Antibiotic prophylaxis for operative vaginal delivery.

BACKGROUND: Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics may be prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. This is an update of a review last published in 2017. OBJECTIVES: To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum or forceps delivery, or both. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 July 2019), and reference lists of retrieved studies. SELECTION CRITERIA: All randomised controlled trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium). DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias. Two review authors extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all review authors. We assessed methodological quality of the two included studies using the GRADE approach. MAIN RESULTS: Two studies, involving 3813 women undergoing either vacuum or forceps deliveries, were included. One study involving 393 women compared the antibiotic intravenous cefotetan after cord clamping compared with no treatment. The other study involving 3420 women compared a single dose of intravenous amoxicillin and clavulanic acid with placebo using 20 mL of intravenous sterile 0.9% saline. The evidence suggests that prophylactic antibiotics reduce superficial perineal wound infection (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.40 to 0.69; women = 3420; 1 study; high-certainty evidence), deep perineal wound infection (RR 0.46, 95% CI 0.31 to 0.69; women = 3420; 1 study; high-certainty evidence) and probably reduce wound breakdown (RR 0.52, 95% CI 0.43 to 0.63; women = 2593; 1 study; moderate-certainty evidence). We are unclear about the effect on organ or space perineal wound infection (RR 0.11, 95% CI 0.01 to 2.05; women = 3420; 1 study) and endometritis (average RR 0.32, 95% CI 0.04 to 2.64; 15/1907 versus 30/1906; women = 3813; 2 studies) based on low-certainty evidence with wide CIs that include no effect. Prophylactic antibiotics probably lower serious infectious complications (RR 0.44, 95% CI 0.22 to 0.89; women = 3420; 1 study; high-certainty evidence). They also have an important effect on reduction of confirmed or suspected maternal infection. The two included studies did not report on fever or urinary tract infection. It is unclear, based on low-certainty evidence, whether prophylactic antibiotics have any impact on maternal adverse reactions (RR 2.00, 95% CI 0.18 to 22.05; women = 2593; 1 study) and maternal length of stay (MD 0.09 days, 95% CI -0.23 to 0.41; women = 393; 1 study) as the CIs were wide and included no effect. Prophylactic antibiotics slightly improve perineal pain and health consequences of perineal pain and probably reduce costs. Prophylactic antibiotics did not have an important effect on dyspareunia (difficult or painful sexual intercourse) or breastfeeding at six weeks. Antibiotic prophylaxis may slightly improve maternal hospital re-admission and maternal health-related quality of life. Neonatal adverse reactions were not reported in any included trials. AUTHORS' CONCLUSIONS: Prophylactic intravenous antibiotics are effective in reducing infectious puerperal morbidities in terms of superficial and deep perineal wound infection or serious infectious complications in women undergoing operative vaginal deliveries without clinical indications for antibiotic administration after delivery. Prophylactic antibiotics slightly improve perineal pain and health consequences of perineal pain, probably reduce the costs, and may slightly reduce the maternal hospital re-admission and health-related quality of life. However, the effect on reduction of endometritis, organ or space perineal wound infection, maternal adverse reactions and maternal length of stay is unclear due to low-certainty evidence. As the evidence was mainly derived from a single multi-centre study conducted in a high-income setting, future well-designed randomised trials in other settings, particularly in low- and middle-income settings, are required to confirm the effect of antibiotic prophylaxis for operative vaginal delivery.

Antibiotic prophylaxis for third- and fourth-degree perineal tear during vaginal birth.

