Disposition of Cefepime in the Central Nervous System of Patients With External Ventricular Drains

Denise H. Rhoney, Pharm.D., Vincent H. Tam, Pharm.D., Dennis Parker, Jr., Pharm.D., Peggy S. McKinnon, Pharm.D., William M. Coplin, M.D.

Disclosures

Pharmacotherapy. 2003;23(3) 

In This Article

Results

The pharmacokinetic parameters of cefepime in serum and CSF are described in Table 1 . The pharmacokinetic model used to fit the data is described in Figure 1. Reasonable model fit to the data was obtained (median r2 for serum and CSF profiles were 0.87 and 0.96, respectively), and the overall model fits are shown in Figure 2. Penetration into the CNS is described as the median ratio of minimum concentrations (Cmin) in CSF and serum (Cmin-CSF:Cmin-serum) and by the ratio of the AUCs in CSF and serum (AUCCSF:AUCserum). Penetration was 4-34% based on AUC and 5-58% based on Cmin.

Description of the pharmacokinetic model used to fit the data. Kcp = intercompartment rate constant from central compartment to cerebrospinal fluid (CSF); Kpc = intercompartment rate constant from CSF to central compartment; and Kel = elimination rate constant from central compartment.

Pharmacokinetic model fit for serum and cerebrospinal fluid concentrations. CSF = cerebrospinal fluid.

Figure 3 describes patients' CSF concentration-time curves in relationship to the MIC90 of common pathogens. The cefepime concentrations attained in the CSF of subjects in this study were higher than the published MIC90 for Escherichia coli (0.06 µg/ml), Citrobacter freundii (0.5 µg/ml), penicillin-sensitive pneumococci (0.25 µg/ml), Haemophilus influenzae (0.06 µg/ml), and Enterobacter sp (1 µg/ml). Fifty-seven percent of patients also achieved concentrations above the MIC90 of Klebsiella pneumoniae (2 µg/ml). However, only one patient achieved CSF concentrations above the MIC90 of Staphylococcus aureus (8 µg/ml), and none of the patients achieved concentrations above the MIC90 of Pseudomonas aeuroginosa (32 µg/ml).

Non-steady-state cerebrospinal fluid concentration-time profile of the seven patients compared with the MIC90 (listed in parentheses next to the organism) of various nosocomial pathogens. Time represents the time of concentration from the end of cefepime infusion.

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