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

Minocycline (MNO) is an old antibiotic that may have an important role in the treatment of multidrugresistant 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. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.