TABLE 2.
Summary of the antimicrobial impact on intracellular global inoculum and SCVsa
| Antimicrobial agent and parameter | Minimal concn |
Bone concn |
Maximal concn |
Dose effect |
||||
|---|---|---|---|---|---|---|---|---|
| Mean (95% CI) | P | Mean (95% CI) | P | Mean (95% CI) | P | R2 | P | |
| Oxacillin | ||||||||
| Δlog CFU | −1.7 (−4.0 to +0.7) | <10−3 | −4.2 (−5.3 to −3.1) | <10−3 | −4.9 (−5.0 to −4.8) | <10−3 | 0.130 | 0.007 |
| SCVs (%) | 34.5 (16.1 to 52.9) | 0.041 | 33.2 (16.3 to 50.0) | 0.053 | 7.8 (1.0 to 14.6) | <10−3 | 0.136 | 0.007 |
| Ceftaroline | ||||||||
| Δlog CFU | +0.5 (−1.9 to +3.0) | 0.006 | −0.1 (−2.5 to +2.3) | 0.002 | −2.6 (−4.4 to −0.7) | <10−3 | 0.084 | 0.033 |
| SCVs (%) | 96.3 (−29.1 to 221.7) | 0.082 | 50.0 (13.1 to 86.8) | 0.071 | 82.9 (−36.4 to 202.1) | 0.044 | <10−3 | 0.992 |
| Vancomycin | ||||||||
| Δlog CFU | +0.8 (−1.7 to +3.3) | 0.333 | +2.9 (+0.8 to +4.9) | 0.830 | −1.7 (−4.1 to 0.6) | 0.002 | 0.085 | 0.033 |
| SCVs (%) | 44.4 (−8.2 to 97.1) | 0.072 | 108.5 (9.4 to 207.6) | 0.800 | 53.5 (3.6 to 103.4) | 0.185 | 0.001 | 0.824 |
| Teicoplanin | ||||||||
| Δlog CFU | −2.3 (−4.5 to −0.0) | <10−3 | −0.2 (−2.7 to +2.3) | 0.001 | −3.9 (−5.3 to −2.6) | <10−3 | 0.058 | 0.080 |
| SCVs (%) | 134.6 (5.2 to 263.9) | 0.978 | 115.3 (56.5 to 174.2) | 0.374 | 117.2 (24.2 to 210.1) | 0.844 | 0.001 | 0.831 |
| Linezolid | ||||||||
| Δlog CFU | −0.9 (−3.1 to +1.3) | <10−3 | −3.1 (−4.8 to −1.4) | <10−3 | −3.1 (−4.8 to −1.4) | <10−3 | 0.016 | 0.361 |
| SCVs (%) | 30.1 (16.3 to 43.9) | 0.025 | 44.6 (13.5 to 75.8) | 0.087 | 35.8 (6.9 to 64.6) | 0.023 | <10−3 | 0.924 |
| Daptomycin | ||||||||
| Δlog CFU | +5.2 (+5.0 to +5.4) | 0.078 | +1.7 (−0.7 to +4.0) | 0.070 | −1.6 (−3.7 to +0.5) | <10−3 | 0.346 | <10−3 |
| SCVs (%) | 65.1 (2.3 to 127.9) | 0.052 | 49.1 (−26.9 to 125.1) | 0.004 | 83.3 (−7.9 to 174.5) | 0.057 | 0.005 | 0.622 |
| Fosfomycin | ||||||||
| Δlog CFU | −3.7 (−5.1 to −2.3) | <10−3 | −2.6 (−4.5 to −0.6) | <10−3 | −2.9 (−4.7 to −1.0) | <10−3 | 0.005 | 0.621 |
| SCVs (%) | 52.5 (−13.1 to 118.1) | 0.015 | 61.7 (5.7 to 117.6) | 0.057 | 5.3 (−2.4 to 12.9) | <10−3 | 0.051 | 0.100 |
| Tigecycline | ||||||||
| Δlog CFU | −3.7 (−5.1 to −2.3) | 0.005 | −3.9 (−4.8 to −2.9) | <10−3 | −3.8 (−4.7 to −1.0) | <10−3 | 0.148 | 0.041 |
| SCVs (%) | 77.1 (22.1 to 132.2) | 0.354 | 71.7 (14.2 to 129.1) | 0.128 | 91.9 (−45.2 to 229.0) | 0.015 | 0.002 | 0.765 |
| Clindamycin | ||||||||
| Δlog CFU | −5.2 (−5.2 to −5.1) | <10−3 | −5.2 (−5.2 to −5.1) | <10−3 | −5.2 (−5.3 to −5.1) | <10−3 | <10−3 | 0.904 |
| SCVs (%) | 59.7 (13.2 to 106.2) | 0.425 | 79.1 (1.3 to 157.0) | 0.415 | 88.9 (16.3 to 161.5) | 0.786 | 0.011 | 0.549 |
| Ofloxacin | ||||||||
| Δlog CFU | −3.2 (−4.9 to −1.4) | <10−3 | −4.9 (−5.0 to −4.9) | <10−3 | −5.0 (−5.0 to −5.0) | <10−3 | 0.083 | 0.035 |
| SCVs (%) | 16.4 (3.3 to 29.6) | 0.003 | 10.4 (3.4 to 17.3) | 0.001 | 12.4 (4.1 to 20.6) | 0.001 | 0.003 | 0.709 |
| Rifampin | ||||||||
| Δlog CFU | −4.7 (−4.9 to −4.6) | <10−3 | −4.9 (−4.9 to −4.8) | <10−3 | −4.7 (−4.9 to −4.6) | <10−3 | <10−3 | 0.886 |
| SCVs (%) | 27.1 (12.5 to 41.8) | 0.021 | 20.3 (11.6 to 29.0) | 0.011 | 18.4 (7.7 to 29.2) | 0.010 | 0.018 | 0.339 |
a
The reduction of intracellular inoculum (Δlog CFU) represents the decrease in intracellular bacteria after 24 h compared to untreated cells by Mann-Whitney U-test. SCVs represent the number of colonies with an area inferior to 5-fold less of the median area measured for all colonies on each plate and are expressed relative to untreated cells. The existence of a dose effect was assessed by linear regression between the three used concentrations.