Pharmacokinetics and Tolerability of Single and Multiple Intravenous Doses of Cefotetan Disodium in Healthy Chinese Volunteers.

BACKGROUND: Cefotetan is highly stable to penicillinase and cephalosporin produced by gram-negative bacteria, and it has strong antimicrobial activity against most gram-negative bacteria, some anaerobic bacteria and streptococcus. The objective of this study was to evaluate the pharmacokinetic profile and tolerability of single and multiple intravenous doses of cefotetan disodium in healthy Chinese volunteers. METHODS: In this single-center, open-label, dose-escalating study, subjects were randomized to receive a single dose of cefotetan disodium 0.5, 1.0, or 2.0 g administered as a 1 h intravenous infusion. After completion of the single-dose phase, subjects continued into the multiple-dose phase, in which they received 1.0 g cefotetan disodium BID for 7 consecutive days. Plasma samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Tolerability was assessed based on physical examinations, vital signs, laboratory tests, and subject interviews. RESULTS: After intravenous administration of single doses of 0.5, 1.0, and 2.0 g cefotetan disodium, the pharmacokinetics of cefotetan were as follows: Cmax was 69.49±12.10 µg·mL-1, 132.03±22.56 µg·mL-1 and 237.75±42.12 µg·mL-1, respectively; AUClast was 278.29±51.13 µg·mL-1·h, 543.25±92.44 µg·mL-1·h and 1003.8±172.39 µg·mL-1·h, respectively; AUC∞ was 284.42±50.76 µg·mL-1·h, 551.38±95.83 µg·mL-1·h and 1020.18±181.19 µg·mL-1·h, respectively; t1/2 was 4.21±0.83 h, 4.39±0.53 h and 4.27±0.74 h, respectively; CL was 1.81±0.33 L·h-1, 1.86±0.32 L·h-1 and 2.02±0.38 L·h-1, respectively; Vd was 10.80±1.89L, 11.78±2.20L and 12.25±1.99L, respectively. In the multiple-dose study, the pharmacokinetics of cefotetan were as follows: Cmax,ss was 147.58±22.71 µg·mL-1; Cmin,ss was 12.92±3.70 µg·mL-1; Cavg was 45.10±7.78 µg·mL-1; AUCτ,ss was 541.15±93.36 µg·mL-1·h; AUC∞ was 612.06±114.23 µg·mL-1·h; t1/2 was 4.30±0.63 h; CL was 1.90±0.35L·h-1; Vd was 8.91±1.57L; DF was 300.92±33.28%; Accumulation Index was 1.17±0.05. No serious adverse events were reported. Adverse events were generally mild. CONCLUSION: Cefotetan disodium showed favorable tolerability in this study. The Cmax and AUCs of cefotetan disodium demonstrated dose-dependent pharmacokinetic characteristics after single dose over a dose range (0.5-2.0 g) in healthy subjects, whereas the t1/2 was independent of dose. Except for Vd, there was no difference in other pharmacokinetic parameters between multiple and single administration.

Higher versus Lower Dose of Cefotetan or Cefoxitin for Surgical Prophylaxis in Patients Weighing One Hundred Twenty Kilograms or More.

