Abstract

BackgroundTreatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. We assessed the efficacy of ceftazidime (CAZ), ceftazidime-avibactam (CAZ-AVI), aztreonam (ATM), and aztreonam-avibactam (ATM-AVI) against a selection of 76 S. maltophilia out of the 1179 strains isolated from the First Affiliated Hospital of Chongqing Medical University during 2011–2018.MethodsWe investigated the antimicrobial resistance profiles of the 1179 S. maltophilia clinical isolates from the first affiliated hospital of Chongqing Medical University during 2011–2018, a collection of 76 isolates were selected for further study of microbiological characterization. Minimum inhibitory concentrations (MICs) of CAZ, CAZ-AVI, ATM and ATM-AVI were determined via the broth microdilution method. We deemed that CAZ-AVI or ATM-AVI was more active in vitro than CAZ or ATM alone when CAZ-AVI or ATM-AVI led to a category change from “Resistant” or “Intermediate” with CAZ or ATM alone to “Susceptible” with CAZ-AVI or ATM-AVI, or if the MIC of CAZ-AVI or ATM-AVI was at least 4-fold lower than the MIC of CAZ or ATM alone.ResultsFor the 76 clinical isolates included in the study, MICs of CAZ, ATM, CAZ-AVI and ATM-AVI ranged from 0.03–64, 1–1024, 0.016–64, and 0.06–64 μg/mL, respectively. In combined therapy, AVI was active at restoring the activity of 48.48% (16/33) and 89.71% (61/68) of S. maltophilia to CAZ and ATM, respectively. Furthermore, CAZ-AVI showed better results in terms of the proportion of susceptible isolates (77.63% vs. 56.58%, P < 0.001), and MIC50 (2 μg/mL vs. 8 μg/mL, P < 0.05) when compared to CAZ. According to our definition, CAZ-AVI was more active in vitro than CAZ alone for 81.58% (62/76) of the isolates. Similarly, ATM-AVI also showed better results in terms of the proportion of susceptible isolates (90.79% vs.10.53%, P < 0.001) and MIC50 (2 μg/mL vs. 64 μg/mL, P < 0.001) when compared to ATM. According to our definition, ATM-AVI was also more active in vitro than ATM alone for 94.74% (72/76) of the isolates.ConclusionsAVI potentiated the activity of both CAZ and ATM against S. maltophilia clinical isolates in vitro. We demonstrated that CAZ-AVI and ATM-AVI are both useful therapeutic options to treat infections caused by S. maltophilia.

Highlights

  • Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited

  • Microbiological characteristics and antimicrobial susceptibility profiles of S. maltophilia isolates In total, 1179 non-repetitive S. maltophilia strains were isolated during the study period, among which the predominant sample origins were sputum (73.0%), followed by secretion from various body sites such as secretions from surgical incisions, burns, or conjunctival sacs (7.0%) and urine (5.0%)

  • Inhibitory activities of CAZ-AVI and ATM-AVI against S. maltophilia isolates To assess the potential efficacy of CAZ-AVI and ATMAVI against S. maltophilia isolates, we have tested these combinations in vitro on a collection of 76 non-repetitive isolates available for microbiological characterization

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Summary

Introduction

Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. S. maltophilia is primarily associated with respiratory tract infections, this pathogen can cause a wide range of clinical syndromes, including catheter-associated bloodstream infections, and skin and soft tissue infections [2,3,4] It has emerged as an important nosocomial pathogen associated with crude mortality rates ranging from 14 to 69% in patients with bacteremia [5, 6]. S. maltophilia is intrinsically resistant to different classes of antibiotics used in clinical practices, which was mediated by the expression of aminoglycoside-modifying enzymes, qnrB-like quinolone-resistant determinants, multidrug efflux pumps, and two β-lactamases (L1 and L2) [1, 8, 9] These characteristics, together with its ability to adapt to environmental changes, contribute to the difficulty in effectively managing S. maltophilia infections

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