Department of Medical Laboratory Science and Biotechnologya and Research Center for Medical Laboratory Biotechnology, Taiwan.
J Clin Microbiol. 2012 Mar;50(3):721-6. doi: 10.1128/JCM.05085-11. Epub 2011 Dec 21.
Heteroresistance to antimicrobial agents may affect susceptibility test results and therapeutic success. In this study, we investigated heteroresistance to cephalosporins and penicillins in Acinetobacter baumannii, a major pathogen causing nosocomial infections. Two A. baumannii isolates exhibited heteroresistance to ampicillin-sulbactam, ticarcillin-clavulanic acid, cefepime, and cefpirome, showing a distinct colony morphology of circular rings within the inhibition halos. Pulsed-field gel electrophoresis (PFGE) and outer membrane protein (OMP) analysis demonstrated that subpopulations around the disks/Etest strips and the original strains all belonged to the same PFGE type and OMP profile. Population analysis profile (PAP) showed the presence of heteroresistant subpopulations with high cefepime resistance levels in two isolates (008 and 328). Interestingly, A. baumannii 008 contained two peaks: one was grown in the presence of up to 1 μg of cefepime/ml, the other apparently occurred when the concentration of cefepime was raised to 256 μg/ml. After serial passages without exposure to cefepime, the PAP curve maintained the same trend observed for the original strain of A. baumannii 008. However, the PAP curve showed a shift to relatively lower cefepime resistance (from 256 to 64 μg/ml) in A. baumannii 328 after 10 passages in antibiotic-free Mueller-Hinton agar plates. Convergence to a monotypic resistance phenotype did not occur. Growth rate analysis revealed that slower growth in resistant subpopulations may provide a strategy against antibiotic challenge. To our knowledge, this is the first report of heteroresistance to cephalosporins and penicillins in A. baumannii.
抗微生物药物的异质性耐药可能影响药敏试验结果和治疗成功。在这项研究中，我们研究了鲍曼不动杆菌对头孢菌素和青霉素的异质性耐药性，鲍曼不动杆菌是引起医院感染的主要病原体。两株鲍曼不动杆菌对氨苄西林-舒巴坦、替卡西林-克拉维酸、头孢吡肟和头孢匹罗表现出异质性耐药性，在抑菌环内显示出明显的圆形环菌落形态。脉冲场凝胶电泳（PFGE）和外膜蛋白（OMP）分析表明，围绕纸片/ Etest 条的亚群和原始菌株都属于相同的 PFGE 型和 OMP 图谱。种群分析谱（PAP）显示，两株菌（008 和 328）中存在具有高头孢吡肟耐药水平的异质性耐药亚群。有趣的是，鲍曼不动杆菌 008 含有两个峰：一个在存在高达 1μg/ml 的头孢吡肟的情况下生长，另一个显然是在头孢吡肟浓度升高至 256μg/ml 时出现的。在没有暴露于头孢吡肟的情况下连续传代后，PAP 曲线保持与原始鲍曼不动杆菌 008 菌株相同的趋势。然而，在抗生素自由 Mueller-Hinton 琼脂平板中传代 10 次后，鲍曼不动杆菌 328 的 PAP 曲线显示出相对较低的头孢吡肟耐药性（从 256μg/ml 到 64μg/ml）的转变。没有出现向单一耐药表型的收敛。生长速率分析表明，耐药亚群的生长速度较慢可能是对抗生素挑战的一种策略。据我们所知，这是鲍曼不动杆菌对头孢菌素和青霉素异质性耐药的首次报道。
