OBJECTIVES: To evaluate the in vitro activity of the combination of apramycin with colistin, meropenem, minocycline or sulbactam, against some well-characterized XDR Acinetobacter baumannii clinical isolates from Greece, to understand how apramycin can be best incorporated into clinical practice and optimize effectiveness.
METHODS: In vitro interactions of apramycin (0.5��, 1�� and 2�� the MIC value) with colistin (2���mg/L), meropenem (30���mg/L), minocycline (3.5���mg/L) or sulbactam (24���mg/L) were tested using time-kill methodology. Twenty-one clinical A. baumannii isolates were chosen, exhibiting apramycin MICs of 4-16���mg/L, which were at or below the apramycin preliminary epidemiological cut-off value of 16���mg/L. These isolates were selected for a range of colistin (4-32���mg/L), meropenem (16-256���mg/L), minocycline (8-32���mg/L) and sulbactam (8-32���mg/L) MICs across the resistant range. Synergy was defined as a ���2���log10���cfu/mL reduction compared with the most active agent.
RESULTS: The combination of apramycin with colistin, meropenem, minocycline or sulbactam was synergistic, at least at one of the concentrations of apramycin (0.5��, 1�� or 2�� MIC), against 83.3%, 90.5%, 90.9% or 92.3% of the tested isolates, respectively. Apramycin alone was bactericidal at 24���h against 9.5% and 33.3% of the tested isolates at concentrations equal to 1�� and 2�� MIC, while the combination of apramycin at 2�� MIC with colistin, meropenem or sulbactam was bactericidal against all isolates tested (100%). The apramycin 2�� MIC/minocycline combination had bactericidal activity against 90.9% of the tested isolates.
CONCLUSIONS: Apramycin combinations may have potential as a treatment option for XDR/pandrug-resistant (PDR) A. baumannii infections and warrant validation in the clinical setting, when this new aminoglycoside is available for clinical use.
Acinetobacter baumannii
Greece
Anti-Bacterial Agents
Microbial Sensitivity Tests
Humans
Acinetobacter Infections
Nebramycin
Sulbactam
Drug Synergism
Meropenem
Colistin
Drug Resistance, Multiple, Bacterial
Microbial Viability
Minocycline
