Use of teicoplanin in preterm neonates with staphylococcal late-onset neonatal sepsis.

OBJECTIVE: To study the clinical pharmacology of teicoplanin in babies admitted to a newborn intensive care unit, by monitoring serum levels, efficacy and potential side effects. METHODS: An open, nonrandomized descriptive study was performed in the neonatal intensive and high care unit of the University Hospital Maastricht, The Netherlands. Twenty-three preterm neonates, gestational age ranging from 26 to 32 weeks (median 28.4 weeks), postnatal age from 5 to 47 days, and birth weight from 570 to 1,740 g, presenting with (suspected) late onset septicemia, were studied. Of 21 culture-proven septicemias, 20 were caused by staphylococci. The teicoplanin loading dose was 15 mg/kg i.v., followed by a maintenance dose of 8 mg/kg every 24 h. Intravenous gentamicin was also administered pending blood culture. Serum teicoplanin concentrations were measured by fluorescence polarization immunoassay. Clinical and microbiological cure/failure rates were determined and possible side effects were monitored. RESULTS: The study of individual pharmacokinetics during multiple-dose intravenous infusions was rendered impossible by apparently inaccurate dosing. Peak (30 min after end of the infusion) and trough teicoplanin levels were stable throughout the study and averaged 27.8 (interquartile range 23.7-32.9) and 12.3 (interquartile range 9.1-16.8) mg/l, respectively. The microbiological and clinical cure rates were 90% in gram-positive septicemia. There was no apparent toxicity. CONCLUSIONS: Inaccurate drug administration was a problem in this study, making a multidose pharmacokinetic study impossible. It is possible that inaccurate drug administration and not current dosage guidelines yielded trough levels below 10 mg/l in 57 (32%) of 176 instances. This pharmaceutical aspect clearly warrants further study. However, microbiological and clinical cure rates were high in gram-positive septicemias. No side effects attributable to teicoplanin therapy were encountered.

Evaluation of genotoxic risk of handling cytostatic drugs in clinical pharmacy practice.

The genotoxic risk of handling antineoplastic drugs was evaluated in fifteen women preparing chemotherapeutics in the Pharmacy Department of the University Hospital Maastricht. Twenty nurses of the same hospital, who were not exposed to cytostatics, acted as controls. Endogenous exposure to antineoplastic drugs was assessed by determination of urine mutagenicity, as well as by analysis of urinary methotrexate levels. As genotoxicological end-points, sister chromatid exchanges and hypoxanthine guanine phosphoribosyl transferase locus point mutations were studied in peripheral lymphocytes obtained via venous puncture. No differences in urine mutagenic activity, in sister chromatid exchange frequencies and in hypoxanthine guanine phosphoribosyl transferase point mutation frequencies between exposed and non-exposed groups were detected. Higher sister chromatid exchange frequency was observed in smokers as compared to non-smokers.