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. 2020 May 21;64(6):e00552-20. doi: 10.1128/AAC.00552-20

TABLE 1.

PVmax of QPX7728 for enhancement of the activity of meropenem against isogenic strains of KPC-3-producing K. pneumoniae with various combinations of efflux and porin mutationsa

KPC-3-producing strain Recipient strain Genotype/construction Expression
Meropenem MIC (μg/ml) for KPC-3-producing strain with:
Meropenem MIC (μg/ml) for recipient PVmax (μg/ml)
OmpK35 OmpK36 AcrAB No drug QPX VAB QPX VAB
KPM1271 KPM1026a Wild type FL FL BL 16 0.016 0.06 0.06 0.125 0.25
KPM2601 KPM2600 ΔompK35 NF FL BL 32 0.016 0.06 0.06 0.125 1
KPM2599 KPM2592 ΔompK36 FL NF BL 32 0.03 0.25 0.06 1 16
KPM2067 KPM2040 ompK36_fs FL NF BL 64 0.03 0.5 0.125 2 16
KPM2631 KPM2613 ompK36_fs ΔompK35 NF NF BL 256 0.25 4 0.25 2 64
KPM2965 KPM2966 ramR* ompK36_fs ΔompK35 NF NF Up 256 0.5 8 0.5 4 64
KPM1272 KPM1027 ramR_fs Down FL Up 16 0.016 0.06 0.06 0.25 2
KPM2818 KPM2658 ramR_fs ΔompK36 Down NF Up 256 0.5 8 0.5 4 64
KPM1007 ΔacrB FL FL NF ND ND ND 0.06 ND ND
KP1004 KPM1206 ompK35_fs NF FL BL 32 0.016 0.03 0.03 0.25 2
KP1074 KPM1211 ompK35_fs ompK36_GD NF GD BL 128 0.06 1 0.125 2 32
a

All strains produced KPC-3 and TEM-1, the genes for which were carried by plasmid pKpQIL. Both the KPM1026a derivatives and clinical isolates also produced a chromosomal SHV enzyme, encoded by blaSHV-24 and blaSHV-11, respectively. ompK35_fs and ompK36_fs, truncated porins due to the frameshift mutation; ramR*, truncated ramR due to the stop codon; FL, full length; NF, nonfunctional; BL, basal level; Up, overexpressed; Down, downregulated; QPX, QPX7728; VAB, vaborbactam at 4 μg/ml; ND, not determined; GD, duplication of two amino acids, Gly134 and Asp135, located within the L3 internal loop and associated with the reduced susceptibility to carbapenems due to constriction of the channel; PVmax, maximal potentiating value, which is the concentration of the BLI that reduces the meropenem MIC to the level seen in the parent strain that lacks KPC, which corresponds to the complete inhibition of KPC. KPC-3-producing strain was not constructed for KPM1007.