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Published in: Acta Neurochirurgica 11/2018

01-11-2018 | Original Article - Infection

Intrathecal penetration of meropenem and vancomycin administered by continuous infusion in patients suffering from ventriculitis—a retrospective analysis

Authors: Marius Marc-Daniel Mader, Patrick Czorlich, Christina König, Valentin Fuhrmann, Stefan Kluge, Manfred Westphal, Jörn Grensemann

Published in: Acta Neurochirurgica | Issue 11/2018

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Abstract

Background

Vancomycin and meropenem are frequently used as empiric treatment for ventriculitis. Penetration into the cerebrospinal fluid (CSF) depends on various factors with a high inter-individual variability. Because attaining and maintaining adequate concentrations of meropenem and vancomycin in the CSF is crucial for their bactericidal effect, we introduced a routine therapeutic drug monitoring (TDM) from CSF and serum for both antibiotics. We studied the antibiotic penetration into the CSF.

Methods

Patient data including serum and CSF concentrations for meropenem and vancomycin were collected in a retrospective fashion. Antibiotic CSF penetration ratio was calculated for each patient. Antibiotics were administered by continuous infusion aiming for serum target concentrations of 20–30 mg/L for vancomycin and 16–32 mg/L for meropenem.

Results

Twenty-two patients with 36 CSF/serum pairs for meropenem and 43 pairs for vancomycin were studied. No patient suffered from renal or liver insufficiency. Mean vancomycin serum concentration was 22 ± 8 mg/L and the mean CSF concentration 4.5 ± 2.6 mg/L. CSF penetration was 20 ± 11% (coefficient of determination (R2) 0.02). For meropenem, the mean serum concentration was 30.7 ± 14.9 mg/L, mean CSF concentration 5.5 ± 5.2 mg/L, and a penetration of 18 ± 12%, R2 = 0.42.

Conclusion

Penetration of meropenem and vancomycin into the CSF is low while showing a high interindividual variability. Various patients in our study cohort were at risk for insufficient target attainment in CSF. Continuous administration of antibiotics under routine TDM appears to be a feasible and reasonable approach for optimization of intrathecal drug levels in patients suffering from ventriculitis. TDM might guide individual dosing adaptation and efforts to predict the CSF penetration of meropenem and vancomycin in cases of ventriculitis.
Literature
1.
go back to reference Albanese J, Leone M, Bruguerolle B, Ayem ML, Lacarelle B, Martin C (2000) Cerebrospinal fluid penetration and pharmacokinetics of vancomycin administered by continuous infusion to mechanically ventilated patients in an intensive care unit. Antimicrob Agents Chemother 44:1356–1358CrossRef Albanese J, Leone M, Bruguerolle B, Ayem ML, Lacarelle B, Martin C (2000) Cerebrospinal fluid penetration and pharmacokinetics of vancomycin administered by continuous infusion to mechanically ventilated patients in an intensive care unit. Antimicrob Agents Chemother 44:1356–1358CrossRef
7.
8.
go back to reference Le Gall JR, Lemeshow S, Saulnier F (1993) A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963CrossRef Le Gall JR, Lemeshow S, Saulnier F (1993) A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963CrossRef
9.
go back to reference Ichie T, Urano K, Suzuki D, Okada T, Kobayashi N, Hayashi H, Sugiura Y, Yamamura K, Sugiyama T (2015) Influence of cerebral fluid drainage on the pharmacokinetics of vancomycin in neurosurgical patients. Pharmazie 70:404–409PubMed Ichie T, Urano K, Suzuki D, Okada T, Kobayashi N, Hayashi H, Sugiura Y, Yamamura K, Sugiyama T (2015) Influence of cerebral fluid drainage on the pharmacokinetics of vancomycin in neurosurgical patients. Pharmazie 70:404–409PubMed
10.
go back to reference Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet 1:480–484CrossRef Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet 1:480–484CrossRef
11.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRef Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRef
18.
go back to reference No Authors (2000) The management of neurosurgical patients with postoperative bacterial or aseptic meningitis or external ventricular drain-associated ventriculitis. Infection in Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy. Br J Neurosurg 14:7–12CrossRef No Authors (2000) The management of neurosurgical patients with postoperative bacterial or aseptic meningitis or external ventricular drain-associated ventriculitis. Infection in Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy. Br J Neurosurg 14:7–12CrossRef
20.
go back to reference Roberts JA, Lipman J (2009) Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med 37:840–851CrossRef Roberts JA, Lipman J (2009) Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med 37:840–851CrossRef
21.
go back to reference Roberts JA, Paul SK, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, Kaukonen KM, Koulenti D, Martin C, Montravers P, Rello J, Rhodes A, Starr T, Wallis SC, Lipman J (2014) DALI: defining antibiotic levels in intensive care unit patients: are current beta-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis 58:1072–1083. https://doi.org/10.1093/cid/ciu027 CrossRefPubMed Roberts JA, Paul SK, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, Kaukonen KM, Koulenti D, Martin C, Montravers P, Rello J, Rhodes A, Starr T, Wallis SC, Lipman J (2014) DALI: defining antibiotic levels in intensive care unit patients: are current beta-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis 58:1072–1083. https://​doi.​org/​10.​1093/​cid/​ciu027 CrossRefPubMed
23.
go back to reference Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, Dalovisio JR, Levine DP (2009) Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 66:82–98. https://doi.org/10.2146/ajhp080434 CrossRef Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, Dalovisio JR, Levine DP (2009) Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 66:82–98. https://​doi.​org/​10.​2146/​ajhp080434 CrossRef
27.
29.
go back to reference Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Michael Scheld W, van de Beek D, Bleck TP, Garton HJ, Zunt JR (2017) 2017 Infectious Diseases Society of America’s clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. https://doi.org/10.1093/cid/ciw861 CrossRef Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Michael Scheld W, van de Beek D, Bleck TP, Garton HJ, Zunt JR (2017) 2017 Infectious Diseases Society of America’s clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. https://​doi.​org/​10.​1093/​cid/​ciw861 CrossRef
32.
go back to reference Wen DY, Bottini AG, Hall WA, Haines SJ (1992) Infections in neurologic surgery. The intraventricular use of antibiotics. Neurosurg Clin N Am 3:343–354CrossRef Wen DY, Bottini AG, Hall WA, Haines SJ (1992) Infections in neurologic surgery. The intraventricular use of antibiotics. Neurosurg Clin N Am 3:343–354CrossRef
33.
go back to reference Wolff M, Regnier B, Garaud JJ, Faurisson F (1983) Intracisternal concentrations of vancomycin and amikacin after lumbar injections. Presse Med 12:2185PubMed Wolff M, Regnier B, Garaud JJ, Faurisson F (1983) Intracisternal concentrations of vancomycin and amikacin after lumbar injections. Presse Med 12:2185PubMed
Metadata
Title
Intrathecal penetration of meropenem and vancomycin administered by continuous infusion in patients suffering from ventriculitis—a retrospective analysis
Authors
Marius Marc-Daniel Mader
Patrick Czorlich
Christina König
Valentin Fuhrmann
Stefan Kluge
Manfred Westphal
Jörn Grensemann
Publication date
01-11-2018
Publisher
Springer Vienna
Published in
Acta Neurochirurgica / Issue 11/2018
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-018-3680-z

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