Related Experiment Videos
Cerebrospinal fluid pharmacokinetics of cefpodoxime proxetil in piglets
S M Abdel-Rahman1, S Maxson, C Teo
1Department of Pediatrics, University of Missouri-Kansas City, USA.
Insights
Cefpodoxime oral antibiotic use in children may affect cerebrospinal fluid (CSF) culture results for meningitis. This study found cefpodoxime penetrates the CSF, potentially impacting diagnosis and treatment decisions.
Area of Science:
- Pharmacology
- Infectious Diseases
- Pediatrics
Background:
- Cefpodoxime is an oral third-generation cephalosporin prescribed for pediatric upper respiratory tract infections.
- Its use may interfere with cerebrospinal fluid (CSF) culture interpretation in children who develop meningitis.
- This interference occurs if sufficient cefpodoxime concentrations reach the CSF.
Purpose of the Study:
- To evaluate the disposition and CSF penetration of cefpodoxime in a preclinical model.
- To determine cefpodoxime concentrations in plasma and CSF after oral administration.
Main Methods:
- Fifteen piglets (10-20 days old) received an oral cefpodoxime proxetil suspension (10 mg/kg).
- Plasma and CSF samples were collected over 24 hours.
- Cefpodoxime concentrations were quantified using High-Performance Liquid Chromatography (HPLC).
- Pharmacokinetic analysis was performed on plasma and CSF data.
Main Results:
- Cefpodoxime plasma concentrations were characterized by a one-compartment model.
- Mean pharmacokinetic parameters included Cmax (23.3 mg/L), tmax (3.9 h), and AUC0-infinity (237 mg/L.h).
- Mean CSF/plasma AUC ratio indicated approximately 5% cefpodoxime penetration into the CSF.
- CSF concentrations approached or exceeded the MIC90 for susceptible pathogens.
Conclusions:
- Oral cefpodoxime proxetil suspension demonstrates penetration into the CSF in piglets.
- Clinicians must exercise caution when interpreting CSF cultures in patients treated with cefpodoxime who present with meningitis symptoms.
- The findings highlight the potential for antibiotic interference in diagnosing central nervous system infections.
Abstract:
Cefpodoxime is an oral third-generation cephalosporin used for the treatment of acute upper-respiratory tract infections caused by susceptible bacteria in children. Although not indicated for the treatment of bacterial meningitis, it is used to treat other infections produced by organisms associated with meningitis and may obscure the result of cerebrospinal fluid (CSF) cultures in children who develop meningitis while receiving oral antibiotics if sufficient concentrations are achieved in the CSF. This study evaluated the disposition of cefpodoxime and penetration into CSF in piglets. Fifteen Landacre-Camborough cross piglets (10-20 days old) received cefpodoxime proxetil oral suspension (10 mg/kg). Repeated plasma and CSF samples were collected over 24 hours for quantitation of cefpodoxime by HPLC. Pharmacokinetic analysis was performed on both plasma and CSF data. The plasma concentration versus time data for cefpodoxime were best characterized using a one-compartment model with first-order absorption. The mean (+/- SD) pharmacokinetic parameters for Cmax, tmax, and AUC0-infinity were 23.3 +/- 12.9 mg/L, 3.9 +/- 1.4 h, and 237 +/- 129 mg/L.h, respectively. CSF/plasma ratios for AUC0-infinity demonstrated a mean cefpodoxime penetration of approximately 5%. CSF penetration of cefpodoxime was evident following a single oral dose of cefpodoxime proxetil suspension. Despite the small percentage of total cefpodoxime dose distributing into the CSF, the resultant concentrations approached or exceeded the MIC90 for many bacterial pathogens considered susceptible to cefpodoxime. Accordingly, clinicians should use caution in the interpretation of CSF cultures in patients who develop clinical signs and symptoms consistent with meningitis and who have been previously treated with cefpodoxime.