Table 1 MICs (mg/L) of ceftazidime-avibactam (CZA), meropenem and meropenem in combination with CZA determined on E. cloacae KPC-3 (RD26), and a subset of CZA resistant mutants obtained after exposure to cytotoxic agents (Dacarbazine (Dc10), azacitidine (Az0.5), cyclophosphamide (Cyclo2.5), mitoxantrone (Mtx5), daunorubicin (Dn50) used at the concentrations of 10, 0.5, 2.5, 5 and 50 mg/L respectively), and on E. coli TOP10 electroporated with pBR322 plasmid harboring the same blaKPC genes. MICs of antibiotics and mutations in blaKPC observed in E. cloacae KPC-3 (RD26) of CZA-resistant mutants and transformantsa, selected after exposure to cytotoxic agents.
Cytotoxic agent | Isolates | MIC (mg/L) | Identified mutation in blaKPC | Reference | ||
|---|---|---|---|---|---|---|
Ceftazidime-Avibactam | Meropenem | Meropenem + Ceftazidime-Avibactam | ||||
— | RD26 (KPC-3) | 4 | 16 | 0.023 | ||
Top10-pBR322-RD26 | 1 | 1.5 | 0.016 | |||
Dc10 | RD26-1 | 16 | 0.094 | 0.047 | R164P | Winkler et al. |
— | — | — | — | |||
Dc10 | RD26-2 | 32 | 0.094 | 0.032 | R164P | Winkler et al. |
Top10-pBR322-RD26-2 | 24 | 0.032 | 0.012 | |||
Az0.5 | RD26-3 | 16 | 0.125 | 0.047 | D179H | This study |
Top10-pBR322-RD26-3 | 24 | 0.032 | 0.016 | |||
Dc10 | RD26-4 | 32 | 0.125 | 0.064 | D179Y | Livermore et al. |
— | — | — | ||||
Dc10 | RD26-5 | 12 | 0.38 | 0.023 | T243M | Haidar et al. |
Top10-pBR322-RD26-5 | 12 | 0.064 | 0.016 | |||
Mito5 | RD26-6 | 32 | 2 | 0.032 | G175-S-A-I-P-G-D176 | This study |
Top10-pBR322-RD26-6 | 24 | 0.023 | 0.016 | |||
Cyclo2.5 | RD26-7 | 48 | 0.094 | 0.047 | D176-∆A177-∆R178-∆D179-T180 | This study |
Top10-pBR322-RD26-7 | 24 | 0.064 | 0.016 | |||
Dc10 | RD26-8 | 32 | 1 | 0.032 | K273-D-D-K-Y274 | KPC-29 |
Top10-pBR322-RD26-8 | 24 | 0.125 | 0.023 | |||
Dn50 | RD26-9 | 32 | 0.125 | 0.047 | C238-∆G239-∆V240-Y241 | This study |
Top10-pBR322-RD26-9 | 64 | 0.023 | 0.023 | |||
