Download PDF
Cent Eur Neurosurg 2007; 68(1): 14-18
DOI: 10.1055/s-2007-968168
Original Article

© Georg Thieme Verlag KG Stuttgart · New York

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

Antibiotikaprophylaxe bei Liquorshuntoperationen: Neubewertung der Cefotiampenetration in den menschlichen LiquorM. Knoop 1 , M. Schütze 2 , J. Piek 2 , B. Drewelow 3 , R. Mundkowski 3
  • 1HELIOS Hospital, Neurosurgery, Bad Saarow, Germany
  • 2University Rostock, Neurosurgery, Rostock, Germany
  • 3University Rostock, Department of Pharmacology and Toxicology
Further Information

Publication History

Publication Date:
08 May 2007 (online)

    Permissions and Reprints

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

References

  • 1 Arnaboldi L. Antimicrobial prophylaxis with ceftriaxone in neurosurgical procedures. A prospective study of 100 patients undergoing shunt operations.  Chemotherapy. 1996;  42 384-390
    PubMedGoogle Scholar
  • 2 Bayston R. Hydrocephalus shunt infections.  Journal of Antimicrobial Chemotherapy. 1994;  34 ((Suppl A)) 75-84
    CrossrefPubMedGoogle Scholar
  • 3 Bodey G, Fainstein V, Hinkle AM. Comparative in vitro study of new cephalosporins.  Antimicrob Agents Chemother. 1981;  20 ((2)) 226-230
    PubMedGoogle Scholar
  • 4 Borgbjerg BM, Gjerris F, Albeck MJ, Borgesen SE. Risk of infection after cerebrospinal fluid shunt: An analysis of 884 first-time shunts.  Acta Neurochir. 1995;  136 1-7
    CrossrefPubMedGoogle Scholar
  • 5 Brogard JM, Jehl F, Willemin B, Lamalle AM, Blickle JF, Monteil H. Clinical pharmacokinetics of Cefotiam.  Clin Pharmacokinet. 1989;  17 163-174
    PubMedGoogle Scholar
  • 6 Daschner FD, Hemmer KA, Offermann P, Slanicka J. Pharmacokinetics of Cefotiam in normal humans.  Antimicrob Agents Chemother. 1982;  22 958-960
    PubMedGoogle Scholar
  • 7 Eguchi T, Mayanagi Y, Hanamura T, Iai S, Asai A. The migration of Cefotiam to cerebrospinal fluid [in Japanese].  Jpn J Antibiot. 1983;  36 ((2)) 213-220
    PubMedGoogle Scholar
  • 8 Gaillard T, Gilsbach JM. Intra-operative antibiotic prophylaxis in neurosurgery. A prospective, randomized, controlled study on Cefotiam.  Acta Neurochir. 1991;  113 103-109
    CrossrefPubMedGoogle Scholar
  • 9 Garzone P, Lyon J, Yu VL. Third-generation and investigational cephalosporins: II. Microbiologic review and clinical summaries.  Drug Intell Clin Pharm. 1983;  17 ((9)) 615-622
    PubMedGoogle Scholar
  • 10 George R, Leibrock L, Epstein M. Long-term analysis of cerebrospinal fluid shunt infections. A 25-year experience.  J Neurosurg. 1979;  51 804-881
    CrossrefPubMedGoogle Scholar
  • 11 Hoellman DB, Spangler SK, Jacobs MR, Appelbaum PC. In vitro activities of Cefminox against anaerobic bacteria compared with those of nine other compounds.  Antimicrob Agents Chemother. 1998;  42 ((3)) 495-501
    PubMedGoogle Scholar
  • 12 Holloway KL, Smith KW, Wilberger JE, Jemsek JG, Giguere GC, Collins JJ. Antibiotic prophylaxis during clean neurosurgery: A large, multicenter study using cefuroxime.  Clinical Therapeut. 1996;  18 84-94
    PubMedGoogle Scholar
  • 13 Imagawa K, Kawasaki M, Toda I, Hayashi M, Asai A, Nomura T. A study on penetration of antibiotics into the cerebrospinal fluid after ventriculo-peritoneal shunt [in Japanese].  Jpn J Antibiot. 1982;  35 ((4)) 1072-1079
    PubMedGoogle Scholar
  • 14 Imagawa K, Nomura T, Asai A, Hayashi M, Toda I, Kawasaki M. Prophylactic administration of an antibiotic in neurosurgical operations - penetration of Cefotiam into cerebrospinal fluid [in Japanese].  Jpn J Antibiot. 1983;  36 ((12)) 3422-3428
    PubMedGoogle Scholar
  • 15 Ito H, Uno E, Tsuji T, Sato K, Yamamoto S. Concentration of Cefotiam in cerebrospinal fluid [in Japanese].  Jpn J Antibiot. 1982;  35 ((5)) 1183-1186
