Table 2.
Pertinent regression parameters of dose-response curves for extracellular (broth) and intracellular (THP-1 cells) activities of antibiotics against strain PAO1a
| Antibiotic(s) | Mean extracellular activity (95% confidence interval) |
Mean intracellular activity (95% confidence interval) |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Eminb | Emaxc | EC50d | Cse | R2 | Eminb | Emaxc | EC50d | Cse | R2 | |
| Aminoglycosides | 3.80 (3.37–4.23)aAf | >−4.5A | 1.77 (1.31–2.37)aA | 1.18 | 0.90 | 3.34 (3.04–3.64)aA | −1.31 (−1.62 to −1.00)aB | 4.22 (3.01–5.93)aA | 10.77 | 0.83 |
| β-Lactams | 3.77 (3.57–3.98)aA | >−4.5A | 1.58 (1.37–1.83)aA | 1.17 | 0.93 | 2.74 (2.60–2.88)bB | −1.23 (−1.34 to −1.11)aB | 0.44 (0.36–0.53)bA | 0.98 | 0.90 |
| Fluoroquinolones | 4.10 (3.57–4.63)aA | >−4.5A | 1.61 (1.29–2.00)aA | 1.21 | 0.94 | 3.02 (2.65–3.39)aB | −2.88 (−3.13 to −2.63)bB | 1.00 (0.73–1.36)bA | 1.04 | 0.91 |
| Colistin | 3.81 (2.75–4.87)aA | >−4.5A | 1.78 (1.08–2.95)aA | 1.25 | 0.92 | 2.84 (2.50–3.18)bB | −1.04 (−1.22 to −0.86)aB | 0.94 (0.63–1.40)bA | 2.52 | 0.92 |
Cells were incubated for 24 h with extracellular drug concentrations ranging from 0.01 to 200 mg/liter. A single curve was fitted to the data obtained for different antipseudomonal antibiotics within a single class. The corresponding data are shown in Fig. 5; for the parameters for the individual fits, see Table S1 in the supplemental material.
CFU count increase (in log10 units) at 24 h from the corresponding initial inoculum as extrapolated for an infinitely low antibiotic concentration.
CFU count decrease (in log10 units) at 24 h from the corresponding initial inoculum as extrapolated from an infinitely high antibiotic concentration.
Extracellular concentration (total drug; in multiples of the MIC) causing a reduction halfway between Emin and Emax, as calculated from the Hill equation of the concentration-response curve (slope factor of 1).
Cs, i.e., the extracellular concentration (total drug; in multiples of the MIC) resulting in no apparent bacterial growth (number of CFU identical to the initial inoculum), as calculated from the Hill equation of the concentration-response curve.
Statistical analysis per column was done by one-way analysis of variance with Tukey's test for multiple comparisons of each parameter for all classes. Values followed by different lowercase letters are significantly different from each other (P < 0.05). Statistical analysis per row was done by unpaired, two-tailed t test between corresponding parameters of extracellular and intracellular activities. Values followed by different uppercase letters are significantly different from each other (P < 0.05).