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.

Prophylactic antibiotics for suction curettage in incomplete abortion.

OBJECTIVE: The purpose of this study was to investigate the efficacy of 200 mg of prophylactic doxycycline in preventing pelvic infection after curettage for spontaneous (incomplete) abortion. METHODS: A randomized, prospective, double-blinded study was carried out involving 300 women with an incomplete abortion who were given either placebo or 200 mg of doxycycline orally 30-60 min prior to curettage. A hematocrit, WBC count, pregnancy test, syphilis serology, Neisseria gonorrhoeae culture, and Micro Trak (monoclonal antibody test, Syba, San Jose, CA) for Chlamydia trachomatis were performed. The patients were scheduled for follow-up 2 weeks later. Antibiotic administration for any reason as well as the postoperative infection rate in these women was assessed. RESULTS: Eleven women were excluded from analysis, leaving 289 evaluable. N. gonorrhoeae was isolated from 6 (2%) women and C. trachomatis from 8 (3%) women, and the syphilis serology was serofast in 4 (1%) women. Endometritis complicated the procedure in 4 women who received placebo and in 1 woman who received doxycycline (P = 0.22). CONCLUSION: Prophylactic doxycycline is not effective in preventing pelvic infection after curettage for spontaneous (incomplete) abortion.

Inpatient treatment for uncomplicated and complicated acute pelvic inflammatory disease: ampicillin/sulbactam vs. Cefoxitin.

OBJECTIVE: Ampicillin plus sulbactam, an irreversible beta-lactamase inhibitor, was compared to cefoxitin in the treatment of women with acute pelvic inflammatory disease (PID) with and without inflammatory mass(es). METHODS: Participation in an open, prospective, randomized clinical trial was offered to all women given the clinical diagnosis of acute PID who required inpatient therapy. Neisseria gonorrhoeae and Chlamydia trachomatis were sought in cervical and endometrial samples and aerobic and anaerobic species were sought in endometrial samples prior to treatment initiation. Treatment was given on at least 4 days and until women were afebrile for at least 48 h. Daily examinations were performed to assess response to therapy and safety. Only women in whom C. trachomatis was identified were discharged from the hospital on oral doxycycline to be taken for 10-14 days. RESULTS: One hundred twenty-four women were evaluated for safety; 117 (94%) were evaluated for efficacy. Demographic characteristics were similar for women in each treatment group. N. gonorrhoeae was recovered from 59% and C. trachomatis was recovered from 42% of study subjects. Inflammatory masses were identified in 35/76 (46%) women given ampicillin/sulbactam and 17/41 (41%) women given cefoxitin. Ampicillin/sulbactam cured 75 ,of 76 women (98.7%) [95% confidence interval (CI) 92.9-100.0%] and cefoxitin cured 37 of,41,omen (90.2%) (95% CI 76.9-97.3%) in that treatment regimen. CONCLUSIONS: Overall ampicillin/sulbactam was more effective (P = 0.05) than cefoxitin, due to superior efficacy in infection complicated by inflammatory mass(es).35/35 vs. 12/17 cured; P = 0.007).

A randomized trial of ofloxacin versus cefoxitin and doxycycline in the outpatient treatment of acute salpingitis.

The object of this randomized study was to compare the safety and efficacy of oral ofloxacin, 400 mg twice daily for 10 days, versus intramuscular cefoxitin, 2 gm, plus oral probenecid, 1 gm, followed by oral doxycycline, 100 mg twice daily for 10 days, in the outpatient treatment of uncomplicated acute salpingitis. Thirty-eight women (53%) had Neisseria gonorrhoeae from their pretreatment endocervical or endometrial cultures, and 18 had Chlamydia trachomatis (25%). Thirty-five of 37 women (95%) treated with the ofloxacin regimen were clinically cured, and 34 of 35 (97%) were cured with the cefoxitin-doxycycline regimen (p = 0.52). One clinical failure occurred in each group with N. gonorrhoeae infection, and one failure occurred in the ofloxacin group because of side effects. The bacteriologic response for N. gonorrhoeae in both groups was 100%. The eradication of C. trachomatis was 100% (10/10) for the cefoxitin/doxycycline group and 86% (6/7) for ofloxacin. The side effects were similar in both groups of subjects. In this study both regimens were effective for the outpatient treatment of uncomplicated acute salpingitis.

Cefazolin for hysterectomy prophylaxis.

