The study collected 108 blood specimens and60 sputum specimens from 12 enrolled patients Subsequently, these specimens were assayedfor tigecycline drug concentrations by high-performance liquid chromatography (HPLC).The relevant pharmacokinetic (PK) parameters were estimated by the non-compartmental model usingWinNonlin software. And Crystal Ball software was used to carry out Monte Carlosimulations. The results of this study showed that the mean lung penetrationrate calculated by the sputum was 127.27% and the probability of targetattainments (PTAs) in plasma and sputum ≥90.00% when the minimal inhibit concentration (MIC) ≤ 4 mg/L. Hence, the findings of PK/PD parameters of high-dosetigecycline in patients with HAP caused by MDRB demonstrated that high-dosetigecycline could achieve better antimicrobial effects when the MIC was ≤4 mg/L.
Abstract
What is Known and Objective
To Investigate the pharmacokinetic/pharmacodynamic (PK/PD) parameters of high-dose tigecycline in plasma and sputum of patients with hospital-acquired pneumonia (HAP), and provide a therapeutic regimen of multidrug-resistant bacteria (MDRB) infections.
Methods
Blood/sputum samples were collected at intervals after tigecycline had reached a steady-state. Tigecycline concentrations in specimens were determined by high-performance liquid chromatography (HLPC), PK parameters were evaluated by WinNonlin software using a non-compartment model. The probability of target attainments (PTAs) at different minimal inhibitory concentrations (MICs) were calculated for achieving the PK/PD index with Crystal Ball software by 10,000-patient Monte Carlo Simulation.
Results
In plasma, the maximum concentration (C max) and area under the concentration–time curve from 0 to 12 h (AUC0–12h) were 2.21 ± 0.17 mg/L and 15.29 ± 1.13 h mg/L, respectively. In sputum, they were 2.48 ± 0.21 mg/L and 19.46 ± 1.82 h mg/L, respectively. The mean lung penetration rate was 127.27%. At the MIC ≤4 mg/L, the PTAs in plasma and sputum were 100.00%. When the MIC increased to 8 mg/L, the PTAs in plasma and sputum mostly were < 90.00% according to two criteria.
What is New and Conclusion
In this study, we explored PK/PD of high-dose tigecycline in plasma and sputum. From a PK/PD perspective, high-dose tigecycline had greater therapeutic outcomes in HAP treatment caused by MDRB. Antimicrobial-drug concentrations should be determined to optimize their clinical use.
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