Nemonoxacin pharmacokinetics/pharmacodynamics against Escherichia coli in an in vitro dynamic urinary tract infection model
Abstract
ABSTRACT Nemonoxacin, a novel non-fluorinated quinolone, is approved for community-acquired pneumonia, but its efficacy against uncomplicated urinary tract infections (uUTIs) caused by Escherichia coli ( E. coli ) is uncertain. We aimed to establish an in vitro uUTIs model simulating urinary concentrations to evaluate dosing regimens. An in vitro model was developed using cation-adjusted Mueller–Hinton broth (CAMHB) and synthetic human urine (SHU) to reproduce urinary exposure. The model was applied to 12 E. coli clinical isolates and ATCC 25922 (MICs 512 mg/L) over 24 h. The effects of medium type on MICs and bacterial growth were assessed. Pharmacokinetics/pharmacodynamics (PK/PD) relationships were described using a sigmoid E max model, with change in bacterial density (Δlog 10 CFU/mL) and the area under the bacterial kill curve (AUBKC) as efficacy endpoints. Monte Carlo simulation (MCS) estimated the probability of target attainment (PTA) and cumulative fraction of response (CFR) for 500 mg and 750 mg once-daily regimens. Nemonoxacin MICs were higher in SHU, and bacterial growth showed early inhibition. The AUC 0–24 /MIC ratio best correlated with antibacterial effect ( R ² = 0.951 in CAMHB; 0.982 in SHU). For a 1-log CFU reduction, AUC 0–24 /MIC targets were 46.5 in CAMHB and 199 in SHU. The 500 mg regimen achieved ≥90% PTA for isolates with MIC ≤ 16 mg/L (CFR 92.1%) using CAMHB-derived targets but only ≤8 mg/L (CFR 59.4%) in SHU. A 500 mg once-daily regimen of…
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