cefoxitin and Body-Weight

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 μg/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.

Topics: Adult; Antibiotic Prophylaxis; Body Weight; Cefoxitin; Dose-Response Relationship, Drug; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Obesity; Obesity, Morbid; Surgical Wound Infection; Tissue Distribution

There are several limitations to the existing method of administering cefoxitin as a prophylactic antibiotic, and the limitations may be overcome by applying the target-concentration controlled infusion (TCI) method. Population pharmacokinetic parameters are required to administer cefoxitin by the TCI method. The aim of this study was to construct a new pharmacokinetic model of cefoxitin for the TCI method in colorectal surgical patients.. In patients undergoing colorectal surgery, 2 g of cefoxitin was dissolved in 50 mL of saline and administered for 10 minutes prior to skin incision. Arterial blood samples were obtained at preset intervals to measure the total and free plasma concentrations of cefoxitin. Population pharmacokinetic analysis was performed using NONMEM software (ICON Development Solutions, Dublin, Ireland). Additionally, stochastic simulation was used to indirectly evaluate the effectiveness of the two administration methods (standard method vs TCI).. In total, 297 plasma concentration measurements from 31 patients were used to characterize the pharmacokinetics of cefoxitin. A three-compartment mammillary model described the pharmacokinetics of cefoxitin. Body weight and creatinine clearance were significant covariates for clearance. The stochastic simulation showed that when compared with the standard method, the TCI method has a significantly higher fraction of time that the free concentration of cefoxitin is maintained above the minimum inhibitory concentration (P < .001).. TCI has the potential to become a new infusion method for patient-tailored dosing in surgical patients. To administer cefoxitin via TCI in clinical practice, the newly constructed pharmacokinetic model should undergo proper external validation.

Topics: Anti-Bacterial Agents; Body Weight; Cefoxitin; Colorectal Neoplasms; Humans; Microbial Sensitivity Tests

Neonatal hyperoxia increases oxidative stress and adversely disturbs glomerular and tubular maturity. Maternal Tn immunization induces anti-Tn antibody titer and attenuates hyperoxia-induced lung injury in neonatal rats.. We intraperitoneally immunized female Sprague-Dawley rats (6 weeks old) with Tn immunogen (50 μg/dose) or carrier protein five times at biweekly intervals on 8, 6, 4, 2, and 0 weeks before the delivery day. The pups were reared for 2 weeks in either room air (RA) or in 85% oxygen-enriched atmosphere (O. Hyperoxia reduced body weight, induced tubular and glomerular injuries, and increased 8-OHdG and NF-κB expression and collagen deposition in the kidneys. By contrast, maternal Tn immunization reduced kidney injury and collagen deposition in neonatal rats. Furthermore, kidney injury attenuation was accompanied by a reduction in 8-OHdG and NF-κB expression.. Maternal Tn immunization protects against hyperoxia-induced kidney injury in neonatal rats by attenuating oxidative stress and NF-κB activity.. Hyperoxia increased nuclear factor-κB (NF-κB) activity and collagen deposition in neonatal rat kidney. Maternal Tn immunization reduced kidney injury as well as collagen deposition in neonatal rats. Maternal Tn immunization reduced kidney injury and was associated with a reduction in 8-hydroxy-2'-deoxyguanosine and NF-κB activity. Tn vaccine can be a promising treatment modality against hyperoxia-induced kidney injury in neonates.

Topics: Acute Kidney Injury; Animals; Animals, Newborn; Antigens, Tumor-Associated, Carbohydrate; Body Weight; Collagen; Deoxyadenosines; Female; Hyperoxia; Immunotherapy, Active; Kidney Tubules; NF-kappa B; Organ Size; Oxidative Stress; Pregnancy; Random Allocation; Rats; Rats, Sprague-Dawley; Vaccination; Vacuoles

To compare 30-day postoperative surgical site infections (SSIs) and rates of antibiotic discontinuation within 24 hours after surgery in patients receiving continuous-infusion versus intermittent-infusion cefoxitin for postoperative antibiotic prophylaxis.. Retrospective, cohort-matched pilot study.. Tertiary-care medical center.. One hundred sixteen adults undergoing colorectal surgery between August 1, 2004, and February 28, 2007.. Cefoxitin prophylaxis was administered as a continuous infusion in 58 patients and as an intermittent infusion in 58 patients (controls). The controls received weight-based doses of cefoxitin (1 g if < or = 80 kg or 2 g if > 80 kg) every 8 hours for three doses, starting 3 hours after surgery and completed within 24 hours. The continuous-infusion group were given weight-based doses of cefoxitin (3 g if < or = 80 kg, 6 g if > 80 kg), started immediately after surgery and infused over 20 hours.. Patients and controls were matched according to colorectal procedure and risk index category. They were stratified by medium risk (50 patients) and low risk (66 patients) for the end point of 30-day postoperative SSI. For the 25 medium-risk patients who received the continuous infusion, a 50% relative reduction in the 30-day postoperative SSI rate was observed with continuous versus intermittent infusion (4% vs 8%, p=0.55). For the 66 low-risk patients, 30-day postoperative SSI rates were equal (3%) with both intermittent and continuous infusions. Risk stratification was not performed for the proportion of patients who discontinued antibiotic prophylaxis within 24 hours after surgery. All patients receiving the continuous infusion met this end point compared with 47 (83.9%) of the 56 controls (p=0.0015) included in the analysis.. Compared with intermittent infusion, continuous infusion of cefoxitin for postoperative prophylaxis resulted in a nonsignificant reduction in 30-day postoperative SSI rates in medium-risk patients undergoing colorectal surgery. Continuous infusion also resulted in reliable discontinuation of postoperative prophylaxis within 24 hours.

Topics: Aged; Anti-Bacterial Agents; Body Weight; Cefoxitin; Cohort Studies; Colon; Endpoint Determination; Feces; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Pilot Projects; Rectum; Retrospective Studies; Risk Assessment; Surgical Wound Infection

To compare the potential therapeutic effect of liposomal vs. free cefoxitin.. Randomized, controlled study, using a rat model of peritonitis.. Government research facility.. Male Sprague-Dawley rats.. Rats were infused intraperitoneally with 6.5 x 10(8) colony forming units of Escherichia coli over 12 hrs. Animals were then randomized to receive intravenous saline, free cefoxitin, liposomal cefoxitin, or plain liposomes twice daily until they were killed.. Free cefoxitin significantly reduced the number of E. coli after 24 hrs compared with saline treatment in both liver and spleen. However, liposomal cefoxitin further decreased the bacterial content by five-fold to ten-fold in these organs. Minimal bactericidal effect was observed in animals injected with plain liposomes. Although administration of liposomal cefoxitin for 7 days further reduced bacterial counts in liver and spleen, there was no apparent beneficial bactericidal effect of free cefoxitin over saline at 7 days. There was approximately a ten-fold reduction in bacterial content in the lungs after 24 hrs in all three treatments, but no further reduction was observed after 7 days. There was no difference in 7-day survival rate in animals treated with plain liposomes or saline (45% vs. 39%). Although survival tended to increase with free cefoxitin treatment (64%), this outcome was significantly improved with the use of liposomal cefoxitin (82%).. Liposomal cefoxitin enhanced bacterial killing in liver and spleen in this model of E. coli peritonitis. It also improved survival outcome relative to no treatment but not compared with free cefoxitin.

Topics: Animals; Body Weight; Cefoxitin; Cephamycins; Disease Models, Animal; Drug Carriers; Escherichia coli Infections; Infusions, Intravenous; Liposomes; Male; Peritonitis; Random Allocation; Rats; Rats, Sprague-Dawley