Pharmacodynamics of minocycline against Acinetobacter baumannii studied in a pharmacokinetic model of infection

Abstract

Minocycline (MNO) is an old antibiotic that may have an important role in the treatment of multidrug-resistant Gram-negative bacterial infections as the burden of such infections increases. In this study, a single-compartment dilutional pharmacokinetic model was used to determine the relationship between MNO exposure and antibacterial effect, including the risk of resistance emergence, against strains of Acinetobacter baumannii. The mean ± standard deviation area under the unbound drug concentration–time curve to minimum inhibitory concentration ratio (fAUC/MIC) associated with a 24-h bacteriostatic effect was 16.4 ± 2.6 and with a −1 log reduction in bacterial load at 24 h was 23.3 ± 3.7. None of the strains reached a −2 log reduction over 48 h. Changes in population profiles were noted for two of the three strains studied, especially at fAUC/MIC ratios of >5–15. A reasonable translational pharmacodynamic target for MNO against A. baumannii could be an fAUC/MIC of 20–25. However, if maximum standard 24-h doses of intravenous MNO are used (400 mg/day), many strains would be exposed to MNO concentrations likely to change population profiles and associated with the emergence of resistance. Either MNO combination therapy or an increased MNO dose (>400 mg/day) should be considered when treating A. baumannii infections.