氨基糖苷类药物在联合用药时缩小抗菌药物对鲍曼不动杆菌耐药突变选择窗中的作用

Effect of aminoglycosides on reducing the mutant selective window of Acinetobacter baumannii in combination therapy

目的探讨氨基糖苷类药物与其他抗鲍曼不动杆菌药物联合应用时,在缩小抗菌药物对鲍曼不动杆菌的耐药突变选择窗的作用。方法选择阿米卡星、妥布霉素及奈替米星3种氨基糖苷类药物,同时选择4种临床常用的抗鲍曼不动杆菌药物:头孢哌酮-舒巴坦、亚胺培南-西司他丁、环丙沙星及左氧氟沙星进行试验。应用E试验法测定4种抗鲍曼不动杆菌药物和3种氨基糖苷类药物对鲍曼不动杆菌ATCC19606的MIC;琼脂平皿稀释法测定4种抗鲍曼不动杆菌药物单药及联合3种氨基糖苷类药物后对鲍曼不动杆菌ATCC19606的防耐药突变浓度,计算选择指数,根据联合前后选择指数的变化,观察氨基糖苷类药物和其他抗菌药物联合后对其耐药突变选择窗的影响。结果头孢哌酮-舒巴坦、亚胺培南-西司他丁、环丙沙星、左氧氟沙星单药对鲍曼不动杆菌ATCC19606的选择指数分别为:16、>32、16、32;联合阿米卡星后其选择指数分别为:1、2、4、4;联合妥布霉素后其选择指数分别为:2、2、8、8;联合奈替米星后其选择指数分别为:2、4、8、16。结论 4种抗鲍曼不动杆菌药物在分别联合3种氨基糖苷类药物后,对鲍曼不动杆菌的耐药突变选择窗明显缩小,可以有效减少耐药突变株产生,以联合阿米卡星后的作用最为明显。

Objective To explore the effect of combination therapy of aminoglycosides with other antibiotics on reducing the mutant selective window of Acinetobacter baumannii. Methods Three aminoglycoside antibiotics （amikacin, tobramycin, netilmicin） and four frequently used antibiotics against Acinetobacter baumannii in clinical practice （cefoperazone-sulbactam, imipenem-cilastatin, ciprofloxacin and levofloxacin） were studied. The minimum inhibitory concentrations of these antibiotics against Acinetobacter baumannii ATCC19606 were determined by E-test. The mutant prevention concentrations of the four antibiotics against Acinetobacter baumannii alone or in combination with aminoglycosides were determined by agar dilution method. The selective index was calculated. The effect of aminoglycosides on mutant selective window of Acinetobacter baurnannii was evaluated according to the change of selective index after combination. Results The selective index of cefoperazone-sulhactam, imipenem-cilastatin, ciprofIoxacin and levofloxacin against A. baumannii ATCC19606 was 16, 〉32, 16 and 32. When combined with amikacin, the selective index was 1, 2, 4 and 4, respectively. When combined with tobramycin, the index was 2, 2, 8 and 8, respectively. When combined with netilmicin, the index was 2, 4, 8 and 16, respectively. Conclusions The mutant prevention concentration of the four antibiotics against Acinetobacter baumannii is significantly reduced when combined with any of the three aminoglycosides, which is helpful to decrease the incidence of mutants and control resistant acinetobacter baurnannii. Amikacin-based combination shows the most evident effect on reducing the mutant selective window of Acinetobacter baumannii.