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Cefoxitin penetration into cerebrospinal fluid in patients with purulent meningitis
Abstract:
The penetration of cefoxitin into cerebrospinal fluid (CSF) was studied in 25 patients with purulent meningitis treated with antibiotics other than cefoxitin. Each patient received three 2-g doses of cefoxitin at 6-h intervals. Blood and CSF samples were obtained before and at 2, 4, or 6 h after the first and third doses. CSF cefoxitin concentrations were found in all patients and varied between 1.2 and 22.0 microgram/ml, with a majority of the concentrations falling within a range from 1.2 to 6.2 microgram/ml. The concentrations tended to be higher in CSF samples drawn after the third cefoxitin dose than in those drawn after the first cefoxitin dose, indicating an accumulation of cefoxitin in CSF with repeated doses. Peak cefoxitin concentrations in CSF seemed to occur between 2 and 6 h after intravenous administration of the drug since the highest concentrations were found in patients from whom CSF samples were taken 4 h after the doses. In patients with bacterial meningitis, it should be possible to achieve therapeutic cefoxitin levels in CSF by using nontoxic doses of the antibiotic.
Insights
Cefoxitin effectively penetrates cerebrospinal fluid (CSF) in patients with purulent meningitis. Repeated doses increase cefoxitin accumulation in CSF, suggesting therapeutic levels are achievable.
Area of Science:
- Pharmacology
- Infectious Diseases
- Neuroscience
Background:
- Purulent meningitis requires effective antibiotic penetration into the cerebrospinal fluid (CSF).
- Understanding cefoxitin's CSF penetration is crucial for optimizing meningitis treatment.
Purpose of the Study:
- To evaluate cefoxitin penetration into the CSF in patients with purulent meningitis.
- To determine cefoxitin concentrations in CSF after single and multiple doses.
- To assess the potential for achieving therapeutic CSF levels of cefoxitin.
Main Methods:
- A study involving 25 patients with purulent meningitis.
- Administration of three 2-g doses of cefoxitin at 6-hour intervals.
- Collection of blood and CSF samples at various time points post-administration.
- Quantification of cefoxitin concentrations in CSF samples.
Main Results:
- Cefoxitin was detected in the CSF of all patients, with concentrations ranging from 1.2 to 22.0 microgram/ml.
- Majority of CSF cefoxitin concentrations were between 1.2 and 6.2 microgram/ml.
- Higher cefoxitin concentrations were observed after the third dose compared to the first, indicating accumulation.
- Peak CSF cefoxitin concentrations appeared to occur 2-6 hours post-administration, with highest levels at 4 hours.
Conclusions:
- Cefoxitin demonstrates significant penetration into the CSF in patients with purulent meningitis.
- Repeated cefoxitin dosing leads to increased accumulation in the CSF.
- Nontoxic doses of cefoxitin can likely achieve therapeutic concentrations in the CSF for bacterial meningitis treatment.