Majewski Piotr, Wieczorek Piotr, Ojdana Dominika, Sacha Paweł Tomasz, Wieczorek Anna, Tryniszewska Elżbieta Anna
From the Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok , Bialystok , Poland.
Scand J Infect Dis. 2014 Apr;46(4):260-4. doi: 10.3109/00365548.2013.865141. Epub 2014 Jan 21.
The growing incidence of multidrug resistance (MDR) in bacteria is an emerging challenge in the treatment of infections. Acinetobacter baumannii is an opportunistic pathogen prone to exhibit MDR that contributes significantly to nosocomial infections, particularly in severely ill patients. Thus, we performed research on rifampicin activity against selected MDR OXA-72 carbapenemase-producing A. baumannii strains. Since it is widely accepted that rifampicin should not be used as monotherapy in order to avoid the rapid development of rifampicin resistance, we evaluated the efficacy of combination therapy with imipenem.
Minimal inhibitory concentrations (MICs) of both rifampicin and imipenem were determined by use of the broth microdilution method. Evaluations of the interactions between rifampicin and imipenem were performed by analysis of the fractional inhibitory concentration index (∑FIC), determined using the checkerboard titration method.
All tested isolates showed full susceptibility to rifampicin. The checkerboard method revealed synergism in 5 isolates (29%) and an additive effect in another 5 isolates (29%); no difference was reported in the remaining 7 isolates (41%). Strains moderately resistant to imipenem (MIC ≤ 64 mg/l) tended to show synergy or additive interaction.
We conclude that in vitro synergism or an additive interaction between rifampicin and imipenem most likely occurs in A. baumannii strains showing moderate resistance to imipenem (MIC ≤ 64 mg/l). Moreover, utilizing this combination in the therapy of infections caused by strains exhibiting higher levels of resistance (MIC > 64 mg/l) is not recommended since in this setting imipenem could not prevent the development of rifampicin resistance.
细菌中多重耐药（MDR）发生率的不断上升是感染治疗中一个新出现的挑战。鲍曼不动杆菌是一种机会致病菌，易于表现出多重耐药，这对医院感染有显著影响，尤其是在重症患者中。因此，我们开展了关于利福平对选定的产MDR OXA - 72碳青霉烯酶鲍曼不动杆菌菌株活性的研究。由于人们普遍认为利福平不应作为单一疗法使用，以避免利福平耐药性的快速产生，我们评估了亚胺培南联合治疗的疗效。
采用肉汤微量稀释法测定利福平和亚胺培南的最低抑菌浓度（MIC）。通过分析使用棋盘滴定法测定的分数抑菌浓度指数（∑FIC）来评估利福平和亚胺培南之间的相互作用。
所有测试菌株对利福平均表现出完全敏感性。棋盘法显示5株菌株（29%）呈现协同作用，另外5株菌株（29%）呈现相加作用；其余7株菌株（41%）未观察到差异。对亚胺培南中度耐药（MIC≤64mg/l）的菌株倾向于表现出协同或相加相互作用。
我们得出结论，利福平和亚胺培南之间的体外协同或相加相互作用很可能发生在对亚胺培南中度耐药（MIC≤64mg/l）的鲍曼不动杆菌菌株中。此外，不建议在治疗由耐药性较高（MIC>64mg/l）的菌株引起的感染时使用这种联合疗法，因为在这种情况下亚胺培南无法防止利福平耐药性的产生。