Efficacy data for single-dose cefazolin prophylaxis at hysterectomy are meager, and there are none evaluating the impact of route of administration on efficacy. For these reasons, 772 women undergoing elective abdominal or vaginal hysterectomy for benign diseases were given 1 g cefazolin either intramuscularly or intravenously in a randomized clinical trial. Preoperative diagnoses and clinical, surgical, and outcome variables were similar by route of administration for each surgical approach. Risk factors for infection after abdominal hysterectomy included younger age, lower postoperative hemoglobin concentration, and pelvic hematoma; women who developed infection after vaginal hysterectomy were heavier than those who remained uninfected and were more likely to have a pelvic hematoma. The overall incidence of major operative site infection requiring parenteral antimicrobial therapy in evaluable women was 7.2%: 7.6% for 539 women undergoing abdominal hysterectomy and 6.3% for 207 women undergoing vaginal hysterectomy. Postoperative infection was unrelated to route of cefazolin administration.

Single-agent therapy for acute pelvic inflammatory disease: sulbactam/ampicillin versus cefoxitin.

A total of 54 women with acute salpingitis were treated intravenously with ampicillin/sulbactam or cefoxitin in a prospective, randomized, ongoing study. Of the organisms isolated, Gram-negative species (excluding Neisseria gonorrhoeae) were considerably more likely to produce beta-lactamase than were Gram-positive species. Clinical efficacy was 94% for 2 g ampicillin plus 1 g sulbactam and 89% for 2 g cefoxitin, all given intravenously every 6 h. The addition of sulbactam, an irreversible beta-lactamase inhibitor, to ampicillin restored both the microbiological and clinical activities of ampicillin. Both regimens were equally safe and demonstrated good efficacy in the treatment of the acute, symptomatic phase of infection.

Endometrial bacteria in asymptomatic, nonpregnant women.

The existence of normal lower reproductive tract flora has been recognized for many years. A study was conducted to identify the possible existence of upper reproductive tract (endometrial) bacteria in asymptomatic women with no history of previous pelvic infection and a normal pelvic examination. Bacteria were recovered from the endometria of 55 women with a double-lumen-catheter-protected brush; six cultures were sterile. Two hundred thirty-one bacterial species were present in 54 endocervical cultures. Type of contraception and phase of the menstrual cycle had no significant effect on the bacterial species recovered. Although contamination by cervical bacteria was possible, there was evidence of separate endometrial flora.

Preventing major operative site infection after radical abdominal hysterectomy and pelvic lymphadenectomy.

Twenty-one women who underwent radical abdominal hysterectomy and pelvic lymphadenectomy were enrolled in a prospective, comparative, randomized, placebo-controlled clinical trial of antimicrobial prophylaxis. Preoperative endocervical flora was identified and was similar in pre- and postmenopausal private and clinic service women; 46% of the 119 preoperative isolates produced beta-lactamase enzyme. Women were given three doses of either placebo or cefoperazone plus sulbactam, an irreversible beta-lactamase enzyme inhibitor. Three women (27%) given placebo developed abdominal incision infections; one women given placebo also developed a pelvic infection. None given antibiotic developed operative site infection, but one women developed a drain site infection. A major operative site infection rate of 27% observed with placebo is high enough to warrant prophylaxis. Although antimicrobial prophylaxis at radical hysterectomy and pelvic lymphadenectomy eradicted operative site infection in our patient populations, a literature review indicates that individual determination of a requirement for prophylaxis is necessary.

Single-dose piperacillin versus triple-dose cefoxitin prophylaxis at vaginal and abdominal hysterectomy.

Two hundred fourteen women having vaginal or abdominal hysterectomy were entered into a prospective, randomized, blind clinical trial comparing a preoperative intravenous dose of piperacillin to three perioperative intravenous doses of cefoxitin given over an eight-hour period. Interregimen clinical, surgical, and outcome variables of the 207 evaluable subjects were statistically similar, but there were significant interprocedure differences in a variety of categories; many benefits exist when vaginal hysterectomy is possible. Efficacy of a single dose of piperacillin was similar to that of three cefoxitin doses. Seven women (3.4%) had major postoperative infection requiring parenteral antimicrobial therapy, two (1.9%) after vaginal hysterectomy and five (4.8%) after abdominal hysterectomy. Three of the latter five infections (60%) occurred after discharge from the hospital. Even with prophylaxis, postoperative anemia was associated with increased frequency of infection at the operative site after both procedures, and diabetes was associated with late infection of the abdominal incision after abdominal hysterectomy.

Single-dose antimicrobial prophylaxis at abdominal hysterectomy. Cefamandole vs. cefotaxime.

