TABLE 1

Parameter estimates for the piperacillin-tobramycin combination model against clinical P. aeruginosa ICU isolate Pa1280a

Parameter (unit)SymbolPopulation mean (SE [%])
Initial inoculum (log10 CFU/ml)Log CFU07.47 (2.67)
Maximum population size (log10 CFU/ml)Log CFUmax9.64 (1.29)
Replication rate constant (h−1)k2150 (fixed)
Mean generation time (min)
    PIPs/TOBsk12,SS−157.5 (7.8)
    PIPR/TOBIk12,RI−1180 (6.6)
    PIPI/TOBRk12,IR−157.5 (7.8)
Log10 mutant frequencies
    PIPLogMUT,PIP−4.69 (2.01)
    TOBLogMUT,TOB−6.67 (2.55)
Bacterial killing by PIP
    Maximum killing rate constant (h−1)Kmax,PIP0.31 (10.1)
    PIP concn causing 50% of Kmax,PIP (mg/liter)
        PIPs/TOBsKC50,SS,PIP1.49 (13.6)
        PIPR/TOBIKC50,RI,PIP58.4 (9.51)
        PIPI/TOBRKC50,IR,PIP5.01 (11)
    Hill coefficient for PIPHillPIP2.18 (3.4)
    Inhibition of probability of successful replication by PIP (InhREP)
    Maximum inhibitionImax,REP1.0 (fixed)
    Concn causing 50% of Imax,REP (mg/liter)
        PIPs/TOBsIC50,SS,REP0.911 (11)
        PIPR/TOBIIC50,RI,REP163 (14.6)
        PIPI/TOBRIC50,IR,REP163 (14.6)
    Hill coefficient for inhibition of successful replicationHillREP3.61 (11)
Bacterial killing by TOB
    Maximum killing rate constant (h−1)
        PIPs/TOBsKmax,SS,TOB7.79 (7.8)
        PIPR/TOBIKmax,RI,TOB15 (11.1)
        PIPI/TOBRKmax,IR,TOB7.79 (7.8)
    Tobramycin concn causing 50% of Kmax,TOB (mg/liter)
        PIPs/TOBsKC50,SS,TOB0.072 (16.2)
        PIPR/TOBIKC50,RI,TOB1.01 (8.9)
        PIPI/TOBRKC50,IR,TOB311 (10.5)
Permeabilization of the outer membrane by TOB
    Maximum fractional decrease of KC50,PIP by TOB via outer membrane disruptionImax,OM,TOB0.656 (32.6)
    TOB concn causing 50% of Imax,OM,TOB (mg/liter)IC50,OM,TOB4.7 (2.4)
    SD of residual error on log10 scaleSDCFU0.52 (29.7)
  • a PIP, piperacillin; TOB, tobramycin.