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Pharmacokinetics and tissue penetration of cefoxitin in obesity: implications for risk of surgical site infection.

Publication ,  Journal Article
Toma, O; Suntrup, P; Stefanescu, A; London, A; Mutch, M; Kharasch, E
Published in: Anesth Analg
October 2011

BACKGROUND: Obesity is a significant risk factor for surgical site infections (SSIs), for poorly understood reasons. SSIs are a major cause of morbidity, prolonged hospitalization, and increased health care cost. Drug disposition in general is frequently altered in the obese. Preoperative antibiotic administration, achieving adequate tissue concentrations at the time of incision, is an essential strategy to prevent SSIs. Nonetheless, there is little information regarding antibiotic concentrations in obese surgical patients. This investigation tested the hypothesis that the prophylactic antibiotic cefoxitin may have delayed and/or diminished tissue penetration in the obese. METHODS: Plasma and tissue concentrations of cefoxitin were determined in obese patients undergoing abdominal and pelvic surgery (body mass index 43 ± 10 kg/m(2), n = 14, 2 g cefoxitin) and in normal-weight patients and healthy volunteers (body mass index 20 ± 2 kg/m(2), n = 13, 1 g cefoxitin). Tissue concentrations were measured using a microdialysis probe in the subcutaneous layer of the abdomen, and in adipose tissue excised at the time of incision and wound closure. RESULTS: Plasma concentrations and area under the concentration-time curve (AUC) were approximately 2-fold higher in the obese patients because of the 2-fold-higher dose. Dose-normalized concentrations were higher, although AUCs were not significantly different. Measured and dose-normalized subcutaneous cefoxitin concentrations and AUCs in the obese patients were significantly lower than in the normal-weight subjects. There was an inverse relationship between cefoxitin tissue penetration (AUC(tissue)/AUC(plasma) ratio) and body mass index. Tissue penetration was substantially lower in the obese patients (0.08 ± 0.07 vs 0.37 ± 0.26, P < 0.05). Adipose tissue cefoxitin concentrations in obese patients were only 7.8 ± 7.3 and 2.7 ± 1.4 μg/g, respectively, at incision and closure, below the minimum inhibitory concentration of 8 and 16 μg/mL, respectively, for aerobic and anaerobic microorganisms. CONCLUSION: Obese surgical patients have impaired tissue penetration of the prophylactic antibiotic cefoxitin, and inadequate tissue concentrations despite increased clinical dose (2 g). Inadequate tissue antibiotic concentrations may be a factor in the increased risk of SSIs in obese surgical patients. Additional studies are needed to define doses achieving adequate tissue concentrations.

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Published In

Anesth Analg

DOI

EISSN

1526-7598

Publication Date

October 2011

Volume

113

Issue

4

Start / End Page

730 / 737

Location

United States

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Tissue Distribution
  • Surgical Wound Infection
  • Surgical Procedures, Operative
  • Risk Factors
  • Risk Assessment
  • Pelvis
  • Obesity
  • Missouri
 

Citation

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Toma, O., Suntrup, P., Stefanescu, A., London, A., Mutch, M., & Kharasch, E. (2011). Pharmacokinetics and tissue penetration of cefoxitin in obesity: implications for risk of surgical site infection. Anesth Analg, 113(4), 730–737. https://doi.org/10.1213/ANE.0b013e31821fff74
Toma, Octavian, Patty Suntrup, Andrei Stefanescu, Amy London, Matthew Mutch, and Evan Kharasch. “Pharmacokinetics and tissue penetration of cefoxitin in obesity: implications for risk of surgical site infection.Anesth Analg 113, no. 4 (October 2011): 730–37. https://doi.org/10.1213/ANE.0b013e31821fff74.
Toma O, Suntrup P, Stefanescu A, London A, Mutch M, Kharasch E. Pharmacokinetics and tissue penetration of cefoxitin in obesity: implications for risk of surgical site infection. Anesth Analg. 2011 Oct;113(4):730–7.
Toma, Octavian, et al. “Pharmacokinetics and tissue penetration of cefoxitin in obesity: implications for risk of surgical site infection.Anesth Analg, vol. 113, no. 4, Oct. 2011, pp. 730–37. Pubmed, doi:10.1213/ANE.0b013e31821fff74.
Toma O, Suntrup P, Stefanescu A, London A, Mutch M, Kharasch E. Pharmacokinetics and tissue penetration of cefoxitin in obesity: implications for risk of surgical site infection. Anesth Analg. 2011 Oct;113(4):730–737.

Published In

Anesth Analg

DOI

EISSN

1526-7598

Publication Date

October 2011

Volume

113

Issue

4

Start / End Page

730 / 737

Location

United States

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Tissue Distribution
  • Surgical Wound Infection
  • Surgical Procedures, Operative
  • Risk Factors
  • Risk Assessment
  • Pelvis
  • Obesity
  • Missouri