us new hope. The goal of our research was to assess the clinical efficacy of tigecycline at different doses by using a pharmacokinetic/pharmacodynamic (PK/PD) model which can incorporate pharmacokinetic data of tigecycline from patients with pneumonia and MICs of MDR-Ab from a tertiary hospital. A 10000-patient Monte-Carlo Simulation based on the PK/PD model was conducted to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of tigecycline. 97% isolates displayed susceptibility and 3% were tigecycline-intermediate strains and the values of MIC ranged from 0.125 to 4 μ g/ml. A CFR of 61.62% was predicted for tigecycline at current dosage (50 mg q12h). When the dosage was increased, the predicted CFRs for 75 mg q12h, 100 mg q12h, 125 mg q12h, 150 mg q12h were 81.00%, 89.86%, and 94.57%, 96.77%, respectively. Despite presented higher susceptibility, the CFR obtained was not optimal at current dosage. A higher CFR indicating a better clinical efficacy can be gained by the increased dosage.
authors.affiliation: Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Wen-tao
authors.initials: WT
authors.lastname: Ni
authors.affiliation: Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Bei-bei
authors.initials: BB
authors.lastname: Liang
authors.affiliation: Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
authors.forename: Yin-ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Bai
authors.affiliation: Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Jun-chang
authors.initials: JC
authors.lastname: Cui
authors.affiliation: Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003428:Cross Infection / Q000188:drug therapy*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D009010:Monte Carlo Method; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline