Abstract
Polymyxin-based combination therapy is commonly used to treat carbapenem-resistant Acinetobacter baumannii (CRAB) infections. In the present study, the bactericidal effect of polymyxin B and minocycline combination was tested in three CRAB strains containing blaOXA-23 by the checkerboard assay and in vitro dynamic pharmacokinetics/pharmacodynamics (PK/PD) model. The combination showed synergistic or partial synergistic effect (fractional inhibitory concentration index ≤0.56) on the tested strains in checkboard assays. The antibacterial activity was enhanced in the combination group compared with either monotherapy in in vitro PK/PD model. The combination regimen (simultaneous infusion of 0.75 mg/kg polymyxin B and 100 mg minocycline via 2 h infusion) reduced bacterial colony counts by 0.9–3.5 log10 colony forming units per milliliter (CFU/mL) compared with either drug alone at 24 h. In conclusion, 0.75 mg/kg polymyxin B combined with 100 mg minocycline via 2 h infusion could be a promising treatment option for CRAB bloodstream infections.
Highlights
Bloodstream infections are most common (37/131 studies, 28%) severe infections among reported studies, and Acinetobacter baumannii is the top pathogen (52/131 studies, 38.5% and 4395/11,546 patients, 38%) [1]
The three strains were intermediate to polymyxin B with minimum inhibitory concentration (MIC) of 0.5, 0.5, and 0.25 mg/L, respectively (Table 2)
The genome annotation revealed that all the strains contained multiple antibiotic resistance genes including OXA23, OXA-66 encoding the beta-lactamase resistance, which are consistent with the MICs over 16 mg/L for meropenem and doripenem
Summary
Bloodstream infections are most common (37/131 studies, 28%) severe infections among reported studies, and Acinetobacter baumannii is the top pathogen (52/131 studies, 38.5% and 4395/11,546 patients, 38%) [1]. The mortality of Acinetobacter baumannii-related bloodstream infections showed an increasing trend in a 10-year prospective study in. There is an urgent need for rational and effective medication schemes to be developed in clinics. Polymyxins have become a last-resort treatment for multi-drug resistant. Gram-negative bacterial infections, including Acinetobacter baumannii [3]. Higher doses resulted in better therapeutic outcomes, greater incidence of toxicity tended to follow, such as nephrotoxicity and neurotoxicity [4]. The adverse effects limited the clinical use of polymyxins and deficient drug doses may induce the development of polymyxin-resistant
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