Levofloxacin pharmacokinetics in children with drug-resistant TB exposure
According to data published in Antimicrobial Agents and Chemotherapy, the dosing recommendations regarding levofloxacin for the treatment and prevention of drug-resistant tuberculosis (DR-TB) in children may need to be re-evaluated.
The study investigators conducted a pharmacokinetic assessment of children receiving levofloxacinâbased preventive therapy under programmatic conditions for DR-TB exposure in Karachi, Pakistan. A sample of 24 children aged 2 to 10 years who were receiving treatments for at least 1 month were enrolled. Independent of the study, clinicians treated children with daily levofloxacin doses of 15 to 20 mg/kg for children ≤5 years old and 7.5 to 10 mg/kg for children aged >5 years. Children also received either ethambutol (15-25 mg/kg) or ethionamide (15-20 mg/kg) as a companion drug, depending on availability.
The study investigators found that 9 children achieved adequate drug exposure. They also found that target serum drug concentration was met in 4 of 15 children dosed consistently with World Health Organization recommendations, and in 4 of 5 who received higher-than-recommended doses.
This study was limited by a small sample size, the absence of children younger than 2 years, and a lack of time points beyond 6 hours. The study investigators also noted that several children in the study received a lower-than-recommended dose because “available pill sizes left little room for adjustment for children who experienced adverse events.” However, the researchers concluded that the results add to the evidence that current dosing recommendations may be insufficient in regions where commonly available tablets are used.
The study investigators noted that although a recently developed pediatric dispersible formulation has been shown to provide higher drug exposure, many programs still only have access to adult oral tablets. They believe therefore that, “there is thus need to re-evaluate the current levofloxacin dosing recommendations for children being treated for DR-TB disease and exposure in order to ensure that they are treated appropriately.”
Reference
Malik AA, Brooks MB, Siddiqui S, et al. Pharmacokinetics of levofloxacin in children treated for drug-resistant TB exposure [published online February 25, 2019]. Antimicrob Agents Chemother. doi: 10.1128/AAC.02569-18
Source: Infectious Disease Advisor
