Should gentamicin trough levels be routinely obtained in term neonates?

OBJECTIVE: Gentamicin is a common antibiotic used to treat sepsis in neonates. We hypothesize that obtaining routine gentamicin trough levels may not be necessary in low-risk, term infants. STUDY DESIGN: We performed a retrospective cohort study of term infants (n=346) treated with gentamicin in a single level III neonatal intensive care unit (NICU). The results of gentamicin trough levels and the correlation with risk factors and potential side effects were recorded. In addition, we conducted a survey of 75 academic NICUs across the United States regarding their gentamicin monitoring practice. RESULTS: Routine trough levels did not predict potential gentamicin toxicity in neonates with low risk factors. Regression analysis demonstrated a positive correlation between gentamicin trough levels and serum creatinine. The survey of the NICUs in the United States demonstrated significant inconsistency in gentamicin monitoring practice. CONCLUSION: Obtaining gentamicin trough levels guided by risk factors is more appropriate than obtaining routine trough levels in low-risk term neonates.

Extended-interval gentamicin administration in neonates: a simplified approach.

OBJECTIVE: Gentamicin dosing is highly variable and remains complicated in the neonatal population. Traditional dosing in our unit resulted in an excessive number of elevated trough serum gentamicin levels. We hypothesized that one uniform gentamicin dose for neonates of all gestational ages will reduce the incidence of elevated trough levels from 50 to 10%. STUDY DESIGN: Our prospective, randomized, controlled trial enrolled eligible neonates into two groups, according to gestational age (⩽34 6/7 (group I) and >35 0/7 weeks (group II)). Patients in the study arm received a dose of gentamicin 5 mg kg(-1) intravenous (i.v.) every 36 h, whereas patients in the control arm received traditional dosage. Patients were monitored for resolution of infection, serum gentamicin levels and adverse effects. We confirmed our findings in a follow-up study. Fisher's exact and Mann-Whitney tests were used for statistical analysis. RESULTS: We enrolled 96 neonates, 50 in group I (n=25 per arm) and 46 in group II (n=23 per arm). Elevated trough levels were reduced by 66% in group I (P=0.61) and 100% in group II (P=0.0015). In the study arm of both groups, 48/49 neonates had Cmin serum gentamicin concentration (SGC) <2 mg l(-1) and the majority had a trough SGC <1 mg l(-1) (P<0.0001). The study dose resulted in maximum gentamicin levels in the goal range and a 50% reduction in dosage modifications. There were no treatment failures or adverse effects. Our follow-up study phase confirmed these results. CONCLUSION: A standardized gentamicin dosage of 5 mg kg(-1) i.v. every 36 h to neonates of all gestational ages was safe and resulted in SGCs in goal therapeutic ranges. The implications of this simplified gentamicin dosage are to reduce health-care costs by less frequent dosing of gentamicin and reducing medication errors in physician prescribing from complicated dosing schemes.

The role of carnitine supplementation during valproic acid therapy.

OBJECTIVE: To review the pathophysiology and significance of valproic acid-induced carnitine deficiency; to present and evaluate the literature pertaining to carnitine supplementation in pediatric patients receiving valproic acid; and to present the consensus guidelines for carnitine supplementation during valproic acid therapy. DATA SOURCES: A MEDLINE search (1966-December 1998) restricted to English-language literature, using MeSH headings of carnitine and valproic acid, was conducted to identify clinically relevant articles. Selected articles and references focusing on the pediatric population were included for review. DATA EXTRACTION: Study design, patient population, methods, and clinical outcomes were evaluated. DATA SYNTHESIS: Valproic acid, a widely used antiepileptic agent in the pediatric population, is limited by a 1/800 incidence of fatal hepatotoxicity in children under the age of two years. Carnitine is an essential amino acid necessary in beta-oxidation of fatty acids and energy production in cellular mitochondria. It has been hypothesized that valproic acid may induce a carnitine deficiency in children and cause nonspecific symptoms of deficiency, hepatotoxicity, and hyperammonemia. Relevant published case reports and trials studying this relationship are evaluated, and a consensus statement by the Pediatric Neurology Advisory Committee is reviewed. CONCLUSIONS: Despite the lack of prospective, randomized clinical trials documenting efficacy of carnitine supplementation in preventing valproic acid-induced hepatotoxicity, the few limited studies available have shown carnitine supplementation to result in subjective and objective improvements along with increases in carnitine serum concentrations in patients receiving valproic acid. The Pediatric Neurology Advisory Committee in 1996 provided more concrete indications on the role of carnitine in valproic acid therapy, such as valproic acid overdose and valproic acid-induced hepatotoxicity. Carnitine was strongly recommended for children at risk of developing a carnitine deficiency. Although carnitine has been well tolerated, future studies are needed to evaluate the efficacy of prophylactic carnitine supplementation for the prevention of hepatotoxicity.

The use of phentolamine in the prevention of dopamine-induced tissue extravasation.

PURPOSE: The purpose of this study was to determine whether dopamine-induced tissue extravasation injury could be prevented with phentolamine. MATERIALS AND METHODS: This was a prospective, randomized, blinded, and controlled animal study. Forty rats were evaluated to document the effects of dopamine compared with normal saline on tissue integrity, whether any tissue damage was concentration or volume dependent, and to determine the minimum concentration of dopamine resulting in tissue injury. Dopamine concentrations of 0.8 mg/mL and 3.2 mg/mL were tested. In a second part of this study, an additional 40 rats were evaluated to assess the efficacy of two different doses of phentolamine (0.5 mg and 1 mg) or normal saline, when injected within 10 minutes of dopamine administration to prevent or reverse tissue extravasation. Extravasation sites were evaluated clinically and histologically at 2, 4, 6, and 8 hours and were compared with a baseline sample. Outcome measures were as follows: (1) prebiopsy was ectodermal erythema, induration, and blanching; (2) postbiopsy was bubbling, darkening, pallor, and hematoma of the muscle fascia. Histology included neutrophil migration, mast cell degranulation, edema, and hemorrhage. Fisher's Exact Test with the Bonferroni method were used for statistical analysis. RESULTS: Dopamine-induced extravasation resulted in tissue injury characterized by blanching and hematoma. Damage did not appear to be volume dependent, but may be related to the duration of infiltration. Subcutaneous injection with either dose of phentolamine appeared to be clinically effective in preventing tissue injury. However, microscopic evaluation of tissue samples was inconclusive. CONCLUSION: This study clinically supported the use of phentolamine for the prevention of dopamine-induced extravasation injury.