BACKGROUND: One to eight per cent of women suffer third-degree perineal tear (anal sphincter injury) and fourth-degree perineal tear (rectal mucosa injury) during vaginal birth, and these tears are more common after forceps delivery (28%) and midline episiotomies. Third- and fourth-degree tears can become contaminated with bacteria from the rectum and this significantly increases in the chance of perineal wound infection. Prophylactic antibiotics might have a role in preventing this infection. OBJECTIVES: To assess the effectiveness of antibiotic prophylaxis for reducing maternal morbidity and side effects in third- and fourth-degree perineal tear during vaginal birth. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2014) and the reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials comparing outcomes of prophylactic antibiotics versus placebo or no antibiotics in third- and fourth-degree perineal tear during vaginal birth. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the trial reports for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We identified and included one trial (147 women from a pre-planned sample size of 310 women) that compared the effect of prophylactic antibiotic (single-dose, second-generation cephalosporin - cefotetan or cefoxitin, 1 g intravenously) on postpartum perineal wound complications in third- or fourth-degree perineal tears compared with placebo. Perineal wound complications (wound disruption and purulent discharge) at the two-week postpartum check up were 8.20% and 24.10% in the treatment and the control groups respectively (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.12 to 0.96). However, the high failed-appointment rate may limit the generalisability of the results. The overall risk of bias was low except for incomplete outcome data. The quality of the evidence using GRADE was moderate for infection rate at two weeks' postpartum, and low for infection rate at six weeks' postpartum. AUTHORS' CONCLUSIONS: Although the data suggest that prophylactic antibiotics help to prevent perineal wound complications following third- or fourth-degree perineal tear, loss to follow-up was very high. The results should be interpreted with caution as they are based on one small trial.

Antibiotic regimens for management of intra-amniotic infection.

BACKGROUND: Chorioamnionitis is a common infection that affects both mother and infant. Infant complications associated with chorioamnionitis include early neonatal sepsis, pneumonia, and meningitis. Chorioamnionitis can also result in maternal morbidity such as pelvic infection and septic shock.Clinical chorioamnionitis is estimated to occur in 1% to 2% of term births and in 5% to 10% of preterm births; histologic chorioamnionitis is found in nearly 20% of term births and in 50% of preterm births. Women with chorioamnionitis have a two to three times higher risk for cesarean delivery and a three to four times greater risk for endomyometritis, wound infection, pelvic abscess, bacteremia, and postpartum hemorrhage. OBJECTIVES: To assess the effects of administering antibiotic regimens for intra-amniotic infection on maternal and perinatal morbidity and mortality and on infection-related complications. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 October 2014), CENTRAL, MEDLINE, Embase, LILACS, and the WHO ICTRP (September 2014). We also searched reference lists of retrieved studies and contacted experts in the field. SELECTION CRITERIA: Randomized controlled trials (RCTs) that included women who experienced intra-amniotic infection. Trials were included if they compared antibiotic treatment with placebo or no treatment (if applicable), treatment with different antibiotic regimens, or timing of antibiotic therapy (intrapartum and/or postpartum). Therefore, this review assesses trials evaluating intrapartum antibiotics, intrapartum and postpartum antibiotic regimens, and postpartum antibiotics. Diagnosis of intra-amniotic infection was based on standard criteria (clinical/test), and no limit was placed on gestational age. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and trial quality. Two review authors independently extracted data and checked them for accuracy. We assessed the quality of the evidence using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach and included a 'Summary of findings' table. MAIN RESULTS: Our prespecified primary outcomes were maternal and neonatal mortality, maternal and neonatal severe infection, and duration of maternal and neonatal hospital stay.We included 11 studies (involving 1296 women) and assessed them as having low to moderate risk of bias - mainly because allocation concealment methods were not adequately reported, most studies were open, and outcome reporting was incomplete. The quality of the evidence was low to very low for most outcomes, as per the GRADE approach. The following antibiotics were assessed in the included trials: ampicillin, ampicillin/sulbactam, gentamicin, clindamycin, and cefotetan. During labor: meta-analysis of two studies found no clear differences in rates of neonatal sepsis (163 neonates; risk ratio (RR) 1.07, 95% confidence interval (CI) 0.40 to 2.86; I² = 9%; low quality of evidence), treatment failure (endometritis) (163 participants; RR 0.86, 95% CI 0.27 to 2.70; I² = 0%; low quality of evidence), and postpartum hemorrhage (RR 1.39, 95% CI 0.76 to 2.56; I² = 0%; low quality of evidence) when two different dosages/regimens of gentamicin were assessed. No clear differences between groups were found for any reported maternal or neonatal outcomes. The review did not identify data for a comparison of antibiotics versus no treatment/placebo. Postpartum: meta-analysis of two studies that evaluated use of antibiotics versus placebo after vaginal delivery showed no significant differences between groups in rates of treatment failure or postpartum endometritis. No significant differences were found in rates of neonatal death and postpartum endometritis when use of antibiotics was compared with no treatment. Four trials assessing two different dosages/regimens of gentamicin or dual-agent therapy versus triple-agent therapy, or comparing antibiotics, found no significant differences in most reported neonatal or maternal outcomes; the duration of hospital stay showed a difference in favor of the group of women who received short-duration antibiotics (one study, 292 women; mean difference (MD) -0.90 days, 95% CI -1.64 to -0.16; moderate quality of evidence). Intrapartum versus postpartum: one small study (45 women) evaluating use of ampicillin/gentamicin during intrapartum versus immediate postpartum treatment found significant differences favoring the intrapartum group in the mean number of days of maternal postpartum hospital stay (one trial, 45 women; MD -1.00 days, 95% CI -1.94 to - 0.06; very low quality of evidence) and the mean number of neonatal hospital stay days (one trial, 45 neonates; MD -1.90 days, 95% CI -3.91 to -0.49; very low quality of evidence). Although no significant differences were found in the rate of maternal bacteremia or early neonatal sepsis, for the outcome of neonatal pneumonia or sepsis we observed a significant difference favoring intrapartum treatment (one trial, 45 neonates; RR 0.06, 95% CI 0.00 to 0.95; very low quality of evidence). AUTHORS' CONCLUSIONS: This review included 11 studies (having low to moderate risk of bias). The quality of the evidence was low to very low for most outcomes, as per the GRADE approach. Only one outcome (duration of hospital stay) was considered to provide moderate quality of evidence when antibiotics (short duration) were compared with antibiotics (long duration) during postpartum management of intra-amniotic infection. Our main reasons for downgrading the quality of evidence were limitations in study design or execution (risk of bias), imprecision, and inconsistency of results.Currently, limited evidence is available to reveal the most appropriate antimicrobial regimen for the treatment of patients with intra-amniotic infection; whether antibiotics should be continued during the postpartum period; and which antibiotic regimen or what treatment duration should be used. Also, no evidence was found on adverse effects of the intervention (not reported in any of the included studies). One small RCT showed that use of antibiotics during the intrapartum period is superior to their use during the postpartum period in reducing the number of days of maternal and neonatal hospital stay.

