TABLE 1.
MICs of β-lactams and non-β-lactams for K. pneumoniae strains producing wild-type and modified KPC-2 and KPC-3b
Isolate or mutant | MIC (μg/ml) of: |
KPC mutation characteristic |
||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
PIP | PIP-TAZ | CAZ | CAZ-AVI | ETP | IPM | IPM-REL | MEM | MEM-VAB | ATM | ATM-AVI | Mutation | Source, reference, or allelea | Position in protein | |
P-KPC−2 | ≥256 | ≥256 | 32 | 0.5 | 8 | 8 | 0.5 | 8 | 0.5 | 128 | 0.5 | NA | NA | NA |
M1a | ≥256 | 128 | 64 | 16 | 0.5 | 2 | 0.25 | 1 | 0.064 | 64 | 0.5 | T243M | This study | β7-β8 |
M2a | ≥256 | 128 | 128 | 8 | 1 | 4 | 0.5 | 2 | 0.064 | 128 | 0.5 | R164H | This study | Ω-loop |
M3a | ≥256 | 16 | 64 | 8 | 1 | 4 | 0.25 | 1 | 0.064 | 64 | 0.5 | S109P | This study | α3-α4 |
M4a | ≥256 | 8 | 64 | 8 | 0.25 | 0.5 | 0.125 | 0.5 | 0.064 | 8 | 0.125 | D179A | 23 | Ω-loop |
M5a | ≥256 | 8 | 64 | 8 | 0.5 | 2 | 0.25 | 1 | 0.064 | 8 | 0.125 | T243P | This study | β7-β8 |
M6a | ≥256 | 32 | 64 | 8 | 0.5 | 2 | 0.125 | 0.5 | 0.064 | 16 | 0.25 | A35G | This study | α1 |
M7a | 128 | 4 | ≥256 | 32 | 0.125 | 0.25 | 0.125 | 0.125 | 0.064 | 2 | 0.125 | D179V | KPC-57 | Ω-loop |
M8a | ≥256 | 16 | ≥256 | 64 | 0.25 | 0.25 | 0.125 | 0.5 | 0.064 | 4 | 0.125 | D179Y | KPC-33 | Ω-loop |
M9a | ≥256 | 128 | 64 | 16 | 1 | 2 | 0.25 | 0.5 | 0.064 | 32 | 0.25 | R178P | This study | Ω-loop |
M10a | ≥256 | 128 | ≥256 | 16 | 1 | 4 | 0.5 | 0.5 | 0.064 | 128 | 0.5 | D176N | This study | Ω-loop |
M11a | 128 | 16 | 64 | 16 | 0.25 | 1 | 0.125 | 0.25 | 0.032 | 8 | 0.125 | D176Y | 21 | Ω-loop |
M12a | ≥256 | 4 | 64 | 16 | 0.125 | 0.25 | 0.125 | 0.064 | 0.064 | 2 | 0.125 | R164P | 23 | Ω-loop |
M13a | ≥256 | 32 | 128 | 32 | 0.125 | 0.5 | 0.25 | 0.064 | 0.064 | 2 | 0.125 | Del174–Del177 | This study | Ω-loop |
M14a | ≥256 | 4 | 64 | 32 | 0.064 | 0.25 | 0.125 | 0.064 | 0.064 | 2 | 0.125 | Del171–Del174 | This study | Ω-loop |
M15a | ≥256 | 16 | 64 | 16 | 0.064 | 4 | 0.5 | 0.064 | 0.064 | 2 | 0.125 | AT ins at 243 | This study | β7-β8 |
M16a | ≥256 | 16 | 128 | 64 | 0.125 | 2 | 0.25 | 0.125 | 0.064 | 8 | 0.125 | 20-aa ins at 288 | This study | α12 |
P-KPC-3 | ≥256 | ≥256 | 32 | 2 | 8 | 4 | 0.25 | 4 | 0.5 | 128 | 0.5 | NA | NA | NA |
M1b | ≥256 | 256 | ≥256 | 64 | 0.25 | 2 | 0.125 | 0.5 | 0.064 | 128 | 0.5 | 8-aa ins at 271 | This study | β9-α12 |
M2b | ≥256 | 64 | ≥256 | 64 | 0.125 | 0.5 | 0.125 | 0.5 | 0.064 | 128 | 0.5 | S171P | KPC-61 | Ω-loop |
M3b | ≥256 | 16 | 128 | 16 | 0.125 | 0.25 | 0.125 | 0.125 | 0.032 | 32 | 0.125 | D179G | This study | Ω-loop |
M4b | ≥256 | 8 | 64 | 16 | 0.125 | 0.25 | 0.125 | 0.125 | 0.032 | 64 | 0.5 | P67Q | This study | β3 |
M5b | ≥256 | 256 | 64 | 16 | 0.25 | 1 | 0.125 | 0.125 | 0.032 | 32 | 0.125 | P174L | 22 | Ω-loop |
M6b | ≥256 | 16 | 64 | 32 | 0.125 | 0.5 | 0.125 | 0.064 | 0.032 | 4 | 0.125 | D176Y | 22 | Ω-loop |
M7b | ≥256 | 16 | 256 | 64 | 0.125 | 0.25 | 0.125 | 0.064 | 0.032 | 32 | 0.5 | D179Y | KPC-31 | Ω-loop |
M8b | ≥256 | 32 | 128 | 32 | 0.125 | 2 | 0.25 | 0.064 | 0.032 | 64 | 0.5 | T243P | 22 | β7-β8 |
M9b | ≥256 | 16 | 64 | 16 | 0.125 | 2 | 0.125 | 0.064 | 0.032 | 64 | 0.25 | T243M | 22 | β7-β8 |
M10b | ≥256 | 32 | 128 | 64 | 0.125 | 2 | 0.125 | 0.064 | 0.032 | 64 | 0.5 | A172P | 22 | Ω-loop |
Reference given if in vitro mutant was identified in a previous study.
Resistant strains based on EUCAST breakpoints are highlighted with shading. CAZ, ceftazidime; AVI, avibactam; PIP, piperacillin; TAZ, tazobactam; ETP, ertapenem; IPM, imipenem; REL, relebactam; MEM, meropenem; VAB, vaborbactam; ATM, aztreonam; aa, amino acid; ins, insertion.