Multiple dose pharmacokinetics of ciprofloxacin in preterm babies.

ABSTRACT

BACKGROUND: Ciprofloxacin is increasingly used in preterm neonates to treat multi-drug resistant infections, however the pharmacokinetics of this drug in preterm newborns is not well studied. OBJECTIVES: To determine the multi-dose pharmacokinetics of intravenous ciprofloxacin in pre-term infants. DESIGN: Prospective, cohort study. SETTING: Level III Neonatal Intensive Care Unit in a tertiary Care hospital in North India. METHODS: 24 preterm neonates with age < 28 days, who received intravenous ciprofloxacin 10 mg/kg/dose 12 hourly for clinical and/or culture proven sepsis, were enrolled. Serum levels of ciprofloxacin were analyzed after first dose on day 1 and at the end of days 3 and 7. Results: Of 24 babies included in the study [mean gestation (SD) 32 wks (2.4 wks)], 3 died and 1 dropped out in the initial few days, leaving 20 patients whose data on serum ciprofloxacin were available. Peak values on days 1, 3 and 7 were [mean +/- SEM] 2.3 +/- 0.39 microg/mL, 3.0 +/- 0.44 microg/mL and 2.7 +/- 0.39 microg/mL respectively (P >0.05). Trough values on these days were 0.7 +/- 0.14 microg/mL 0.8 +/- 0.14 microg/mL and 1.0 +/- 0.21 microg/mL respectively (P > 0.05). There were no differences between the <1500 g and > 1500 g sub-groups and the < 7 days and >7 days sub-groups with respect to the corresponding peak and trough values on days 1, 3 and 7. The 95% C.I. of serum concentrations were above the MIC90 for most Enterobacteriaceae species, however the lower bound of the 95% C.I. of the mean trough levels was lower than MIC90 for Pseudomonas aeruginosa and Staphylococcus aureus. No adverse effects were observed. CONCLUSIONS: Intravenous ciprofloxacin in a dose of 10 mg/kg/dose 12 hourly is an effective treatment of neonatal sepsis, but higher doses may be required for treating Staphylococcus aureus and Pseudomonas.