Pharmacokinetics of Levofloxacin in Children Treated for Exposure to Drug-Resistant Tuberculosis

Abstract

Levofloxacin is used to treat and prevent drug-resistant tuberculosis in children. We assessed levofloxacin serum drug concentrations in 24 children aged 2 to 10 years who received levofloxacin-based tuberculosis preventive therapy in Karachi, Pakistan. Only 9 children (37.5%) achieved adequate drug exposure. Target serum drug concentration was met in 4 (26.7%) of 15 children dosed consistently with World Health Organization recommendations and 4 (80.0%) of 5 who received higher-than-recommended doses. Levofloxacin dosing recommendations may require reevaluation.

Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis

“…Our study showed that levofloxacin exposure in children aged <10 years or who weighed <24 kg was substantially lower than the target exposure derived from adults who received a standard daily dose of 750 mg. Failure to meet the adult levofloxacin exposure median places children at higher risk for unfavorable treatment outcomes. Our model structure did not significantly differ from previously published models of levofloxacin pharmacokinetics in children, and we consistently report that exposure in children is below the target extrapolated from adults and similar model-informed dosing recommendations [ 26–29 ]. It is also important to highlight that even though there were 20 children (8%) with HIV, an effect of the disease or of concomitant administration of antiretrovirals could not be identified in the model.…”

“…Studies of first-line treatments for TB, as well as moxifloxacin, have found that age, weight, and nutritional status can affect expected exposure in children [ 30–32 ]. Here, we perform an individual patient data meta-analysis (IPD-MA) of levofloxacin for the treatment and prevention of RR/MDR-TB in children using data from 4 previously published studies [ 26–29 ] and an additional study, MDR-PK2 for which linezolid and moxifloxacin, but not levofloxacin, data had been previously published, to identify covariates that affect exposure and derive more optimal dosing recommendations [ 30 , 33 ].…”

Pharmacokinetics and Safety of WHO-Recommended Dosage and Higher Dosage of Levofloxacin for Tuberculosis Treatment in Children: a Pilot Study

“…In 2014, the WHO DR-TB treatment guideline recommended a weight-based dosage of 15-20 mg/kg for children aged under 5 years and 10-15 mg/kg for older children ( Thee et al ., 2014 ). However, Malik et al reported that most children aged more than 5 years did not achieve optimal drug exposure and suggested an increased dosage of levofloxacin to be nearly 30 mg/kg ( Malik et al ., 2019 ). In 2020, the WHO recommended the levofloxacin dosage for children aged under 15 years on the basis of body weight as follows: 15-20 mg/kg for body weight of 5-34 kg, 750 mg for body weight of 35-45 kg, and 10 0 0 mg for body weight of more than 45 kg.…”

“…In 2014, the WHO DR-TB treatment guideline recommended a body weight-based dosage of 15-20 mg/kg/day for children aged under 5 years and 10-15 mg/kg/day for older children ( World Health Organization, 2014 ). However, several studies reported low concentrations of levofloxacin in older children, which raised concerns regarding the development of drug resistance ( Malik et al ., 2019 ;Mase et al ., 2016 ;Savic et al ., 2015 ;Thee et al ., 2014 ). In 2020, the WHO recommended a revised levofloxacin dosage for prevention and treatment in children aged under 15 years as 15-20 mg/kg/day.…”