Dataset Information

Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands.

ABSTRACT: In the Federated States of Micronesia and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics were studied in children receiving directly observed once-daily regimens (10 mg/kg, age >5 years; 15-20 mg/kg, age ?5 years) for either multidrug-resistant tuberculosis disease or latent infection after multidrug-resistant tuberculosis exposure, to inform future dosing strategies.Blood samples were collected at 0 (RMI only), 1, 2 and 6 hours (50 children, aged 6 months to 15 years) after oral levofloxacin at >6 weeks of treatment. Clinical characteristics and maximal drug concentration (Cmax) of levofloxacin, elimination half-life and area under the curve from 0 to 24 hours (AUC0-24 hours × ?g/mL) were correlated to determine the optimal dosage and to examine associations. Population pharmacokinetics and target attainment were modeled. With results from the Federated States of Micronesia, dosages were increased in RMI toward the target Cmax for Mycobacterium tuberculosis, 8-12 µg/mL.Cmax correlated linearly with per-weight dosage. Neither Cmax nor half-life was associated with gender, age, body mass index, concurrent medications or predose meals. At levofloxacin dosage of 15-20 mg/kg, Cmax ?8 µg/mL was observed, and modeling corroborated a high target attainment across the ratio of the area under the free concentration versus time curve to minimum inhibitory concentration (fAUCss,0-24/MIC) values.Levofloxacin dosage should be 15-20 mg/kg for Cmax ?8 µg/mL and a high target attainment across fAUCss,0-24/MIC values in children ?2 years of age.

SUBMITTER: Mase SR

PROVIDER: S-EPMC5117358 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands.

Mase Sundari R SR Jereb John A JA Gonzalez Daniel D Martin Fatma F Daley Charles L CL Fred Dorina D Loeffler Ann M AM Menon Lakshmy R LR Bamrah Morris Sapna S Brostrom Richard R Chorba Terence T Peloquin Charles A CA

The Pediatric infectious disease journal 20160401 4

<h4>Background</h4>In the Federated States of Micronesia and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics were studied in children receiving directly observed once-daily regimens (10 mg/kg, age >5 years; 15-20 mg/kg, age ≤5 years) for either multidrug-resistant tuberculosis disease or latent infection after multidrug-resistant tuberculosis exposure, to inform future dosing strategies.<h4>Methods</h4>Blood samples were collected at 0 (RMI only), 1, 2 and 6 hours ...[more]

PMID: 26658531

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Project description:BackgroundVaccination coverage is typically measured as the proportion of individuals who have received recommended vaccine doses by the date of assessment. This approach does not provide information about receipt of vaccines by the recommended age, which is critical for ensuring optimal protection from vaccine-preventable diseases (VPDs).ObjectiveTo assess vaccination timeliness in the Federated States of Micronesia (FSM), and the projected impact of suboptimal vaccination in the event of an outbreak.MethodsTimeliness of the 4th dose of diphtheria, tetanus, and acellular pertussis vaccine (DTaP) and 1st dose of measles, mumps, and rubella vaccine (MMR) among children 24-35 months was assessed in FSM. Both doses are defined as on time if administered from 361 through 395 days in age. Timeliness was calculated by one-way frequency analysis, and dose delays, measured in months after recommended age, were described using inverse Kaplan-Meier analysis. A time-series susceptible-exposed-infected-recovery (TSEIR) model simulated measles outbreaks in populations with on time and late vaccination.ResultsTotal coverage for the 4th dose of DTaP ranged from 36.6% to 98.8%, and for the 1st dose of MMR ranged from 80.9% to 100.0% across FSM states. On time coverage for the 4th dose of DTaP ranged from 3.2% to 52.3%, and for the 1st dose of MMR ranged from 21.1% to 66.9%. Maximum and median dose delays beyond the recommended age varied by state. TSEIR models predicted 10.8-13.7% increases in measles cases during an outbreak based on these delays.ConclusionsIn each of the FSM states, a substantial proportion of children received DTaP and MMR doses outside the recommended timeframe. Children who receive vaccinations later than recommended remain susceptible to VPDs during the period they remain unvaccinated, which may have a substantial impact on health systems during an outbreak. Immunization programs should consider vaccination timeliness in addition to coverage as a measure of susceptibility to VPDs in young children.

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Dataset Information

Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands.

Publications

Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands.

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