Use of single agent Cefotetan for Gustilo-Anderson type III open fracture prophylaxis.

INTRODUCTION: The prophylactic intravenous antibiotic regimen for Gustilo-Anderson Type III open fractures traditionally consists of cefazolin with an aminoglycoside plus penicillin for gross contamination. Cefotetan, a second-generation cephalosporin, offers a wide spectrum of activity against both aerobes and anaerobes as well as against Gram-positive and Gram-negative bacteria. Cefotetan has not been previously established within orthopedic surgery as a prophylactic intravenous agent. PATIENTS AND METHODS: Cefotetan monotherapeutic prophylaxis versus any other antibiotic regimen (standard/literature-supported and otherwise) was studied for patient encounters between September 2010 and December 2019 within a single Level 1 regional trauma center. Patient comorbidities, preoperative fracture characteristics, and in-hospital/operative metrics (including length of stay [LOS], number of antibiotic doses, and antibiotic costs [US$]) were included for analysis. Postoperative outcomes up to 1 year included rates of surgical site infection (SSI), deep infection necessitating return to the operating room (OR), non-union, prescribed outpatient antibiotics, hospital readmissions, and related returns to the emergency department (ED). Sensitivity analyses were also conducted to include standard/literature-supported antibiotic regimens as a nested random factor within the non-cefotetan cohort. RESULTS: The nested variable accounting for standard/literature-supported antibiotic regimens had no significant effect in any model for any outcome (for each, P ≥ 0.302). Thus, 1-year data for 138 Type III open fractures were included, accounting for only the binary effect of cefotetan (n = 42) versus non-cefotetan cohorts. The cohorts did not differ significantly at baseline. The cefotetan cohort received fewer in-house dose/day antibiotics (P < 0.001), was less likely to receive outpatient antibiotics in the following year (P = 0.023), had decreased return to the OR (35.7% versus 54.2%, P = 0.045), and demonstrated non-union rates of 16.7% versus 28.1% (P = 0.151). When adjusted for length of stay (LOS), the dose/day total costs for antibiotics were $8.71/day more expensive for the cefotetan cohort (P = 0.002). Type III open fractures incurred overall rates of SSI reaching 16.7% in the cefotetan cohort and 14.7% for non-cefotetan (P = 0.773). Deep infections necessitating return to the OR were 9.5% and 11.6%, respectively (P = 0.719). CONCLUSION: Cefotetan alone may provide superior antibiotic stewardship with similar infectious sequalae compared to more traditional antibiotic prophylaxis regimens for Gustilo-Anderson Type III open long bone fractures. LEVEL OF EVIDENCE: Level III Retrospective Cohort Study.

