Table 2. Antimicrobial Susceptibility of the Optimized NBTIs against a Panel of Gram-Positive and Gram-Negative Bacterial Pathogens.
MIC
(μg/mL) |
||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
compound | 1a | 2a | 3a | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | Gepo |
S. aureus (ATCC 29213) | 0.125 | 0.031 | 0.008 | 0.031 | 0.008 | 0.008 | 0.008 | 0.004 | 0.008 | 0.031 | 0.008 | 1 | 0.125 | 0.125 |
E. coli (ATCC 25922) | 4 | 2 | 2 | 2 | 1 | 0.5 | 0.5 | 0.5 | 1 | 4 | 2 | 32 | 32 | 1 |
E. coli D22b | 2 | 0.125 | 0.125 | 0.25 | 0.062 | 0.062 | 0.031 | 0.016 | 0.25 | 0.5 | 0.125 | 4 | 16 | 0.125 |
E. coli N43c (CGSC no. 5583) | 0.5 | 0.125 | 0.078 | 0.062 | 0.031 | 0.016 | 0.062 | 0.008 | 0.062 | 0.125 | 0.031 | 8 | 8 | 0.016 |
MRSA (QA-11.7)d | 0.5 | 0.062 | 0.008 | 0.031 | 0.016 | 0.016 | 0.031 | 0.016 | 0.016 | 0.062 | 0.031 | 1 | 0.25 | 0.062 |
MRSA (QA-12.1)e | ND | ND | ND | 0.031 | 0.031 | 0.016 | 0.031 | 0.016 | 0.016 | 0.062 | 0.062 | 2 | 0.25 | 0.125 |
Klebsiella pneumoniae | ND | ND | ND | 32 | 16 | 8 | 8 | 8 | 64 | 64 | 32 | >128 | >128 | 8 |
Salmonella alachua RDK 030c (QA-1482/04) | 32 | 16 | 8 | 8 | 4 | 2 | 2 | 1 | 16 | 16 | 8 | >128 | >128 | 4 |
Pseudomonas aeruginosa RDK 184 (DSM 939) | >128 | 128 | 32 | 64 | 32 | 16 | 16 | 8 | 128 | >128 | 64 | >128 | >128 | 8 |
Streptococcus agalactiae RDK 047 (QA-990/02) | 1 | 0.5 | 0.125 | 1 | 2 | 0.25 | 0.5 | 0.25 | 0.25 | 2 | 0.5 | 64 | 8 | ND |
Enterococcus faecalis DRK 057 (ATCC 29212) | 1 | 1 | 1 | 2 | 0.5 | 0.25 | 0.5 | 0.5 | 0.5 | 2 | 0.5 | 32 | 4 | ND |
Ref (31). ATCC, American Type Culture Collection; CGSC, Coli Genetic Stock Centre; QA, quality assurance; DSM, German Collection of Microorganisms and Cell Cultures; ND, not determined; Gepo, gepotidacin.
With a mutation in the lpxC gene that increases membrane permeability.
With the AcrA knockout (cell membrane efflux pump).
Resistant to cefoxitin, ciprofloxacin, clindamycin, erythromycin, tetracycline, thiamulin, and trimethoprim.
Resistant to cefoxitin, gentamicin, kanamycin, rifampicin, streptomycin, sulfamethoxazole, and tetracycline.