TABLE 2.
Hill PD parameters describing the concentration-response profiles of colistin (0–16 mg/L) in the presence of fixed tigecycline concentrations (0–0.5 mg/L) at low and high inoculumsa.
TGC (mg/L) in combination |
106 cfu/mL |
108 cfu/mL |
||||
Emax | EC50 | N | Emax | EC50 | N | |
PD parameters for E. coli ATCC 25922 | ||||||
0 | −9.61 | 1.58 | 2.24 | −6.46 | 6.19 | 1.94 |
0.03 | −9.85 | 1.01 | 1.53 | −8.95 | 4.95 | 1.12 |
0.06 | −8.74 | 0.83 | 1.30 | −9.09 | 3.47 | 1.40 |
0.13 | −7.22 | 0.55 | 1.73 | −9.13 | 2.01 | 1.43 |
PD parameters for E. coli carrying blaNDM–5 (i.e., isolate 2630) | ||||||
0 | −9.43 | 0.82 | 8.13 | −9.11 | 6.75 | 4.68 |
0.13 | −9.68 | 0.49 | 10.7 | −9.14 | 5.45 | 3.71 |
0.25 | −9.56 | 0.27 | 10.1 | −9.17 | 4.98 | 1.18 |
0.50 | −9.57 | 0.26 | 12.9 | −9.41 | 2.36 | 1.22 |
PD parameters for E. coli carrying mcr-1 only (i.e., isolate 3112) | ||||||
0 | −5.60 | 5.98 | 2.07 | −2.28 | 8.68 | 1.04 |
0.13 | −9.48 | 3.96 | 2.55 | −4.33 | 6.01 | 1.71 |
0.25 | −9.42 | 2.34 | 2.37 | −7.05 | 3.55 | 1.49 |
0.50 | −9.30 | 1.05 | 1.84 | −7.52 | 3.48 | 1.59 |
Mean PD parameters for E. coli carrying blaNDM–5 and mcr-1 (i.e., 1320, 2610, and 2121) | ||||||
0 | −6.53 | 7.37 | 5.66 | −2.31 | 10.6 | 4.34 |
0.13 | −8.23 | 5.50 | 3.97 | −5.25 | 9.91 | 3.69 |
0.25 | −9.42 | 2.09 | 2.56 | −7.49 | 7.02 | 2.83 |
0.50 | −9.36 | 0.80 | 4.17 | −8.60 | 3.98 | 2.13 |
aEmax, maximum effect compared to the no drug control for a log10 change of bacterial density after the 48 h study period; EC50, colistin concentration required to achieve 50% Emax; N, slope of the concentration-effect curve.