TY - JOUR
T1 - Pharmacokinetics and tissue penetration of cefoxitin in obesity
T2 - Implications for risk of surgical site infection
AU - Toma, Octavian
AU - Suntrup, Patty
AU - Stefanescu, Andrei
AU - London, Amy
AU - Mutch, Matthew
AU - Kharasch, Evan
PY - 2011/10
Y1 - 2011/10
N2 - 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, n = 14, 2 g cefoxitin) and in normal-weight patients and healthy volunteers (body mass index 20 ± 2 kg/m, 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 (AUCtissue/AUCplasma 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.
AB - 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, n = 14, 2 g cefoxitin) and in normal-weight patients and healthy volunteers (body mass index 20 ± 2 kg/m, 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 (AUCtissue/AUCplasma 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.
UR - http://www.scopus.com/inward/record.url?scp=80053297798&partnerID=8YFLogxK
U2 - 10.1213/ANE.0b013e31821fff74
DO - 10.1213/ANE.0b013e31821fff74
M3 - Article
C2 - 21642605
AN - SCOPUS:80053297798
SN - 0003-2999
VL - 113
SP - 730
EP - 737
JO - Anesthesia and analgesia
JF - Anesthesia and analgesia
IS - 4
ER -