Summary Statistics for Tebipenem Day 1 Free-Drug Plasma AUC, Baseline MIC, and Free-Drug Plasma AUC:MIC Ratio × 1/τ or Ertapenem Baseline MIC and Day 1 Free-Drug Plasma %T > MIC Based on Data From the Patients in the ME Analysis Populationa Infected With Enterobacterales Pathogen(s) at Baseline
| Summary Statistic . | Tebipenem (n = 366) . | Ertapenem (n = 378) . | |||
|---|---|---|---|---|---|
| Day 1 Free-Drug Plasma AUC (mg•h/L)b . | Baseline MIC (µg/mL) . | Day 1 Free-Drug Plasma AUC:MIC Ratio x 1/τc . | Baseline MIC (µg/mL) . | Day 1 Free-Drug Plasma %T > MICd,e . | |
| Mean (%CV) | 43.5 (70.8) | 321 (96.2) | 95.1 (17.3) | ||
| Median or MIC50, MIC90 (Min, Max) | 35.9 (6.64, 388) | 0.015, 0.12 (≤0.004, 2) | 238 (3.31, 2223) | 0.008, 0.12 (≤0.002, >8) | 99.6 (0, 99.6) |
| Summary Statistic . | Tebipenem (n = 366) . | Ertapenem (n = 378) . | |||
|---|---|---|---|---|---|
| Day 1 Free-Drug Plasma AUC (mg•h/L)b . | Baseline MIC (µg/mL) . | Day 1 Free-Drug Plasma AUC:MIC Ratio x 1/τc . | Baseline MIC (µg/mL) . | Day 1 Free-Drug Plasma %T > MICd,e . | |
| Mean (%CV) | 43.5 (70.8) | 321 (96.2) | 95.1 (17.3) | ||
| Median or MIC50, MIC90 (Min, Max) | 35.9 (6.64, 388) | 0.015, 0.12 (≤0.004, 2) | 238 (3.31, 2223) | 0.008, 0.12 (≤0.002, >8) | 99.6 (0, 99.6) |
Abbreviations: AUC, area under the curve; CV, coefficient of variation; EOT, end-of-treatment; LFU, late follow-up; ME, microbiologically evaluable; MIC, minimum inhibitory concentration; PK-PD, pharmacokinetic-pharmacodynamic; TOC, test-of-cure.
aThe ME population contains all patients in any one of the populations, including ME-EOT, ME-TOC, or ME-LFU.
bTebipenem free-drug plasma AUC was calculated using a protein binding estimate of 42%.
cThe percentage of TBP-PI-HBr–treated patients that achieved median tebipenem free-drug plasma AUC:MIC ratio × 1/τ targets associated with net bacterial stasis of 6.42 and a 1-log10 CFU reduction from baseline of 9.56 for Enterobacterales isolates studied in a 1-compartment in vitro infection model [21] was 98.6 and 98.4%, respectively. The percentage of patients achieving median tebipenem free-drug plasma AUC:MIC ratio × 1/τ targets associated with the same endpoints (21.4 and 45.1, respectively) based on data for Enterobacterales isolates from a neutropenic acute pyelonephritis model [22] was 95.1 and 89.9%, respectively.
dErtapenem free-drug plasma %T > MIC was determined using the concentration-dependent relationship between ertapenem free-drug and total-drug plasma concentrations based on data from Majumdar et al. [20].
eStudies with carbapenems carried out using data from a neutropenic murine thigh infection model were used to estimate the magnitude of the PK-PD index required for ertapenem endpoints. The percentage of ertapenem-treated patients that achieved ertapenem free-drug plasma %T > MIC targets associated with net bacterial stasis of 30% and a 1-log10 CFU reduction from baseline of 40% based on data for Gram-negative bacilli studied in a neutropenic murine thigh infection model [23–25] was 97.4 and 96.0%, respectively.
Summary Statistics for Tebipenem Day 1 Free-Drug Plasma AUC, Baseline MIC, and Free-Drug Plasma AUC:MIC Ratio × 1/τ or Ertapenem Baseline MIC and Day 1 Free-Drug Plasma %T > MIC Based on Data From the Patients in the ME Analysis Populationa Infected With Enterobacterales Pathogen(s) at Baseline
| Summary Statistic . | Tebipenem (n = 366) . | Ertapenem (n = 378) . | |||
|---|---|---|---|---|---|
| Day 1 Free-Drug Plasma AUC (mg•h/L)b . | Baseline MIC (µg/mL) . | Day 1 Free-Drug Plasma AUC:MIC Ratio x 1/τc . | Baseline MIC (µg/mL) . | Day 1 Free-Drug Plasma %T > MICd,e . | |
| Mean (%CV) | 43.5 (70.8) | 321 (96.2) | 95.1 (17.3) | ||
| Median or MIC50, MIC90 (Min, Max) | 35.9 (6.64, 388) | 0.015, 0.12 (≤0.004, 2) | 238 (3.31, 2223) | 0.008, 0.12 (≤0.002, >8) | 99.6 (0, 99.6) |
| Summary Statistic . | Tebipenem (n = 366) . | Ertapenem (n = 378) . | |||
|---|---|---|---|---|---|
| Day 1 Free-Drug Plasma AUC (mg•h/L)b . | Baseline MIC (µg/mL) . | Day 1 Free-Drug Plasma AUC:MIC Ratio x 1/τc . | Baseline MIC (µg/mL) . | Day 1 Free-Drug Plasma %T > MICd,e . | |
| Mean (%CV) | 43.5 (70.8) | 321 (96.2) | 95.1 (17.3) | ||
| Median or MIC50, MIC90 (Min, Max) | 35.9 (6.64, 388) | 0.015, 0.12 (≤0.004, 2) | 238 (3.31, 2223) | 0.008, 0.12 (≤0.002, >8) | 99.6 (0, 99.6) |
Abbreviations: AUC, area under the curve; CV, coefficient of variation; EOT, end-of-treatment; LFU, late follow-up; ME, microbiologically evaluable; MIC, minimum inhibitory concentration; PK-PD, pharmacokinetic-pharmacodynamic; TOC, test-of-cure.
aThe ME population contains all patients in any one of the populations, including ME-EOT, ME-TOC, or ME-LFU.
bTebipenem free-drug plasma AUC was calculated using a protein binding estimate of 42%.
cThe percentage of TBP-PI-HBr–treated patients that achieved median tebipenem free-drug plasma AUC:MIC ratio × 1/τ targets associated with net bacterial stasis of 6.42 and a 1-log10 CFU reduction from baseline of 9.56 for Enterobacterales isolates studied in a 1-compartment in vitro infection model [21] was 98.6 and 98.4%, respectively. The percentage of patients achieving median tebipenem free-drug plasma AUC:MIC ratio × 1/τ targets associated with the same endpoints (21.4 and 45.1, respectively) based on data for Enterobacterales isolates from a neutropenic acute pyelonephritis model [22] was 95.1 and 89.9%, respectively.
dErtapenem free-drug plasma %T > MIC was determined using the concentration-dependent relationship between ertapenem free-drug and total-drug plasma concentrations based on data from Majumdar et al. [20].
eStudies with carbapenems carried out using data from a neutropenic murine thigh infection model were used to estimate the magnitude of the PK-PD index required for ertapenem endpoints. The percentage of ertapenem-treated patients that achieved ertapenem free-drug plasma %T > MIC targets associated with net bacterial stasis of 30% and a 1-log10 CFU reduction from baseline of 40% based on data for Gram-negative bacilli studied in a neutropenic murine thigh infection model [23–25] was 97.4 and 96.0%, respectively.
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