RT Journal Article
T1 In vitro and in vivo evaluation of two combined β-lactamase inhibitors against carbapenem-resistant Acinetobacter baumannii
A1 Vila Domínguez, Andrea
A1 Molina Panadero, Irene
A1 Smani, Younes
K1 Acinetobacter baumannii
K1 Clavulanic acid
K1 Tazobactam
K1 Combination
AB The objective of this study was to evaluate the in vitro and in vivo efficacy of clavulanic acid (C/A) in combination with tazobactam against clinical strains of carbapenem-resistant Acinetobacter baumannii. The MIC of 24 clinical strains of A. baumannii was determined, and a checkerboard assay and time-kill curve analysis were performed in selected strains to determine the synergy between C/A and tazobactam. The efficacy of C/A in monotherapy and in combination with tazobactam was evaluated in vitro in cell culture experiments and in a murine peritoneal sepsis model. The C/A and C/A plus tazobactam MIC50 were 128 and <1 mg/L, respectively. The checkerboard assay showed that tazobactam (4 and 8 mg/L) demonstrated synergy with C/A against A. baumannii Ab40, an OXA-24 producer strain, and Ab293, a lacking OXA β-lactamase strain. The time-kill curve assay showed both bactericidal and synergistic effects against Ab40 and Ab293, with C/A 1xMIC and tazobactam (4 and 8 mg/L) at 24 h. In the murine peritoneal sepsis model with Ab293 strain, the combination of C/A and tazobactam reduced bacterial loads in tissues and blood by 2 and 4 log10 CFU/g or mL compared with C/A alone. Combining C/A with tazobactam could be considered as a potential alternative strategy to treat A. baumannii in some cases, and future work with more strains is needed to confirm this possibility.
PB Springer
YR 2023
FD 2023-09-15
LK http://hdl.handle.net/10433/16566
UL http://hdl.handle.net/10433/16566
LA en
NO European Journal of Clinical Microbiology & Infectious Diseases (2023)
NO Centro Andaluz de Biología del Desarrollo
NO Universidad Pablo de Olavide
DS RIO
RD May 9, 2026