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Published online: 20 May 2017
© Springer International Publishing Switzerland 2017
Abstract
Introduction Infectious disease and pharmacokinetic textbooks indicate that vancomycin has poor penetration into the central nervous system due to its hydrophilic nature and high molecular weight. Recent literature suggests that penetration of vancomycin into cerebrospinal fluid (CSF) is higher than previously reported; therefore, we conducted a systematic review to assess the penetration of vancomycin into CSF.
Methods We searched the MEDLINE, EMBASE, and CENTRAL electronic databases for English-language human studies evaluating serum and CSF concentrations of intravenous vancomycin.
Results In 13 identified studies, the CSF-to-serum ratio of vancomycin varied from 0.00 to 0.81. CSF penetration ranged 0.06-0.81 in patients with meningitis, 0.05-0.17 in ventriculitis, 0.00-0.36 in other infections, and 0-0.13 in patients without infection. Despite variable CSF penetration, 83% of patients with meningitis and 100% of patients with ventriculitis achieved clinical cure. No factor predicted vancomycin CSF penetration.
Conclusion Contrary to prior belief, studies included in our review did not show universally low penetration of vancomycin into CSF. CSF vancomycin levels were variable and did not predict clinical cure.
1Introduction
Gram-positive organisms account for most central nervous system (CNS) infections, including meningitis and ventriculitis. Due to the emergence of penicillin-resistant Grampositive organisms (e.g. Streptococcus pneumoniae, Staphylococcus aureus, and Staphylococcus epidermidis), vancomycin is a standard component of empiric treatment for bacterial CNS infections [1, 2]. Despite widespread use, vancomycin may be suboptimal, owing to concerns that it does not effectively cross the blood-brain barrier (BBB) into the CNS. Factors impacting penetration into cerebrospinal fluid (CSF) include molecular size, lipophilicity, plasma protein binding, and affinity for active transport mechanisms [3]. Vancomycin is hydrophilic, with plasma protein binding <50% [3] and a molecular weight of 1450 Da [4]. Vancomycin enters the CNS via paracellular pathways rather than active transport; thus, its transport is dependent on opening of the tight junctions [5]. Owing to these factors, standard infectious disease and pharmacokinetic textbooks describe the poor penetration of vancomycin into CSF, reporting CSF-to-plasma ratios of 0.07-0.30 [6, 7].
Vancomycin exhibits time-dependent bacterial killing. Area under the curve to minimum inhibitory concentration ratio (AUC/MIC) appears to be the pharmacodynamic parameter correlating best to clinical outcomes [4]. The usual vancomycin MIC for staphylococci and streptococci is <1 mg/L [8]....