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Analysis of Cefepime Tissue Penetration Into Human Appendix
Author(s) -
Okamoto Mark P.,
Chin Alfred,
Gill Mark A.,
Yellin Albert E.,
Berne Thomas V.,
Heseltine Peter N.R.,
Appleman Maria D.,
Knupp Catherine A.,
Sclar David A.
Publication year - 1991
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1991.tb02644.x
Subject(s) - cefepime , peritoneal fluid , appendix , medicine , cephalosporin , metronidazole , appendicitis , antibiotics , gastroenterology , anesthesia , surgery , chemistry , biology , paleontology , biochemistry , antibiotic resistance , imipenem
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°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 A 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 μg/ml, 4.84 ± 6.15 μg/g, and 14.4 ± 22.84 μg/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<0.0001), peritoneal fluid concentration (r=‐0.783; p=0.0002), and appendix tissue concentration (r=‐0.704; p=0.0016) versus Δ time. There was a significant correlation between peritoneal fluid and plasma concentration (r=0.853; p<0.0001), and appendix tissue and plasma concentration (r=0.815; p=0.0001). These results indicate that tissue and peritoneal fluid concentrations are approximately 51% and 74%, respectively, of a simultaneous plasma sampling after approximately 5.8 hours.