BACKGROUND: Clinical practice guidelines recommend a 2-g dose of cefotetan and cefoxitin for surgical prophylaxis. Pharmacokinetic data suggest benefit from higher cefotetan and cefoxitin dosing in obese patients. However, clinical studies examining higher dosing strategies in this at-risk population are lacking. The purpose of this study was to determine whether 3 g of cefotetan or cefoxitin administered pre-operatively for patients who weigh 120 kg or more is associated with a lower proportion of surgical site infection (SSI) compared with 2 g. PATIENTS AND METHODS: Medical records of patients weighing 120 kg or more who had received cefotetan or cefoxitin (2 or 3 g) as surgical prophylaxis for intra-abdominal procedures between July 2012 and August 2015 were reviewed for the development of an SSI (primary outcome), study drug-related adverse events, and re-admissions attributed to SSIs (secondary outcomes). Relative risk calculations were performed for analysis of the primary and secondary outcomes. RESULTS: One-hundred seventy-five procedures in 169 patients were included in the study. Cefotetan was used in 81% (141/175) of procedures. Three grams of cefotetan or cefoxitin was used in 20% (35/175) of procedures. The median body mass index (BMI) in both dosing groups was 42 kg/m2 and patients who received 3 g more often weighed more than 130 kg (relative risk [RR] 1.36, 1.01-1.76; p = 0.04). Surgical site infections occurred in 20.7% within the 2-g group and 22.9% in the 3-g group (RR 1.10, 0.55-2.20; p = 0.78). There was no difference in the number of study drug-related adverse effects in the 3-g compared with the 2-g group. Thirty-day re-admissions because of SSI also did not differ between the 2-g and 3-g groups (7.9% vs. 17.1%, respectively; p = 0.11). CONCLUSION: This small retrospective study did not find a difference in SSI rates between 3-g and 2-g surgical prophylaxis dosing for patients 120 kg or more with a median BMI >40 kg/m2.

Pharmacokinetic differences between the epimers of cefotetan disodium after single intravenous injection in healthy Chinese volunteers.

The pharmacokinetic behaviors of the epimers of cefotetan disodium (R-CTT, S-CTT) after a single intravenous injection dose in healthy Chinese volunteers were explored in this study. In an open-label, randomized, three-way, cross-over study, 12 volunteers (6 females and 6 males) received a cross-over fashion doses of 0.5, 1.0, and 2.0 g of cefotetan disodium, separated by washout periods of 7 days. The plasma concentrations of both epimers were measured by validated high-performance liquid chromatography assays. Pharmacokinetic parameters of R-CTT, S-CTT, and total-CTT (R + S mixture) were calculated using a noncompartmental analysis. Generally, the R and S epimers showed different pharmacokinetic behaviors. Following 0.5, 1.0, and 2.0 g doses of cefotetan disodium, values of the total area under the plasma concentration-time curve (AUC(0-∞)) were 124.23 ± 19.54, 231.34 ± 39.34, and 459.09 ± 80.65 for R-CTT; 100.95 ± 14.19, 193.80 ± 30.42, and 372.66 ± 67.32 for S-CTT, respectively. Total body clearance values were 4.13, 4.43, and 4.46 L/h for R-CTT and 5.05, 5.28, and 5.50 L/h for S-CTT, respectively. Mean plasma elimination half-life (t (1/2)) values of R-CTT were 4.16, 4.13, and 4.01 h for 0.5, 1.0, and 2.0 g doses, respectively, and those of S-CTT were 3.15, 3.25, and 3.21 h. There were significant differences in t (1/2) between the two epimers (P < 0.05). The t (1/2) of R-CTT was 28% longer than that of S-CTT, which indicated that the elimination of the S-CTT was greater than that of the R-CTT. All treatments were well tolerated.

Pharmacokinetics and tolerability of intravenous cefotetan disodium for injection in healthy Chinese volunteers: A randomized, open-label, single- and multiple-dose study.