Cefotetan versus conventional triple antibiotic prophylaxis in elective colorectal cancer surgery.

This study examined infectious outcomes in elective colorectal cancer surgery between cefotetan alone or conventional triple antibiotics. From January to December 2007, 461 consecutive primary colorectal cancer patients underwent elective surgery. Group A contained 225 patients who received conventional triple antibiotics (cephalosporin, aminoglycoside and metronidazole) for prophylaxis, and group B contained 236 patients who received cefotetan alone for prophylaxis. Treatment failure was defined as the presence of postoperative infection including surgical-site infection (SSI), anastomotic leakage, and pneumonia or urinary tract infection. The two groups were similar in terms of demographics, American Society of Anesthesiologists (ASA) score, tumour location, stage, surgical approach (conventional open vs. laparoscopy-assisted), and type of operation. The treatment failure rates were 3.1% in Group A and 3.4% in Group B (absolute difference, -0.3%; 95% confidence interval [CI], 0.39 to 3.07, P=0.866), with SSI being the most common reason for failure in both groups (2.7% in Group A and 3.0% in Group B [absolute difference, -0.3%; 95% CI, 0.37 to 3.37, P=0.846]). Cefotetan alone is as effective as triple antibiotics for prophylaxis in primary colorectal cancer patients undergoing elective surgery.

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].).

Infection after elective colorectal surgery: bacteriological analysis of failures in a randomized trial of cefotetan vs. ertapenem prophylaxis.

BACKGROUND: A randomized study comparing single-dose cefotetan and ertapenem prophylaxis for elective colorectal surgery in 1,002 patients found ertapenem to be significantly more effective (p < 0.001). Failures of prophylaxis were thought to involve organisms resistant to both antimicrobial agents, isolated most often from deep or superficial incision sites. METHODS: Further testing and analysis of the microbial data was performed. Susceptibility results were correlated with the clinical outcomes reported previously. RESULTS: Of the 216 aerobes tested, 62.6% were resistant to cefotetan and 44% to ertapenem. Enterococci and methicillin-resistant Staphylococcus epidermidis were the aerobes recovered most frequently, and Bacteroides thetaiotaomicron, Clostridium innocuum, and Eubacterium lentum were the most frequent anaerobes. Enterococcus faecalis usually was associated in mixed culture with Bacteroides fragilis group species. Approximately one-half of the 158 anaerobes (50.7%), including all the species above, were resistant to cefotetan; most of these (61.4%) came from superficial incision sites. Only one anaerobe (Desulfovibrio fairfieldensis), found in a superficial incisional infection, was resistant to ertapenem, and no ertapenem-resistant enteric bacteria were recovered. In vitro resistance was associated with therapeutic failure. CONCLUSIONS: The in vitro activity of ertapenem was superior to that of cefotetan against all anaerobic and many aerobic bacteria isolated from postoperative cultures of patients who failed prophylaxis with these agents. Our findings help to elucidate the results of the clinical trial.

Effect of body mass index and ertapenem versus cefotetan prophylaxis on surgical site infection in elective colorectal surgery.

