Dosing of aminoglycosides to rapidly attain pharmacodynamic goals and hasten therapeutic response by using individualized pharmacokinetic monitoring of patients with pneumonia caused by gram-negative organisms.

Achieving a peak aminoglycoside concentration (Cmax)/MIC of > or = 10 within 48 h of initiation of therapy for pneumonia caused by gram-negative organisms results in a 90% probability of therapeutic response by day 7. Targeting an MIC of 1 microgram/ml, empirical aminoglycoside loading doses of 348 (25th- to 75th-percentile range, 275 to 432) mg were calculated to obtain a Cmax/MIC of 10 in our patient population. Individualized pharmacokinetic monitoring coupled with MIC data should determine subsequent dosing regimens to minimize the potential for toxicity and maximize the probability of clinical response.

Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions.

The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers.

Barbiturate and nonbarbiturate sedative hypnotic intoxication in children.

This article reviews the pharmacology, toxicology, and treatment of both barbiturate and nonbarbiturate sedative hypnotic overdose. Although poisoning with these agents has declined over recent years, intoxication with them can still result in a life-threatening situation requiring immediate assessment and treatment.

Prophylaxis and treatment of childhood rickets with parenteral cholecalciferol.

The safety and efficacy of parenteral cholecalciferol was evaluated in the treatment and prevention of childhood rickets. Children with active disease, and those at high risk for developing rickets were treated either with intravenous or intramuscular cholecalciferol in dosages of 1000 to 1500 IU daily, for periods of 28 to 450 days. All children with rickets responded with radiographic evidence of healing. No child in the prophylaxis group developed bone disease. Side effects were minimal. Parenteral cholecalciferol is a safe and effective therapy for the treatment and prevention of childhood rickets.

Use of intravenous iron dextran injection in children receiving total parenteral nutrition.

We conducted studies using intravenous (IV) iron dextran injection in 14 hospitalized infants and children with iron deficiency who required total parenteral nutrition. A single, total dose of IV iron dextran was administered during a two-hour period (preceded by a test dose of 25 mg). Doses administered ranged from 50 to 782 mg, with an average dose of 15.2 mg/kg body weight. No adverse reactions were noted during the test dose or infusion. The IV administration of iron dextran appears to be a safe method of treatment for iron repletion in children who are unable to tolerate feedings as a result of malabsorption, inflammatory bowel disease, or chronic debilitating diseases.