title: Cefepime in critically ill patients: continuous infusion vs. an intermittent dosing regimen.
abstract: The aim of this study was to compare the pharmacokinetic and pharmacodynamic parameters of a continuous infusion of cefepime vs. an intermittent regimen in critically ill adult patients with Gram-negative bacilli infection. The prospective randomized parallel study was carried out in 50 patients with severe pneumonia (n = 41) or bacteremia (n = 9). They received cefepime 4 g/d either as a continuous infusion or intermittent administration 2 x 2 g in combination with amikacin. Patient characteristics and the minimal inhibitory concentration (MIC) of the isolated bacteria were comparable. Clinical outcomes were assessed along with pharmacodynamic indices and compared in both groups (chi2 and Mann-Whitney U-tests). Mechanical ventilation, clinical outcome and bacteriological eradication did not significantly differ between the two groups. Also, the area under the plasma cefepime concentration curve at steady state (AUCss: 612 +/- 369 vs. 623 +/- 319 mg x 1(-1) x h), AUCss > MIC (595 +/- 364 vs. 606 +/- 316 mg x 1(-1) x h) and the area under the inhibitory concentration curve (AUICss: 4258 +/- 5819 vs. 5194 +/- 7465 mg x 1(-1) x h) were similar. If the time above MIC (t > MIC) was not significantly higher in Group 1 (100 +/- 0%) than in Group 2 (90 +/- 11%), t > five-fold MIC in Group 1 (100 +/- 0%) was significantly higher (p < 0.01) than in Group 2 (82 +/- 25%). The mean time over the French breakpoint (4 mg/l) was 100 +/- 0% and 72 +/- 27% in Group 1 and 2 (p < 0.001), respectively. In contrast to intermittent cefepime administration, continuous infusion of cefepime consistently maintained a serum concentration > 5 x the MIC of typical Gram-negative nosocomial pathogens. This results in greater bactericidal activity against organisms with a higher (2 mg/l) cefepime breakpoint even if the clinical outcome is not significantly modified.
authors.affiliation: Anesthesia Reanimation, CHU Rangueil, UMR 181 Experimental Physiopathology and Toxicology (UPTE INRA-ENVT), Faculty of Pharmaceutic Sciences, Toulouse, France.
authors.forename: B
authors.initials: B
authors.lastname: Georges
authors.forename: J M
authors.initials: JM
authors.lastname: Conil
authors.forename: P
authors.initials: P
authors.lastname: Cougot
authors.forename: J F
authors.initials: JF
authors.lastname: Decun
authors.forename: M
authors.initials: M
authors.lastname: Archambaud
authors.forename: T
authors.initials: T
authors.lastname: Seguin
authors.forename: G
authors.initials: G
authors.lastname: Chabanon
authors.forename: C
authors.initials: C
authors.lastname: Virenque
authors.forename: G
authors.initials: G
authors.lastname: Houin
authors.forename: S
authors.initials: S
authors.lastname: Saivin
mesh_terms: D000328:Adult; D000368:Aged; D000583:Amikacin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D019540:Area Under Curve; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D016638:Critical Illness; D004359:Drug Therapy, Combination; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime; D000583:Amikacin