BACKGROUND: Cefotetan disodium for injection is a semisynthetic cephamycin antibiotic that exerts its bactericidal effects by inhibition of cell-wall synthesis. Despite being widely used in the treatment of various infections, little information is available on the pharmacokinetic properties of cefotetan disodium in Chinese subjects. OBJECTIVES: This study evaluated the pharmacokinetics of single and multiple intravenous doses of a generic formulation of cefotetan disodium in healthy Chinese volunteers. The effect of sex on the pharmacokinetics of cefotetan disodium was evaluated as a secondary objective. METHODS: In this open-label, dose-escalating study, subjects were randomized to receive a single dose of cefotetan disodium 0.5, 1.0, or 2.0 g administered as a 1-hour intravenous infusion. Those allocated to the 1.0-g dose continued into the multiple-dose phase, in which they received 1.0 g BID for 7 consecutive days. During the single-dose phase, blood samples were collected at regular intervals from 0 to 15 hours after drug administration and were analyzed using a validated HPLC method. During the multiple-dose phase, blood samples were obtained before drug administration on days 5, 6, and 7 to determine the C(min) at steady state; on day 7, blood samples were also collected from 0 to 15 hours after drug administration. Tolerability was assessed based on physical examinations, vital signs, laboratory tests (hematology, biochemistry, hepatic and renal function, and urinalysis), and subject interviews. RESULTS: Three groups, each consisting of 5 men and 5 women, were enrolled in the single-dose phase. The mean (SD) age of subjects was 23.2 (2.2) years (range, 19-30 years). Their mean weight was 57.0 (6.3) kg (range, 46.4-72.0 kg), and their mean height was 1.66 (0.08) m (range, 1.48-1.81 m). After intravenous administration of single doses of 0.5, 1.0, and 2.0 g, the cefotetan disodium C(max) was 35.01 (6.98), 76.67 (10.52), and 154.33 (27.17) mg/L, respectively; the AUC0₋15(h) was 145.35 (18.36), 307.45 (33.07), and 746.09 (103.07) mg · h/L; the AUC0₋(∞) was 171.51 (20.61), 347.25 (44.20), and 843.84 (131.13) mg · h/L; the t(1/2) was 5.80 (1.29), 4.91 (1.15), and 5.04 (1.26) hours; the CL was 2.96 (0.41), 2.92 (0.39), and 2.42 (0.39) L/h; and the V(d) was 24.55 (5.19), 20.37 (3.66), and 17.30 (3.52) L. After administration of multiple doses, the cefotetan disodium C(max,ss) was 80.53 (10.04) mg/L; the C(mix,ss) was 11.00 (4.04) mg/L; the AUC(ss) was 347.92 (50.04) mg · h/L; the steady-state plasma concentration was 28.99 (4.17) mg/L; the t(1/2) was 6.24 (2.52) hours; the CL was 2.32 (0.64) L/h; and the Vd was 19.19 (4.58) L. No significant differences in pharmacokinetic parameters were noted by sex in the multiple-dose phase. Cefotetan disodium appeared to be well tolerated. CONCLUSIONS: In these healthy Chinese subjects, the cefotetan disodium AUC and C(max) increased in a dose-proportional manner, whereas the t(1/2) was independent of dose. The pharmacokinetic properties of cefotetan disodium were linear at doses of 0.5 to 2.0 g. After multiple doses, the pharmacokinetic parameters of cefotetan disodium were consistent with those after single doses. At the doses studied, cefotetan disodium appeared to be well tolerated in these healthy volunteers.

Ertapenem versus cefotetan prophylaxis in elective colorectal surgery.

BACKGROUND: Ertapenem, a long-acting carbapenem, may be an alternative to the recommended prophylactic antibiotic cefotetan. METHODS: In this randomized, double-blind trial, we assessed the efficacy and safety of antibiotic prophylaxis with ertapenem, as compared with cefotetan, in patients undergoing elective colorectal surgery. A successful outcome was defined as the absence of surgical-site infection, anastomotic leakage, or antibiotic use 4 weeks postoperatively. All adverse events were collected until 14 days after the administration of antibiotic prophylaxis. RESULTS: Of the 1002 patients randomly assigned to study groups, 901 (451 in the ertapenem group and 450 in the cefotetan group) qualified for the modified intention-to-treat analysis, and 672 (338 in the ertapenem group and 334 in the cefotetan group) were included in the per-protocol analysis. After adjustment for strata, in the modified intention-to-treat analysis, the rate of overall prophylactic failure was 40.2% in the ertapenem group and 50.9% in the cefotetan group (absolute difference, -10.7%; 95% confidence interval [CI], -17.1 to -4.2); in the per-protocol analysis, the failure rate was 28.0% in the ertapenem group and 42.8% in the cefotetan group (absolute difference, -14.8%; 95% CI, -21.9 to -7.5). Both analyses fulfilled statistical criteria for the superiority of ertapenem. In the modified intention-to-treat analysis, the most common reason for failure of prophylaxis in both groups was surgical-site infection: 17.1% in the ertapenem group and 26.2% in the cefotetan group (absolute difference, -9.1; 95% CI, -14.4 to -3.7). In the treated population, the overall incidence of Clostridium difficile infection was 1.7% in the ertapenem group and 0.6% in the cefotetan group (P=0.22). CONCLUSIONS: Ertapenem is more effective than cefotetan in the prevention of surgical-site infection in patients undergoing elective colorectal surgery but may be associated with an increase in C. difficile infection. (ClinicalTrials.gov number, NCT00090272 [ClinicalTrials.gov].).

