Etiology of cervicitis and treatment with minocycline.

OBJECTIVE: To evaluate the etiology of cervicitis using the recommended Canadian definition, and to evaluate the efficacy and tolerability of seven days of minocycline treatment, 100 versus 200 mg at bedtime. DESIGN: Randomized double-blind study with initial microbiological evaluation, and intended follow-up through 12 weeks. SETTING: Women attending the major sexually transmitted disease clinic in Vancouver and the major teaching hospital in Winnipeg. POPULATION STUDIED: Women with cervicitis (inclusion criteria were an off-white or yellow colour of cervical mucus when viewed on a white-tipped swab, and a mean of 10 or more polymorphonuclear leukocytes per oil immersion [× 1000] field on Gram stain of cervical mucus). Fourty-four women were enrolled but two were excluded because of contaminated cultures. INTERVENTIONS: Treatment with two identical appearing capsules of 50 mg (100 mg dose) or 100 mg (200 mg dose) of minocycline taken at bedtime with water for seven days. MAIN RESULTS: Of the 42 evaluable women, Chlamydia trachomatis was initially isolated from 19 (45%) and Neisseria gonorrhoeae from four (10%). The study was prematurely terminated because of an unacceptable and significantly higher frequency of adverse reactions on the higher dose regimen of minocycline - severe reactions in one (4%) on 100 mg compared with six (30%) on 200 mg (P=0.05). Major reactions were dizziness, mood alterations and nausea. Clinical parameters, but not numbers of polymorphonuclear leukocytes, improved significantly irrespective of initial microbiology or the regimen received. Cultures became and stayed negative for C trachomatis in seven of eight on minocycline 100 mg and five of six on minocycline 200 mg. Both 'failures' had an intervening negative culture and were re-exposed to untreated sexual partners. CONCLUSIONS: Although not a definitive study in terms of proving efficacy of lower dose regimens, the results are consistent with efficacy and demonstrate the significant advantage of the lower dose regimen in terms of adverse reactions.

Randomized, double-blind comparison of the efficacies, costs, and vaginal flora alterations with single-dose ceftriaxone and multidose cefazolin prophylaxis in vaginal hysterectomy.

A comparison of efficacies, costs, and effects on vaginal microflora of one preoperative and three postoperative 1-g doses of cefazolin versus those of one preoperative 1-g dose of ceftriaxone was done with 65 and 73 women, respectively, undergoing elective vaginal hysterectomy. Patient infection rates were not statistically different between the cefazolin group (six events in 6 of 73 patients [8.2%]) and the ceftriaxone group (11 events in 9 of 65 patients [13.8%]). Side effects, including diarrhea, were minimal and similar between the two groups. Significant shifts in the cervicovaginal microflora of the patients occurred postoperatively, with a marked increase in enterococci and a drop in nonenterococcal streptococci. No shifts among aerobic, facultative gram-negative rods and staphylococci were observed. Among the anaerobes, a significant decrease in the number of patients harboring nonsporulating, gram-positive rods and a less striking concomitant increase in Bacteriodes species and members of the family Peptococcaceae were noted. No qualitative differences were noted between the two groups that received prophylactic therapy. Aside from enterococci, cefazolin or ceftriaxone resistance among vaginal isolates (greater than or equal to 10(3)/ml) was minimal. Selection of resistant isolates was not different between the treatment groups. We could not detect a difference between a single 1-g dose of ceftriaxone and multidose cefazolin for infection prophylaxis in patients undergoing a vaginal hysterectomy. However, the total acquisition, preparation, and administration costs were greater for the ceftriaxone regimen than they were for the cefazolin regimen. Cefazolin should therefore remain the drug of choice for infection prophylaxis in uncomplicated vaginal hysterectomies.

Screening for Chlamydia trachomatis infection in a pregnancy counseling clinic.

Five hundred twenty asymptomatic women attending a pregnancy counseling clinic were interviewed and screened for cervical Chlamydia trachomatis infection before therapeutic abortion. Overall, 56 (10.8%) women were culture positive for C. trachomatis. Restricting testing to women with risk factors for infection or who had cervical leukocytosis on Gram staining of cervical mucus, or who were seropositive for C. trachomatis antibodies proved impractical because of insensitivity or nonspecificity. We evaluated three chlamydia diagnostic tests to determine which test had the best performance characteristics. In comparison with culture, the direct fluorescent antigen test had a sensitivity of 89% and a positive predictive value of 78%, whereas the enzyme immunoassay had 96% and 69%, respectively. When analysis was redone with any two positive laboratory tests to define true infection status, the performance parameters of enzyme immunoassay were sensitivity 98%, specificity 98%, and positive predictive value 87%. We conclude that all women undergoing therapeutic abortion require testing for C. trachomatis infection and that enzyme immunoassay is the most effective and practical test in this group of women.

PIP: In approximately 10% of women, therapeutic abortion is the precipitating factor for acute salpingitis, and 0.5-2% of women develop acute salpingitis after the procedure. A major cause of acute salpingitis in this situation is Chlamydia trachomatis infection, with studies having found 20-34% of C. trachomatis-infected women to develop postoperative infections of the upper genital tract. The detection and treatment of chlamydial infection in such a context are therefore of significant importance. C. trachomatis infections are best detected through the isolation and identification of the organism in cell culture. Culture methodology, however, is labor intensive and the organism may not survive transportation to the laboratory because of difficulties in maintaining a suitable cold chain. Two techniques are commercially available for the nonculture detection of C. trachomatis. This paper reports findings from the clinical valuation of their performance. 520 asymptomatic women attending a pregnancy counseling clinic were interviewed and screened for cervical C. trachomatis infection before therapeutic abortion. 56 were culture positive for C. trachomatis. In comparison with culture, the direct fluorescent antigen test had a sensitivity of 89% and a positive predictive value of 78%, while the enzyme immunoassay had respective values of 96% and 69%. When analysis was reconducted with any two positive laboratory tests to define true infection status, the performance parameters of enzyme immunoassay were sensitivity 98%, specificity 98%, and positive predictive value 87%. The authors believe that all women undergoing therapeutic abortion should be tested for C. trachomatis infection and that enzyme immunoassay is the most effective and practical test for that group of women.

