Comparison of oral and vaginal metronidazole therapy for nonspecific bacterial vaginosis

A prospective, randomized, nonblind study was performed to compare the efficacy of a 7-day vaginal regimen with 500 mg metronidazole (Flagyl) once a day and that of oral treatment with 400 mg metronidazole twice daily for 7 days in the treatment of nonspecific bacterial vaginosis. No treatment was given to the sexual partners and there was no restriction of sexual intercourse. 38 women completed the study and at follow-up after 4 weeks, women receiving vaginal therapy had a cure rate of 79% compared with 74% in the women on oral therapy. Cure rates were lower among users of an intrauterine contraceptive device (57 versus 88% among nonusers). The occurrence of lactate-producing bacteria (lactobacilli and aerobic streptococci) in the vagina was significantly higher in women after vaginal compared with oral therapy. Gardnerella vaginalis was isolated in 58% of the women after vaginal and in 44% of the women after oral treatment. It is concluded that vaginal application of 500 mg metronidazole daily for 7 days is equally effective as oral administration in the treatment of bacterial vaginosis.     

Bacterial vaginosis: treatment with clindamycin cream versus oral metronidazole.

In a randomized, double-blind study, 48 women with symptomatic bacterial vaginosis were assigned to receive either 5 g of 2% clindamycin vaginal cream daily or 500 mg metronidazole oral tablets twice a day for 7 days. After completion of therapy, there was no significant difference in cure rates (clindamycin 72% versus metronidazole 87%). One month later, 61% of the patients in each group were still cured. Adverse reactions were mild in both groups. We conclude that clindamycin cream is a safe, well tolerated, and effective alternative to oral metronidazole for treatment of bacterial vaginosis.     

Efficacy and tolerance of metronidazole and miconazole nitrate in treatment of vaginitis.

OBJECTIVE: To evaluate the efficacy and tolerability of a vaginal pessary containing 750 mg of metronidazole and 200 mg of miconazole nitrate used daily for 7 days in the treatment of vaginitis. METHODS: Ninety-two women with vaginitis participated in this phase 3 study using one vaginal pessary daily for 7 days. Gynecological and microbiological evaluations were carried out prior to and following treatment. RESULTS: Reductions occurred in symptoms and signs of vaginitis. Clinical cure rate was 87.7%, while the cure rates according to microscopy and Candida albicans culture were 81.8% and 73.9%, respectively. The cure rate for bacterial vaginosis was 75% and culture of Gardnerella vaginalis turned negative in 63.6% of cases following treatment. The medication was well tolerated. CONCLUSION: Use of a combination of 750 mg of metronidazole and 200 mg of miconazole in a single daily application was found to be effective in the treatment of the most common causes of vaginitis.     

Therapeutic regimens for treating bacterial vaginosis in pregnant women

The study comprises 128 pregnant women examined at different gestational weeks. The diagnosis of bacterial vaginosis was made using: a) the complex clinical criteria--vaginal discharge, vaginal pH, amine test and "clue cells" b) Nugent scoring system c) Spiegel criteria. Two therapeutic regimens were compared--intravaginal 2% clindamycin creme (Dalacin V) 5 g three consecutive days and intravaginal metronidazole (Flagyl) 500 mg once daily for 5 consecutive days. Control examination was carried out 5-7 days after completion of therapy using the same protocol. 28 women from the first group and 31 women from the second group had the control examination. Bacterial vaginosis was eradicated in 93% of women using intravaginal clindamycin and in 87% of women using intravaginal metronidazole. Both regimes were more effective compared to treatment with oral ampicillin for 7 days, where the cure rate was 62%.     

