Serum and cerebrospinal fluid kinetics of ceftazidime

Ceftazidime serum concentrations and cerebrospinal fluid (CSF) penetration across non-inflamed meninges were evaluated in 10 patients after intravenous application of 2 g ceftazidime over a period of 30 min. After a continuous increase during infusion the highest level of ceftazidime in serum with 172.27 micrograms/ml (+/- 60.43 micrograms/ml) was ascertained at the end of the infusion. The further development demonstrated a continuous decrease of serum concentrations. Concentrations in serum followed a two-compartment open kinetic model. Mean distribution volume was 17.6 l, the total clearance was 142.97 ml/min, half-life was 1.8 h and the determined area under the curve was 139.89 micrograms x min/ml. Penetration of ceftazidime into CSF could only be pointed out in 5 patients. The highest level with 5.11 micrograms/ml (+/- 1.2 micrograms/ml) was observed 32 min after starting the infusion. A steady state with CSF-concentrations over 2 micrograms/ml could be ascertained during the following 4 hours in these patients. Obviously high statistic significance (p less than or equal to 0.01) was present when penetration into CSF was correlated to body surface area (BSA) using the exact Fisher test with Yates correction. Penetration of ceftazidime into CSF across non-inflamed meninges with therapeutic concentrations over a period of 4 hours could only be achieved when BSA was less than 1.95 m2. Further investigations in more patients are necessary to evaluate if BSA is the only parameter which affects distribution of ceftazidime into CSF.