Huang Yuqin, Wang Wenguo, Huang Qiang, Wang Zhengyan, Xu Zhuanzhuan, Tu Chaochao, Wan Dongli, He Miaobo, Yang Xiaoyi, Xu Huaqiang, Wang Hanqin, Zhao Ying, Tu Mingli, Zhou Quan
Intensive Care Unit, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, China.
Department of Respiratory Medicine, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, China.
Front Pharmacol. 2022 Aug 10;13:944965. doi: 10.3389/fphar.2022.944965. eCollection 2022.
The aim of the research was to study the effect of azithromycin (AZM) in the treatment of MDR VAP combined with other antimicrobial therapies. The clinical outcomes were retrospectively collected and analyzed to elucidate the efficacy of different combinations involving azithromycin in the treatment of MDR-PA VAP. The minimal inhibitory concentration (MIC) of five drugs was measured by the agar dilution method against 27 isolates of MDR-PA, alone or in combination. The incidence of VAP has increased approximately to 10.4% (961/9245) in 5 years and 18.4% (177/961) caused by ranking fourth. A total of 151 cases of MDR were included in the clinical retrospective study. Clinical efficacy results are as follows: meropenem + azithromycin (MEM + AZM) was 69.2% (9/13), cefoperazone/sulbactam + azithromycin (SCF + AZM) was 60% (6/10), and the combination of three drugs containing AZM was 69.2% (9/13). The curative effect of meropenem + amikacin (MEM + AMK) was better than that of the meropenem + levofloxacin (MEM + LEV) group, = 0.029 ( < 0.05). The curative effect of cefoperazone/sulbactam + amikacin (SCF + AMK) was better than that of the cefoperazone/sulbactam + levofloxacin (SCF + LEV) group, = 0.025 ( < 0.05). There was no significant difference between combinations of two or three drugs containing AZM, > 0.05 ( = 0.806). From the MIC results, the AMK single drug was already very sensitive to the selected strains. When MEM or SCF was combined with AZM, the sensitivity of them to strains can be significantly increased. When combined with MEM and AZM, the MIC and MIC of MEM decreased to 1 and 2 ug/mL from 8 to 32 ug/mL. When combined with SCF + AZM, the MIC of SCF decreased to 16 ug/mL, and the curve shifted obviously. However, for the combination of SCF + LEV + AZM, MIC and MIC could not achieve substantive changes. From the FIC index results, the main actions of MEM + AZM were additive effects, accounting for 72%; for the combination of SCF + AZM, the additive effect was 40%. The combination of AMK or LEV with AZM mainly showed unrelated effects, and the combination of three drugs could not improve the positive correlation between LEV and AZM. AZM may increase the effect of MEM or SCF against MDR VAP. Based on MEM or SCF combined with AMK or AZM, we can achieve a good effect in the treatment of MDR VAP.
该研究的目的是探讨阿奇霉素（AZM）联合其他抗菌疗法治疗多重耐药呼吸机相关性肺炎（MDR-VAP）的效果。回顾性收集并分析临床结果，以阐明含阿奇霉素的不同联合用药方案治疗多重耐药鲍曼不动杆菌（MDR-PA）VAP的疗效。采用琼脂稀释法测定5种药物对27株MDR-PA单独或联合使用时的最低抑菌浓度（MIC）。5年内VAP的发病率约增至10.4%（961/9245），其中由MDR-PA引起的占18.4%（177/961），位列第四。临床回顾性研究共纳入151例MDR患者。临床疗效结果如下：美罗培南+阿奇霉素（MEM+AZM）为69.2%（9/13），头孢哌酮/舒巴坦+阿奇霉素（SCF+AZM）为60%（6/10），含AZM的三联药物组合为69.2%（9/13）。美罗培南+阿米卡星（MEM+AMK）的疗效优于美罗培南+左氧氟沙星（MEM+LEV）组，P=0.029（P<0.05）。头孢哌酮/舒巴坦+阿米卡星（SCF+AMK）的疗效优于头孢哌酮/舒巴坦+左氧氟沙星（SCF+LEV）组，P=0.025（P<0.05）。含AZM的二联或三联药物组合之间无显著差异，P>0.05（P=0.806）。从MIC结果来看，阿米卡星单药对所选菌株已非常敏感。当MEM或SCF与AZM联合时，它们对菌株的敏感性可显著提高。与MEM联合时，MEM的MIC和MIC25从8至32μg/mL降至1和2μg/mL。与SCF+AZM联合时，SCF的MIC降至16μg/mL，曲线明显偏移。然而，对于SCF+LEV+AZM组合，MIC和MIC25未实现实质性变化。从FIC指数结果来看，MEM+AZM的主要作用为相加作用，占72%；对于SCF+AZM组合，相加作用为40%。阿米卡星或左氧氟沙星与AZM联合主要表现为无关作用，三联药物组合未能改善左氧氟沙星与AZM之间的正相关性。AZM可能增强MEM或SCF对MDR-VAP的治疗效果。基于MEM或SCF联合阿米卡星或AZM，我们在治疗MDR-VAP方面可取得良好效果。