Effect of human immunodeficiency virus-1 infection on treatment outcome of acute salpingitis.

OBJECTIVE: To examine the effect of human immunodeficiency virus (HIV)-1 infection on treatment outcome of laparoscopically verified acute salpingitis. METHODS: Women aged 18-40 years with laparoscopically verified acute salpingitis received antibiotic therapy that included cefotetan 2 g intravenously and doxycycline 100 mg orally every 12 hours and laparoscopically guided drainage of tuboovarian abscesses of 4 cm or more. Clinical investigators blinded to HIV-1 serostatus used predetermined clinical criteria, including calculation of a clinical severity score and a standard treatment protocol to assess response to therapy. RESULTS: Of the 140 women with laparoscopically confirmed acute salpingitis, 61 (44%) women had mild, 38 (27%) had moderate, and 41 (29%) had severe disease (ie, pyosalpinx, tuboovarian abscesses, or both). Fifty-three (38%) were HIV-1-infected. Severe disease was more common in HIV-1-infected in comparison with HIV-1-uninfected women (20 [38%] compared with 21 [24%], P = .02). Defined as time of hospital discharge or 75% or more reduction in baseline clinical severity score, HIV-1-infected women with severe (6 days [4-16] compared with 5 days [3-9], P = .09) but not those with either mild (4 days [2-6] compared with 4 days [2-6] P = .4) or moderate salpingitis (4 days [3-7] compared with 4 days [3-6] P = .32) tended to take longer to meet criteria for clinical improvement. The need for intravenous clindamycin or additional surgery was not different in HIV-1-infected and uninfected cases (15 [28%] compared with 18 [21%], P = .3). CONCLUSION: Although HIV-1 infection may prolong hospitalization in women with severe salpingitis, all women hospitalized with acute salpingitis responded promptly to antibiotic therapy and surgical drainage regardless of HIV-1 infection status. LEVEL OF EVIDENCE: II-2.

Cefotetan-induced hemolytic anemia after perioperative prophylaxis.

Cephalosporin-induced hemolytic anemia is an acquired form of hemolytic anemia caused by interaction of drug with the immune system. Drug adsorption, drug-dependent antibody, and autoimmune induction are the three mechanisms of hemolysis. Cefotetan-induced hemolytic anemia (CIHA) has been described to occur through all three mechanisms. We report four cases of CIHA that occurred after appropriate perioperative use of cefotetan. All of our patients developed an acute and severe hemolytic episode that caused significant symptoms and led to hospitalization within 1-2 weeks after exposure to cefotetan. The hemolytic process was self-limited, and all our patients responded to supportive measures and blood transfusion. This report adds to our knowledge of CIHA, a rare complication of cefotetan use. Our cases suggest that cefotetan-induced acute severe hemolysis is caused by membrane modification (nonimmunologic protein adsorption) in addition to immune complex formation. Prompt diagnosis and aggressive supportive measures are essential in minimizing morbidity and mortality from hemolysis. Physicians should warn their patients about this complication. Given that hemolysis occurs when the subject is no longer under direct clinical supervision, patient awareness on how to recognize signs and symptoms of hemolysis is paramount to reducing the likelihood of this potentially lethal side effect. Finally, physicians might consider restricting cefotetan use.