Two hundred twenty-three women were given a single, 1-g, intravenous dose of cefamandole or cefotaxime at elective abdominal hysterectomy in a multicenter, prospective, randomized, blind clinical trial of efficacy and safety. The demographic, surgical, efficacy and safety variables were statistically similar. Prior to discharge from the hospital, 12 women (5.3%) developed major postoperative pelvic infections that required parenteral antimicrobial therapy; no wound infections occurred. There was no correlation between a depressed antimicrobial development of significant postoperative infection. An expanded spectrum of antibacterial activity and a longer serum half-life did not improve clinical efficacy, and single-dose intravenous cephalosporin prophylaxis before abdominal hysterectomy was associated with a low incidence of pelvic infection.

Alterations in lower reproductive tract flora after single-dose piperacillin and triple-dose cefoxitin at vaginal and abdominal hysterectomy.

There are no current data regarding the effect of a newer, broad-spectrum penicillin on lower reproductive flora at hysterectomy. To identify any existing differential effect on species and their susceptibilities, we obtained pre- and postoperative lower reproductive tract culture material from 209 women who were given single-dose piperacillin, then placebo or triple-dose cefoxitin, intravenously for prophylaxis at vaginal and abdominal hysterectomy in a prospective, randomized, blinded clinical trial. Significantly more preoperative endocervical bacteria were susceptible to piperacillin. Piperacillin caused less alteration in the numbers of lower reproductive tract flora when preoperative species were compared with postoperative species. More resistance to cefoxitin was identified postoperatively in bacteria recovered from the vaginal cuff of women who remained uninfected.

Upper and lower reproductive tract bacteria in 126 women with acute pelvic inflammatory disease. Microbial susceptibility and clinical response to four therapeutic regimens.

To more clearly understand the microbiology of acute salpingitis in our patients and to evaluate the clinical efficacy and safety of recommended and new therapeutic regimens, 126 women who met clinical diagnostic criteria for acute community-acquired pelvic inflammatory disease underwent endocervical and endometrial cultures prior to random intravenous therapy with cefoxitin plus doxycycline, ceftizoxime plus doxycycline or ceftizoxime alone (two regimens). Nine women (7%) had Chlamydia, and 70 (56%) had gonococci in endometrial specimens (P less than .001). Only two women (3.4%) given monotherapy required altered medical therapy, and none required surgery. Parenteral combination therapy was associated more frequently with adverse clinical and laboratory events.

Sulbactam/ampicillin versus cefoxitin for uncomplicated and complicated acute pelvic inflammatory disease.

In this study, 17 women were treated for uncomplicated acute pelvic inflammatory disease requiring hospitalisation for therapy, and 5 women were treated for the same infection complicated by pelvic abscesses. Treatment regimens were sulbactam 1g plus ampicillin 2g (14 women) or cefoxitin 2g (8 women) given by intravenous infusion every 6 hours. On the third day of therapy, a rash developed in 1 woman who was being successfully treated for uncomplicated disease with sulbactam/ampicillin. The other 21 women were cured. No other adverse clinical reactions and no significant abnormal laboratory results were observed with either regimen. Bacteriological efficacy, 98% for sulbactam/ampicillin and 94% for cefoxitin, closely paralleled clinical efficacy. Sulbactam, a suicide-type beta-lactamase inhibitor, appears to have restored and expanded the antibacterial activity of ampicillin.

Piperacillin and a combination of clindamycin and gentamicin for the treatment of hospital and community acquired acute pelvic infections including pelvic abscess.

Therapy for acute polymicrobial pelvic infections is empiric and must include predictable anaerobic coverage. Single agent therapy, if effective, is advantageous for the patient, nurses, pharmacy and hospital. Piperacillin sodium was compared with a combination of clindamycin and gentamicin as therapy for 63 female patients who were hospitalized with acute pelvic infections including pelvic abscess complicating community acquired salpingitis. Over-all clinical efficacy with piperacillin was 96.8 per cent and 90.3 per cent for clindamycin and gentamicin. Fewer bacteria demonstrated in vitro resistance to piperacillin (p = 0.008) and the cost of treatment for these infections was significantly less with piperacillin (p less than 0.05). Serious adverse reactions were not observed with either regimen. Piperacillin provides effective, cost-efficient therapy for women with acute polymicrobial pelvic infections.

Single-agent therapy for women with acute polymicrobial pelvic infections.

Pathogens that cause acute polymicrobial female pelvic infections usually do not differ from those that compose the normal flora of the lower reproductive tract. Accurate identification of these bacteria is difficult because cultures obtained via the lower tract can easily be contaminated. Although use of a double-lumen catheter-protected brush culture cannot completely eliminate the risk of contamination, it is the least invasive method for obtaining culture material from the upper reproductive tract. Compounding the problem of accurately identifying pathogens that cause acute upper tract infections is the fact that bacteria appear to be present in the upper tracts of asymptomatic women with normal examinations. Because of these problems and because of the polymicrobial nature of these infections, empiric therapy frequently includes more than one antimicrobial agent. Newer, semisynthetic penicillins and cephalosporins have expanded spectrums of in vitro activity against most of the bacteria frequently recovered from pelvic infection sites. Comparative clinical trials have shown these agents to be as effective when used alone as is combination therapy. With few exceptions, empiric monotherapy with one of these newer antimicrobials will be curative for women with acute upper tract infection, will have less potential toxicity, will require less space, materials, and manpower to administer, and will be less expensive.