Etiology and outcome of acute pelvic inflammatory disease.

We studied 71 women with the clinical diagnosis of acute pelvic inflammatory disease (PID) by laparoscopy and comprehensive microbiology in order to define the major etiologic determinants of poor fertility prognosis after tubal infection. Fifty women were found to have acute PID. Of the 50 women, 23 were pregnancy seeking and had a subsequent evaluation to determine fertility outcome. Seven of 13 women with non-gonococcal infection had an adverse reproductive outcome, compared with none of 10 women with gonococcal infection (P = .007). Two groups of causes for adverse reproductive outcome were found. Of the seven infertile women, four had initial tubal abscess, and three had evidence of Chlamydia trachomatis infection. This study directly documents the poor fertility prognosis for women with tubal abscess and suggests that women with culture and/or serological evidence of chlamydial infection also have a poor fertility prognosis.

Chlamydia trachomatis infection in women with ectopic pregnancy.

Fifty women with ectopic pregnancy and 49 control women with intrauterine pregnancy were interviewed and evaluated for evidence of Chlamydia trachomatis infection. Among women with ectopic pregnancy, 14 women were wearing an intrauterine contraceptive device or had a tubal ligation (group A), and 36 women had no readily identifiable risk factors (group B). Group B women had greater total numbers of sexual partners than did control women with intrauterine pregnancy (P less than .005). Group B women more often had C trachomatis antibody than group A (P = .03) and control women (P = .002). Of 27 C trachomatis cultures from fallopian tube tissue from women with ectopic pregnancy, none were positive. Fallopian tube tissue distant from the site of ectopic implantation was available for histopathology of 41 cases. Nine (22%) had extensive subepithelial plasma cell infiltration. All nine were among group B women (P = .06) and all seven with plasma cell salpingitis who were tested for C trachomatis antibody were seropositive (P = .004). It is concluded that a subset of women with ectopic pregnancy were at increased risk for acquiring a sexually transmitted disease by virtue of their sexual behavior and that women in this subset frequently have serologic evidence of C trachomatis infection and histologic evidence of plasma cell salpingitis. Because few of these women recall having had pelvic infection, the authors speculate that subclinical C trachomatis tubal infection producing plasma cell salpingitis may commonly underly ectopic pregnancy.

Chlamydia trachomatis: its role in tubal infertility.

We compared the prevalence of antibody to Chlamydia trachomatis among 88 women undergoing an evaluation for infertility and 49 women attending an antenatal clinic. Demographic data regarding sexual behavior were also collected. Eighteen women had tubal infertility and 70 had infertility due to a variety of other reasons. In comparison with women who had other causes for infertility, women with tubal infertility began coitus sooner (17.7 +/- 2.2 years vs. 19.5 +/- 3.4 years, P less than .05) and had more lifetime sex partners (4.5 vs. 1.33, P less than .001). Women with tubal infertility had a higher prevalence of antibody to C. trachomatis (13 of 18) than did women with nontubal causes for infertility (6 of 70, P less than .0001) or pregnant women (11 of 49, P = .0003). This high prevalence of antibody to C. trachomatis among women with tubal infertility was independent of sexual experience. By immunoblot analysis, an antigen of approximately 57,000 Da was immunodominant in 11 of 13 seropositive subjects with tubal infertility vs. 2 of 6 seropositive subjects with nontubal infertility (P = .046) and 1 of 11 seropositive pregnant women (P = .0003). Thus, women with tubal infertility frequently have serological evidence of prior infection with C. trachomatis and have a distinctive antigen-specific humoral immune response. These results further support the etiologic role of infection with C. trachomatis in tubal infertility.

Cefotaxime, cefazolin, or ampicillin prophylaxis of febrile morbidity in emergency cesarean sections.

Cefotaxime, a new third-generation cephalosporin, was compared with ampicillin and cefazolin in a randomized double-blind trial to evaluate the efficacy of antibiotic prophylaxis of febrile morbidity associated with emergency cesarean sections. A 1-gm intravenous dose of one of the three antibiotics was given by bolus injection immediately after clamping of the umbilical cord and six and 12 hours later. All patients were in labor with membranes ruptured and had a temperature less than or equal to 37.8 C, and none had a history of penicillin or cephalosporin allergy. A total of 195 women were entered into the trial. Initially, the study included a placebo control group which was switched to ampicillin after 30 patients. Of the 188 evaluable patients, 51 of 59 (86.5%) ampicillin recipients, 59 of 67 (88.1%) cefazolin recipients, 48 of 55 (87.3%) cefotaxime recipients, and two of seven (28.5%) placebo recipients had uneventful postoperative courses. During the study, an additional 39 women who were in labor with ruptured membranes but who were allergic to penicillin or who declined antibiotic prophylaxis were classified as untreated patients and observed for postoperative complications. Standard febrile morbidity, primarily related to endometritis or wound infections, occurred in 6 of 59 (10.1%) ampicillin, 5 of 67 (7.5%) cefazolin, 5 of 55 (9.1%) cefotaxime, and 18 (40.0%) of placebo or untreated patients. Cefotaxime, cefazolin, and ampicillin were equally effective in reducing febrile morbidity in emergency cesarean sections.