In vitro activity of meropenem-vaborbactam combinations and eravacycline against carbapenem-resistant Acinetobacter baumannii

美罗培南-伐巴坦组合和依拉环素对耐碳青霉烯类鲍曼不动杆菌的体外活性

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Abstract

Treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) presents a growing clinical challenge. This study evaluated the in vitro efficacy of eravacycline and the potential synergistic activity of meropenem-vaborbactam in combination with either gentamicin or ceftazidime against carbapenemase-producing Acinetobacter baumannii isolates. A total of 25 CRAB isolates were collected from different clinical samples. Antimicrobial susceptibility was determined via disc diffusion. Meropenem was tested by both disc diffusion and gradient strips. Polymerase chain reaction (PCR) was used to screen these isolates for the carbapenemase genes bla(OXA-51,) bla(OXA-23,) bla(IMP), bla(VIM), bla(OXA-48), bla(NDM) and bla(KPC). Extensively drug-resistant (XDR) CRAB isolates were selected for evaluating colistin, eravacycline and the in vitro synergy of antimicrobial combinations via gradient strips for meropenem-vaborbactam, gentamicin, and ceftazidime. All CRAB isolates were sensitive to tigecycline and were either multidrug resistant or XDR. The minimum inhibitory concentrations (MIC50s and MIC90s) of meropenem were 32 μg/mL and 256 μg/mL, respectively. Among these genes, bla(OXA-23) was the most prevalent gene. The MIC(50) and MIC(90) of colistin were 1 and 2 μg/mL, respectively. The MIC(50) and MIC(90) of eravacycline were 0.125 μg/mL and 0.5 μg/mL, respectively. Meropenem-vaborbactam in combination with ceftazidime or gentamicin showed synergy in 45.5% and 36.4% of the XDR isolates and additivity/indifference in 54.5% and 63.6% of them, respectively, with no antagonism. Our findings suggest that eravacycline, as well as combination therapies involving meropenem-vaborbactam with either gentamicin or ceftazidime, may offer promising therapeutic potential for CRAB infections pending further clinical evaluation. These agents demonstrated notable in vitro activity, including potential synergistic effects, particularly against isolates harboring carbapenemase enzymes.

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