Single-dose prophylaxis for vaginal and abdominal hysterectomy.

The practice of administering perioperative antimicrobials to uninfected patients undergoing elective surgical procedures has been subjected to careful prospective investigative scrutiny during the past two decades. A wound classification system was developed, helping to identify procedures for which prophylaxis did not provide benefit to the patient. Guidelines for prophylaxis in hysterectomy were proposed and risk factors were sought. Pharmacokinetics and spectrum of antibacterial activity, although variables of paramount importance in predicting success in the treatment of established infections, were discovered to have questionable impact on prophylactic efficacy. Duration of antimicrobial administration has gradually diminished from the total length of hospital stay to a single preoperative dose without increased risk of infection; efficacy may be related to route of administration. The wisdom of using newer agents for prophylaxis is addressed and questioned.

Single-dose cephalosporin for prevention of major pelvic infection after vaginal hysterectomy: cefazolin versus cefoxitin versus cefotaxime.

Antimicrobial overutilization accelerates the development of bacterial resistance. A prospective, randomized, blinded clinical trial of vaginal hysterectomy prophylaxis was designed to compare the efficacy, safety, and costs of cefazolin with those of cefoxitin and cefotaxime. Sixteen women (7.5%) developed febrile morbidity only, 10 (4.7%) developed major pelvic infection requiring parenteral antimicrobial therapy, and neither clinical nor laboratory adverse reactions of significance were observed. Anemia, diabetes, and additional surgical procedures were associated with a significantly increased incidence of postoperative infection; no regimen was more protective for women with or without these risk factors. Infections almost doubled hospital stay and the charges for health care. Diagnosis-related group reimbursement would have been more than $1,300 less than the mean hospital charge for women who developed infection. Utilizing cefazolin for prophylaxis and reserving cefoxitin and cefotaxime for therapy is cost and antimicrobial efficient.

Doxycycline and cefamandole prophylaxis for premenopausal women undergoing vaginal hysterectomy.

Fifty-one premenopausal women were given perioperative intravenous antimicrobial prophylaxis at vaginal hysterectomy in a prospective, blinded comparative study. Febrile morbidity developed in 14 women (27.4 per cent), but only nine (17.6 per cent) required antimicrobial treatment. The incidence of postoperative pelvic infection was 19.2 per cent for 26 women given 200 milligrams of doxycycline preoperatively and 16 per cent for 25 women given 5 grams of cefamandole in four doses over a period of 18 hours. Infections were polymicrobial, usually occurred during the initial hospitalization and significantly prolonged hospital stay (p less than 0.01). No variables were identified that allowed prediction of infection. A single dosage of doxycycline was as effective at preventing posthysterectomy pelvic infection as were multiple dosages of cefamandole.

Ceftriaxone and cefazolin prophylaxis for hysterectomy.

Two hundred and twenty-five women scheduled for elective hysterectomy were entered into a prospective, comparative, randomized, double-blind clinical trial of antibiotic prophylaxis; 117 had vaginal hysterectomy and 108 had abdominal hysterectomy. They were given a 1 gram preoperative dose of ceftriaxone, an investigational cephalosporin or three 1 gram parenteral doses of cefazolin over a 16 hour period. Antibiotic concentrations were measured in serum and vagina, myometrium, fallopian tube or ovary and mean ceftriaxone concentrations were consistently higher than those of cefazolin. Both regimens were safe, well tolerated and equally effective at preventing major postoperative infection. Diabetes increased the risk for infection regardless of regimen and surgical approach (p = 0.009) and specific risk factors were identified for women undergoing vaginal hysterectomy. The incidence of infection was 1.7 per cent after vaginal hysterectomy, significantly lower than the 7.4 per cent observed after abdominal hysterectomy (p = 0.039). Several of the clinical and surgical variables were identified that could explain this difference.

Preoperative cefoxitin prophylaxis for elective abdominal hysterectomy.

Fifty women were randomly given one, two, or three 2 gm parenteral doses of cefoxitin with placebo blinding perioperatively at abdominal hysterectomy. A single preoperative intramuscular dose was more efficient, less frequently associated with the development of bacterial resistance, and less expensive than two or three doses.