Dataset Information

Pharmacokinetic-pharmacodynamic modelling to investigate in vitro synergy between colistin and fusidic acid against MDR Acinetobacter baumannii.

ABSTRACT:

Objectives

The potential for synergy between colistin and fusidic acid in the treatment of MDR Acinetobacter baumannii has recently been shown. The aim of this study was to perform an extensive in vitro characterization of this effect using pharmacokinetic-pharmacodynamic modelling (PKPD) of time-kill experiments in order to estimate clinical efficacy.

Methods

For six clinical strains, 312 individual time-kill experiments were performed including 113 unique pathogen-antimicrobial combinations. A wide range of concentrations (0.25-8192?mg/L for colistin and 1-8192?mg/L for fusidic acid) were explored, alone and in combination. PKPD modelling sought to quantify synergistic effects.

Results

A PKPD model confirmed synergy in that colistin EC50 was found to decrease by 83% in the presence of fusidic acid, and fusidic acid maximum increase in killing rate (Emax) also increased 58% in the presence of colistin. Simulations indicated, however, that at clinically achievable free concentrations, the combination may be bacteriostatic in colistin-susceptible strains, but growth inhibition probability was <20% in a colistin-resistant strain.

Conclusions

Fusidic acid may be a useful agent to add to colistin in a multidrug combination for MDR Acinetobacter baumannii.

SUBMITTER: Phee LM

PROVIDER: S-EPMC6419616 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Pharmacokinetic-pharmacodynamic modelling to investigate in vitro synergy between colistin and fusidic acid against MDR Acinetobacter baumannii.

Phee Lynette M LM Kloprogge Frank F Morris Rebecca R Barrett John J Wareham David W DW Standing Joseph F JF

The Journal of antimicrobial chemotherapy 20190401 4

<h4>Objectives</h4>The potential for synergy between colistin and fusidic acid in the treatment of MDR Acinetobacter baumannii has recently been shown. The aim of this study was to perform an extensive in vitro characterization of this effect using pharmacokinetic-pharmacodynamic modelling (PKPD) of time-kill experiments in order to estimate clinical efficacy.<h4>Methods</h4>For six clinical strains, 312 individual time-kill experiments were performed including 113 unique pathogen-antimicrobial ...[more]

PMID: 30624656

Similar Datasets

Project description:To the best of our knowledge, to date, no study has investigated the optimal dosage regimens of either colistin or sitafloxacin against drug-resistant Acinetobacter baumannii (A. baumannii) infections by using specific parameters. In the current study, we aimed to explore the optimal dosage regimens of colistin and sitafloxacin, either in monotherapy or in combination therapy, for the treatment of carbapenem-, multidrug-, and colistin-resistant A. baumannii infections. A Monte Carlo simulation was applied to determine the dosage regimen that could achieve the optimal probability of target attainment (PTA) and cumulative fraction of response (CFR) (≥90%) based on the specific parameters of each agent and the minimal inhibitory concentration (MIC) of the clinical isolates. This study explored the dosage regimen of 90, 50, 30, and 10 mL/min for patients with creatinine clearance (CrCL). We also explored the dosage regimen for each patient with CrCL using combination therapy because there is a higher possibility of reaching the desired PTA or CFR. Focusing on the MIC90 of each agent in combination therapy, the dosage regimen for colistin was a loading dose of 300 mg followed by a maintenance dose ranging from 50 mg every 48 h to 225 mg every 12 h and the dosage regimen for sitafloxacin was 325 mg every 48 h to 750 mg every 12 h. We concluded that a lower-than-usual dose of colistin based on specific pharmacokinetic data in combination with a higher-than-usual dose of sitafloxacin could be an option for the treatment of carbapenem-, multidrug-, and colistin-resistant. A. baumannii. The lower dose of colistin might show a low probability of adverse reaction, while the high dose of sitafloxacin should be considered. In the current study, we attempted to find if there is a strong possibility of drug selection against crucial drug-resistant pathogen infections in a situation where there is a lack of new antibiotics. However, further study is needed to confirm the results of this simulation study.

Dataset Information

Pharmacokinetic-pharmacodynamic modelling to investigate in vitro synergy between colistin and fusidic acid against MDR Acinetobacter baumannii.

Objectives

Methods

Results

Conclusions

Publications

Pharmacokinetic-pharmacodynamic modelling to investigate in vitro synergy between colistin and fusidic acid against MDR Acinetobacter baumannii.

Similar Datasets

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