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

TABLE 3.

PV50 and PVmax of QPX7728 for enhancement of activity of biapenem against isogenic strains of KPC-2-producing P. aeruginosa overexpressing or lacking MDR RND efflux pumps

Straina Genotype/description BLI Biapenem MIC (μg/ml) in the presence of the following concn of BLIs (μg/ml)b:
 Biapenem MIC (μg/ml) for vector-only control GM biapenem MICc (μg/ml) PV50d (μg/ml) PVmaxe (μg/ml)
0 0.06 0.13 0.25 0.5 1 2 4 8 16 32 64
PAM4224 Wild type QPX7728 64 64 32 32 16 2 1 0.06 0.06 0.06 0.06 0.03 0.25 4 1 4
PAM4135 oprM::Hg QPX7728 64 32 32 32 16 2 0.5 0.06 0.03 NG NG NG 0.25 4 1 4
PAM4365 mexA::Tet QPX7728 64 32 32 16 8 2 0.5 0.125 0.125 NG NG NG 0.25 4 1 4
PAM4126 mexR (MexAB-OprM)f QPX7728 64 16 16 16 16 4 1 0.25 0.125 0.125 0.125 0.125 0.125 2.8 2 8
PAM4129 nfxB (MexCD-OprJ) QPX7728 8 8 4 4 0.5 0.06 0.03 0.03 0.03 0.03 0.3 NG 0.03 0.5 0.5 2
PAM4132 mexT (MexEF-OprM)g QPX7728 128 128 128 64 32 8 2 0.5 0.25 0.25 0.25 0.125 0.5 8 1 4
PAM4150 mexZ (MexXY-OprM) QPX7728 64 32 32 16 8 2 1 0.25 0.25 0.25 0.25 0.125 0.25 4 1 4
PAM4224 Wild type Vaborbactam 64 64 64 64 32 32 16 8 4 2 2 1 0.25 4 8 >64
PAM4135 oprM::Hg Vaborbactam 64 32 32 16 4 2 0.5 0.5 0.25 0.25 0.25 0.25 0.25 4 0.5 8
PAM4365 mexA::Tet Vaborbactam 64 32 32 16 4 2 1 0.5 0.25 0.25 0.25 0.25 0.25 4 0.5 4
PAM4126 mexR (MexAB-OprM) Vaborbactam 64 64 64 64 64 64 64 16 16 8 4 2 0.125 2.8 64 >64
PAM4129 nfxB (MexCD-OprJ) Vaborbactam 8 8 8 8 4 2 1 0.5 0.25 0.125 0.06 0.03 0.03 0.5 4 64
PAM4132 mexT (MexEF-OprM) Vaborbactam 128 32 32 32 32 32 32 32 32 32 32 64 0.5 8 >64 >64
PAM4150 mexZ (MexXY-OprM) Vaborbactam 64 64 64 32 32 32 16 8 4 4 2 1 0.25 4 8 >64
a

All strains produced KPC-2, the gene for which was carried by recombinant plasmid pUCP24-KPC-2.

b

Biapenem MICs in the presence of BLIs at PV50 and PVmax are marked in italics and boldface, respectively. NG, no growth.

c

GM MIC, the geometric mean of the antibiotic MIC values for the beta-lactamase-producing and the vector-only control strain (calculated as the square root of the product of the antibiotic MIC values for the beta-lactamase-producing and the vector-only control strain).

d

PV50, the concentration of a BLI required to achieve a 50% antibiotic potentiation effect or the concentration of a BLI required to reduce the antibiotic MIC to or below the middle point of the MIC range between the MIC for the beta-lactamase-producing strain and the MIC for the vector-only control strain. The MIC middle point is the geometric mean of the antibiotic MIC values for the beta-lactamase-producing and the vector-only control strain.

e

PVmax, maximal potentiating value, or the concentration of the BLI that reduces the antibiotic MIC to the level seen in the parent strain that lacks KPC (corresponding to the complete inhibition of KPC).

f

The specific efflux pump overexpressed due to mutations in respective regulators is shown in parentheses.

g

A mutation in mexT also results in a partial downregulation of the carbapenem-specific porin oprD.