title: Analysis of cefepime tissue penetration into human appendix.
abstract: Cefepime is a new extended-spectrum cephalosporin with gram-positive and gram-negative coverage including Staphylococcus aureus and Pseudomonas aeruginosa. We evaluated the drug's plasma, peritoneal fluid, and appendix tissue concentrations in patients with a postoperative diagnosis of perforated or gangrenous appendicitis. Patients 18 years of age or older were randomly assigned to receive either cefepime 2 g every 12 hours plus metronidazole 500 mg every 6 hours intravenously, or gentamicin 1.5 mg/kg plus clindamycin 900 mg every 8 hours intravenously. During surgery, appendix tissue, plasma, and peritoneal fluid samples were obtained, and frozen at -70 degrees C for high-pressure liquid chromatographic analysis. Thirty-five patients with perforated (26) or gangrenous (9) appendicitis had concentrations acceptable for analysis. The mean time between the administration of cefepime and the time of sampling (referred to as delta time) was 5.99 +/- 3.75 hours (mean +/- SD). The values for plasma (n = 34), tissue (n = 33), and peritoneal fluid (n = 25) concentrations were 16.27 +/- 21.87 micrograms/ml, 4.84 +/- 6.15 micrograms/g, and 14.4 +/- 22.84 micrograms/ml, respectively. The appendix tissue:plasma ratio was 0.66 +/- 0.52 and the peritoneal fluid:plasma ratio was 0.66 +/- 0.51. Spearman rank correlations indicated statistically significant correlations between plasma concentration (r = -0.889; p less than 0.0001), peritoneal fluid concentration (r = -0.783; p = 0.0002), and appendix tissue concentration (r = -0.704; p = 0.0016) versus delta time.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: School of Pharmacy, University of Southern California, Los Angeles 90033.
authors.forename: M P
authors.initials: MP
authors.lastname: Okamoto
authors.forename: A
authors.initials: A
authors.lastname: Chin
authors.forename: M A
authors.initials: MA
authors.lastname: Gill
authors.forename: A E
authors.initials: AE
authors.lastname: Yellin
authors.forename: T V
authors.initials: TV
authors.lastname: Berne
authors.forename: P N
authors.initials: PN
authors.lastname: Heseltine
authors.forename: M D
authors.initials: MD
authors.lastname: Appleman
authors.forename: C A
authors.initials: CA
authors.lastname: Knupp
authors.forename: D A
authors.initials: DA
authors.lastname: Sclar
mesh_terms: D000293:Adolescent; D000328:Adult; D001062:Appendectomy; D001064:Appendicitis / Q000378:metabolism; D001065:Appendix / Q000378:metabolism*; D001202:Ascitic Fluid / Q000378:metabolism*; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002981:Clindamycin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005734:Gangrene / Q000378:metabolism; D005839:Gentamicins / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous; D007416:Intestinal Perforation / Q000378:metabolism; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000627:therapeutic use; D012422:Rupture, Spontaneous
chemical_list: D002511:Cephalosporins; D005839:Gentamicins; D008795:Metronidazole; D002981:Clindamycin; D000077723:Cefepime