Table 3.
Static dose, maximum killing and 24 h AUC/MIC ratio required for a static effect of lefamulin (q12h) against 10 organisms
| Organism/ strain | MICa (mg/L) | Comments | Static dose (mg/kg/12 h) | Total 24 h AUC/MIC derived from static dose | 24 h fAUC/MICb derived from static dose | 1 log kill dose (mg/kg/12 h) | 24 h fAUC/MICb derived from 1 log kill dose | Maximal killing (log10 cfu/thigh) |
|---|---|---|---|---|---|---|---|---|
| S. pneumoniae | ||||||||
| ATCC 10813 | 0.12 | PSSP | 18.6 | 32.1 | 6.42 | 34.7 | 15.12 | –2.86 |
| CDC 145 | 0.06 | PRSP, MR | 5.45 | 15.0 | 3 | 7.98 | 4.38 | –2.62 |
| CDC 1020 | 0.12 | PRSP, MR | 7.23 | 9.92 | 1.984 | 11.9 | 3.48 | –3.69 |
| CDC 1293 | 0.12 | PRSP, MR | 8.34 | 11.4 | 2.28 | 19.8 | 7.00 | –2.56 |
| CDC 1329 | 0.06 | PRSP, MR | 5.25 | 14.4 | 2.88 | 9.59 | 5.26 | –2.43 |
| mean (range) | 8.97 (5.25–18.6) | 16.6 (9.92–32.11) | 3.31 (1.98–6.42) | 16.8 (7.98–34.7) | 7.04 (3.48–15.12) | –2.83 | ||
| S. aureus | ||||||||
| ATCC 25923 | 0.12 | MSSA | 31.9 | 67.4 | 13.48 | 56.0 | 21.8 | –1.98 |
| ATCC 33591 | 0.06 | MRSA | 22.2 | 81.9 | 16.38 | 42.9 | 38.0 | –1.53 |
| ATCC Smith | 0.06 | MSSA | 13.2 | 40.2 | 8.04 | 44.6 | 38.8 | –1.84 |
| WIS-1 | 0.06 | HA-MRSA | 22.3 | 82.5 | 16.5 | 52.1 | 42.2 | –1.22 |
| UW 307109 | 0.12 | HA-MRSA | 36.1 | 79.8 | 15.96 | 64.3 | 23.4 | –2.13 |
| mean (range) | 25.1 (13.2–36.1) | 70.4 (40.2–82.5) | 14.07 (8.04–16.50) | 52.0 (42.9–64.3) | 32.8 (21.8–42.2) | –1.74 |
HA, hospital-acquired; MR, macrolide resistant; PSSP, penicillin-susceptible S. pneumoniae; PRSP, penicillin-resistant S. pneumoniae.
a
MICs were determined in Mueller–Hinton broth (MHB) by standard CLSI microdilution techniques. MHB was supplemented with 3% lysed horse blood for MIC determinations with S. pneumoniae. MICs were determined twice in triplicate; mean values are shown.
b
A value of 20% unbound lefamulin was used for calculations of 24 h fAUC/MIC, corresponding to the value of in vitro plasma protein binding assay at 3 mg/L.