A reappraisal of current dosing strategies for intravenous fosfomycin in children and neonates.

The rising incidence of multi-drug resistant bacterial pathogens has renewed interest in the long-known antibacterial fosfomycin. Not least because of its low toxicological potential, there is good clinical experience with intravenous fosfomycin for various Gram-positive and Gram-negative infections in the treatment of children and neonates. However, the current dosing recommendations for intravenous fosfomycin vary widely in paediatric patients. In the present review, we summarized available plasma pharmacokinetic data derived from neonates or children following intravenous administration of fosfomycin. Subsequently, we used this information for recalculation of different dosing strategies and simulated a variety of clinically applied dosing regimens. The percentage of time above the minimal inhibitory concentration (T>MIC) was calculated for each dosing strategy, as this pharmacokinetic-pharmacodynamic parameter was shown to be most predictive of antimicrobial and clinical success of fosfomycin treatment. Our data corroborate the current practice of selecting the dosage of intravenous fosfomycin primarily on the basis of bodyweight and age in paediatric patients. As with other 'time-dependent' antibacterials, a dosing interval of 6-8 hours should be preferred over 12 hours except for immature neonates. Given a T>MIC target of 40-70%, currently recommended dosing strategies appear to be insufficient in children aged 1-12 years, if pathogens with MICs of ≥32 mg/L are suspected and subjects are presenting with normal renal function. Likewise, the lowest recommended daily dose for neonates and infants (aged up to 12 months) of 100 mg/kg bodyweight of fosfomycin should be considered only for pre-term neonates with a postmenstrual age below 40 weeks.