Background Gonococcal minimal inhibitory concentrations (MIC) to 3rd generation-cephalosporins have been rising worldwide. New treatments for resistant gonococci are urgently needed. We developed pharmacokinetic models to assess whether multiple doses of 600mg or 800mg of cefixime would achieve serum levels sufficient to treat gonococcal isolates with elevated cefixime MICs (≥ 0.5 µg/mL).
Methods Based on published data, we assumed 800mg of cefixime has a peak total concentration (Cmax) of 4.9 µg/mL, an elimination half-life of 3.5 hours, and a volume of distribution of 32 L. We extrapolated a 600mg dose Cmax as the midpoint (4.25 µg/mL) between the 400mg Cmax (3.7 µg/mL) and 800mg. We created simulation models to identify regimens which could achieve total serum cefixime concentrations that exceed 4 times the MIC for over 20 hours, a previously proposed criterion for defining pharyngeal gonorrhoea treatment regimens. We also assessed the pharmacokinetics of free serum cefixime concentrations assuming a 30% unbound fraction, an alternative criterion for gonorrhoea therapy.
Results Simulations suggest that 600mg or 800mg every 12 hours for two doses would achieve total serum cefixime levels sufficient to treat pharyngeal infections caused by gonococci with an MIC ≤ 0.5 µg/mL. A regimen of 800mg orally every 8 hours for three doses would achieve total levels high enough to treat gonococci with an MIC ≤ 1.0 µg/mL. Free cefixime levels attained with 800mg of cefixime every 12 hours for two doses would exceed 0.5 µg/mL for over 24 hours; 800mg every 6 hours for three doses would achieve free levels that exceed 1.0 µg/mL for nearly 24 hours.
Conclusion Two-to-three 800mg doses of cefixime could be an effective therapy for pharyngeal infections with gonococci with cefixime MICs of 0.5–1.0 µg/mL. A pharmacokinetics trial to evaluate the accuracy of these simulations and the safety and tolerability of the proposed regimens is currently underway.