Abstract
AIMS: Cefuroxime axetil exists in several dosage forms for oral administration, and is indicated for treatment of respiratory, genitourinary, skin and soft tissue infections. Evolving patterns of bacterial susceptibility, expressed as increasing minimum inhibitory concentrations (MICs), warrant monitoring of antibiotic efficacy. Here we investigate the performance of different cefuroxime axetil doses required to yield the desired target exposure against the predominant pathogens for each indication. METHODS: The pharmacokinetics of cefuroxime in plasma/serum and urine was characterized after oral, intravenous and intramuscular administration. Covariates included the effect of weight on clearance and volume of distribution, and formulation on absorption parameters. Subsequently, systemic cefuroxime concentrations over time were simulated to assess the time above the MIC (T > MIC) and the probability of target attainment (PTA) for different dosing regimens in adults and children. RESULTS: Tablet doses of 250 and 500 mg twice daily achieved the target T > MIC (40%) and PTA (≥90%) for MICs up to 0.25 and 0.5 mg/L, respectively, thereby covering most European Committee on Antimicrobial Susceptibility Testing breakpoints for key pathogens. Due to its absorption profile, the oral suspension covers even higher MICs, up to 1.0 mg/L. As cefuroxime is mostly excreted unchanged in urine, cefuroxime axetil doses of 250 mg twice daily for urinary tract infection yield a PTA of 100% for MIC values up to 8 mg/L. CONCLUSIONS: Our analysis provides insight into the performance of different doses and dosing regimens for cefuroxime axetil for key pathogens. As resistance patterns evolve, and differ between countries or regions, cefuroxime doses may require adjustments considering local bacterial susceptibility.