Bone and tissue changes following prostaglandin therapy in neonates.

OBJECTIVE: To review case reports describing prostaglandin-induced bone changes and tissue swelling in neonates. DATA SOURCES: An Index Medicus and bibliographic search of the English-language literature pertaining to prostaglandin-induced bone changes and tissue swelling in neonates. DATA SYNTHESIS: Short- and long-term prostaglandin infusion in neonates is associated with cortical proliferation throughout the skeletal system. Total resolution of these changes has occurred in seven patients described to date; other reports did not note either the time or the regression of these changes. Skeletal changes may occur within 9 days of initiation of prostaglandin therapy and include widened fontanelles, pretibial and soft-tissue swelling, and swelling of the upper and lower extremities. These reactions may last up to 38 weeks following discontinuation of therapy. Alkaline phosphatase (AP) concentrations have been shown to be increased in four cases, as well as in one retrospective analysis. Although these were not prospective studies, evaluation of AP may provide a means to monitor neonates receiving prostaglandin therapy. CONCLUSIONS: Pharmacists need to be aware of the potentially serious skeletal changes, encourage dosage titration as soon as possible, and limit the duration of time neonates are exposed to prostaglandin therapy. Monitoring of AP concentrations during therapy with prostaglandins may be beneficial in predicting or preventing further complications.

Randomized, double blind comparison of brand and generic antibiotic suspensions: I. A study of taste in adults.

BACKGROUND: A belief that brand oral liquid medications taste better than their generic counterparts may influence prescribing habits among pediatricians. METHODS: We undertook a prospective, randomized, double blinded, comparative evaluation of the taste of brand and generic erythromycin ethylsuccinate, cephalexin monohydrate, erythromycin ethylsuccinate/sulfisoxazole, penicillin V potassium and trimethoprim-sulfamethoxazole in 42 adult volunteers. Subjects tasted one class of brand and generic antibiotics and rated them according to smell, texture, taste and aftertaste. RESULTS: At least one generic preparation of cephalexin, erythromycin ethylsuccinate/sulfisoxazole and penicillin V potassium was rated equal in taste to the respective brand name products. However, brand erythromycin estolate and trimethoprim-sulfamethoxazole name brand suspensions rated significantly higher than the other products tested. CONCLUSIONS: Based on our results brand name oral antibiotic formulations do not necessarily taste better than their generic counterparts.

Randomized, double blind comparison of brand and generic antibiotic suspensions: II. A study of taste and compliance in children.

BACKGROUND: The taste of oral liquid medications influences compliance in children. Generic preparations are prescribed to reduce cost and may taste worse than brand name products. METHODS: This was a prospective, randomized, double blind, crossover trial of the differences in taste and compliance between brand and generic antibiotic suspensions in children 3 to 14 years of age. Verbal and visual assessment methods were used to assess taste, and compliance was measured by the amount of drug returned after use. RESULTS: Ten children in each of the cephalexin and erythromycin-sulfisoxazole groups did not report that the brand and generic formulations tasted differently. Fifteen children thought that brand trimethoprim-sulfamethoxazole tasted better than the generic preparation. CONCLUSIONS: Brand name oral liquid antibiotics do not necessarily taste better than their generic counterparts. Despite preference for the taste of brand trimethoprim-sulfamethoxazole, all of the children in this study were compliant with both brand and generic medications.

New drugs on the horizon.

The agents covered in this article are useful in a wide range of illnesses, including infections, cancers, cardiovascular and gastrointestinal diseases, and others. One of the major forces driving the development of new drugs is the use of biotechnology. Biotechnology encompasses the techniques of recombinant DNA and monoclonal antibody technologies to produce protein drugs that have not been previously available in sufficiently pure form or in adequate quantities. As new drugs are developed, the authors hope that intensified efforts will be geared towards the development of unique drugs that offer important therapeutic gains.

Stability of amphotericin B in four concentrations of dextrose injection.

The stability of amphotericin B in 5%, 10%, 15%, and 20% dextrose injection was investigated. The dextrose solutions were prepared in triplicate from sterile water for injection and 70% dextrose injection and placed in empty 50-mL polyvinyl chloride bags. The pH of each solution was determined before amphotericin B was added to a concentration of approximately 100 micrograms/mL. The bags were stored at 15-25 degrees C and protected from light. Three 1-mL samples were taken from each bag at various times up to 24 hours. One sample was analyzed for precipitation and color and pH changes. Two samples were analyzed in duplicate by stability-indicating high-performance liquid chromatography. No visual changes were observed, and pH did not change substantially. The mean amphotericin B concentration was greater than 90% of the initial concentration at each sampling time. However, the drug concentration in 3 of the 27 samples from the admixtures with 10% dextrose injection and 5 of the 27 samples from the admixtures with 20% dextrose injection fell below 90% of the initial concentration. Amphotericin B 100 micrograms/mL was stable in 5%, 10%, 15%, and 20% dextrose injection when stored for up to 24 hours at 15-25 degrees C and protected from light.