Clinical Efficacy and In Vitro Drug Sensitivity Test Results of Azithromycin Combined With Other Antimicrobial Therapies in the Treatment of MDR P. aeruginosa Ventilator-Associated Pneumonia

Yuqin Huang; Wenguo Wang; Qiang Huang; Zhengyan Wang; Zhuanzhuan Xu; Chaochao Tu; Dongli Wan; Miaobo He; Xiaoyi Yang; Huaqiang Xu; Hanqin Wang; Ying Zhao; Mingli Tu; Quan Zhou

doi:10.3389/fphar.2022.944965

Clinical Efficacy and In Vitro Drug Sensitivity Test Results of Azithromycin Combined With Other Antimicrobial Therapies in the Treatment of MDR P. aeruginosa Ventilator-Associated Pneumonia

Front Pharmacol. 2022 Aug 10:13:944965. doi: 10.3389/fphar.2022.944965. eCollection 2022.

Authors

Yuqin Huang¹, Wenguo Wang¹, Qiang Huang¹, Zhengyan Wang², Zhuanzhuan Xu², Chaochao Tu², Dongli Wan¹, Miaobo He¹, Xiaoyi Yang³, Huaqiang Xu¹, Hanqin Wang⁴, Ying Zhao⁵, Mingli Tu², Quan Zhou¹

Affiliations

¹ Intensive Care Unit, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, China.
² Department of Respiratory Medicine, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, China.
³ Department of Medicine, First Clinical School, Guangzhou Medical University, Guangzhou, China.
⁴ Center for Translational Medicine, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, China.
⁵ Department of Clinical Laboratory, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

Abstract

Objective: The aim of the research was to study the effect of azithromycin (AZM) in the treatment of MDR P. aeruginosa VAP combined with other antimicrobial therapies. Methods: 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. Results: The incidence of VAP has increased approximately to 10.4% (961/9245) in 5 years and 18.4% (177/961) caused by P. aeruginosa ranking fourth. A total of 151 cases of MDR P. aeruginosa 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, p = 0.029 (p < 0.05). The curative effect of cefoperazone/sulbactam + amikacin (SCF + AMK) was better than that of the cefoperazone/sulbactam + levofloxacin (SCF + LEV) group, p = 0.025 (p < 0.05). There was no significant difference between combinations of two or three drugs containing AZM, p > 0.05 (p = 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 MIC₅₀ and MIC₉₀ of MEM decreased to 1 and 2 ug/mL from 8 to 32 ug/mL. When combined with SCF + AZM, the MIC₅₀ of SCF decreased to 16 ug/mL, and the curve shifted obviously. However, for the combination of SCF + LEV + AZM, MIC₅₀ and MIC₉₀ 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. Conclusion: AZM may increase the effect of MEM or SCF against MDR P. aeruginosa VAP. Based on MEM or SCF combined with AMK or AZM, we can achieve a good effect in the treatment of MDR P. aeruginosa VAP.

Keywords: Pseudomonas aeruginosa; azithromycin; in vitro drug sensitivity test; multidrug-resistant; ventilator-associated pneumonia.