Abstract
Infections due to carbapenem-resistant Escherichia coli (CREC) are problematic due to limitation in treatment options. Combination therapies of existing antimicrobial agents have become a reliable strategy to control these infections. In this study, the synergistic effects of meropenem in combination with aminoglycosides were assessed by checkerboard and time-kill assays. Of the 35 isolates, 19 isolates (54.3%) were resistant to carbapenems (imipenem and meropenem) with the MIC ranges from 16 to 128 µg/mL. These isolates were resistant to almost all antibiotic classes. Molecular characteristics revealed co-harboring of carbapenemase (blaNDM-1, blaNDM-5 and blaOXA-48) and extended-spectrum β-lactamases (ESBL) genes (blaCTX-M, blaSHV and blaTEM). The checkerboard assay displayed synergistic effects of meropenem and several aminoglycosides against most CREC isolates. Time-kill assays further demonstrated strong synergistic effects of meropenem in combination with either amikacin, gentamicin, kanamycin, streptomycin, and tobramycin. The results suggested that meropenem in combination with aminoglycoside therapy might be an efficient optional treatment for infections cause by CREC.
Highlights
Infections due to carbapenem-resistant Escherichia coli (CREC), the New Delhi metallo-β-lactamases (NDM)-producing isolates, are critically problematic to global health care [1]
This study evaluated the effects of meropenem in combination with several commonly used aminoglycosides on CREC isolates harboring blaNDM genes
Similar to previous reports of risk factors associated with carbapenem-resistant Enterobacteriaceae (CRE) acquisition or infection [27,28], most of patients in this study had previous exposure to various antimicrobial agents, carbapenems
Summary
Infections due to carbapenem-resistant Escherichia coli (CREC), the New Delhi metallo-β-lactamases (NDM)-producing isolates, are critically problematic to global health care [1]. These infections usually yield unfavorable clinical outcomes, prolonged length of hospitalization and high hospital costs [2]. Previous studies have reported that ceftazidime-avibactam binds reversibly to class A, C, and some D β-lactamases [12,13], whereas imipenem-cilastatin-relebactam and meropenem-vaborbactam reversibly and competitively inhibited class A and C βlactamases [14,15] These antibiotics did not inhibit metallo-β-lactamases such as NDM carbapenemases [12,14,15]. This study evaluated the effects of meropenem in combination with several commonly used aminoglycosides (amikacin, gentamicin, kanamycin, streptomycin, and tobramycin) on CREC isolates harboring blaNDM genes
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