Bacterial vaginosis and risk of pelvic inflammatory disease

BACKGROUND: Bacterial vaginosis commonly is found in women with pelvic inflammatory disease (PID), but it is unclear whether bacterial vaginosis leads to incident PID. METHODS: Women (n = 1,179) from 5 U.S. centers were evaluated for a median of 3 years. Every 6-12 months, vaginal swabs were obtained for gram stain and culture of microflora. A vaginal microflora gram stain score of 7-10 was categorized as bacterial vaginosis. Pelvic inflammatory disease was diagnosed by presence of either histologic endometritis or pelvic pain and tenderness plus one of the following: oral temperature greater than 38.3 degrees C; sedimentation rate greater than 15 mm/hour; white blood count greater than 10,000; or lower genital tract detection of leukorrhea, mucopus, or Neisseria gonorrhoeae or Chlamydia trachomatis. RESULTS: After adjustment for relevant demographic and lifestyle factors, baseline bacterial vaginosis was not associated with the development of PID (adjusted hazard ratio 0.89, 95% confidence interval 0.55-1.45). Carriage of bacterial vaginosis in the previous 6 months before a diagnosis (adjusted risk ratio 1.31, 95% confidence interval 0.71-2.42) also was not significantly associated with PID. Similarly, neither absence of hydrogen peroxide-producing Lactobacillus nor high levels of Gardnerella vaginalis significantly increased the risk of PID. Dense growth of pigmented, anaerobic gram-negative rods in the 6 months before diagnosis did significantly increase a woman's risk of PID (P =.04). One subgroup of women, women with 2 or more recent sexual partners, demonstrated associations among bacterial vaginosis, Gardnerella vaginalis, anaerobic gram-negative rods, and PID. CONCLUSION: In this cohort of high-risk women, after adjustment for confounding factors, we found no overall increased risk of developing incident PID among women with bacterial vaginosis. LEVEL OF EVIDENCE: II-2     

Impact of metronidazole therapy on preterm birth in women with bacterial vaginosis flora (Gardnerella vaginalis): a randomised, placebo controlled trial

Objective To ascertain whether metronidazole treatment of women with a heavy growth of Gardnerella vaginalis during mid-pregnancy would reduce the risk of spontaneous preterm birth.
Design A multicentre, randomised, placebo-controlled trial
Setting Four metropolitan hospitals.
Participants Eight hundred and seventy-nine singleton women with a heavy growth of G. vaginalis or Gram stain indicative of bacterial vaginosis at 19 weeks of gestation.
Interventions Oral metronidazole (400 mg) or placebo twice daily for two days at 24 weeks of gestation, and at 29 weeks if G. vaginalis found in test-of-cure swab four weeks after treatment.
Main outcome measures Spontaneous preterm birth less than 37 weeks.
Results Intention-to-treat analysis showed no difference between metronidazole and placebo groups in overall preterm birth (31/429 [7.2%] vs 32/428 [7.5%]) or spontaneous preterm birth (20/429 [4.7%] vs 24/428 [5.6%]). Among the 480 women with bacterial vaginosis, treatment had no effect on spontaneous preterm birth (11/242 [4.5%] vs 15/238 [6.3%]). In the subset of 46 women with a previous preterm birth, women in the metronidazole group showed a significant reduction in spontaneous preterm birth (2/22 [9.1%] vs 10/24 [41.7%], OR 0.14, 95%CI 0.01–0.84). A treatment effect was also found in compliant women with a previous preterm birth and bacterial vaginosis (0/14 [0%] vs 6/17 [35.3%], OR 0.0,95%CI 0.0–0.94).
Conclusion Metronidazole treatment of women with a heavy growth of G. vaginalis or bacterial vaginosis did not reduce the preterm birth rate. Among women with a previous preterm birth, treatment reduced the risk of spontaneous preterm birth. Further studies are required to confirm these findings.     

Clindamycin versus metronidazole in the treatment of bacterial vaginosis

One hundred forty-three women with complaints of vaginitis were assigned to receive either 500 mg of metronidazole twice daily for 7 days or clindamycin 300 mg twice daily for 7 days. There was no significant difference in the failure rate between patients treated with clindamycin (6.1%) and those treated with metronidazole (4%). Adverse reactions were infrequent and mild in both treatment groups. Three patients who received clindamycin developed non-bloody diarrhea, which was mild and did not necessitate discontinuing therapy. We conclude that clindamycin may be a safe and effective alternative to metronidazole for treating women with bacterial vaginosis.     

