Introduction Carbapenem antibiotics are among the last-resort treatments for infections caused by multidrug-resistant bacteria. The emergence and spread of carbapenem resistance (CR) have led researchers to seek alternative treatment approaches to antibiotic monotherapy. The goal of this study was to investigate the effect of combining meropenem, a carbapenem antibiotic, with other antibiotics and bacteriophages in vitro against CR Gram-negative uropathogens to detect potential synergism.
Methods The checkerboard assay was used to explore potential synergistic effects against 19 CR- Gram-negative uropathogens when combining meropenem with amikacin, colistin, and tigecycline. Bacteriophages were isolated from hospital sewage, morphologically classified, and lytic phages were combined with meropenem for detecting potential synergistic effects against the tested CR Gram-negative uropathogens.
Results Combining meropenem with amikacin, colistin, and tigecycline showed additive effects against 89.4%, 63.2%, and 68.4% of the tested CR uropathogens, respectively. Synergism was observed against a CR K. terrigena isolate when meropenem and amikacin were combined at doses of 4 and 8 µg/ml, respectively. The isolated phages belong to the Myoviridae family of the order Caudovirales. In plaque assay, translucent halos were formed around the clear plaques of phages infecting a CR A. baumannii isolate, suggesting the depolymerase-producing ability of these phages. Combining the isolated phages in this study with meropenem did not exhibit any synergistic effect in vitro against the tested isolates.
Conclusions Meropenem/amikacin combination showed in vitro synergistic activity against a clinical CR K. terrigena isolate. Synergism was absent upon combining meropenem with the isolated phages in this study against CR Gram-negative uropathogens.