Drug-induced hemolysis: cefotetan-dependent hemolytic anemia mimicking an acute intravascular immune transfusion reaction.

Numerous cases of drug-induced hemolytic anemia have been described in patients treated with penicillin or cephalosporin. Second and third generation cephalosporins are more commonly implicated in hemolytic reactions than first generation cephalosporins. We report a case of severe cefotetan-induced hemolytic anemia in a previously healthy 46-year-old woman undergoing an elective hysterectomy. The patient received 2 g of intravenous cefotetan intraoperatively and subsequently at 12 and 24 h post-operatively. She complained of diarrhea and fever on the third post-operative day and was seen in her gynecologist's office on the fifth post-operative day (hemoglobin = 10.5 g/dL). On the seventh post-operative day, she complained of fever and soreness around the suprapubic catheter site and was given a prescription for 500 mg oral cephalexin four times a day. The next day she was seen in the gynecologist's office and reported feeling better. Ten days after the operation her fatigue worsened and her hemoglobin was 4.8 g/dL. She was transfused with 3 units of packed red blood cells (PRBC) and was given 1 g of cefotetan intravenously. During the transfusion of the second unit of PRBC nursing staff observed gross hemoglobinuria and she subsequently developed acute renal failure. Laboratory chemistry parameters were consistent with severe acute hemolysis. The patient's direct antiglobulin test was reactive and her serum reacted with cefotetan-coated red blood cells (RBCs) and serum plus soluble cefotetan reacted with untreated RBCs. The titration endpoint of the serum against cefotetan-coated RBCs was 40,960, while the serum plus soluble cefotetan against uncoated RBCs was 2,560. This case of severe cefotetan-induced hemolysis was complicated by an acute hemolytic event that occurred during the transfusion of PRBC. Clinical and transfusion service staff must consider drug-induced hemolysis in the differential diagnosis of acute anemia.

Antibiotic prophylaxis at Cesarean delivery.

OBJECTIVE: Our aim was to compare the efficacy of ampicillin, cefotetan, and ampicillin/sulbactam in the prevention of post-Cesarean endomyometritis. METHODS: Consenting patients undergoing Cesarean delivery at the University of Louisville Hospital were enrolled in a prospective, double-blinded randomization to receive either ampicillin/sulbactam (Group 1), cefotetan (Group 2), or ampicillin (Group 3) single dose antibiotic prophylaxis following umbilical cord clamping. The primary outcome variable was the frequency of endomyometritis in the respective groups. RESULTS: Among 301 randomized patients, outcome data was available for 298 patients. Fourteen patients (4.7%), all of whom underwent non-elective Cesarean delivery, developed endomyometritis. The frequency of endomyometritis was not different among groups: Group 1, 4/101 (4%); Group 2, 4/96 (4.2%); and Group 3, 6/101 (5.9%). Wound infections were infrequently observed 4/298 (1.3%) without significant differences among groups. Stepwise discriminative analysis identified only last cervical dilatation as a significant predictor of endomyometritis (P = 0.006). CONCLUSION: Post-Cesarean endomyometritis occurs infrequently following single dose antibiotic prophylaxis after umbilical cord clamping. An advantage of broader spectrum antibiotics over ampicillin was not demonstrated.

Incidence of postpartum endomyometritis following single-dose antibiotic prophylaxis with either ampicillin/sulbactam, cefazolin, or cefotetan in high-risk cesarean section patients.

