Population pharmacokinetics of prophylactic cefoxitin in patients undergoing colorectal surgery

Isla, Arantxazu; Trocóniz, Iñaki F.; Tejada, I. López de; Vázquez, Silvia Guzmán; Canut, Andrés; López, Jesús Muriel; Solinís, Maria Ángelés; Rodríguez-Gascón, Alicia

doi:10.1007/s00228-011-1206-1

Cited by 27 publications

(18 citation statements)

References 37 publications

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“…dose (24); this half-life is slightly prolonged compared to that previously reported for nonobese adults (35). Despite administration of substantially higher doses, the mean C max observed in the present study was similar to concentrations previously reported for other populations, including nonobese adults receiving fixed cefoxitin doses (24,33,37). This decreased C max /D ratio and the prolonged half-life are both consistent with a 2-fold-higher V observed in this study compared to that reported for nonobese individuals.…”

Section: Discussionsupporting

confidence: 86%

“…Five thousand simulations were performed at each MIC and for each of the selected pathogens. For pharmacodynamic evaluation of free (unbound) drug levels, the approximate free fraction of cefoxitin in human blood (average, 0.30; range, 0.21 to 0.48) was incorporated into Monte Carlo simulations to obtain corresponding pharmacodynamic parameters for free drug (fTϾMIC) (33). The targeted pharmacodynamic goal was the cefoxitin concentration above the MIC of these common pathogens (TϾMIC) for 100% of the prophylactic dosing interval (i.e., fTϾMIC ϭ 100%) as suggested by previous literature (34).…”

Section: Methodsmentioning

confidence: 99%

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Pharmacokinetic and Pharmacodynamic Evaluation of a Weight-Based Dosing Regimen of Cefoxitin for Perioperative Surgical Prophylaxis in Obese and Morbidly Obese Patients

Moine

Mueller

Schoen

et al. 2016

Antimicrob Agents Chemother

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The objective of this study was to determine the pharmacokinetics and pharmacodynamics (PK/PD) of a weight-based cefoxitin dosing regimen for surgical prophylaxis in obese patients. Patients received a single dose of cefoxitin at 40 mg/kg based on total body weight. Cefoxitin samples were obtained over 3 h from serum and adipose tissue, and concentrations were determined by validated high-performance liquid chromatography. Noncompartmental pharmacokinetic analysis was performed, followed by Monte Carlo simulations to estimate probability of target attainment (PTA) for Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis over 4-h periods postdose. Thirty patients undergoing bariatric procedures were enrolled. The body mass index (mean ؎ standard deviation [SD])was 45.9 ؎ 8.0 kg/m 2 (range, 35.0 to 76.7 kg/m 2 ); the median cefoxitin dose was 5 g (range, 4.0 to 7.5 g). The mean maximum concentrations were 216.15 ؎ 41.80 g/ml in serum and 12.62 ؎ 5.89 in tissue; the mean tissue/serum ratio was 8% ؎ 3%. In serum, weight-based regimens achieved >90% PTA (goal time during which free [unbound] drug concentrations exceed pathogen MICs [fT>MIC] of 100%) for E. coli and S. aureus over 2 h and for B. fragilis over 1 h; in tissue this regimen failed to achieve goal PTA at any time point. The 40-mg/kg regimens achieved higher PTAs over longer periods in both serum and tissue than did the standard 2-g doses. However, although weight-based cefoxitin regimens were better than fixed doses, achievement of desired pharmacodynamic targets was suboptimal in both serum and tissue. Alternative dosing regimens and agents should be explored in order to achieve more favorable antibiotic performance during surgical prophylaxis in obese patients. Surgical site infections (SSIs) are the leading cause of postoperative morbidity and mortality and add significantly to the cost of care (1). Perioperative antibiotic prophylaxis is therefore a standard of care and a keystone for the prevention of SSIs (2-6). Recommendations regarding the use of specific antibiotics for prophylaxis during surgical procedures have been published since the early 1990s and have been frequently revisited since that time (1, 2, 5-9). More recently, specific recommendations provided by the National Surgical Infection Prevention (SIP) Project have focused on appropriate timing of administration of prophylactic antibiotics, appropriate drug selection, and the discontinuation of prophylactic antibiotics within 24 h after surgery (2, 9). However, the actual recommended drugs and dosing regimens for surgical prophylaxis have been relatively unchanged over the past 20 years. Limited published data exist regarding appropriate dosing of antimicrobials for prophylaxis. It is generally stated that the drug should be given in an adequate dose based on patient weight, adjusted dosing weight, or body mass index (BMI) (2, 6, 9). Furthermore, antibiotic administration should be repeated intraoperatively if the procedure continues beyond one to two pharmacokinetic (PK) hal...

