Plasma cell endometritis in women with symptomatic bacterial vaginosis.

OBJECTIVE: To evaluate the endometrial microbiology and histopathology in women with symptomatic bacterial vaginosis but no signs or symptoms of upper genital tract disease or other vaginal or cervical infections. METHODS: Endometrial biopsies were performed on 41 women complaining of vaginal discharge or pelvic pain at a sexually transmitted disease clinic. These women had neither culture nor serologic evidence of Neisseria gonorrhoeae or Chlamydia trachomatis infection. Twenty-two women with bacterial vaginosis diagnosed by Gram stain examination of vaginal fluid, but with neither signs nor symptoms of upper genital tract infection, were compared with 19 women who had no evidence of bacterial vaginosis on vaginal fluid Gram stain. Endometrial biopsies were evaluated for histopathologic evidence of plasma cell endometritis and were cultured for N gonorrhoeae, C trachomatis, aerobic and anaerobic bacteria, Mycoplasma species, and Ureaplasma urealyticum. RESULTS: Ten of 22 women with bacterial vaginosis had plasma cell endometritis, compared with one of 19 controls (odds ratio [OR] 15, 95% confidence interval [CI] 2-686; P < .01). Bacterial vaginosis-associated organisms were cultured from the endometria of nine of 11 women with and eight of 30 women without plasma cell endometritis (OR 12.4, 95% CI 2-132; P = .002). CONCLUSION: Plasma cell endometritis was frequently present in women with bacterial vaginosis and without other vaginal or cervical infections. This suggests the possibility of an association between bacterial vaginosis and nonchlamydial, nongonococcal, upper genital tract infection.

Comparison of rapid tests for detection of group B streptococcal colonization.

Accurate rapid detection of maternal lower genital tract colonization with group B streptococci (GBS) in high-risk patients is essential for selective institution of intrapartum antibiotic treatment to reduce neonatal GBS infection. In this study, pure GBS isolates were used to evaluate five commercially available rapid tests in terms of speed, ease of use, and sensitivity. The products tested were Directigen, Equate, Bactigen, PathoDx, and Phadebact. Although each test could be performed relatively quickly, the ease of performance and level of sensitivity (10(5) to 10(8) CFU/ml) varied markedly. Quantitative cultures obtained from 17 known GBS carriers showed concentrations ranging from less than 10(2) to greater than 10(8) CFU/gm of vaginal material. Since only 40% of the women had greater than or equal to 10(5) CFU/gm of vaginal material, it appears that many colonized women would not be identified by these rapid tests.

Comparison of cefotetan plus doxycycline with cefoxitin plus doxycycline in the inpatient treatment of acute salpingitis.

Pelvic inflammatory disease (PID), one of the major sequelae of the current epidemic of sexually transmitted diseases, has been shown to be a polymicrobial infection. This study compares the efficacy and safety of two broad-spectrum combination drug regimens, cefotetan with doxycycline and cefoxitin with doxycycline, in the treatment of PID. A total of 108 patients with acute salpingitis were hospitalized and randomized into two treatment groups: cefotetan/doxycycline (N = 54) and cefoxitin/doxycycline (N = 54). Before antibiotic administration, Chlamydia trachomatis was identified in 17 (16%) of the patients, Neisseria gonorrhoeae from 72 (67%), and anaerobic and aerobic bacteria were identified from the endometrial cultures of 86 (80%). There were seven tubo-ovarian abscesses (TOAs) that were diagnosed in the cefotetan group, and six in the cefoxitin group. Clinical cure was achieved in 51 of 54 (94%) patients in each group. Of the six patients whose treatment failed, all had positive cultures for N. gonorrhoeae and facultative/anaerobic bacteria, whereas none had C. trachomatis. Two patients from each study arm whose treatment failed were diagnosed with TOAs and responded subsequently to clindamycin plus an aminoglycoside. Cultures that were obtained after the completion of inpatient treatment showed the eradication of C. trachomatis and N. gonorrhoeae in all patients. Also, both regimens were effective in reducing aerobic and anaerobic pathogens. Finally, both regimens were well tolerated, with few side-effects.

Combination antimicrobial therapy in the treatment of acute pelvic inflammatory disease.

