Antibacterial activity of colistin against Pseudomonas aeruginosa isolates co-resistant to carbapenem and ceftazidime-avibactam in vitro
Objective Ceftazidime-avibactam(CZA)is an effective alternative antibiotic for the clinical treatment of carbapenem-resistant Pseudomonas aeruginosa(CRPA)strains.However,the emergence of CZA-resistant CRPA in clinics has increased the difficulty of treating P.aeruginosa infections.The objective of our study was to investigate the in vitro bactericidal activity of colistin(COL)against CZA-resistant P.aeruginosa isolates carrying different carbapenemase genes using time-kill analysis,which provided a scientific basis for the clinical treatment of P.aeruginosa infections.Methods CZA-resistant P.aeruginosa isolates were collected from a tertiary hospital in Zhejiang Province,China.Five representative P.aeruginosa isolates carrying carbapenemase genes,including P.aeruginosa PA 4696 carrying blaKPC-2,P.aeruginosa PA 2207 carrying blaKPC-90,P.aeruginosa PA 1308 carrying blaKPC-33,P.aeruginosa PA 2070 carrying blaVIM,P.aeruginosa and PA 6227 carrying blaIMP-45 were selected by polymerase chain reaction(PCR)and whole genome sequencing.Antibiotic susceptibility was confirmed by broth microdilution.Time-kill experiments were performed in duplicates for each isolate.Results All five isolates were resistant to CZA(MIC≥ 16/4 mg/L)and sensitive to COL(MIC≤2 mg/L).And P.aeruginosa PA 6227,which carried blaIMP-45,showed a specific drug-sensitive phenotype(ISMR)and was sensitive to IPM(MIC=2 mg/L)but resistant to other carbapenems such as MEM(MIC=128 mg/L).Time-killing curves showed that the five CZA-resistant P.aeruginosa isolates were completely inhibited for the first 2～8 hours at different concentrations of COL,but then resumed regrowth.Conclusion COL had in vitro bactericidal activity against CZA-resistant CRPA isolates but could not be used alone.The presence of different carbapenem resistance genes affected the efficacy of CZA,but was not related to the bactericidal activity of COL,and isolates carrying different carbapenem resistance genes all showed regeneration at different times.In the treatment of P.aeruginosa infections,the dosing interval or drug concentration can be adjusted to maintain the concentration of COL to achieve a better treatment effect.Attention should also be paid to the clinical presence of CRPA with this particular phenotype of ISMR to avoid the irrational application of antibiotics.
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