Antibiotic Prophylaxis in Cerebrospinal Fluid Shunting: Reassessment of Cefotiam Penetration into Human CSF

Abstract

Objects Shunt infection is a major complication of shunt implantation. Numerous clinical studies give evidence that antibiotic prophylaxis is efficacious in preventing infections after cerebrospinal fluid shunting. In CSF shunting, antibiotics need to reach sufficient concentrations not only in the blood shielding the operative field but also in tissues and the CSF compartment. Cefotiam is widely used for prophylaxis in neurosurgery. Some clinical trials report that this β-lactam is able to penetrate considerably into the CSF. However, these studies include disease patterns which are most likely to be associated with a pathological permeability of the blood-brain barrier. Therefore, this study was designed to investigate the extent of penetration of Cefotiam into human CSF in patients without morphological disruption of the blood-brain barrier.

Methods: The penetration of Cefotiam into human CSF was investigated in 23 patients without morphological disruption of the blood-brain barrier undergoing CSF shunt surgery. 2 g Cefotiam was administered prior to surgery as a short-term infusion for a period of 15 min. Samples of blood and CSF were collected intraoperatively. The concentrations of Cefotiam were determined by bioassay.

Results: All patients (n=23) showed moderate to high plasma levels of Cefotiam (range: 19.8-146.2 mg/L); the pharmacokinetic profiles in blood accorded well with published data. In contrast to earlier studies, no Cefotiam was detected in CSF.

Conclusion: This study clearly demonstrates that Cefotiam does not penetrate through an intact blood-brain barrier into human CSF. Although Cefotiam has been shown to be valuable for the perioperative prophylaxis of shunt infection, other antibiotics might be superior if they are capable of entering the CSF. Further studies are required to address this assumption.

Zusammenfassung

Einleitung: Shuntinfektionen stellen eine große Komplikation bei der Liquorshuntimplantation dar. Einige klinische Studie unterstellen, dass die perioperative Gabe von Antiinfektiva die Infektionsrate nach Shuntimplantation deutlich vermindert. Prophylaktisch applizierte Antiinfektiva benötigen - zu jedem Zeitpunkt des operativen Eingriffes - eine wirksame Konzentration in allen Geweben des Operationsgebietes. Cefotiam wird häufig zur Infektionsprophylaxe in der Neurochirurgie angewendet. Frühere Studien zur Penetration von Cefotiam in den Liquor cerebrospinalis schlossen Patienten mit verschiedenen morphologischen Störung der Blut-Hirn-Schranke ein. Die Studie hat zum Ziel, unter Operationsbedingungen die Penetration von Cefotiam in den menschlichen Liquor erneut zu untersuchen.

Material und Methoden: Es wurde die Penetration von Cefotiam in den menschlichen Liquor cerebrospinalis in Korrelation zum Cefotiam-Plasmaspiegel untersucht. In die Studie eingeschlossen wurden 23 Patienten ohne klinische oder laborchemische Zeichen einer Meningitis sowie ohne eine morphologische Störung der Blut-Hirn-Schranke, bei denen elektiv ein primärer Liquorshunt implantiert wurde beziehungsweise primäre Eingriffe am Liquorsystem notwendig waren. Alle Patienten erhielten präoperativ als Kurzinfusion über 15 Minuten 2 g Cefotiam intravenös appliziert. Liquor- und Blutproben wurden intraoperativ gesammelt; die Konzentration des Cefotiam wurde durch einen Bioassay bestimmt.

Ergebnisse: Die Cefotiam-Plasmaspiegel waren bei allen Patienten (n=23) moderat bis hoch (19,8-146,2 mg/L). Das C/t-Profil befand sich in guter Übereinstimmung mit den bisher publizierten Daten. Im Liquor cerebrospinalis konnte kein Cefotiam in antibakteriell wirksamer Konzentration detektiert werden.

Schlussfolgerung: Die Studie demonstriert, dass bei intakter Blut-Hirn-Schranke beziehungsweise intakter Blut-Liquor-Schranke für eine Infektionsprophylaxe intravenös appliziertes Cefotiam nicht ausreichend in den menschlichen Liquor cerebrospinalis penetriert. Cefotiam kann deshalb nur eingeschränkt zur perioperativen Infektionsprophylaxe bei der Liquorshuntimplantation empfohlen werden. Weitere Studien zur Penetration von Antiinfektiva in den Liquor cerebrospinalis unter Operationsbedingungen sind notwendig.

Key words

antibiotic prophylaxis - cerebrospinal fluid - Cefotiam penetration - blood-brain barrier - shunting

Schlüsselwörter

Antibiotikaprophylaxe - Liquor cerebrospinalis - Liquor-Penetration - Blut-Hirn-Schranke - Shuntimplantation

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