Table 3.
MSSA and MRSA time-kill curves at antibiotic MICsa
| Strain (baseline [0 h] log10 no. of CFU/ml) | Change in log10 CFU/ml |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Control |
Fosfomycin |
Daptomycin |
Fosfomycin + daptomycin |
|||||||||
| 4 h | 8 h | 24 h | 4 h | 8 h | 24 h | 4 h | 8 h | 24 h | 4 h | 8 h | 24 h | |
| MSSA strains | ||||||||||||
| MSSA 1112 (6.1) | +0.9 | +3.6 | +4.1 | +0.1 | −2.1 | +0.4 | −1.2 | −1.1 | +2.9 | −1.7 | −3.9 | −2.5 |
| MSSA P4 (5.8) | +2 | +4.1 | +4.6 | −0.3 | −1.7 | +1.2 | −0.8 | −1.1 | +3.7 | −4.2 | −4.8 | −4.8 |
| MSSA P5 (6) | +0.8 | +3.6 | +4.3 | −0.5 | −2 | +3.5 | −2.2 | −2.4 | +3.4 | −2.7 | −3.9 | −5 |
| MSSA P7 (6.1) | +0.9 | +2.9 | +4 | −0.8 | −2.5 | +0.1 | −0.8 | +0.6 | +2.9 | −1.9 | −3.7 | −3.3 |
| MSSA 4297 (6.3) | +0.7 | +2.7 | +3.8 | −0.2 | −1.3 | +2.2 | −1.3 | −2.4 | +2.7 | −1.6 | −2.9 | −1.7 |
| MSSA RN4220 (5.7) | +0.8 | +3.1 | +4.2 | −5.4 | −1.1 | −0.7 | −1.2 | −2.4 | +3.8 | −1.8 | −3.6 | −4.7 |
| Patient 1 MSSA 678 (6.1) | +1.5 | +2.9 | +3 | +0.1 | −1.5 | +0.6 | −1 | −2 | +2.6 | −1.1 | −2.1 | −4.1 |
| MRSA strains | ||||||||||||
| MRSA 277 (5.6) | +1.1 | +3 | +4.5 | +0.2 | −0.3 | +3 | −0.8 | −1.1 | +4 | −1.2 | −3.4 | −2.3 |
| MRSA P8 (6.1) | +1.5 | +3.4 | +4.1 | −0.8 | −1.8 | −1.2 | −2.3 | −3.3 | −1.1 | −3.4 | −4.5 | −3.2 |
| MRSA 2167 (6) | +1 | +3.3 | +4.3 | −0.7 | −1.5 | +0.2 | −2.2 | −3.2 | +0.4 | −3 | −3.6 | −1.8 |
| MRSA 4194 (5.9) | +1 | +3.4 | +4.2 | +0.5 | +0.7 | +1 | +0.1 | −0.9 | +3.1 | 0 | −1.4 | −1.8 |
| Patient 3 MRSA 726 (6.1) | +1.5 | +2.6 | +2.9 | −0.2 | −1.7 | −0.5 | +0.6 | +1.9 | +2.7 | −1.6 | −2.7 | −4.1 |
| GISA PC3 (5.9) | +0.5 | +2.1 | +4.1 | +0.2 | −0.3 | +1.9 | −0.1 | −0.9 | +2.5 | −3 | −4.6 | −1.5 |
| GISA ATCC (5.9) | +1 | +2.7 | +4 | +0.3 | −0.7 | +2.5 | −0.3 | −0.5 | +3.8 | −1.4 | −4 | −3.6 |
Antibiotics were used alone and in combination at the MIC of each drug for the organism. If the MIC of a single drug eliminated viable organisms at 24 h, a concentration of 0.5 times the MIC was used so that the effect of a single drug would not obscure that of a drug combination. Daptomycin was tested at 0.5 times the MIC for two MSSA strains (1112 and P7) and one MRSA strain (726). Synergy was defined as a ≥2-log10 decrease in the number of CFU/ml between the combination and the most active agent tested alone and as a ≥2-log10 decrease in the colony count from the starting inoculum after 8 or 24 h. Indifference was defined as a <2-log10 change (increase or decrease) in the number of CFU/ml after 24 h between the combination and the most active agent tested alone. Antagonism was defined as a ≥2-log10 increase in the number of CFU/ml after 8 or 24 h between the combination and the most active agent tested alone. Bactericidal activity was defined as a decrease of ≥3 log10 CFU/ml after 24 h of incubation. The lower limit of detection for time-kill assays was 1 log10 CFU/ml.