Comparison of in vitro and in vivo antimicrobial activity of ceftazidime/avibactam alone or in combination with aztreonam against carbapenem-re-sistant Enterobacterales
Objective To investigate the in vivo and in vitro antimicrobial activity of ceftazidime/avibactam(CZA)alone or in combination with aztreonam(ATM)against carbapenem-resistant Enterobacterales(CRE),and provide evidence for clinical anti-infective therapy.Methods The minimum inhibitory concentrations(MICs)of CZA and ATM against 52 clinically isolated non-repetitive CRE strains in a hospital from 2018 to 2022 were deter-mined with microbroth dilution method,and the combined antimicrobial susceptibility testing was performed with the chessboard dilution method.Time-killing curve and Galleria mellonella infection model were used to test the bac-tericidal effect of CZA alone or in combination with ATM.Results Among the 23 KPC-producing CRE strains,91.3％(n=21)had MIC ≤ 4 μg/mL for CZA,and 8.7％(n=2)had MIC ≥128 μg/mL for CZA.MIC of CZA to 29 CRE strains(strains producing NDM,IMP,KPC+IMP,and KPC+NDM)were all ≥128 μg/mL.Of the 31 CZA-resistant strains,93.5％(n=29)strains had fractional inhibitory concentration(FIC)＜0.5 for combination of CZA and ATM,while 6.5％(n=2)had FIC of 0-1.The time-killing curve showed that CZA had bactericidal effect on KPC-producing strains,and CZA combined with ATM had bactericidal effect on CZA-resistant strains.Compared with the monotherapy group,CZA combined with ATM treatment significantly improved the survival rate of CRE-infected Galleria mellonella(median survival time 120 hour,P=0.001).Conclusion CZA has good antimi-crobial activity against KPC-producing bacteria.The combination of CZA and ATM had synergistic bacteriostatic effect on CZA-resistant strains.
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