    PubMedGoogle Scholar
  • 16 Kodama Y, Sakata K, Fujiwara M, Kitsugi T. Study on penetration of Cefotiam into cerebrospinal fluid [in Japanese].  Jpn J Antibiot. 1984;  37 ((10)) 1757-1762
    PubMedGoogle Scholar
  • 17 Kojima T, Waga S, Morikawa A, Okada M, Furuno M, Shimizu T. Penetration of Cefotiam dihydrochloride into cerebrospinal fluid [in Japanese].  Jpn J Antibiot. 1982;  35 ((4)) 1063-1067
    PubMedGoogle Scholar
  • 18 Konishi K, Ozawa Y. Pharmacokinetics of Cefotiam in patients with impaired renal function and in those undergoing hemodialysis.  Antimicrob Agents Chemother. 1984;  26 647-651
    PubMedGoogle Scholar
  • 19 Kropec A, Daschner F. In vitro activity of fleroxacin and 14 other antimicrobials against slime- and non-slime-producing Staphylococcus epidermidis.  Chemotherapy. 1989;  35 351-354
    PubMedGoogle Scholar
  • 20 Kubota M, Sakai T, Mizutani H. Clinical evaluation of Cefotiam in the cerebrospinal fluid of patients with ruptured cerebral aneurysms in the acute stage [in Japanese].  Jpn J Antibiot. 1985;  38 ((8)) 2139-2144
    PubMedGoogle Scholar
  • 21 Kulkarni AV, Drake JM, Lamberti-Pasculli M. Cerebrospinal fluid shunt infection: a prospective study of risk factors.  J Neurosurg. 2001;  94 195-201
    CrossrefPubMedGoogle Scholar
  • 22 Lutsar I, McCracken, GH, Friedland IR. Antibiotic pharmacodynamics in cerebrospinal fluid.  Clinical Infectious Diseases. 1998;  27 1117-1129
    PubMedGoogle Scholar
  • 23 Maier W, Strutz J. Concentrations of cephalosporins in tissues of the head and neck after parenteral infusion.  Chemotherapy. 1995;  41 ((6)) 421-426
    PubMedGoogle Scholar
  • 24 Matsumoto M, Tamaoka H, Ishikawa H, Kikuchi M. In vitro and in vivo antibacterial activities of OPC-20011, a novel parenteral broad-spectrum 2-oxaisocephem antibiotic.  Antimicrob Agents Chemother. 1998;  42 ((11)) 2943-2949
    PubMedGoogle Scholar
  • 25 Meier H, Zerfowski M, Schlegel P. Excretion of beta-lactam antibiotics in human parotid [in German].  HNO. 1991;  39 ((3)) 102-107
    PubMedGoogle Scholar
  • 26 Nakashio S, Nakamura M. In vitro activity of cefotaxime against clinically significant pathogens.  Drugs. 1988;  35 ((Suppl. 2)) 14-21
    PubMedGoogle Scholar
  • 27 Renier D, Lacombe J, Pierre-Kahn A, Sainte-Rose C, Hirsch JF. Factors causing acute shunt infection.  J Neurosurg. 1984;  61 1072-1078
    PubMedGoogle Scholar
  • 28 Ronan A, Hogg GG, Klug GL. Cerebrospinal fluid shunt infections in children.  Pediatr Infect Dis J. 1995;  14 782-786
    PubMedGoogle Scholar
  • 29 Rouan MC, Lecaillon JB, Guibert J, Modai J, Schoeller JP. Pharmacokinetics of Cefotiam in humans.  Antimicrob Agents Chemother. 1985;  27 177-180
    PubMedGoogle Scholar
  • 30 Spanu G, Karussos G, Adinolfi D, Bonfanti N. An analysis of cerebrospinal fluid shunt infections in adults. A clinical experience of twelve years.  Acta Neurochir. 1986;  80 79-82
    CrossrefPubMedGoogle Scholar
  • 31 Watanabe NA, Katsu K, Moriyama M, Kitoh K. In vitro evaluation of E1040, a new cephalosporin with potent antipseudomonal activity.  Antimicrob Agents Chemother. 1988;  32 ((5)) 693-701
    PubMedGoogle Scholar
  • 32 Yoshihara T, Kitaoka T, Tomihara K, Nomura M, Uozumi T. Cerebrospinal fluid transfer of Cefotiam (CTM). Its relationship to CT [in Japanese].  No Shinkei Geka. 1985;  13 ((9)) 965-971
    PubMedGoogle Scholar
  • 33 Zentner J, Gilsbach J, Felder T. Antibiotic prophylaxis in cerebrospinal fluid shunting: a prospective randomized trial in 129 patients.  Neurosurg Rev. 1995;  18 169-172
    PubMedGoogle Scholar

Correspondence

Dr. M. Knoop

HELIOS Klinikum Bad Saarow

Pieskower Straße 33

15526 Bad Saarow

Germany

Phone: +49/33631/73386

Fax: +49/33631/73190

Email: michael.knoop@helios-kliniken.de

      >