TABLE 1

Pertinent regression parameters of concentration-response curves for extracellular (broth) and intracellular (THP-1 cells) activity of antibiotics against P. aeruginosa strainsa

Antibiotic and strainMICb (mg/liter)Extracellular activityIntracellular activity
EmincEmaxdCseEC50fEminEmaxCsEC50
CIP
    PAO10.253.9 (2.8 to 4.9)>−4.50.6 (0.4 to 0.9)0.2 (0.1 to 0.4)2.8 (2.0 to 3.5)−2.7*# (−3.1 to −2.3)1.5 (0.9 to 2.4)0.4 (0.2 to 0.8)
    PA50164.0 (3.3 to 4.7)>−4.51.3 (0.9 to 1.7)38.8*# (21.7 to 69.1)3.3 (2.89 to 3.7)−2.3*# (−3.1 to −1.5)1.9 (1.4 to 2.5)21.0*# (12.1 to 36.4)
    PA2910.53.3 (2.7 to 3.9)>−4.51.9 (1.5 to 2.5)2.4 (1.7 to 3.4)2.0* (1.5 to 2.6)−3.1# (−3.5 to −2.8)1.2 (0.8 to 1.6)0.9 (0.5 to 1.4)
CST
    PAO113.6 (2.5 to 4.7)>−4.51.2 (0.8 to 1.8)1.8 (1.0 to 3.4)2.9 (2.5 to 3.3)−0.9 (−1.1 to −0.7)2.1 (1.5 to 3.0)0.7 (0.4 to 1.2)
    PA5043.9 (3.3 to 4.5)>−4.51.4 (1.2 to 1.6)6.7 (4.8 to 9.5)3.5* (2.9 to 4.0)−0.35# (−0.6 to −0.1)0.7 (0.3 to 1.7)0.2 (0.1 to 0.5)
    PA29113.1 (2.7 to 3.6)>−4.52.3 (1.8 to 3.0)3.2 (2.0 to 5.1)2.7 (2.1 to 3.2)−1.7* (−2.0 to −1.5)0.8 (0.5 to 1.3)0.6 (0.3 to 1.3)
MEM
    PAO113.8 (3.0 to 4.3)>−4.50.8 (0.7 to 1.0)1.2 (0.9 to 1.6)2.7 (2.2 to 3.2)−1.7# (−2.0 to −1.4)1.4 (1.0 to 2.1)0.5 (0.3 to 0.8)
    PA5024.0 (3.3 to 4.7)>−4.51.4 (1.1 to 1.7)3.8 (2.6 to 5.5)2.9 (2.5 to 3.4)−1.4 (−1.7 to −1.1)1.2 (0.8 to 1.7)1.1 (0.7 to 1.9)
    PA291643.3 (2.9 to 3.8)>−4.50.6 (0.5 to 0.8)119.9*# (59.6 to 241.6)2.1* (1.9 to 2.4)ND1.2 (1.0 to 1.6)222.1*# (62.7 to 786.8)
TOB
    PAO10.53.9 (3.1 to 4.8)>−4.50.6 (0.4 to 1.0)0.4 (0.2 to 0.7)3.2 (2.9 to 3.6)−0.9 (−1.2 to −0.6)10.3# (7.2 to 14.7)2.8# (1.8 to 4.4)
    PA5014.1 (2.8 to 5.4)>−4.51.2 (0.9 to 1.6)1.8 (1.2 to 2.9)3.4 (2.9 to 3.8)−0.9# (−1.3 to −0.6)11.5# (7.6 to 17.3)3.0 (1.8 to 5.0)
    PA29113.5 (3.3 to 3.8)>−4.50.9 (0.8 to 1.0)1.2 (1.0 to 1.4)2.3* (1.8 to 2.9)−2.0* (−2.4 to −1.5)5.4*# (4.3 to 6.7)2.5 (1.3 to 4.7)
  • a After 24 h of incubation with extracellular concentrations ranging from 0.01 to 100 to 200 mg/liter. CIP, ciprofloxacin; CST, colistin; MEM, meropenem; TOB, tobramycin. r2 > 0.91; values are given as means with 95% confidence intervals in parentheses. Statistical analysis was done by one-way analysis of variance with Tukey's test for multiple comparisons of each parameter. *, denotes significant difference among strains for the same antibiotic; #, significant difference between antibiotics for the same strain (P ≤ 0.05). ND, not determined (plateau not reached at the highest concentration tested).

  • b EUCAST/CLSI susceptibility breakpoints (susceptible): CIP, ≤0.5/1; CST, 4/2; MEM, 2/2; TOB, 4/4.

  • c CFU increase (in log10 units) from the corresponding initial inoculum at 24 h as extrapolated for an infinitely low antibiotic concentration.

  • d CFU decrease (in log10 units) from the corresponding initial inoculum at 24 h as extrapolated from an infinitely large antibiotic concentration.

  • e Static concentration, 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.

  • f Extracellular antibiotic concentration (mg/liter) causing a reduction of the inoculum halfway between the number of CFU extrapolated for Emin and Emax.