We compared the clinical and microbiologic efficacy of two broad-spectrum combination antimicrobial regimens in the treatment of 148 patients with acute pelvic inflammatory disease. Patients were randomized to inpatient treatment with either cefoxitin and doxycycline (n = 75) or clindamycin and tobramycin (n = 73). These antibiotics were administered intravenously for at least 4 days, and up to 48 hours beyond defervescence. Patients were discharged on a regimen of oral doxycycline or clindamycin in accordance with the intravenous regimen to complete a total duration of therapy of 2 weeks. Neisseria gonorrhoeae (53%) and Chlamydia trachomatis (31%) were the microorganisms that were isolated most frequently from the genital tract of enrolled patients. At follow-up, N. gonorrhoeae was isolated in two patients, and C. trachomatis was isolated in none. The overall initial favorable response rate to combination antimicrobial therapy was 98.5% (130/132) in patients with uncomplicated pelvic inflammatory disease and 81% (13/16) in patients with pelvic inflammatory disease that was complicated by tuboovarian abscess. A greater than 70% decrease in abdominal tenderness score occurred in 89% of 111 patients within 6 weeks of hospital discharge. There were no significant differences between antibiotic treatment groups in any response categories or in toxicity. During the initial hospitalization, five patients (three with tuboovarian abscess; one with a pyosalpinx, and one with intractable acute and chronic pelvic inflammatory disease) required surgical intervention. These results support the recommendation to use broad-spectrum combination antimicrobial therapy for the treatment of acute pelvic inflammatory disease.

Efficacy of single-agent therapy for the treatment of acute pelvic inflammatory disease with ciprofloxacin.

A prospective, randomized, controlled, non-blind clinical trial was conducted to compare the efficacy of monotherapy with ciprofloxacin with that of a combination of clindamycin plus gentamicin in the treatment of patients with acute pelvic inflammatory disease. Pretreatment and post-treatment cervical culture specimens were obtained for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum. Pretreatment and post-treatment endometrial culture specimens were obtained for those organisms plus facultative and anaerobic bacteria. Minimal inhibitory concentrations were determined on all isolates by agar dilution. Clinical resolution of infection was seen in 31 of 33 (94 percent) ciprofloxacin-treated patients compared with 34 of 35 (97 percent) clindamycin/gentamicin-treated patients. N. gonorrhoeae was eradicated in all cases and C. trachomatis in 12 of 13 cases (92 percent). Ciprofloxacin appeared less effective than clindamycin/gentamicin in eradicating bacterial-vaginosis-associated organisms from post-treatment culture specimens obtained from the endometrium. Comparable clinical response was seen with both regimens. The significance of persistent bacterial-vaginosis-associated organisms following ciprofloxacin therapy is unclear. However, since one goal of treatment of pelvic inflammatory disease should be to eliminate organisms from the upper genital tract, ciprofloxacin may not provide optimal single-agent therapy for pelvic inflammatory disease.

Prophylaxis in caesarean section with cefmetazole and cefoxitin.

A prospective, randomized, open comparison of three 1 g doses of cefmetazole with three 2 g doses of cefoxitin for non-elective Caesarean section was performed. Sixty-nine patients were evaluated. The two groups were comparable with respect to labour characteristics that might influence risk of postoperative infectious morbidity. Similarly, the nature of the bacterial contamination/infection of the amniotic fluid at the time of Caesarean section was comparable in the two groups. The only infectious morbidity noted was endomyometritis. The incidence was the same in both groups, 5/50 (10%) in the cefmetazole group and 2/19 (10.5%) in the cefoxitin group. Febrile morbidity, as reflected in the fever index, was not significantly different between the groups, 10.2 +/- 18.5 degree hours in the cefmetazole group and 7.5 +/- 11.7 degree hours in the cefoxitin group. Cefmetazole appeared to be equivalent to cefoxitin in reducing post-Caesarean section endomyometritis.

Treatment of hospitalized patients with acute pelvic inflammatory disease: comparison of cefotetan plus doxycycline and cefoxitin plus doxycycline.

