Infectious Diseases Laboratory, 4th Department of Internal Medicine, National and Kapodistrian University of Athens, School of Medicine, University General Hospital 'ATTIKON', Rimini 1, 124 62 Chaidari, Athens, Greece.
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
J Antimicrob Chemother. 2024 May 2;79(5):1101-1108. doi: 10.1093/jac/dkae077.
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.
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.
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.
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.
评估安普霉素与多黏菌素、美罗培南、米诺环素或舒巴坦联合使用对一些来自希腊的具有明确特征的 XDR 鲍曼不动杆菌临床分离株的体外活性，以了解如何将安普霉素最佳地纳入临床实践并优化其疗效。
采用时间杀菌法检测安普霉素（0.5×、1×和 2×MIC 值）与多黏菌素（2mg/L）、美罗培南（30mg/L）、米诺环素（3.5mg/L）或舒巴坦（24mg/L）的体外相互作用。选择了 21 株安普霉素 MIC 值为 4-16mg/L 的临床鲍曼不动杆菌分离株，这些分离株的 MIC 值处于或低于安普霉素初步的流行病学折点值 16mg/L。这些分离株对多黏菌素（4-32mg/L）、美罗培南（16-256mg/L）、米诺环素（8-32mg/L）和舒巴坦（8-32mg/L）的 MIC 值在耐药范围内进行了一系列检测。协同作用定义为与最有效的药物相比，减少≥2log10cfu/mL。
安普霉素与多黏菌素、美罗培南、米诺环素或舒巴坦联合使用时，至少在安普霉素（0.5×、1×或 2×MIC）的一种浓度下，对 83.3%、90.5%、90.9%或 92.3%的测试分离株具有协同作用。安普霉素单独使用时，在浓度等于 1×和 2×MIC 时，在 24h 时对 9.5%和 33.3%的测试分离株具有杀菌作用，而安普霉素 2×MIC 与多黏菌素、美罗培南或舒巴坦联合使用时对所有测试分离株均具有杀菌作用（100%）。安普霉素 2×MIC/米诺环素联合用药对 90.9%的测试分离株具有杀菌活性。
安普霉素联合用药可能成为治疗 XDR/泛耐药（PDR）鲍曼不动杆菌感染的一种治疗选择，当这种新的氨基糖苷类药物可用于临床应用时，需要在临床环境中进行验证。
