CSF penetration of vancomycin in critical care patients with proven or suspected ventriculitis: a prospective observational study

Blassmann, Ute; Hope, William; Roehr, Anka C; Frey, Otto; Vetter-Kerkhoff, Cornelia; Thon, Niklas; Briegel, Josef; Huge, Volker

doi:10.1093/jac/dky543

Cited by 21 publications

(25 citation statements)

References 27 publications

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“…Dose optimization according to TDM ensured sufficient CSF concentrations in all patients within 48 h. However, there was considerable variation in serum and CSF concentrations as well as resultant CSF/serum ratios. These findings are concordant with those derived from previous studies in which researchers have also described large interindividual variability [ 10 ]. Therefore, our study suggests routine TDM of meropenem and vancomycin in CSF further on to avoid underexposure potentially resulting in treatment failures.…”

Section: Discussionsupporting

confidence: 93%

“…In ventriculitis, the meninges are typically normal or only minimally inflamed [ 20 ]. Serum-to-CSF ratios range between 1 and 18% [ 1 , 10 , 11 ] for vancomycin and between 5 and 9% for meropenem in ventriculitis patients [ 1 , 10 , 11 ], compared with reported serum-to-CSF ratios of between 6 and 81% for vancomycin and 21 and 39% for meropenem in patients with bacterial meningitis [ 1 , 11 ]. Hence, the poor penetration into the CSF described in previous studies led us to aim at vancomycin and meropenem serum concentrations of 20–30 mg/L.…”

Section: Discussionmentioning

confidence: 99%

“…Recent data show a highly variable penetration of vancomycin and meropenem into the CSF in ventriculitis patients [ 8 , 9 , 10 , 11 ]. Data from Blassmann et al [ 9 , 10 ] suggest that traditional meropenem dosing (3 × 2 g administered as intermittent infusion) as well as traditional vancomycin dosing (2 × 1 g administered as intermittent infusion) do not achieve CSF concentrations above the minimum inhibitory concentration (MIC) in the majority of patients. High daily doses of up to 20 g meropenem or rather up to 8 g vancomycin and/or continuous infusion are proposed to ensure sufficient concentration.…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal Fluid Concentrations of Meropenem and Vancomycin in Ventriculitis Patients Obtained by TDM-Guided Continuous Infusion

et al. 2021

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Effective antibiotic therapy of cerebral infections such as meningitis or ventriculitis is hindered by low penetration into the cerebrospinal fluid (CSF). Because continuous infusion of meropenem and vancomycin and routine therapeutic drug monitoring (TDM) have been proposed to optimize antimicrobial exposure in ventriculitis patients, an individualized dosing strategy was implemented in our department. We present a retrospective analysis of meropenem and vancomycin concentrations in serum and CSF in the first nine ventriculitis patients treated with continuous infusion and TDM-guided dose optimization aiming at 20–30 mg/L. Median initial dosing was 8.8 g/24 h meropenem and 4.25 g/24 h vancomycin, respectively, resulting in median serum concentrations of 21.3 mg/L for meropenem and 24.5 mg/L for vancomycin and CSF concentrations of 3.4 mg/L for meropenem and 1.7 mg/L for vancomycin. Median CSF penetration was 15% for meropenem and 7% for vancomycin. With initial dosing, all but one patient achieved CSF concentrations above 1 mg/L. Dose adjustment according to TDM ensured sufficient CSF concentrations in all patients within 48 h of treatment. Given the limited penetration, continuous infusion of meropenem and vancomycin based on renal function and TDM-guided dose optimization appears a reasonable approach to attain sufficient CSF concentrations in ventriculitis patients.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal Fluid Concentrations of Meropenem and Vancomycin in Ventriculitis Patients Obtained by TDM-Guided Continuous Infusion

