TABLE 2.
MICs of seven fluoroquinolones and penicillin G against S. pneumoniae strains with defined mechanisms of resistancea
| Strain | Efflux | Mutant amino acid at position:
|
MIC (μg/ml)
|
||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ParC
|
GyrA
|
ParE
|
PEF | CIP | CIP+R | SPX | LVX | MXF | GAR | GAR+R | GEM | PEN | |||||
| 79 | 83 | 81 | 85 | 435 | 460 | ||||||||||||
| R6 (WT) | − | S | D | S | E | D | I | 8 | 1 | 1 | 0.25 | 0.5 | 0.125 | 0.032 | 0.032 | 0.016 | 0.008 |
| R6Lv2 | − | N | 32 | 4 | 4 | 1 | 2 | 0.5 | 0.125 | 0.125 | 0.064 | 0.016 | |||||
| R6Tr1 | − | Y | 64 | 4 | 2 | 0.5 | 1 | 0.25 | 0.064 | 0.064 | 0.064 | 0.016 | |||||
| R6Tr2 | − | F | 64 | 4 | 2 | 0.5 | 1 | 0.25 | 0.064 | 0.064 | 0.064 | 0.008 | |||||
| R6Tr3 | − | G | 64 | 4 | 2 | 0.5 | 1 | 0.25 | 0.064 | 0.064 | 0.064 | 0.016 | |||||
| R6Tr4 | − | Y | Y | 64 | 4 | 2 | 0.5 | 1 | 0.25 | 0.064 | 0.064 | 0.064 | 0.016 | ||||
| R6Mx8 | − | A | 8 | 1 | 1 | 0.5 | 1 | 0.5 | 0.064 | 0.064 | 0.064 | 0.016 | |||||
| R6Tr5 | − | Y | 8 | 1-2 | 1 | 1 | 0.5 | 0.5 | 0.125 | 0.125 | 0.064 | 0.016 | |||||
| R6Tr6 | − | F | 8 | 2 | 1 | 1 | 0.5 | 0.5 | 0.125 | 0.125 | 0.064 | 0.016 | |||||
| R6Tr7 | − | K | 8 | 1-2 | 0.5-1 | 2 | 0.5 | 0.5 | 0.125 | 0.125 | 0.064 | 0.016 | |||||
| R6Tr8 | − | Y | K | 8 | 1-2 | 1 | 2 | 0.5 | 0.5 | 0.125 | 0.125 | 0.064 | 0.016 | ||||
| SP012 | − | V | 4 | 1 | 0.5 | 0.25 | 0.5 | 0.125 | 0.064 | 0.064 | 0.032 | 0.016 | |||||
| SP003 | − | N | V | 32 | 8 | 4 | 1 | 2 | 0.25 | 0.125 | 0.125 | 0.125 | 0.016 | ||||
| R6Mx9Mx5 | − | F | N | 64 | 16 | 16 | 4 | 8 | 2 | 0.5 | 0.5 | 0.25 | 0.016 | ||||
| R6Lv2Mx6 | − | N | G | 32 | 8 | 8 | 16 | 8 | 4 | 0.5 | 0.5 | 0.25 | 0.016 | ||||
| R6Lv2Mx1 | − | N | Y | 32 | 16 | 16 | 8 | 8 | 4 | 0.5 | 0.5 | 0.125 | 0.016 | ||||
| R6Lv2Mx3 | − | N | F | 64 | 16 | 16 | 16 | 8 | 4 | 0.5 | 0.25 | 0.25 | 0.016 | ||||
| R6Tr13 | − | G | Y | 128 | 32 | 32 | 8 | 4 | 4 | 0.5 | 0.5 | 0.125 | 0.016 | ||||
| SP008 | − | F | G | 64 | 32 | 16 | 4 | 4 | 2 | 0.5 | 0.5 | 0.25 | 0.016 | ||||
| R6Tr12 | − | Y | K | 128 | 32 | 32 | 32 | 8 | 4 | 1 | 1 | 0.5 | 0.016 | ||||
| R6Tr9 | − | Y | Y | 128 | 32 | 32 | 16 | 8 | 4 | 1 | 1 | 0.25 | 0.016 | ||||
| R6Tr10 | − | Y | F | 128 | 32 | 32 | 16 | 8 | 4 | 1 | 1 | 0.25 | 0.016 | ||||
| R6Tr11 | − | F | F | 128 | 32 | 32 | 16 | 8 | 4 | 1 | 1 | 0.25 | 0.016 | ||||
| SP021 | − | Y | F | V | 64 | 32 | 16 | 4 | 8 | 2 | 1 | 1 | 0.25 | 0.016 | |||
| R6Tr17 | − | Y | Y | Y | 128 | 64 | 32 | 16 | 16 | 4 | 1 | 1 | 0.5 | 0.016 | |||
| R6Tr18 | − | Y | Y | F | 128 | 32 | 32 | 16 | 32 | 8 | 1 | 1 | 0.5 | 0.016 | |||
| R6Tr16 | − | Y | Y | K | 128 | 32 | 32 | 64 | 32 | 8 | 2 | 2 | 1 | 0.016 | |||
| R6Tr19 | − | Y | Y | K | 128 | 32 | 32 | 64 | 32 | 8 | 2 | 2 | 1 | 0.016 | |||
| R6Tr20 | − | Y | Y | Y | K | 128 | 64 | 32 | 128 | 128 | 256 | 64 | 64 | 16 | 0.016 | ||
| R6Tr5929 | + | 8 | 4 | 1 | 0.25 | 0.5 | 0.125 | 0.064 | 0.064 | 0.064 | 0.016 | ||||||
| R6TrSOB5 | + | 8 | 8 | 1 | 0.25 | 1 | 0.25 | 0.125 | 0.125 | 0.064 | 0.016 | ||||||
a
R6Lv, first-step mutants selected on levofloxacin; R6Mx, first-step mutant selected on moxifloxacin; R6MxMx, resistant mutant selected in two steps on moxifloxacin; R6LvMx, resistant mutants first selected on levofloxacin and in a second step on moxifloxacin (16). R6Tr, R6 transformed with genes harboring the indicated mutation(s) (27). SP, clinical isolates of S. pneumoniae. The efflux mechanism of S. oralis SOB5 was transformed into R6 (12). PEF, pefloxacin; CIP, ciprofloxacin; R, reserpine (10μg/ml); SPX, sparfloxacin; LVX, levofloxacin; MXF, moxifloxacin; GAR, garenoxacin; GEM, gemifloxacin; PEN, penicillin G.