Serum bactericidal activity of ceftazidime: Continuous infusion versus intermittent injections

Since beta-lactam antibiotics have concentration-independent killing, bacterial eradication is a function of the time the serum drug concentration remains above the drug's MIC (T > MIG), We compared the serum bactericidal titers (SBTs) of ceftazidime given by continuous infusion (CI) or by intermittent bolus dosing (ED) against two clinical isolates each of Pseudomonas aeruginosa and Escherichia coli to determine if CI would allow lower daily dosing while still providing equal bactericidal activity compared with ED. This was an open-labeled, randomized, steady-state, four-way crossover study with 12 healthy volunteers, The ceftazidime regimens were 1 g every 8 h (q8h) ED, 1 g q12h ED, 3 g over 24 h CI, and 2 g over 24 h CI, The areas under the bactericidal curves were calculated by the trapezoidal rule using the reciprocal of the SET. For all organisms the areas under the bactericidal curves for intermittent versus the CI regimens were the same for equal doses (P > 0.05), For both strains off. coli all four regimens provided SBTs of greater than or equal to 1:2 over the dosing interval and 100% T > MIG. The 1-g q8h ED and q12h ED regimens provided T > MIC of 82 and 52%, respectively, for both P. aeruginosa isolates (MICs, 4 mu g/ml). In comparison, the 2- and 3-g CI regimens always maintained SBTs of greater than or equal to 1:2 and T > MIC over the 24-h period as serum drug concentrations were 12.8 +/- 3.0 and 18.2 +/- 4.5 mu g/ml, respectively, CI optimizes the pharmacodynamic and pharmacoeconomic profile of ceftazidime by providing adequate antibacterial activity over the 24-h dosing period with a reduction in the total daily dose of the antimicrobial agent.