Antibacterial activity of fosfomycin in combination with eight antimicrobial agents against carbapenem-resistant Enterobacteriaceae

Abstract

Objective To investigate the antimicrobial activity of fosfomycin combined with other antibiotics against carbapenem-resistant enterobacteriaceae(CRE). Methods A total of 233 non-repititive CRE isolates were collected from January 2010 to December 2014 from 4 hospitals, including Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou Traditional Chinese Medicine Hospital, Zhejiang Provincial People's Hospital and Second Hospital of Jiaxing. Antimicrobial susceptibility of fosfomycin, imipenem, meropenem, cefepime, ceftazidime, ceftriaxone, cefperazone-sulbactam, piperacillin-tazobactam, ciprofloxacin, amikacin, tobramycin, polymyxin B and tigecycline were determined by agar dilution method. Synergistic effect between fosfomycin and other antibiotics, including meropenem, cefepime, ceftazidime, cefperazone-sulbactam, ciprofloxacin, amikacin, tobramycin and tigecycline against 30 CRE isolates was determined by chequerboard assay.Chi-Square test was used for statistical analysis, and the difference was statistical significant when P<0.05. Results An overall 45.1%(105/233) of 233 CRE isolates were resistant to fosfomycin. Among which, Klebsiella spp. possessed the highest resistance rate (61.9%, 73/118), followed by Enterobacter spp. (50%, 15/30), Serratia marcescens (25%, 7/28), and Escherichia coli (8.2%, 4/49). Fosfomycin in combination with tigecyclin showed best activity against CRE isolates with a synergy rate of 76.7%(23/30). Fosfomycin and aminoglycosides also presented good activity against CRE isolates with synergy rate of 53.3%(16/30) to 70.0%(21/30). Synergism was observed only in 30%(9/30) of CRE isolates for the combination of fosfomycin and ciprofloxacin. As for the combination of fosfomycin and β-lactam antibiotics, even less synergism was observed (0%-3.3%)(1/30). No antagonism was demonstrates among all of the combinations. Conclusions Fosfomycin demonstrates certain in vitro activity against CRE isolates. A combination of fosfomycin and tigecyclin or aminoglycosides shows good activity, which suggests a new strategy in the campaign against serious infections caused by CRE.(Chin J Lab Med, 2016, 39: 629-632) Key words: Enterobacteriaceae; Fosfomycin; Anti-bacterial agents; Drug therapy, combination; Drug synergism; Drug resistance, bacterial