Cefoxitin Plasma and Subcutaneous Adipose Tissue Concentration in Patients Undergoing Sleeve Gastrectomy

Abstract

Purpose Antibiotic dosing in obese surgical patients has not been adequately evaluated. Cefoxitin is an antibiotic commonly utilized for surgical prophylaxis in cases involving the abdominal cavity. The objective of our study was to identify whether currently prescribed doses of cefoxitin achieve adequate and sustained plasma and tissue concentrations in obese patients undergoing sleeve gastrectomy Methods A prospective evaluation of plasma and tissue cefoxitin concentrations in patients undergoing sleeve gastrectomy was performed. On the day of surgical procedure, venous blood samples (5 mL) were collected just prior to cefoxitin administration and then at 5, 30, 60, 120, and 240 minutes after dose administration. In addition subcutaneous adipose tissue was collected from the surgical site and the time of surgical incision and closure. Cefoxitin concentrations in the collected samples were quantified using HPLC – UV. A standard noncompartmental analysis was performed for each individual cefoxitin plasma concentration-time profile. In addition, the ratio of tissue to plasma concentration was calculated for all patients. Findings Plasma and tissue pharmacokinetics of cefoxitin were evaluated in 6 patients undergoing sleeve gastrectomy. At the time of surgical closure subcutaneous adipose tissue cefoxitin concentrations were subtherapeutic (< 8 mcg/mL) in all evaluated patients. Implications Current dosing strategies for cefoxitin in obese surgical patients may be inadequate and there is an urgent need to define the appropriate dosage.

Cefoxitin: A Neglected Intravenous Betalactam with Interesting Perspectives

“…In a study by Toma et al [13] , adipose tissue cefoxitin concentrations in obese patients undergoing abdominal and pelvic surgery were below the minimum inhibitory concentration (MIC) despite giving twice the normal dose. Similarly, Brunetti et al [14] reported that subcutaneous adipose tissue concentrations of cefoxitin at the time of surgical closure were subtherapeutic in six patients undergoing sleeve gastrectomy. Moine showed that a single dose of cefoxitin at 40 mg/kg failed to achieve the desired probability of target attainment in fat tissue for Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis over 4-h periods postdose [15] .…”

Preclinical Pharmacokinetic and Pharmacodynamic Data To Support Cefoxitin Nebulization for the Treatment of Mycobacterium abscessus

“…Interestingly, after systemic administration at the usual dose (2 g) in patients, FOX total plasma concentrations reach values of up to 200 mg/liter (23), which, considering that the unbound fraction is close to 25% (24), corresponds to maximum unbound plasma concentrations on the order of 50 mg/liter. In this range of values, unbound FOX concentrations should demonstrate antimicrobial efficacy only against the susceptible M. abscessus population.…”

Quantification of three beta‐lactam antibiotics in breast milk and human plasma by hydrophilic interaction liquid chromatography/positive‐ion electrospray ionization mass spectrometry

“…[14][15][16][17][18][19] A simple liquid chromatography method with UV detection has been developed and fully validated for the determination of cefazolin in human plasma. [14][15][16][17][18][19] A simple liquid chromatography method with UV detection has been developed and fully validated for the determination of cefazolin in human plasma.…”

“…A literature survey revealed several chromatographic methods with ultraviolet (UV) detection that focuses on the determination of cephalosporins in biofluids. [14][15][16][17][18][19] A simple liquid chromatography method with UV detection has been developed and fully validated for the determination of cefazolin in human plasma. [20] In addition, hyphenated techniques, such as liquid-chromatographytandem mass spectrometry (LC-MS/MS) have also been applied for the determination of cefazolin in human plasma using solidphase extraction (SPE) for sample preparation [21,22] and in human plasma and subcutaneous interstitial fluid of patients undergoing elective/semi-elective abdominal aortic aneurysm open repair surgery, [23] cefuroxime sodium in human plasma or serum [24,25] and cefuroxime lysine in rat brain [26] and in dog plasma.…”