Acinetobacter baumannii is recognized as an urgent public health threat by the Centers for Disease Control and Prevention (CDC). Current treatment options are scarce, particularly against carbapenem-resistant Acinetobacter baumannii (CRAB). We simulated the impact of minocycline standard (200 mg load + 100 mg Q12h) and high (700 mg load + 350 mg Q12h) doses, polymyxin B (2.5 mg/kg Q12h), sulbactam (1 g Q6h and 9 g/24 h as continuous infusion), and meropenem (intermittent 1 or 2 g Q8h and 6 g/24 h as continuous infusion) alone or in combination against CRAB and non-CRAB isolates by simulating human therapeutic dosing regimens in a 72-h, in vitro pharmacodynamic (IVPD) model. There were no monotherapy regimens that demonstrated bactericidal activity against the tested non-CRAB and CRAB strains. Resistance development was common in monotherapy regimens. Against the CRAB isolate, the triple combination of high-dose minocycline (fAUC/MIC 21.2), polymyxin B (fAUC/MIC 15.6), and continuous-infusion sulbactam (67% T>MIC) was the most consistently active regimen. Against non-CRAB, the triple therapy regimen of high-dose minocycline (fAUC/MIC 84.8) with continuous-infusion meropenem (100% T>MIC) and continuous-infusion sulbactam (83% T>MIC), as well as the double therapy of high-dose minocycline (fAUC/MIC 84.8) with continuous-infusion meropenem (100% T>MIC), resulted in persistently bactericidal activity. In conclusion, triple therapy with high-dose minocycline, continuous-infusion sulbactam, and polymyxin B produced the most significant kill against the carbapenem-resistant Acinetobacter baumannii, with no regrowth and minimal resistance development.
Keywords: Acinetobacter baumannii; beta-lactams; continuous infusion; minocycline; polymyxin B.
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