OBJECTIVE: To assess the efficacy of single-dose antibiotic prophylaxis against postpartum endomyometritis in high-risk cesarean section patients. DESIGN: Patients were administered one of three single-dose antibiotic regimens following umbilical cord clamping after cesarean section delivery. SETTING: Prospective randomized trial at a university-based hospital. PATIENTS: The study evaluated 293 consenting women undergoing cesarean section who had either experienced labor for a duration of > or = 6 hr or rupture of amniotic membranes. MAIN OUTCOME MEASURES: Development of postpartum endomyometritis. RESULTS: The incidence of postpartum endomyometritis was 7/95 (7.4%) following the ampicillin/sulbactam regimen, 14/98 (14.3%) after the cefazolin regimen, and 11/99 (11.1%) after the cefotetan regimen. There was no significant difference in postpartum infection among the three study arms. In addition, the incidence of endomyometritis in the three single-dose study arms was not higher than previously noted in studies where three doses of antibiotic were administered. CONCLUSION: Single-dose antibiotic prophylaxis should replace the standard triple-dose therapy for uninfected women undergoing cesarean section who are at risk for postoperative endomyometritis. Ampicillin/sulbactam, cefazolin, and cefotetan are all reasonable antibiotic choices for single-dose therapy.

Randomized trial of single-dose versus multiple-dose cefotetan for the postpartum treatment of intrapartum chorioamnionitis.

OBJECTIVE: Our purpose was to determine whether a single postpartum dose of a cephalosporin would effectively treat women with intrapartum chorioamnionitis and decrease the length of hospitalization. STUDY DESIGN: After vaginal delivery consenting women who had received antibiotics for chorioamnionitis were assigned to postpartum treatment with either a single 2 gm intravenous dose of cefotetan or to cefotetan 2 gm given intravenously every 12 hours for a minimum of 48 hours. Chorioamnionitis was defined as an intrapartum temperature of > or = 100.4 degrees F and maternal or fetal tachycardia, maternal leukocytosis, or uterine tenderness. Patients were discharged when they had received their assigned dosage of cefotetan, were afebrile (temperature < 100.4 degrees F) and > or = 24 hours from delivery. RESULTS: We studied 109 women (55 single dose, 54 multiple dose) with chorioamnionitis. The two groups were similar with regard to demographic and intrapartum characteristics. The median (range) interval from delivery to discharge was 24 hours lower in the single-dose group (33 [16 to 190] vs 57 [36 to 190] hours, p = 0.0001). The incidence of failed therapy was similar (single dose: 6/55, 11%, vs multiple dose: 2/54, 3.7%, p = 0.27). CONCLUSIONS: A single postpartum dose of cefotetan appears to be effective treatment for intrapartum chorioamnionitis after a vaginal delivery and decreases the length of hospital stay.

Studies on the duration of antibiotic administration for surgical prophylaxis.

Patients undergoing 801 elective, clean-contaminated operations were assigned to one of the three following antibiotic regimens: 1) 1 g of cefazolin preoperatively, 2) 1 g of cefazolin preoperatively and another 1-g dose 3 hours later, and 3) 1 g of cefotetan preoperatively. These antibiotic regimens resulted in similar wound infection rates for procedures completed within 3 hours. When the procedure lasted more than 3 hours, the 6.1 per cent infection rate noted when a single dose of cefazolin was given proved significantly greater than the 1.3 per cent infection rates associated with the use of two doses of cefazolin or a single dose of the longer acting antibiotic, cefotetan (P < 0.01). Another series of 768 patients undergoing biliary and gastrointestinal tract operations were assigned to one of two antibiotic regimens: 1) a preoperative dose of 1 g of cefazolin and another 1-g dose 3 hours later if still in the operating room; 2) same as (1), plus 1-g doses every 8 hours for 24 hours. The longer period of antibiotic administration failed to improve the wound infection rate compared to the use of perioperative coverage only. These studies suggest that a single dose of preoperative antibiotic is sufficient for surgical prophylaxis when the operation is completed within 3 hours. Antibiotic coverage must extend for the duration of longer operations. A second dose of antibiotic or a single preoperative dose of an extended half-life antibiotic are equally effective. There is no value to administering antibiotics after the operation has been completed.

Cefazolin is inferior to cefotetan as single-dose prophylaxis for women undergoing elective total abdominal hysterectomy.