BACKGROUND: The effectiveness of prophylactic antibiotics in the prevention of surgical site infection (SSI) after elective colorectal surgery is dependent on many factors, including the body mass index (BMI) of the patient. In this study, the association of BMI and type of antibiotic prophylaxis with SSI was evaluated in patients undergoing elective colorectal surgery. METHOD: A post-hoc analysis was performed using data obtained from a multicenter randomized, double-blind study of 1,002 patients undergoing elective colorectal surgery who received prophylactic administration of ertapenem (1 g) or cefotetan (2 g). Among 650 evaluable patients, the effect of BMI and type of antibiotic prophylaxis on SSI rates was assessed four weeks after surgery. Mechanical bowel preparation was standardized, and no patient received oral antibiotics; intravenous antibiotics were not repeated during or after surgery. RESULTS: The majority of patients had a BMI between 18.5 and 39.9 kg/m2. Regardless of the type of prophylaxis, SSI rates were significantly higher in patients with a BMI > or = 30 kg/m2 than in those with a BMI < 30 kg/m2. However, failure, defined as SSI, was significantly less common after ertapenem than after cefotetan prophylaxis at both BMI < 30 kg/m2 (12.7% vs. 26.4%, respectively; difference -13.7; 95% confidence interval [CI] -21.0, -6.5) and BMI > or = 30 kg/m2 (26.7% vs. 41.9%, respectively; difference -15.3; 95% CI -28.2, -2.0). The most prevalent type of SSI was superficial incisional infection, which was more common with both treatments in patients with a BMI > or = 30 kg/m2; however, the incidence of superficial SSI was lower after ertapenem than cefotetan prophylaxis. CONCLUSION: In patients undergoing elective colorectal surgery, the incidence of SSI, specifically superficial incisional SSI, was higher in patients with a BMI > or = 30 kg/m2, regardless of the prophylactic antibiotic given. Ertapenem prophylaxis was more effective than cefotetan in the prevention of SSI at any BMI.

Comparative costs of ertapenem and cefotetan as prophylaxis for elective colorectal surgery.

BACKGROUND AND PURPOSE: The costs of treating surgical site infections can be considerable. There is a cost associated with the prophylactic use of antibiotics; however, the use of prophylactic agents may reduce infection rates and lengths of stay, thus offsetting the overall treatment cost and potentially generating cost savings to hospitals. This project was intended to determine the potential cost impact of using ertapenem 1 g vs. cefotetan 2 g as prophylaxis for elective colorectal surgery. METHODS: Cost analysis using efficacy data from the PREVENT clinical trial and drug acquisition and total hospital costs in 2005 dollars from Premier's Perspective Comparative Database in patients > or = 18 year of age, evaluable at four weeks after elective surgery of the colon or rectum and prophylactic treatment with ertapenem (n = 338) or cefotetan (n = 334). The primary outcome measures were the rate of prophylactic drug failure and the difference between the ertapenem and cefotetan groups in costs related to and total hospital stay. Prophylactic failure was defined as a surgical site infection, unexplained antibiotic use, or anastomotic leak. RESULTS: Prophylactic failure occurred in 28.1% of the patients receiving ertapenem and 42.8% of those receiving cefotetan (p < 0.05). The most common prophylactic failure was surgical site infection: 18.3% for ertapenem, 31.1% for cefotetan, difference (95% confidence interval) -13.0% (-19.5, -6.5%) (p < 0.05). The mean +/- standard deviation length of stay for all patients, including prophylactic successes and failures, was 7.6 +/- 6.6 days for ertapenem and 8.7 +/- 9.5 days for cefotetan. The mean per-patient cost of prophylactic drugs and hospital room and board was $15,245 with ertapenem and $17,428 cefotetan, a net difference of -$2,181. CONCLUSIONS: Ertapenem used in prophylaxis for elective colorectal operations results in a lower rate of surgical site infection and a shorter average length of stay than cefotetan. The calculated net difference in prophylactic antibiotic drug and hospital costs represents a saving of $2,181 per patient with ertapenem relative to cefotetan.

Use and Effectiveness of Peri-Operative Cefotetan versus Cefazolin Plus Metronidazole for Prevention of Surgical Site Infection in Abdominal Surgery Patients.

