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
ControlFosfomycinDaptomycinFosfomycin + daptomycin
4 h8 h24 h4 h8 h24 h4 h8 h24 h4 h8 h24 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+3.10−1.4−1.8
    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
  • a 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.