Acute pelvic inflammatory disease remains the major medical and economic consequence of sexually transmitted diseases among young women. The polymicrobial origins of pelvic inflammatory disease have been well documented and the major organisms recovered from the upper genital tract in patients with pelvic inflammatory disease include Chlamydia trachomatis, Neisseria gonorrhoeae, and mixed anaerobic and aerobic bacteria. This study was undertaken to compare the efficacy and safety of cefotetan plus doxycycline with that of cefoxitin plus doxycycline in the treatment of hospitalized patients with acute pelvic inflammatory disease. A total of 68 hospitalized patients with acute pelvic inflammatory disease were entered and randomized into two treatment groups: cefotetan (n = 32) and cefoxitin (n = 36). There were six tuboovarian abscesses in each group. C. trachomatis was recovered from 7 (10%) and N. gonorrhoeae from 48 (71%) of the patients. Anaerobic and aerobic bacteria were recovered from the upper genital tract in 53 (78%) of the patients. Cefotetan plus doxycycline and cefoxitin plus doxycycline demonstrated high rates of initial clinical response in the treatment of acute pelvic inflammatory disease. Clinical cure was noted in 30 (94%) of the cefotetan plus doxycycline group and 33 (92%) of the cefoxitin plus doxycycline group. Four failures were sonographically diagnosed tuboovarian abscesses that responded to clindamycin plus gentamicin therapy. The fifth failure was an uncomplicated case that did not respond to cefoxitin and doxycycline and required additional therapy. At 1 week and 3 weeks, respectively, the posttreatment cultures demonstrated eradication, in all instances, of N. gonorrhoeae and C. trachomatis. These regimens also were very effective in eradicating anaerobic and aerobic pathogens from the endometrial cavity. Both regimens were well tolerated by the patients, and few adverse drug affects were noted.

In vitro activity of cefmetazole, cefotetan, amoxicillin-clavulanic acid, and other antimicrobial agents against anaerobic bacteria from endometrial cultures of women with pelvic infections.

The MICs of the new antimicrobial agents cefmetazole, cefotetan, and amoxicillin-clauvulanic acid were compared with the MICs of other antimicrobial agents against anaerobic bacteria from endometrial cultures from women with pelvic inflammatory disease or endometritis. The activity of cefmetazole was similar to that of cefoxitin and generally greater than that of cefotetan. Amoxicillin-clavulanic acid was generally more active than all cephamycins tested.

Cesarean section prophylaxis: comparison of two doses with three doses of mezlocillin.

A prospective randomized double-blind comparison of two doses, with three doses of mezlocillin for nonelective cesarean section prophylaxis was performed. One hundred seven (107) patients were evaluated. Mezlocillin (4 g) was given post-cord clamping and then at 4-h intervals for a total of two doses or three doses. The incidence of febrile morbidity was lower in the three-dose group (2 of 46, 4%) than the two-dose group (14 of 61, 23%) (P less than 0.02). However, the incidence of infectious morbidity was not different between the three-dose group (3 of 46, 7%) and the two-dose group (10 of 61, 16%), and the incidence of endomyometritis was similar in the two groups (6.5% vs 9.8%). Among failures of prophylaxis there were no differences compared to successes in the number of potential commensals or potential pathogens cultured from amniotic fluid. However, the proportion of failures among patients with both commensals and potential pathogens isolated (10/58) was significantly greater than among patients with none or only commensals isolated (1/37) (P less than 0.03). We found mezlocillin to be an effective agent for perioperative cesarean section prophylaxis with two doses as effective as three doses. The presence of clinically important organisms in the amniotic fluid at the time of operation typified patients with postoperative infectious complications despite perioperative prophylaxis.

Ampicillin/sulbactam versus metronidazole-gentamicin in the treatment of soft tissue pelvic infections.

