体外碳青霉烯类抗生素联合舒巴坦对广泛耐药鲍曼不动杆菌抗菌活性研究

In vitro activities of carbapenems combined with sulbactam against XDR Acinetobacter baumannii

目的探讨比阿培南、业胺培南联合舒巴坦对广泛耐药鲍曼不动杆菌体外协同抗菌作用。方法应用棋盘格法测定比阿培南与亚胺培南分别联合舒巴坦对22株广泛耐药鲍曼不动杆菌协同抗菌作用。当比阿培南联合舒巴坦表现出协同作用或拮抗作用时，应用时间杀菌曲线法进一步评价联合用药时抗菌药物相耳：作用。结果应用棋盘格法比阿培南联合舒巴坦对于所测广泛耐药鲍曼不动杆菌表现协同作用的为36．d％（S／22），部分协同作用的为40．9％（9／22），相加作用为4．5%（1／22），无关作州为18．1％（4／22），无菌株出现拮抗作用；亚胺培南联合舒巴坦分别为31．8％（7／22）协同作用，45．5％（10/22）部分协同作用，4．5％（1／22）相加作用，18．1％（4／22）无关作用，九菌株出现拈抗作用。根据敏感性不同将所测菌株分为对比阿培南或亚胺培南低水平耐药组（8mg／L〈MIC≤32rng／L）和高水平耐约组（MC≥64mg／L），低水平耐药组联合舒巴坍后对比阿培南（15株）或亚胺培南（16株）MIC90降至8mg／L，达到敏感范围。对于棋盘格法比阿培南联合舒巴坦表现出协同作用的8株广泛耐药鲍曼小动杆菌，应用时间杀菌曲线法重新评估，3株（3／8）表现出阱同作用，末发现拈抗作用。结论比阿培南联合舒巴坦与亚胺培南联合舒巴坦对与广泛耐药鲍曼不动杆菌多表现出协同或部分协同作用。联合舒巴蛆对于比阿培南或亚胺培南低水平耐药鲍曼不动杆菌感染的治疗可能有效。棋盘格法与时间杀菌曲线法所得结果存在一定差异。

Objective To evaluate tile in vitro synergy effect of biapenem and imipenem combined with sulbactam against XDR A. baumannii. Methods The checkerboard microdilution panel method was used for the MIC determination of biapenem and, imipenem combined with sulbactam. F1CI was calculated for each combination based on the MICs and time kill assays at 0.5 X MIC were performed on the biapenem/sulbaetam combinations found synergistic or antagonistic by checkerboard assays. Results The checkerboard method with biapenem/sulbactam combination demonstrated 36.4 % （8/22） synergism, 10.9%（9/22） partial synergism, 4.5%（1/22） additive, 18.1%（4/22） indifference, and no antagonism. For the combination of imipenem/sulbactam, 31.8% （7/22） synergism, 45.5% （10/22） partial synergism, 4.5%（1/22） additive, 18. 1%（4/22） indifference, and no antagonism was found. Low-level resistanl （8 mg/L〈MIC≤32 mg/L） XDR A. baumannii isolates, when combined with sulbactam. demonstrated a drop in MIC0 for biapenem or imipenem to 8 rag/L, falling within the susceptible range. In the 8 isolates for which biapenem/sulbactam showed synergism by checkerboard microdilution panel method, time-kill assays confirmed the synergistic inleraction between biapenem and sulbactam in three isolates, and no antagonism was confirmed. Conclusions Biapenem/sulhactam and imipenem/sulbactanl combinations show synergism XDR A. baumannii isolates sulbactam may be as a choice o method may disagree with the or partial synergism against of low-level resistant to the f combination therapies. The time-kill test aumannii isolates. For the penem, combination with ：erboard rnicrodilution panel most XDR A. b biapenem or im results from check