In Vitro Synergistic Effect and Mutant Prevention Concentrations of Cefepime Alone or in Combination with Sulbactam Against OXA-48-positive Klebsiella pneumoniae Isolates

Mataracı-Kara E., Yılmaz M., Özbek-Çelik B.

Current Microbiology, vol.77, pp.2137-2142, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 77
  • Publication Date: 2020
  • Doi Number: 10.1007/s00284-020-02094-0
  • Journal Name: Current Microbiology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.2137-2142
  • Istanbul University Affiliated: Yes


The aim of this study is to investigate the combination of cefepime and sulbactam. Sulbactam, when administered , will effectively inhibit all Extended-spectrum beta lactamases (ESBLs) of the microorganism, while cefepime will inhibit the growth of the resistant microorganisms since it will not be hydrolyzed by OXA-48. Forty OXA-48-producingK. pneumoniaestrains were investigated for their Minimum inhibitory concentrations (MICs) for carbapenems, cefepime, and cefepime + sulbactam by broth microdilution method. Also, the mutant prevention concentration (MPC)s of cefepime alone or in combination with sulbactam was determined. Additionally, the bactericidal activities of cefepime and cefepime + sulbactam were evaluated by the time-kill curve (TKC) assay against selected strains. Also, the in vitro synergistic activity of cefepime + sulbactam combination was determined by TKC. Based on MIC results, up to 35/40 and 34/40 of the strains were resistant to carbapenems and cefepime, respectively. Cefepime + sulbactam MIC range was lower than those for cefepime alone against all the studied isolates. Moreover, cefepime + sulbactam combination presented lower MPC values than cefepime alone. The synergistic interactions of cefepime + sulbactam were also achieved against studied strains at 24 h. No antagonism was observed against studiedK. pneumoniaestrains. The findings of this study displayed that cefepime + sulbactam combination had synergistic or additive effect against OXA-48-producingK. pneumoniaestrains. Additionally, it was first observed that this combination could display a lower MPC than cefepime alone. Further investigations may be helpful for understanding the effectiveness of cefepime + sulbactam combinations for OXA-48-positive carbapenem-resistantK. pneumoniaeisolates.