A dosing nomograph for cerebrospinal fluid penetration of meropenem applied by continuous infusion in patients with nosocomial ventriculitis

König, Christina; Grensemann, Jörn; Czorlich, Patrick; Schlemm, Eckhard; Kluge, Stefan; Wicha, Sebastian G.

doi:10.1016/j.cmi.2022.02.017

Cited by 7 publications

(8 citation statements)

References 34 publications

(39 reference statements)

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“…More recently, CSF protein levels could be associated with an improved CSF penetration ratio of meropenem in patients with ventriculitis [ 3 ], whereas in our cohort no such association with variables such as GOS or other laboratory parameters could be identified for fosfomycin.…”

Section: Discussioncontrasting

confidence: 65%

“…Therefore, despite high-dose antibiotic therapy subtherapeutic CSF levels may be present. To prevent from subtherapeutic concentrations a routine therapeutic drug monitoring (TDM) from the cerebrospinal fluid (CSF) has been established in our institution to adjust antibiotic therapy accordingly [ 3 ]. This is only possible within certain limits as toxicity may occur at high serum levels, mandating the measurement of serum concentrations, as well.…”

Section: Introductionmentioning

confidence: 99%

“…Even though, current data show that fosfomycin exhibits time-dependent bactericidal activity it is most often used as intermittent infusion. Assuming that fosfomycin pharmacokinetics are relatively similar to meropenem, where continuous infusion lead to more sufficient CSF levels [ 3 , 9 ], this administration type was adopted for fosfomycin. Moreover, this approach has been used previously in CNS infections with fosfomycin being administered by continuous infusion (24 g/24 h) [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid penetration of fosfomycin in patients with ventriculitis: an observational study

König

Martens‐Lobenhoffer

Czorlich

et al. 2023

Ann Clin Microbiol Antimicrob

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Background For treatment of ventriculitis, vancomycin and meropenem are frequently used as empiric treatment but cerebrospinal fluid (CSF) penetration is highly variable and may result in subtherapeutic concentrations. Fosfomycin has been suggested for combination antibiotic therapy, but data are sparse, so far. Therefore, we studied CSF penetration of fosfomycin in ventriculitis. Methods Adult patients receiving a continuous infusion of fosfomycin (1 g/h) for the treatment of ventriculitis were included. Routine therapeutic drug monitoring (TDM) of fosfomycin in serum and CSF was performed with subsequent dose adaptions. Demographic and routine laboratory data including serum and CSF concentrations for fosfomycin were collected. Antibiotic CSF penetration ratio as well as basic pharmacokinetic parameters were investigated. Results Seventeen patients with 43 CSF/serum pairs were included. Median fosfomycin serum concentration was 200 [159–289] mg/L and the CSF concentration 99 [66–144] mg/L. Considering only the first measurements in each patient before a possible dose adaption, serum and CSF concentrations were 209 [163–438] mg/L and 104 [65–269] mg/L. Median CSF penetration was 46 [36–59]% resulting in 98% of CSF levels above the susceptibility breakpoint of 32 mg/L. Conclusion Penetration of fosfomycin into the CSF is high, reliably leading to appropriate concentrations for the treatment of gram positive and negative bacteria. Moreover, continuous administration of fosfomycin appears to be a reasonable approach for antibiotic combination therapy in patients suffering from ventriculitis. Further studies are needed to evaluate the impact on outcome parameters.

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Section: Discussioncontrasting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid penetration of fosfomycin in patients with ventriculitis: an observational study

König

Martens‐Lobenhoffer

Czorlich

et al. 2023

Ann Clin Microbiol Antimicrob

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“…Interestingly, incorporating the CSF protein/plasma albumin ratio as a marker of meningeal inflammation did not improve our model fit; nor was there an association between CSF protein and achieved concentrations. Increased CSF protein concentration has previously been shown to correlate with increasing meropenem and vancomycin CSF penetration (26,27). This discrepancy between studies could be explained by multiple reasons: differing population sizes, variable CSF drainage through the EVD, heterogenous sampling protocols, difficulty in diagnosing ventriculitis, and CSF sampling occurred on different infection timelines.…”

Section: Discussionmentioning

confidence: 99%

“…This discrepancy between studies could be explained by multiple reasons: differing population sizes, variable CSF drainage through the EVD, heterogenous sampling protocols, difficulty in diagnosing ventriculitis, and CSF sampling occurred on different infection timelines. Konig et al also fixed the volume of CSF, making a physiological assumption (27).…”

Section: Discussionmentioning

confidence: 99%

Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Meropenem in Neurocritical Care Patients: a Prospective Two-Center Study

Kumta

Heffernan

Cotta

et al. 2022

Antimicrob Agents Chemother

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Distribution of Bevacizumab into the Cerebrospinal Fluid of Children and Adolescents with Recurrent Brain Tumors

Minichmayr,

Knaack,

Gojo

et al. 2024

Pediatr Drugs

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Background To date, evidence has been lacking regarding bevacizumab pharmacokinetics in the cerebrospinal fluid (CSF). Objective This study assessed the penetration of bevacizumab, as part of a metronomic antiangiogenic treatment regimen, into the CSF of children, adolescents, and young adults with recurrent brain tumors. Patients and Methods Serum and CSF concentrations, malignant cells, and vascular endothelial growth factor A (VEGF-A) were analyzed in 12 patients (5–27 years) following 10 mg/kg bevacizumab intravenous biweekly administration (EudraCT number 2009-013024-23). A population pharmacokinetic model including body weight, albumin, and tumor type as influential factors was extended to quantify the CSF penetration of bevacizumab. Results Apart from in serum (minimum concentration/maximum concentration [ C min / C max ] 77.0–305/267–612 mg/L, median 144/417 mg/L), bevacizumab could be quantified in the CSF (0.01–2.26 mg/L, median 0.35 mg/L). The CSF/serum ratio was 0.16 and highly variable between patients. Malignant cells could be detected in CSF before initiation of treatment in five of 12 patients; after treatment, the CSF was cleared in all patients. VEGF-A was detected in three patients before treatment (mean ± SD: 20 ± 11 pg/mL), and was still measurable in one of these patients despite treatment (16 pg/mL). Conclusions This pharmacokinetic pilot study indicated penetration of bevacizumab into the CSF in a population of children, adolescents, and young adults with recurrent brain tumors. Supplementary Information The online version contains supplementary material available at 10.1007/s40272-024-00624-y.

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A dosing nomograph for cerebrospinal fluid penetration of meropenem applied by continuous infusion in patients with nosocomial ventriculitis

Cited by 7 publications

References 34 publications

Cerebrospinal fluid penetration of fosfomycin in patients with ventriculitis: an observational study

Cerebrospinal fluid penetration of fosfomycin in patients with ventriculitis: an observational study

Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Meropenem in Neurocritical Care Patients: a Prospective Two-Center Study

Distribution of Bevacizumab into the Cerebrospinal Fluid of Children and Adolescents with Recurrent Brain Tumors

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