The clinical efficacy and safety of ampicillin/sulbactam versus metronidazole-gentamicin were evaluated in a comparative, randomized, prospective study. Forty-four patients were enrolled: 22 received the ampicillin/sulbactam regimen, and 22 received the metronidazole-gentamicin combination. There were 33 cases of severe acute pelvic inflammatory disease, two tuboovarian abscesses, five cases of endomyometritis, and two cases of posthysterectomy pelvic cellulitis. Aerobic and anaerobic cultures from the infection sites yielded 447 microorganisms from 44 patients (an average of 10 bacteria per infection; 6.4 anaerobes and 3.7 aerobes). The most frequent isolates were Bacteroides sp., 54; Bacteroides bivius, 17; black-pigmented Bacteroides, 12; Bacteroides disiens, 11; Fusobacterium, 13; Peptostreptococcus anaerobius, 24; Peptostreptococcus asaccharolyticus, 21; anaerobic gram-positive cocci, 34; Gardnerella vaginalis, 29; Neisseria gonorrhoeae, 17; alpha-hemolytic streptococci, 15; and Escherichia coli, five. Clinical cure was noted in 19 of 20 patients treated with ampicillin/sulbactam and 18 of 21 patients treated with metronidazole-gentamicin. One treatment failure occurred in the ampicillin/sulbactam group in a patient who required antichlamydial therapy and had a complex left adnexal mass consistent with an abscess. The cases of metronidazole-gentamicin failure included two patients initially diagnosed as having tuboovarian abscesses who required a change in antibiotic therapy to control the infections. The third patient had postabortion endomyometritis that did not respond to metronidazole-gentamicin therapy within 48 hours, and required a change of medication. No adverse hematologic, renal, or hepatic effects were noted in either group of patients.

Microflora of the urethra in adolescent boys: relationships to sexual activity and nongonococcal urethritis.

Urethral cultures were obtained from 90 adolescent youth, 16 of whom denied previous sexual activity. Among the sexually active boys was a group of 32 with clinically significant pyuria, consistent with the diagnosis of urethritis, on a first-part urinalysis (FPU) specimen. To relate differences in urethral microflora to sexual activity, 42 sexually active patients with a negative FPU were compared with the never sexually active group. The profile of anaerobic, but not aerobic, bacteria isolated from the urethra was related to the presence or absence of previous sexual activity. Mycoplasma species and Ureaplasma urealyticum were isolated from sexually active patients only, and may be markers of sexual activity in adolescent boys. Of the 32 patients with FPU evidence of urethritis, 22 (69%) had cultures positive for Chlamydia trachomatis, and an additional three (9%) had cultures positive for Neisseria gonorrhoeae. The findings in sexually active patients with a positive FPU were otherwise similar to those of sexually active patients without evidence of urethritis. C. trachomatis appears to be the most important agent of urethritis among adolescent boys with a positive FPU.

Occurrence of clindamycin-resistant anaerobic bacteria isolated from cultures taken following clindamycin therapy.

MICs of clindamycin were determined by the agar dilution method against anaerobic organisms isolated from endometrial cultures in women with pelvic soft tissue infections. Cultures were obtained from 100 women both before and after clindamycin therapy, from 107 women before therapy with clindamycin or another antimicrobial agent or after treatment with an antimicrobial agent other than clindamycin, and from 9 women 1 to 9 weeks after they were discharged from the hospital following clindamycin therapy. Only 5 (0.7%) of 685 isolates tested from women who had not received clindamycin therapy were resistant to clindamycin. From the 100 cultures taken immediately after clindamycin therapy, 57 anaerobic bacteria were isolated from 28 cultures. Of the 40 anaerobic organisms for which MICs of clindamycin were determined, 25 (62.5%) were resistant to clindamycin (MIC greater than or equal to 8 micrograms/ml). The most common organisms isolated after therapy were the anaerobic gram-positive cocci (of which 32 isolates were discovered); of 28 coccal isolates tested, 64% were clindamycin resistant. Four of seven (57%) of the Bacteroides isolates tested, one unidentified gram-positive nonsporing rod, one unidentified gram-negative coccus, and one Mobiluncus sp. were also clindamycin resistant. Of 18 anaerobic isolates from the nine cultures taken 1 to 9 weeks after hospital discharge, 55% were resistant to clindamycin. The clinical significance of these findings is unknown since all patients recovered without incident and remained well. However, the data suggest that physicians need to be aware that patients with recent exposure to clindamycin may have clindamycin-resistant anaerobic organisms in a current infection. This may prevent the infection from responding to clindamycin treatment.

Sulbactam/ampicillin versus metronidazole/gentamicin in the treatment of severe pelvic infections.

