Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens.

PURPOSE: This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme. METHODS: Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dataset. Monte Carlo simulations investigated dosing regimens to achieve a target AUC0-24 h/MIC ratio ≥ 125. RESULTS: A total of 189 children (492 concentrations) were included. A two-compartment model with first-order absorption and elimination best described the data. An allometric model was used to describe bodyweight (BW) influence, and effects of estimated glomerular filtration rate (eGFR) and age were significant on ciprofloxacin clearance. CONCLUSION: The recommended IV dose of 10 mg/kg q8h, not exceeding 400 mg q8h, would achieve AUC0-24 h to successfully treat bacteria with MICs ≤ 0.25 (e.g. Salmonella, Escherichia coli, Proteus, Haemophilus, Enterobacter, and Klebsiella). A dose increase to 600 mg q8h in children > 40 kg and to 15 mg/kg q8h (max 400 mg q8h, max 600 mg q8h if augmented renal clearance, i.e., eGFR > 200 mL/min/1.73 m2) in children < 40 kg would be needed for the strains with highest MIC (16% of Pseudomonas aeruginosa and 47% of Staphylococcus aureus). The oral recommended dose of 20 mg/kg q12h (not exceeding 750 mg) would cover bacteria with MICs ≤ 0.125 but may be insufficient for bacteria with higher MIC and a dose increase according bodyweight and eGFR would be needed. These doses should be prospectively confirmed, and a therapeutic drug monitoring could be used to refine them individually.

Prenatal pelvic MRI: additional clues for assessment of urogenital obstructive anomalies.

OBJECTIVE: Ultrasound prenatal evaluation of pelvic cystic mass can be challenging. After having ruled out a cloaca anterior to a large hydrocolpos, it is important to differentiate between combined urogenital anomalies such as urogenital sinus and isolated genital anomalies. PATIENTS AND METHODS: We reviewed the charts of 13 women referred for a third trimester pelvic MRI for cystic pelvic mass discovered in second trimester ultrasound. We evaluated MRI compared with postnatal surgical findings in order to determine clues for improving prenatal diagnoses. RESULTS: MRI excluded the diagnosis of cloacal malformation in nine cases with no false negative. Once a cloaca is ruled out, a different signal between the bladder and the hydrocolpos on T2 sequences is in favor of an isolated genital obstruction. In contrast, in case of urogenital sinus, the vagina is filled with a mixture of genital secretions and urine, which gives it an MRI signal similar to the bladder on T2 sequences. CONCLUSION: Third trimester fetal MRI is an essential exam for characterization of pelvic cystic mass diagnosed by ultrasound. This exam appears valuable for invalidating the diagnosis of cloacal malformation and for differentiating between isolated genital obstruction and urogenital sinus.