BACKGROUND: Current practice guidelines for antimicrobial prophylaxis in surgery recommend a cephamycin or cefazolin plus metronidazole for various abdominal surgeries. In February 2016, cephamycin drug shortages resulted in a change in The Johns Hopkins Hospital's (JHH) recommendation for peri-operative antibiotic prophylaxis in abdominal surgeries from cefotetan to cefazolin plus metronidazole. The primary objective of this study was to quantify the percentage of abdominal surgeries adherent to JHH peri-operative antibiotic prophylaxis guidelines. A sub-group analysis investigated whether prophylaxis with cefazolin plus metronidazole was associated with a lower rate of surgical site infections (SSIs) versus cefotetan. PATIENTS AND METHODS: This retrospective cohort study included adult inpatients who underwent an abdominal surgery at JHH in September 2015 (Study Period I: cefotetan) or February to March 2016 (Study Period II: cefazolin plus metronidazole). RESULTS: Two hundred abdominal surgery cases were included in the primary analysis. A subset of 156 surgical cases were included in the sub-group analysis. The overall adherence rate to JHH guidelines was 75% in Study Period I versus 17% in Study Period II (p < 0.001). The largest difference in adherence was attributed to pre-operative administration time (87% vs. 23%, p < 0.001), primarily because of the longer infusion time required for metronidazole. Surgical site infections occurred in 14% (12/83) of surgeries with cefotetan versus 8.2% (6/73) with cefazolin plus metronidazole for prophylaxis (p = 0.19). CONCLUSIONS: Adherence to an institution-specific peri-operative antibiotic prophylaxis guideline for abdominal surgeries was limited primarily by the longer infusion time required for pre-operative metronidazole. A higher percentage of SSIs occurred among abdominal surgeries with cefotetan versus cefazolin plus metronidazole for prophylaxis.

Duration of antibiotic therapy for penetrating abdominal trauma: a prospective trial.

BACKGROUND: The optimal duration of antibiotic use in penetrating abdominal trauma is incompletely defined. It is generally accepted that short-term antibiotics are appropriate for low-risk wounds. However, with colon injury and significant degree of injury, abdominal trauma index (ATI) more than 25, concern exists that short-term treatment is not adequate. METHODS: The study was a prospective double-blind trial of 24-hour treatment (cefoxitin or cefotetan) compared with 5-day treatment in 515 patients. Major abdominal infections (MAI) included abscess, necrotizing fasciitis, and diffuse peritonitis. RESULTS: MAI occurred in 8% of those patients with 1-day therapy and 10% with 5-day therapy. Subgroup analysis of high-risk groups (colon wounds and ATI of more than 25) showed the following MAI rates: colon, 1-day therapy, 14%; 5-day therapy, 15%; ATI of more than 25, 1-day therapy, 17%; 5-day therapy, 30%. CONCLUSIONS: Regardless of contamination and degree of injury, 24-hour antibiotic therapy is satisfactory for all penetrating abdominal trauma.

Antibiotic prophylaxis for cesarean delivery: is an extended-spectrum agent necessary?

The purpose of this investigation was to determine whether an extended-spectrum antibiotic with a long duration of action was more effective for prophylaxis for cesarean delivery than a limited-spectrum agent with a shorter duration of action. Patients were eligible for the study if they were in labor or had ruptured membranes at the time of surgery. In a randomized, double-blind manner, 377 women were assigned to receive 2 g of cefazolin (192) or 2 g of cefotetan (185) intravenously immediately after the infant's umbilical cord was clamped. There were no significant differences between groups with respect to the frequency of febrile morbidity (22.4 versus 21.6%), the mean fever index (15.8 versus 14.9 degree-hours), the frequency of endometritis (19.3 versus 21.1%), or the mean duration of postoperative hospitalization (3.8 versus 3.9 days). Among patients who became infected despite prophylaxis, enterococcus was isolated with disproportionate frequency. This organism was responsible for 89% of the postoperative urinary tract infections and all three cases of bacteremia. It was also the second most common isolate in women with endometritis. A single dose of cefazolin is comparable in effectiveness to cefotetan. In view of the cost difference between the two antibiotics, there is no justification for use of the more expensive, extended-spectrum agent.

