In vitro efficacy of ceftazidime/avibactam and cefiderocol against multidrug-resistant Gram-negative uropathogens: insights into β-lactamase-mediated resistance in clinical isolates

Abstract

Abstract Background Urinary tract infections (UTIs) are among the most common bacterial infections in hospitalized patients, frequently caused by Gram-negative bacteria such as Escherichia coli , Klebsiella pneumoniae , Proteus mirabilis , and Pseudomonas aeruginosa . The increasing prevalence of multidrug-resistant (MDR) isolates, mainly those producing β-lactamases, presents a major therapeutic challenge. This study investigates the in vitro efficacy of ceftazidime–avibactam (CZA) and cefiderocol against MDR Gram-negative uropathogens. Methods A total of 110 Gram-negative uropathogens were included in this study. The isolates were re-identified using standard biochemical tests, and antimicrobial susceptibility was assessed via the disk diffusion method. Phenotypic and genotypic methods were performed to detect β-lactamase production in selected MDR isolates. Results Among the retrieved isolates, 89 (80.9%) were MDR. The highest MDR rates were observed in P. mirabilis (100%) and P. aeruginosa (91%), followed by K. pneumoniae (90%) and E. coli (66%). Most isolates showed high resistance to β-lactams, fluoroquinolones, and aminoglycosides. CZA showed variable activity, with the highest susceptibility in P. mirabilis (100%) and E. coli (68.1%), while resistance was significant in K. pneumoniae (83.3%) and P. aeruginosa (77.3%). Notably, cefiderocol exhibited strong in vitro activity against CZA- and carbapenem-resistant isolates, based on disk diffusion testing. Molecular analysis revealed high rates of ESBL and carbapenemase genes, particularly blaNDM-1 , blaVIM-1 , and blaOXA-48 , among CZA-resistant isolates. Conclusion These findings highlight the alarming resistance to CZA among carbapenemase and MBL producers, emphasizing the urgent need for continuous surveillance. Conversely, cefiderocol demonstrated enhanced in vitro efficacy against highly resistant isolates.