et al. 2021

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“…The 5 th and 95 th percentile respectively, show patients with impaired and augmented renal clearance.Publications reporting population pharmacokinetics (PopPK) modelling of vancomycin concentrations in the CSF are rare. Recently, Blassmann et al[50] published a population pharmacokinetic model, that assessed the disposition of vancomycin in EVD patients. Here, the nonparametric approach was used to fit the data, which does not make the assumption, that pharmacokinetic parameter variability is restricted to a normal distribution around the population mean, but rather allows all parameters to be individually estimated across the non-parametric adaptive population grid.Li X et al[51,52] also used a parametric PopPK approach with a three compartment model including one CSF compartment.…”

mentioning

confidence: 99%

Population pharmacokinetics of vancomycin in patients with external ventricular drain‐associated ventriculitis

Jalusic

Hempel

Arnemann

et al. 2020

Brit J Clinical Pharma

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“…The bactericidal activity of five drugs (MEM, LNZ, PEN, VAN, TMP/SMX) against three isolates was determined using the time-kill method described in the CLSI guidelines [16]. The following concentrations referring to human body pharmacokinetics (Supplemental Table 1) were used for serum and CSF concentrations: MEM 14.6 mg/L and 1.1 mg/L [17][18], LNZ 4 mg/L and 1.8 mg/L [18][19], PEN 21 mg/L and 0.56 mg/L [20], VAN 13.32 mg/L and 10.64 mg/L [21], TMP/SMX 1.3/48.3 mg/L and 0.2/5.9 mg/L [18,22]. The time-kill assays were done and interpreted as described previously [18].…”

Section: Time-kill Assaysmentioning

confidence: 99%

Genetic structure characteristics and treatment for Listeria monocytogenes infections

Huang

Guo

et al. 2020

Preprint

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Background: Invasive Listeria monocytogenes (Lm) carry a high mortality despite antibiotic treatment. The aim of this study was to investigate the mechanism of pathogenicity and resistance. In addition, the effect of existing treatment options against Lm were systematically evaluated as well. Methods: Three Lm isolates were collected and 15 antibiotics susceptibility tests were done. Subsequently, whole genome sequencing and bioinformatics analysis were performed. Furthermore, the effect of meropenem, linezolid, benzylpenicillin, vancomycin, trimethoprim/sulfamethoxazole were determined using the time-kill assay.Results: Two sequence types (STs) were identified for isolate 23949 (ST87), 26530 (ST3), 34096 (ST87), respectively. All isolates were resistant to fosfomycin and daptomycin. The resistant genes fosX, mprF, norB and vgaALC were identified in all isolates. Furthermore, 80 virulence genes were detected and 72 genes were found in all three isolates. There were 26 virulent genes associated with the structure, biosynthesis, motor switch of flagellum. And other virulent genes were involved in chemotaxis, protease, internalin and metabolism. It is of note that 8 genes (inlJ, llsB, llsD, llsG, llsH, llsP, llsX, llsY) were only found in 26530 isolated from cerebrospinal fluid (CSF), 7 of which were associated with haemolysin. Further in vitro time-kill assay found trimethoprim/sulfamethoxazole at serum or CSF concentrations had bactericidal effect (>3.5 log10 CFU/ml) against three tested Lm strains at 24 h. Conclusions: The involved virulence factors were mainly associated with bacterial pathogenicity. Notably, trimethoprim/sulfamethoxazole might be greater potential therapeutic option against Lm bloodstream infection or intracranial infection.

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CSF penetration of vancomycin in critical care patients with proven or suspected ventriculitis: a prospective observational study

Cited by 21 publications

References 27 publications

Cerebrospinal Fluid Concentrations of Meropenem and Vancomycin in Ventriculitis Patients Obtained by TDM-Guided Continuous Infusion

Cerebrospinal Fluid Concentrations of Meropenem and Vancomycin in Ventriculitis Patients Obtained by TDM-Guided Continuous Infusion

Population pharmacokinetics of vancomycin in patients with external ventricular drain‐associated ventriculitis

Genetic structure characteristics and treatment for Listeria monocytogenes infections

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