Upper genital tract isolates at delivery as predictors of post-cesarean infections among women receiving antibiotic prophylaxis.

The introduction of antibiotic prophylaxis for cesarean delivery has decreased the risk of postpartum endometritis and wound infection, but factors that contribute to prophylaxis failure are not understood. To determine factors that might contribute to postpartum infections following antibiotic prophylaxis, we cultured amniotic fluid, decidua, and chorioamniotic membrane specimens for anaerobic and facultative bacteria and for genital mycoplasmas at cesarean delivery. Women were assessed daily for the development of infections, and if endometritis developed, a protected endometrial culture was obtained. Postpartum endometritis developed in 16 and wound infection in four of 102 women. Infection rates were similar for women receiving cefotetan (N = 50) or cefoxitin (N = 52) for prophylaxis. The isolation of group B streptococcus (P less than .001) or Enterococcus faecalis (P = .03) from the upper genital tract at delivery was significantly associated with postpartum endometritis. Antibiotic-resistant organisms (other than enterococci) were recovered uncommonly at delivery or with postpartum infections. Group B streptococcus was susceptible to the prophylactic agents used, suggesting that virulence factors other than antibiotic resistance are important for the development of postpartum endometritis. Group B streptococcus, E faecalis, and bacteria associated with bacterial vaginosis were recovered from the endometrium at the time of postpartum endometritis.

Randomized clinical trial of extended spectrum antibiotic prophylaxis with coverage for Ureaplasma urealyticum to reduce post-cesarean delivery endometritis.

OBJECTIVE: To determine if extended spectrum prophylactic antibiotic treatment (with efficacy against Ureaplasma urealyticum) reduces post-cesarean delivery clinical endometritis. METHODS: After cord clamping at cesarean delivery, subjects received prophylaxis with cefotetan. Subjects were then simultaneously randomized (double blind) to receive doxycyline plus azithromycin versus placebo. Post-cesarean delivery endometritis was defined clinically as fever of 100.4F or higher with one or more supporting clinical signs or a physician diagnosis of endometritis plus the absence of a nonpelvic source of fever. RESULTS: A total of 597 women were enrolled, 301 in the doxycycline/azithromycin group and 296 in the placebo group. The study population was 56% black, 25.5 +/- 6.2 years of age, and 43% nulliparous. The groups were similar (P >.05) for black race, parity, maternal age, and most risk factors for post-cesarean delivery endometritis. The frequency of post-cesarean delivery endometritis (16.9% versus 24.7%, P =.020), wound infections (0.8% versus 3.6%, P =.030), and a combination of these two outcomes (19.0% versus 27.8%, P =.019) were significantly lower in the doxycycline/azithromycin group compared with the placebo-treated group. The doxycycline/azithromycin versus placebo groups were dissimilar for maternal leukocytosis (24.9% versus 12.5%, P =.042) and frequency of classic uterine incision (7.6% versus 12.5%, P =.048). Adjusting for these factors did not alter the risk ratio for post-cesarean delivery endometritis in the active versus placebo-treated group (relative risk 0.65, 95% confidence interval 0.43, 0.98). Length of stay was longer in the placebo group overall (104 +/- 56 versus 95 +/- 32 hours, P =.016) and among women with endometritis (146 +/- 52 versus 127 +/- 46 hours, P =.047). CONCLUSION: Extended spectrum prophylactic antibiotic treatment (with presumed efficacy against U urealyticum) given to women undergoing cesarean delivery at term shortens hospital stay and reduces the frequency of post-cesarean delivery endometritis and wound infections.

Prophylactic antibiotics for elective laparoscopic cholecystectomy: are they necessary?

