title: Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T>MIC) as predictors of outcome for cefepime and ceftazidime in serious bacterial infections.
abstract: The objective of this study was to evaluate the relationship of the predicted pharmacodynamic parameters 24-h area under the inhibitory curve (AUIC=area under the concentration-time curve for 24h of dosing/minimum inhibitory concentration (AUC0-24/MIC) and time above the minimum inhibitory concentration (T>MIC) with clinical and microbiological outcomes in patients with bacteraemia and sepsis treated with cefepime or ceftazidime. Pharmacokinetic and pharmacodynamic parameters were derived for 76 of 107 patients enrolled in two prospective, randomised, clinical trials comparing cefepime with ceftazidime for the treatment of sepsis with bacteraemia, lower respiratory tract infection or complicated urinary tract infection. The relationships between the pharmacodynamic parameters and outcomes were examined. Whilst no significant differences in clinical outcomes were observed between cefepime and ceftazidime, there were significant differences in the pharmacodynamic analysis. Patients with an AUIC> or =250 had significantly greater clinical cure (79% vs. 33%; P=0.002) and bacteriological eradication (96% vs. 44%; P<0.001) than patients with an AUIC<250. Patients with T>MIC of 100% had significantly greater clinical cure (82% vs. 33%; P=0.002) and bacteriological eradication (97% vs. 44%; P<0.001) than patients with T>MIC of <100%. Both microbiological and clinical cure rates were suboptimal in patients receiving cefepime or ceftazidime for the treatment of serious infections if the AUIC was <250 or T>MIC was <100%.
authors.affiliation: Clinical Research/Infectious Diseases, Barnes-Jewish Hospital, St Louis, MO 63110, USA.
authors.forename: Peggy S
authors.initials: PS
authors.lastname: McKinnon
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Paladino
authors.forename: Jerome J
authors.initials: JJ
authors.lastname: Schentag
mesh_terms: D018806:APACHE; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D000077723:Cefepime; D002442:Ceftazidime / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D023381:Endpoint Determination; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006801:Humans; D007709:Klebsiella / Q000187:drug effects; D008297:Male; D008826:Microbial Sensitivity Tests; D011237:Predictive Value of Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D051437:Renal Insufficiency / Q000150:complications; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime; D002442:Ceftazidime