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Cefotaxime pharmacokinetics and treatment of meningitis in neonates

Cefotaxim-Pharmakokinetik und Behandlung der Meningitis bei Neugeborenen

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  • Cefotaxime — Recent Experiences
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Summary

Pharmacokinetic studies on cefotaxime/desacetylcefotaxime were carried out in very low birth weight newborns (n=18; 500–1500 g; 28.4±2.4 weeks gestational age) during the first week of life. We have previously reported that the elimination t 1/2 of cefotaxime (3.4–6.4 h) and desacetylcefotaxime (9.4 h) was longer than previously described in term infants and children. In very low birth weight neonates, a single 50 mg/kg daily dose of cefotaxime may produce accumulation of the metabolite desacetylcefotaxime in serum. In a non-comparative prospective clinical trail, 22 infants (one week — three months) were treated for gram-negative enteric bacillary meningitis with cefotaxime at a dosage of 50 mg/kg/day. The predominant pathogen wasEscherichia coli in 14 cases andEnterobacter cloacae in four cases. Cultures of the cerebrospinal fluid obtained 24–48 h after the initiation of treatment were sterile in all subjects. Survival and complication rates of 95% and 19%, respectively, were observed. This compared favorably to previously published experiences with alternative treatment regimens for neonatal gram-negative enteric meningitis. In both the pharmacokinetic and meningitis studies, the safety profile for cefotaxime was excellent with no adverse reactions.

Zusammenfassung

Studien zur Pharmakokinetik von Cefotaxim/Desacetylcefotaxim wurden bei Neugeborenen mit sehr niedrigem Geburtsgewicht (n=18; 500–1500 g; Gestationsalter 28,4 ± 2,4 Wochen) während der ersten Lebenswoche durchgeführt. Wie wir bereits berichtet haben, ist die Eliminations-Halbwertzeit von Cefotaxim (3,4–6,4 h) und Desacetylcefotaxim (9,4 h) bei diesen Kindern länger als bei reifen Neugeborenen und Kindern beschrieben wurde. Bei Neugeborenen mit sehr niedrigem Geburtsgewicht kann es nach Gabe von Cefotaxim in einer Dosis von einmal 50 mg/kg täglich möglicherweise zur Akkumulation des Metaboliten Desacetylcefotaxim im Serum kommen. In einer prospektiven, nicht vergleichenden klinischen Studie wurde Cefotaxim in einer Dosis von 50 mg/kg/Tag bei 22 Säuglingen im Alter von einer Woche bis drei Monaten zur Behandlung einer Meningitis durch gramnegative Enterobakterien eingesetzt. Als häufigster Erreger wurdeEscherichia coli bei 14 Fällen isoliert, in vier FällenEnterobacter cloacae. Bei allen Kindern waren die Liquorkulturen 24–48 h nach Therapiebeginn negativ. 95% der Kinder überlebten, bei 19% traten Komplikationen auf. Diese Ergebnisse stimmen gut mit früheren Erfahrungen mit Alternativtherapien bei der Meningitis durch gramnegative Enterobakterien überein. Das Sicherheitsprofil war sowohl in der Pharmakokinetik- wie in der Meningitis-Therapiestudie ausgezeichnet, unerwünschte Reaktionen traten in keinem Fall auf.

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  1. University of Arkansas for Medical Sciences and Arkansas Children's Hospital, 800 Marshall Street, 72202, Little Rock, Arkansas, USA

    R. F. Jacobs M.D. & G. L. Kearns Pharm.D.

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Jacobs, R.F., Kearns, G.L. Cefotaxime pharmacokinetics and treatment of meningitis in neonates. Infection 17, 338–342 (1989). https://doi.org/10.1007/BF01650725

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