Evidence relating bacterial vaginosis to intraamniotic infection

We performed a two-part study to determine relationships of bacterial vaginosis and intraamniotic infection. In the first part of the study, we determined whether bacterial vaginosis organisms (Gardnerella vaginalis, Mycoplasma hominis, and anaerobes) were associated with each other in the amniotic fluid of 408 cases of intraamniotic infection. In the second part, we determined the association of bacterial vaginosis itself with intraamniotic infection in 125 cases at high risk for intraamniotic infection. Strong associations were observed among the bacterial vaginosis organisms in amniotic fluid (p less than 0.01 to p less than 0.001). Women with bacterial vaginosis were more likely to develop intraamniotic infection than those without bacterial vaginosis (69% vs. 46%, p = 0.03). Women with bacterial vaginosis were more likely to have G. vaginalis and M. hominis in the amniotic fluid (p less than 0.01 and 0.04, respectively). These observations implicate bacterial vaginosis as a cause of intraamniotic infection.     

Clinical and cervical cytokine response to treatment with oral or vaginal metronidazole for bacterial vaginosis during pregnancy: a randomized trial

OBJECTIVE: To compare the efficacy of oral versus vaginal metronidazole treatment in pregnant women with bacterial vaginosis, and to compare cytokine profiles (interleukin-1beta, -6, and -8) in the cervical secretions of these women before and after treatment. METHODS: Pregnant women with bacterial vaginosis diagnosed both by Gram stain and clinical criteria were randomized to receive oral (n=52) or vaginal (n=50) metronidazole therapy. Cervical specimens for cytokine analysis and vaginal fluid for evaluation of bacterial vaginosis were obtained at baseline and 4 weeks after treatment. RESULTS: There was no significant difference in therapeutic cure rates (defined as a Gram stain score of 0-3 and the absence of all four clinical signs of bacterial vaginosis) between the two groups (71% and 70% for the oral and vaginal groups, respectively, P=1.0). Cervical levels of interleukin-1beta, -6, and -8 were significantly lower after treatment among the 72 women cured of bacterial vaginosis (P<.001, P=.001, and P=.02, respectively) but not among women who failed to respond to therapy. For interleukin-1beta and -6, a significant decrease in cytokine level was observed in both the oral and vaginal treatment groups. CONCLUSION: One week of oral metronidazole and 5 days of intravaginal metronidazole are equally efficacious for treatment of bacterial vaginosis during pregnancy. The decrease in cervical interleukin-1beta, -6, and -8 levels among women who established a normal flora after treatment but not among those with persistent bacterial vaginosis suggests a direct linkage between vaginal flora abnormalities and elevated cervical levels of interleukin-1beta, -6, and -8.     

Vaginal clindamycin and oral metronidazole for bacterial vaginosis: a randomized trial

OBJECTIVE: To compare the efficacy and safety of clindamycin vaginal ovules with oral metronidazole for treatment of bacterial vaginosis. METHODS: Women with bacterial vaginosis received either 100-mg ovules of clindamycin (intravaginally for 3 consecutive days) plus placebo capsules (orally twice daily for 7 days) or metronidazole 500 mg (two 250-mg capsules orally twice daily for 7 days) plus placebo ovules (intravaginally for 3 consecutive days). The sample was determined prospectively to provide a probability of.84 of correctly concluding that the rate of success for clindamycin is not more than 15% less than the expected 75% success rate for metronidazole. Clinical outcome was determined on the basis of vaginal fluid amine odor and clue cells. RESULTS: Of the 399 patients enrolled, 233 could be evaluated for efficacy. Of those, 77 (68.1%) of 113 patients were cured with clindamycin, compared with 80 (66. 7%) of 120 who were cured with metronidazole (95% confidence interval -10.6%, 13.4%; P =.810). Treatment-related adverse events were reported more frequently in the metronidazole treatment group. Systemic symptoms, such as nausea and taste perversion, accounted for most of the difference between groups. CONCLUSION: A 3-day regimen of clindamycin, given as intravaginal ovules, was as effective as and better tolerated than a 7-day regimen of oral metronidazole 500 mg, given twice daily, for treatment of bacterial vaginosis.     