The purpose of this prospective, randomized, double-blind clinical trial was to compare the efficacy of 1-g doses of intravenous cefazolin with that of 1-g doses of intravenous cefotetan in preventing major operative site infections after elective abdominal hysterectomy. A major operative site infection requiring parenteral antimicrobial therapy developed in 46 (9%) of 511 evaluable women: 30 (11.6%) of 258 women given cefazolin prophylaxis and 16 (6.3%) of 253 women given cefotetan prophylaxis (relative risk, 1.84; 95% confidence interval, 1.03 to 3.29; P < .05). Risk factors for major operative site infection were younger age, lower postoperative hemoglobin concentration, and a proliferative endometrium. Ten (3.9%) of 258 women given cefazolin prophylaxis had a postoperative pelvic abscess; two of these women required additional surgical procedures, compared with two (0.8%) of 253 women given cefotetan prophylaxis who had an abscess but did not require surgery (relative risk, 4.9; 95% confidence interval, 1.09 to 22.16; P = .04). A greater number of infections and more serious infections occurred following cefazolin prophylaxis; this treatment resulted in 234 additional hospital days for administration of parenteral antimicrobial therapy.

Single-dose cefotetan or cefoxitin versus multiple-dose cefoxitin as prophylaxis in patients undergoing appendectomy for acute nonperforated appendicitis.

OBJECTIVE: A prospective, double-blind study was performed to examine the effects of prophylactic cefotetan and cefoxitin in postoperative wound infection for patients with nonperforated acute appendicitis. METHODS: One hundred thirty-six of 179 patients with a clinical diagnosis of appendicitis were evaluated and divided into three groups: group 1 received 2 g cefotetan preoperatively, group 2 received 2 g cefoxitin preoperatively, and group 3 received 2 g cefoxitin preoperatively followed by three postoperative doses. RESULTS: The overall wound infection rate was 4.6 percent. Group 2 (single-dose cefoxitin) had a significantly higher wound infection rate (11.1 percent) than group 1 (single-dose cefotetan) (zero percent) or group 3 (multiple-dose cefoxitin) (1.9 percent). CONCLUSIONS: Single-dose cefotetan and multiple-dose cefoxitin are equally effective. However, because of the greater convenience and markedly decreased cost, single-dose cefotetan is the prophylaxis of choice in appendectomy for nonperforated appendicitis.

Comparison of single-dose cefotetan and multidose cefoxitin as intravenous prophylaxis in elective, open biliary tract surgery: a multicentre, double-blind, randomized study.

OBJECTIVE: To compare the safety, tolerance and prophylactic effectiveness of a single 2-g dose of cefotetan with a standard prophylactic regimen of cefoxitin in reducing the incidence of postoperative infections after elective, open biliary tract surgery. DESIGN: Multicentre, double-blind, randomized comparative study with a 4-week follow-up. SETTING: Five Canadian university centres. PARTICIPANTS: One hundred and eleven patients scheduled to undergo elective, open biliary tract surgery. INTERVENTIONS: The patients were randomly assigned to receive either cefotetan or cefoxitin in a ratio of 2:1; 76 patients received cefotetan and 35 received cefoxitin. MAIN OUTCOME MEASURES: Wound infection as defined by the Centers for Disease Control and Prevention and by clinical evaluation, adverse events and laboratory parameters. RESULTS: Two incisional wound infections were reported by patients in the cefotetan group, for an overall infection rate of 1.8% (2 of 111). No significant differences were found in the failure rate or in any other indicator of efficacy. The incidence of adverse events for cefotetan (12.6%) was not statistically different from that for cefoxitin (10.4%), and none of the 16 adverse events in the cefotetan group and 5 in the cefoxitin group was serious or severe. Only one event (rash) was possibly related to the study drugs. Several hematologic and biochemical parameters were found to be normal preoperatively and abnormal postoperatively, but no relation was found between these variations and the study drugs. These changes were mainly attributable to the operation. CONCLUSION: Cefotetan was found to be effective and comparable to cefoxitin, both in safety and in reducing the incidence of infection after elective, open biliary tract surgery.