The clinical efficacy and safety of sulbactam/ampicillin versus metronidazole/gentamicin were compared in 39 patients with severe pelvic infections. 30 patients had severe acute pelvic inflammatory disease with peritonitis, 3 tubo-ovarian abscesses, 4 endomyometritis, and 2 posthysterectomy pelvic cellulitis. Aerobic and anaerobic cultures from the sites of infection yielded 259 micro-organisms from 38 patients; an average of 6.8 bacteria per infection (3.9 anaerobes and 2.9 aerobes). The most frequent isolates were Bacteroides spp. (21), B. bivius (13), B. disiens (8), Fusobacterium spp. (9), Peptostreptococcus anaerobius (15), P. asaccharolyticus (8), anaerobic Gram-positive cocci (17), Gardnerella vaginalis (24), Neisseria gonorrhoeae (14), alpha-haemolytic streptococci (6) and Escherichia coli (3). Clinical cure was noted in 19 of 20 patients treated with sulbactam/ampicillin and 16 of 19 treated with metronidazole/gentamicin. The sulbactam/ampicillin failure was a patient with pelvic inflammatory disease with a positive Chlamydia trachomatis culture who required antichlamydial therapy. The metronidazole/gentamicin failures included a patient with a tubo-ovarian abscess requiring surgical drainage and 2 patients with pelvic inflammatory disease requiring antichlamydial treatment. No adverse haematological, renal, or hepatic effects were noted with either regimen.

Microbiology of the lower genital tract in postmenarchal adolescent girls: differences by sexual activity, contraception, and presence of nonspecific vaginitis.

The prevalence of selected microorganisms in the lower genital tract in postmenarchal adolescent girls was assessed, including vaginal Gardnerella vaginalis, group B streptococcus, lactobacillus, Mycoplasma species, Ureaplasma urealyticum, Staphylococcus aureus, and yeast, and endocervical Mycoplasma species, U. urealyticum, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Specific attention was focused on important sexually transmitted disease organisms, and differences in isolations by age, sexual activity, ethnicity, contraception, and the diagnosis of nonspecific vaginitis were measured. Sexually active subjects had a mean of 6.05 organisms (SD = 3.16), compared with 3.12 organisms (SD = 3.92) in non-sexually active subjects (P = 0.001). Sexually active subjects had significantly more vaginal G. vaginalis, lactobacilli, Mycoplasma species, and U. urealyticum, as well as endocervical Mycoplasma species and U. urealyticum, compared with non-sexually active subjects; C. trachomatis, N. gonorrhoea, and T. vaginalis were isolated exclusively from the sexually active group. Significant differences in isolation rates by ethnicity were found in vaginal Mycoplasma species and U. urealyticum, and endocervical Mycoplasma species, U. urealyticum, C. trachomatis, N. gonorrhoeae, and T. vaginalis. In general, organisms were isolated from blacks most frequently; N. gonorrhoea was isolated from blacks exclusively. Differences were found in microbiologic isolations by the presence or absence of nonspecific vaginitis. Vaginal G. vaginalis and Mycoplasma species and endocervical Mycoplasma species and U. urealyticum were found significantly more often in isolates from the group with nonspecific vaginitis. It is important to define the microbial flora of the lower genital tract in adolescent girls in order to understand its role in the pathogenesis of acute salpingitis.

Moxalactam versus clindamycin plus tobramycin in the treatment of obstetric and gynecologic infections.