HYPOTHESIS: Prophylactic antibiotic treatment in elective laparoscopic cholecystectomy does not lower the already low infection rate associated with this procedure. DESIGN AND SETTING: Prospective double-blind randomized trial at a community-based training hospital. PATIENTS: Four hundred fifty patients undergoing elective laparoscopic cholecystectomy were randomized into 1 of 3 treatment arms: (1) preoperative cefotetan disodium, 1g intravenously; (2) preoperative cefazolin, 1g intravenously; and (3) intravenous placebo. There were no demographic differences between groups in age, smoking history, American Society of Anesthesiologists score, infection risk class, time of antibiotic administration prior to surgery, and type of skin preparation. INTERVENTIONS: Laparoscopic cholecystectomy was attempted in all cases; however, 10 patients required conversion to an open cholecystectomy and they were included in the statistical analysis. Preoperatively, all patients were randomized in a blinded manner and received cefotetan, cefazolin, or placebo intravenously. RESULTS: There were 10 postoperative infections. In the cefotetan group, there were 3 cases of superficial surgical site infections. In the cefazolin group, there were 2 superficial surgical site infections-1 pneumonia and 1 rhinosinusitis. In the placebo group, there were 2 superficial surgical site infections and 1 urinary tract infection. The overall infection rate in this series was 2.4%. Follow-up was performed at routine postoperative visits and by telephone contact. Data were evaluated using the chi2 test and analysis of variance with Duncan post hoc test (P<.05). CONCLUSION: Based on our data, use of prophylactic antibiotics does not decrease the rate of wound infections in elective laparoscopic cholecystectomy.

Prospective alterations in therapy for penetrating abdominal trauma.

In a double-blind, randomized study, 170 patients with traumatic perforation of the gastrointestinal tract were administered an advanced-generation cephalosporin. Patients were divided into infection risk groups (< or = 40%, low; 40% to 70%, mid; and > 70%, high) at surgical closure using a logistic regression formula based on four proved risk factors--age, blood replacement, ostomy, and the number of organs injured. Patients in the low group received 2 days of antibiotic therapy; those in the mid to high group received 5 days of antibiotic therapy. Those patients in the low to mid group had primary wound closure; those in the high group had their wounds packed open and closed later. Most of the patients (144 [85%]) were in the low group. Their major and minor infection rates (10% and 12%, respectively) were not significantly different from 145 historic control subjects receiving 5 days of antibiotic therapy (9% major; 14% minor). Patients in the mid to high group showed a greater incidence of major infections (46%) but a similar incidence of minor infections (12%). The results indicate that risk factors can be used to identify low-risk patients who require only short-term antibiotic therapy and primary wound closure. The remaining patients are at greater risk for infection despite prolonged antibiotic therapy and delayed wound closure.

Lack of predictability of cefotetan in vitro susceptibility tests against cefotetan-resistant anaerobic bacteria in determining clinical and bacteriologic efficacies.

Interpretive criteria for cefotetan in vitro susceptibility testing appear to be clinically relevant when applied to aerobic bacteria. To determine whether the same was true for anaerobic bacteria, we conducted a retrospective analysis of intraabdominal, gynecologic, and skin and skin structure infections treated with cefotetan. Of the infections, 202 contained at least one anaerobe isolate. Of the 51 patients, 47 (92.9%) from whom one or more cefotetan-resistant anaerobes were isolated were clinically cured or showed improvement. Similarly, cefotetan was efficacious for 95.4% of the patients harboring only cefotetan-susceptible anaerobes. Favorable bacteriologic responses were observed in 94.1% and 97.4% of these patient groups, respectively. The data suggests that the therapeutic utility of cefotetan against anaerobic bacteria cannot be accurately predicted on the basis of in vitro susceptibility test results alone but may be explained by a variety of factors, as discussed in this report.

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.

A randomized prospective study to compare cefotetan with cefuroxime plus metronidazole as prophylaxis in elective colorectal surgery.

This study compares the efficacy of cefotetan with the combination of cefuroxime plus metronidazole as antibiotic prophylaxis in elective colorectal surgery when given over the first 24 h postoperatively. There was no significant difference in wound infection rates between the two groups (14.7% for cefotetan and 13.9% for cefuroxime plus metronidazole), or the rates of other infective complications. Adverse reactions occurred with equal frequency in both treatment groups and no serious side effects occurred. Cefotetan is a safe and effective antibiotic for use as prophylaxis in elective colorectal surgery. Its advantages are that it is a single agent with a spectrum covering both aerobic Gram-negative rods and anaerobic organisms and, because of its long half-life, needs only to be given at 12-hourly intervals.