TABLE 2

Population mean parameter estimates for the imipenem-aminoglycoside (i.e., tobramycin, gentamicin, amikacin and streptomycin) combination model against AH298-GFP

Parameter (unit)aAbbreviationPopulation mean value (SE[%])
Initial inoculum (log10 CFU/ml)LogCFU07.53 (1.7)
Maximum population size (log10 CFU/ml)Log CFUmax9.21 (1.0)
Replication rate constant (h−1)k2150 (fixed)
Mean generation time (min)
    IPMS/AGSSk12,SS−152.9 (3.8)
    IPMR/AGSIk12,RI−1215 (13.8)
    IPMI/AGSRk12,IR−152.9 (3.8)
Log10 mutation frequencies
    IPMLogMUT,IPM−3.72 (4.2)
    AGSLogMUT,AGS−8.22 (1.1)
Killing by IPM
Maximum killing rate constant (h−1)Kmax,IPM4.66 (14.7)
Imipenem concn causing 50% of Kmax,IPM (mg/liter)
    IPMS/AGSSKC50,SS,IPM2.81 (12.3)
    IPMR/AGSIKC50,RI,IPM105 (18.3)
    IPMI/AGSRKC50,IR,IPM83.5 (7.7)
Maximum killing rate constants (h−1)
    IPMS/AGSSKmax,SS,AGS14.1 (7.9)
    IPMR/AGSIKmax,RI,AGS5.78 (23.7)
    IPMI/AGSRKmax,IR,AGS14.1 (7.9)
AGS concn causing 50% of Kmax,AGS (mg/liter)
TOBGENAMKSTR
    IPMS/AGSSKC50,SS,AGS4.05 (18.5)6.01 (20.0)7.98 (19.3)84.8 (11.9)
    IPMR/AGSIKC50,RI,AGS34.4 (11.2)41.8 (11.5)119 (8.5)699 (10.4)
    IPMI/AGSRKC50,IR,AGS178 (11.4)195 (8.0)372 (7.1)2740 (4.2)
Permeabilization of the outer membrane by AGS
    Maximum fractional decrease of KC50,IPM by AGS via outer membrane disruptionImax,OM,AGS0.773 (0.536 to 0.803)b
    AGS concn causing 50% of Imax,OM,AGS (mg/liter)IC50,OM,AGSTOBGENAMKSTR
0.216 (20.9)0.739 (16.6)1.70 (17.2)5.19 (18.6)
    SD of residual error on log10 scaleSDCFU0.486 (4.0)
  • a AGS, aminoglycoside; IPM, imipenem; TOB, tobramycin; GEN, gentamicin; AMK, amikacin; STR, streptomycin.

  • b 95% confidence interval for Imax,OM,AGS.