SUMMARY The impact of human metapneumovirus (HMPV) in children older than 5 years of age and the risk factors associated with disease severity for all ages have not been well characterized. A retrospective cohort study of 238 children 0–15 years hospitalized over a 3-year period was performed. Medical records were reviewed for demographic, clinical parameters and outcomes. Multivariable analyses were performed to identify independent factors associated with worse disease severity assessed by length of hospitalization (LOS), need for ICU care, respiratory support, and a disease severity score. Pulmonary diseases were associated with all outcomes of care, while congenital heart disease (CHD) and neuromuscular disorders were associated with longer LOS, and CHD and trisomy 21 were associated with worse severity scores independent of other covariables. Fever, retractions, use of steroids and albuterol were also associated with enhanced disease severity. Understanding the determinants of HMPV disease in children may help design targeted preventive strategies.

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The objective of our study was to characterize the pharmacokinetics of azithromycin after the oral administration of multiple doses in suspension to children with acute otitis media. Thirteen children (ranging in age from 7.5 months to 5 years) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Multiple blood samples were collected after the last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The means and standard deviations for the maximum concentration of azithromycin in serum, the time to maximum concentration of azithromycin in serum, the area under the concentration-time curve (from 0 to 24 h), and the elimination half-life were 224 ؎ 120 ng/ml, 1.8 ؎ 0.4 h, 1,841 ؎ 651 ng ⅐ h/ml, and 31.6 ؎ 6.6 h, respectively. Concentrations in serum (means ؎ standard deviations) at 0 h (predose) and at 24, 48, and 72 h after the final dose were 51 ؎ 26, 47 ؎ 21, 27 ؎ 17, and 17 ؎ 13 ng/ml, respectively. Thus, the once-daily administration of azithromycin resulted in sustained systemic exposure to the drug. The drug dosage regimen used in this study should lead to tissue drug concentrations exceeding the MICs for common pathogens.

Azithromycin is an azalide antibiotic. On the basis of data in adults, azithromycin appears to have a greater distribution into tissues, a longer elimination half-life, and a lower incidence of adverse effects than the macrolide antibiotic erythromycin. However, little about the pharmacokinetics of azithromycin in children is known. The objective of our study was to characterize the pharmacokinetics of azithromycin after oral administration of multiple doses of suspension to children with streptococcal pharyngitis. Fourteen children (6 to 15 years of age) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after this last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The mean + standard deviation for maximum concentration of drug in serum, time to maximum concentration of drug in serum, and area under the curve (0 to 24 h) were 383 142 ng/ml, 2.4 + 1.1 h, and 3,109 + 1,033 ng. h/ml, respectively. Concentrations in serum at 0 h (predose) and at 24, 48, and 72 h after the final dose were 67 31, 64 24, 41 + 17, and 29 + 14 ng/ml, respectively. Thus, once-daily administration of azithromycin resulted in sustained systemic exposure to the drug.