TABLE 2.
Pharmacological parameters and statistical analysis of the dose-response curves of antibiotics against all strains tested in THP-1 monocytes
| Antibiotic and strain | Emina,d | Emaxb,d |
Csc,d |
R2 | |
|---|---|---|---|---|---|
| mg/liter | Multiple of MIC | ||||
| Gepotidacin | |||||
| Pooled datae | |||||
| Extracellular | 3.9 (3.46 to 4.38) | −5.5 (−6.4 to −4.6) | Not applicable | 2.69 (2.42 to 2.98) | 0.91 |
| Intracellular | 2.62 (2.46 to 2.77) | −1.21 (−1.35 to −1.07) | Not applicable | 0.68 (0.51 to 0.84) | 0.9 |
| Individual strainsf | |||||
| ATCC 25923 | 3.29 (2.92 to 3.66) A | −1.22 (−1.49 to −0.96) AB, a | 0.34 (0.26 to 0.42) A, ab | 0.68 (0.51 to 0,84) A, a | 0.95 |
| SA040 LZDr | 2.73 (2.45 to 3.02) AB | −0.99 (−1.26 to −0.72) A, a | 0.28 (0.18 to 0.37) A, ab | 0.55 (0.37 to 0.72) A, a | 0.95 |
| SA618 bis | 1.94 (1.61 to 2.27) C | −1.28 (−1.59 to −0.97) A, a | 0.16 (0.15 to 0.16) A, b | 0.63 (0.61 to 0.65) A, a | 0.9 |
| NRS119 | 2.21 (1.89 to 2.53) BC | −1.15 (−1.43 to −0.87) AB, a | 0.42 (0.34 to 0.51) A, a | 0.84 (0.67 to 1.01) A, a | 0.93 |
| MU50 | 2.51 (2.15 to 2.87) C | −1.60 (−1.92 to −1.26) AB, a | 0.16 (0.13 to 0.20) A, b | 0.65 (0.52 to 0.79) A, a | 0.94 |
| SA1 | 2.99 (2.76 to 3.22) A | −1,07 (−1.32 to −0.82) A, a | 0.46 (0.31 to 0.6) A, a | 1.83 (1.23 to 2.42) A, b | 0.96 |
| Linezolid | |||||
| ATCC 25923 | 3.29 (3.10 to 3.49) A | −0.78 (−0.99 to −0.57) BC, a | 4.60 (4.40 to 4.79) C, a | 2.30 (2.20 to 2.40) A, a | 0.98 |
| SA040 LZDr | 3.14 (2.87 to 3.40) AB | −0.25 (−0.51 to 0.01) B, a | 58.6 (27.8 to 108) B, b | 3.66 (1.74 to 6.79) B, a | 0.96 |
| NRS119 | 2.69 (2.45 to 2.93) BC | −1.31 (−1.82 to −0.81) AB, a | 69.3 (47.1 to 96) B, b | 1.08 (0.74 to 1.50) AB, a | 0.95 |
| Clarithromycin | |||||
| ATCC 25923 | 3.35 (3.06 to 3.65) A | −0.38 (−0.73 to −0.04) C, a | 1.23 (1.10 to 1.34) AB | 4.90 (4.42 to 5.37) B | 0.95 |
| MU50 | 2.05 (1.93 to 2.17) C | 1.98 (1.89 to 2.07) C, b | No convergence | No convergence | 0.08 |
| Daptomycin | |||||
| ATCC 25923 | 3.84 (3.42 to 4.25) A | −0.79 (−1.19 to −0.40) BC, a | 2.35 (1.03 to 3.67) B, b | 2.35 (1.03 to 3.67) A, a | 0.96 |
| SA040 LZDr | 3.25 (2.91 to 3.59) AB | −0.35 (−0.62 to −0.08) B, a | 2.36 (1.88 to 2.91) A, b | 1.18 (0.95 to 1.94) AB, a | 0.95 |
| SA618bis | 1.99 (1.70 to 2.29) C | −0.76 (−1.08 to −0.42) A, a | 15.7 (14.90 to 16.50) C, a | 0.49 (0.47 to 0.52) A, a | 0.93 |
| NRS119 | 2.44 (2.20 to 2.68) BC | −0.44 (−0.67 to −0.20) B, a | 3.85 (3.61 to 4.10) A, b | 1.92 (1.80 to 2.05) B, a | 0.95 |
| MU50 | 2.07 (1.87 to 2.27) C | −0.70 (−0.93 to −0.47) B, a | 16.3 (15.20 to 18) C, a | 2.04 (1.90 to 2.23) B, a | 0.96 |
| Moxifloxacin | |||||
| ATCC 25923 | 3.39 (3.02 to 3.76) A | −1.70 (−2.11 to −1.30) A, ab | 0.03 (0.03 to 0.04) A, c | 1.10 (0.95 to 1.25) A, b | 0.97 |
| SA040 LZDr | 2.58 (2.29 to 2.88) AB | −1.14 (−1.46 to −0.81) A, a | 0.54 (0.52 to 0.56) A, bc | 4.33 (4.17 to 4.49) B, a | 0.96 |
| SA618bis | 2.49 (2.20 to 2.79) C | −1.23 (−1.61 to −0.84) A, a | 7.10 (4.51 to 9.68) B, a | 1.77 (1.13 to 2.42) B, b | 0.94 |
| NRS119 | 2.23 (1.91 to 2.54) BC | −2.11 (−2.54 to −1.68) A, ab | 4.50 (3.12 to 5.88) A, ab | 1.12 (0.78 to 1.47) AB, b | 0.95 |
| MU50 | 2.13 (1.82 to 2.43) C | −2.42 (−2.91 to −1.93) A, b | 3.81 (3.75 to 3.88) B, abc | 0.95 (0.94 to 0.97) B, b | 0.95 |
| SA1 | 2.97 (2.66 to 3.29) A | −1.29 (−1.62 to −0.96) A, a | 0.10 (0.08 to 0.11) A, c | 1.52 (1.30 to 1.74) A, b | 0.97 |
| Ciprofloxacin | |||||
| SA1 | 3.13 (2.67 to 3.58) A | −1.25 (−1.64 to −0.85) A | 3.36 (2.97 to 3.76) B | 0.84 (0.74 to 0.94) A | 0.94 |
Increase in the number of CFU (in log10 units, with the confidence interval being given in parentheses) at 24 h from the corresponding initial inoculum, as extrapolated from the Hill equation of the concentration-effect response for an infinitely low antibiotic concentration.
Decrease in the number of CFU (in log10 units, with the confidence interval being given in parentheses) at 24 h from the corresponding initial inoculum, as extrapolated from the Hill equation of the concentration-effect response for an infinitely large antibiotic concentration.
Extracellular antibiotic concentration (with the confidence interval being given in parentheses) resulting in no apparent bacterial growth, as calculated from the Hill equation of the concentration-response curve.
Statistical analyses were performed by one-way analysis of variance with the Tukey-Kramer multiple-comparison t test. For Emax and Cs, values followed by different uppercase letters (response of antibiotics to the same strain) or lowercase letters (response of the strains to the same antibiotic) are significantly different from each other (P < 0.05). For Emin, values followed by different uppercase letters (response of strains disregarding the antibiotic used [since its concentration is infinitely low]) are significantly different from each other (P < 0.05).
One regression for all strains (Fig. 2A).