The rates of PAEs and musculoskeletal PAEs were higher for the FQ group than the control group. This observation supports the American Academy of Pediatrics statement restricting off-label FQ use in pediatric patients to second-line treatment in a limited number of situations.

The therapeutic and toxic effects of amikacin are known to depend on its concentration in plasma, but the pharmacokinetics of this drug in neonates, infants, and children and the influences of clinical and biological variables have been only partially assessed. Therapeutic drug monitoring data collected from 155 patients (49 neonates, 77 infants, and 29 children) receiving amikacin were analyzed by a nonparametric population-based approach, the nonparametric maximum-likelihood method. We assessed the effects of gestational and postnatal age, weight, Apgar score, and plasma creatinine and urea concentrations on pharmacokinetic parameters. There is no specific formulation of amikacin for neonates and infants. We therefore used an error model to account for errors due to dilution during preparation of the infusion. The covariates that reduced the variance of clearance from plasma and the volume of distribution by more than 10% were postnatal age (43 and 28%, respectively) and body weight (30.4 and 17.4%, respectively). The expected reduction of clearance was about 10% for the plasma creatinine concentration. The other covariates studied (Apgar scores, plasma urea concentration, gestational age, sex) were found to have little effect. Simulations showed that a smaller percentage of patients had a maximum concentration in plasma/MIC ratio greater than 8 with a regimen of 7.5 mg/kg of body weight twice daily than with a regimen of 15 mg/kg once a day for MICs of 1 to 8 mg/liter.Amikacin is widely used in neonates and infants, as well as in adults, for the treatment of severe infections caused by gramnegative bacteria. Previous studies have shown that both the therapeutic response and toxic effects depend on plasma amikacin concentrations. Achieving a therapeutic maximum concentration of amikacin in plasma is associated with a significant decrease in the rate of mortality due to infection in critically ill patients (2, 36, 37), and a relationship has also been found between the minimum plasma amikacin concentration and renal toxicity (20,49). Interindividual variability in the pharmacokinetics of amikacin may therefore make it difficult to achieve safe and effective treatment. The pharmacokinetics of aminoglycosides have been shown to be highly variable in neonates and children. Several factors account for the pharmacokinetic variabilities of other aminoglycosides in this population (50). The pharmacokinetics of netilmicin and gentamicin depend on gestational age, postnatal age, weight, renal clearance, and Apgar score (6,9,11,12,14,18,21,43,46,47,(51)(52)(53). Very few data are available concerning the effects of clinical and biological covariates on the pharmacokinetics of amikacin in neonates and the changes in the pharmacokinetic profile of amikacin that occur from birth into infancy. The lack of data on the pharmacokinetics of many drugs in neonates and children is related to blood sampling limitations for this population. One way around this problem is to collect a few samples from many individuals and analyze the...

ABSTRACT. Objective. To compare the antipyretic efficacy of an initial 30-mg/kg acetaminophen loading dose versus a 15-mg/kg maintenance dose.Methods. A double-blind, parallel-group, randomized clinical trial was conducted. A total of 121 febrile (rectal temperature between 39°C and 40°C) but otherwise healthy outpatients who were 4 months to 9 years of age and weighed 4 to 26 kg were assigned randomly to 1 of the dose groups: 15 mg/kg (n ‫؍‬ 62) and 30 mg/kg (n ‫؍‬ 59).Results. In an "intention to treat" analysis, the time to obtain a temperature lower than 38.5°C was significantly shorter in the 30-mg/kg than in the 15-mg/kg group (110 ؎ 94 minutes vs 139 ؎ 113 minutes). The maximum temperature decrease was significantly higher in the 30-mg/kg than in the 15-mg/kg group (2.3 ؎ 0.7°C vs 1.7 ؎ 0.6°C). Duration of rectal temperature below 38.5°C was significantly longer in the 30-mg/kg than in the 15-mg/kg group (250 ؎ 92 minutes vs 185 ؎ 121 minutes, respectively). Adverse events were reported in 6 children in the 30-mg/kg group compared with 5 in the 15-mg/kg group (hyperthermia, hypothermia, vomiting). The difference was not statistically significant.Conclusion. An initial 30-mg/kg acetaminophen loading dose seemed to be more effective in reducing fever than a 15-mg/kg maintenance dose. No difference was observed regarding clinical tolerance. These data suggest that acetaminophen treatment of fever may be more efficient in an initial loading dose. Pediatrics 2001;108(4). URL: http://www.pediatrics.org/cgi/content/full/108/4/ e73; fever, loading dose, acetaminophen, children.ABBREVATIONS. Teff: time to obtain a rectal temperature below 38°C; Rmax, maximum temperature decrease; Tmax, time to maximum temperature decrease.