Pharmacokinetic disposition and bactericidal activities of cefepime, ceftazidime, and cefoperazone in serum and blister fluid

Abstract

Cefepime is a hew broad-spectrum cephalosporin with excellent gram-positive and gram-negative activity including activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacter cloacae. The pharmacokinetic disposition of cefepine is similar to that of ceftazidime. We compared the pharmacokinetic characteristics and the extent and duration of bactericidal activity in serum and suction-induced blister fluid after single 2-g intravenous doses of cefepime, ceftazidime, and cefoperazone given to healthy subjects. One clinical isolate each of E. cloacae, P. aeruginosa, and S. aureus was used to assess bactericidal activity. Results of the pharmacokinetic analysis were similar to previously reported data for these drugs. The high serum protein binding of cefoperazone (-90%) contributed to poor blister fluid penetration. The other drugs penetrated well into this fluid compartment. Cefepime showed significantly greater bactericidal activity in serum and blister fluid against E. cloacae than the other study drugs, ceftazidime was significantly better in serum and blister fluid against P. aeruginosa, and cefoperazone was significantly better against S. aureus only in serum. None of the study drugs had significant bactericidal activity in blister fluid against S. aureus. Cefepime is a promising antimicrobial agent for the treatment of infections due to E. cloacae.Cefepime is an experimental cephalosporin antibiotic with bactericidal activity against many gram-positive and gramnegative microorganisms. Advantages over currently available cephalosporins include the decreased potential for selection of resistant bacterial mutants and retention of activity against ceftazidime-or cefoperazone-resistant enteric gram-negative bacilli such as Enterobacter cloacae (4). Single cefepime doses ranging from 62.5 to 2,000 mg have been administered intravenously over 30 min to healthy male volunteers without significant adverse effects. In addition, 2,000-mg doses of cefepime were well tolerated when administered over infusion times of 15, 10, 5, and 3 min (2).Several models have been developed to study tissue penetration of antibiotics. One of these models, the dermal suction blister, is generally considered to provide valuable information on the kinetics of antibiotics in small abscesses and edema of soft-tissue infections (15). The penetration characteristics of cefepime in a suction blister tissue penetration model have not been described. In addition, data on bactericidal activity in blister fluid of any antimicrobial agent have not yet been published. Clinical Research Center and randomly received single intravenous doses (2 g each) of cefepime, ceftazidime, or cefoperazone on three separate occasions (a minimum of 4 days and a maximum of 14 days between doses). One additional subject received only ceftazidime. The drugs were diluted to a final volume of 20 ml in suitable vehicles and administered over 30 min with a constant-rate syringe pump.Informed consent was obtained from each subject prior to participation, and...

Treatment of Febrile Neutropenia with Cefepime Monotherapy

“…This same finding was observed in a recent summary of three randomized trials comparing cefepime with ceftazidime, where the response rates were 62 vs. 63%, respectively, for patients with neutropenia of less than 10 days and 37 vs. 44%, respectively, when neutropenia lasted 10 or more days [7]. However, with appropriate patient monitoring and modification of therapy, as needed, the overall mortality from a bacterial infection can be kept well below 2% with any initial empirical regimen chosen [1][2][3][4][5][6][7][8].…”

“…Multiple antibiotics have been tested for this indication, without relevant differences between them [1]. Cefepime is a fourth-generation cephalosporin with in vitro activity against most enterobacteria, nonfermenting gram-negative bacilli (including Pseudomonas aeruginosa), methycillin-susceptible staphylococci, and most streptococci [2]. Cefepime has been shown to be effective in the initial empirical therapy of febrile neutropenia [3][4][5][6][7][8].…”

Population Pharmacokinetics of Cefepime in the Neonate

“…Its V is slightly lower than that of total body water, and it exhibits low protein binding of 21% (15). It is almost exclusively eliminated in the urine, with a total CL approximating that of glomerulofiltration (26).…”

Rapid high-performance liquid chromatographic determination of cefepime in human plasma

“…The elimination half-life (T 1/2 ) is approximately 2 h and is dose-independent (Barbhaiya et al, 1992;Kalman et al, 1992;Okamoto et al, 1993;Barradell and Bryson 1994;Van der Auwera and Santelia 1993;Rybak, 1996). The elimination half-life increases in patients with renal impairment.…”