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Section: Discussionsupporting

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Evaluation of a Weight-Based Dosing Regimen of Cefoxitin for Perioperative Surgical Prophylaxis in Obese and Morbidly Obese Patients

Moine

Mueller

Schoen

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Despite antibiotic prophylaxis, subtherapeutic tissue antibiotic concentrations are observed in obese patients and may facilitate wound infection. 35, 36 . In addition, the development of wound infection may be enhanced by an attenuated inflammatory response secondary to endotoxin tolerance in obese patients 37, 38 .…”

Section: Discussionmentioning

confidence: 99%

Quantitative Assessment of Visceral Obesity and Postoperative Colon Cancer Outcomes

Ozoya

Siegel

Srikumar

et al. 2017

Journal of Gastrointestinal Surgery

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Background Quantitative computed tomography (CT) assessment of visceral adiposity may be superior to body mass index (BMI) as a predictor of surgical morbidity. We sought to examine the association of CT measures of obesity and BMI with short-term post-operative outcomes in colon cancer patients. Methods In this retrospective study, 110 patients treated with colectomy for Stage I–III colon cancer were classified as obese or non-obese by pre-operative CT-based measures of adiposity or BMI. [Obese: BMI≥30kg/m2, visceral fat area (VFA) to subcutaneous fat area ratio (V/S) ≥0.4 and VFA>100cm2)]. Post-operative morbidity and mortality rates were compared. Results Obese patients, by V/S and VFA but not BMI, were more likely to be male and have pre-existing hypertension and diabetes. The overall complication rate was 25.5% and there were no mortalities. Obese patients by VFA (with a trend for VS but not BMI) were more likely to develop postoperative complications as compared to patients classified as non-obese; VFA (30.5% vs.10.7%, p= 0.03), VS (29.2% vs. 9.5%, p=0.05) and BMI (32.4% vs. 21.9%, p=0.23). Conclusions Elevated visceral obesity quantified by CT is associated with the presence of key metabolic comorbidities and increased post-operative morbidity and may be superior to BMI for risk stratification.

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“…Normally, exposure of antimicrobials that are eliminated mainly in urine, such as cephalosporins, is higher in patients with renal insufficiency than in patients with normal renal function [26,27] and therefore the probability to reach the pharmacodynamic target significantly increases. This means that patients with normal renal function have more risk of underdosage.…”

Section: Organismmentioning

confidence: 99%

Pharmacokinetic/pharmacodynamic analysis to evaluate ceftaroline fosamil dosing regimens for the treatment of community-acquired bacterial pneumonia and complicated skin and skin-structure infections in patients with normal and impaired renal function

Canut¹,

Isla²,

Rodríguez-Gascón³

2015

International Journal of Antimicrobial Agents

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Population pharmacokinetics of prophylactic cefoxitin in patients undergoing colorectal surgery

Cited by 27 publications

References 37 publications

Pharmacokinetic and Pharmacodynamic Evaluation of a Weight-Based Dosing Regimen of Cefoxitin for Perioperative Surgical Prophylaxis in Obese and Morbidly Obese Patients

Pharmacokinetic and Pharmacodynamic Evaluation of a Weight-Based Dosing Regimen of Cefoxitin for Perioperative Surgical Prophylaxis in Obese and Morbidly Obese Patients

Quantitative Assessment of Visceral Obesity and Postoperative Colon Cancer Outcomes

Pharmacokinetic/pharmacodynamic analysis to evaluate ceftaroline fosamil dosing regimens for the treatment of community-acquired bacterial pneumonia and complicated skin and skin-structure infections in patients with normal and impaired renal function

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