The clinical efficacy of moxalactam versus clindamycin/tobramycin was evaluated in a comparative, randomized, prospective study. Sixty patients were treated: 30 with moxalactam and 30 with clindamycin/tobramycin. There were 15 cases of tuboovarian abscess, 36 cases of severe pelvic inflammatory disease with peritonitis, eight cases of endomyometritis, and one wound abscess. Aerobic and anaerobic cultures from the sites of infection yielded 441 microorganisms from 53 patients; an average of 8.3 bacteria per infection (4.5 anaerobes and 3.8 aerobes). The infections tended to be mixed aerobic-anaerobic with anaerobes isolated in 90% of cases. The most frequently isolated possible pathogens were Bacteroides sp. (37), Bacteroides bivius (23), Bacteroides asaccharolyticus (12), Peptococcus asaccharolyticus (29), Peptostreptococcus anaerobius (19), unidentified anaerobic gram-positive cocci (18), Escherichia coli (17), nonhemolytic streptococci (16), Neisseria gonorrhoeae (13), and Gardnerella vaginalis (38). Clinical cure was noted in 29 of 30 moxalactam-treated and 29 of 30 clindamycin/tobramycin-treated patients. Moxalactam was effective in five of six cases of tuboovarian abscess, all 22 cases of pelvic inflammatory disease with peritonitis, the one case of endomyometritis and the one wound abscess. Clindamycin/tobramycin was effective in eight of nine cases of tuboovarian abscess, all 14 cases of pelvic inflammatory disease with peritonitis, and all seven cases of endomyometritis. No adverse hematologic, renal, or hepatic effects were noted with either regimen.

In vitro activity of cefbuperazone and other antimicrobial agents against isolates from the female genital tract.

Cefbuperazone (BMY 25182), a new cephamycin, showed activity similar to those of moxalactam and other cephalosporin-cephamycins against aerobic and anaerobic bacteria from female genital tract infections. MICs of the antimicrobial agents were less than or equal to 16 micrograms/ml for greater than 97% of organisms tested. All of the anaerobic bacteria tested were susceptible to clindamycin, metronidazole, and chloramphenicol.

Comparative study of piperacillin versus cefoxitin in the treatment of obstetric and gynecologic infections.

Piperacillin sodium (Pipracil, Lederle Laboratories, Wayne, New Jersey), a new semisynthetic penicillin, demonstrated in vitro activity against a broad spectrum of clinical pathogens. It is active against most strains of the clinically important gram-negative aerobic or facultative bacteria and against virtually all the clinically important anaerobic organisms, including Bacteroides fragilis and Bacteroides bivius. This broad antibacterial spectrum suggested that piperacillin might be an effective single antimicrobial agent for the treatment of mixed aerobic/anaerobic infections in obstetric and gynecologic patients. In this study, the clinical efficacy and safety of piperacillin was compared with that of cefoxitin in the management of pelvic infections. There were 23 patients in the piperacillin group (acute salpingitis, 12; endomyometritis, 7; pelvic cellulitis, 2; tuboovarian abscess, 2) and 25 patients in the cefoxitin group (acute salpingitis, 13; endomyometritis, 10; tuboovarian abscess, 2). An average of six bacteria were isolated from each patient. Aerobic bacteria only were recovered from 12.5%, anaerobic bacteria only in 6.5%, and both aerobic and anaerobic bacteria were present in 82.5% of patients. Overall, 21 of 23 (91%) of the piperacillin treatment group and 23 of 25 (92%) of the cefoxitin group responded to therapy with antimicrobial agents alone. The major cause of failure was the presence of an abscess. Piperacillin was shown to be an effective single agent for the management of pelvic infections caused by mixed aerobic and anaerobic bacteria. In addition, piperacillin proved to be safe and well tolerated.

In vitro activity of new beta-lactam antibiotics and other antimicrobial drugs against anaerobic isolates from obstetric and gynecological infections.

The in vitro activities of N-formimidoyl thienamycin, clindamycin, chloramphenicol, metronidazole, cefoperazone, cefotaxime, cefoxitin, moxalactam, penicillin G, and piperacillin were determined against 158 anaerobic bacteria isolated from endometrial wash cultures of women with pelvic infections. In general, N-formimidoyl thienamycin was the most active, with all organisms inhibited by less than or equal to 0.5 microgram/ml. Chloramphenicol, clindamycin, and metronidazole inhibited all organisms by less than or equal to 8 microgram/ml. The penicillins and cephalosporins exhibited variable activity of lesser degrees.

Effect of estrogen treatment on the genital tract flora of postmenopausal women.

The anaerobic and aerobic flora of the vagina was identified in 79 postmenopausal women, 33 of whom received estrogen replacement. Four anaerobic species were more prevalent among estrogen-treated women than among untreated women, whereas 2 anaerobic species were less prevalent in the treated group. The types of organisms isolated from both groups are similar and all organisms isolated were considered usual inhabitants of the genital tract.