Characteristics of three vaginal flora patterns assessed by gram stain among pregnant women. Vaginal Infections and Prematurity Study Group.

This study was undertaken to define the characteristics and persistence of vaginal flora in 7918 pregnant women at 23 to 26 weeks' gestation. Vaginal smears were categorized as normal (predominant lactobacilli), intermediate (reduced lactobacilli), or positive for bacterial vaginosis. The women with normal flora were least likely to have elevated vaginal pH, amine odor, milky discharge, or colonization by Gardnerella, Bacteroides, or genital mycoplasmas. Women with intermediate vaginal flora had intermediate frequencies of these clinical signs and microorganisms. Group B streptococci and yeast were associated with normal or intermediate flora, whereas Neisseria gonorrhoeae and Chlamydia trachomatis were recovered more frequently from women with intermediate flora or bacterial vaginosis. Trichomonas vaginalis was most associated with intermediate flora. At follow-up, 81% of the women with normal flora had remained normal. Of the women with intermediate flora, 32% acquired bacterial vaginosis and 30% shifted to normal flora. Only 12% of the women with bacterial vaginosis had shifted to normal flora. We conclude that there are two primary stable vaginal flora patterns (normal flora or bacterial vaginosis) and a third less distinct transitional flora pattern between these two.     

Bacterial vaginosis and lower genital tract infections in women attending out-patient clinics at a tertiary institution serving a developing community.

The prevalence of bacterial vaginosis and other lower genital tract infections were determined in women from a developing community. Patients were recruited from four out-patient clinics of a large urban tertiary referral hospital serving the indigent Black population of KwaZulu/Natal, South Africa. A total of 208 women attending the sexually transmitted diseases (STD) (n = 51), colposcopy (n =50), family planning (n = 52) and antenatal (n = 55) clinics were investigated. Endocervical and vaginal specimens were collected for microbiological investigation of recognised sexually transmitted pathogens. Estimation of vaginal pH, amine test and wet smear microscopy were performed at the bedside. Peripheral venous blood was obtained for serological tests for syphilis, hepatitis B surface antigen and antibody to the human immunodeficiency virus (HIV). Vaginal infections were detected in a total of 50% (104) of women, endocervical infections alone in 9% (18) and concurrent vagino-endocervical infections in 20% (41). Bacterial vaginosis (BV) was diagnosed in 35% (73) and its prevalence amongst different clinic populations ranged from 25% to 41% with no significant differences between any groups. Trichomoniasis was detected significantly more often in women attending the STD and antenatal clinics. Endocervical infections were found mainly in women attending the STD clinic, though the prevalence of Chlamydia trachomatis amongst the other clinic attenders ranged from 13% to 20%. Micro-organisms such as Gardnerella vaginalis, Mycoplasma hominis, anaerobes and curved Gram-negative rods were found in significantly higher number of women with BV. This study confirms the high prevalence of vaginal, endocervical and mixed vagino-endocervical infections in women from developing communities. The high prevalence of bacterial vaginosis as a single infection and its association with other recognised sexually transmitted pathogens in a large proportion of women, is of significance since such infections not only predispose to ascending upper genital tract infections but are also associated with complications in pregnancy such as premature rupture of membranes, preterm labour and endometritis.     

Anal sphincter disruption at vaginal delivery: is recurrence predictable?

Objectives: To evaluate the efficacy of clindamycin vaginal cream 2% once daily for 7 days in prolonging pregnancy. Study design: Randomised clinical trial of 112 women between 14 and 25 weeks of gestation with diagnosis of asymptomatic bacterial vaginosis were enrolled in a multicenter randomised trial and assigned to active or no treatment. A total of 55 women were assigned to clindamycin and 57 to no treatment. Main outcome measure: frequency of pre-term delivery. Results: The rates of pre-term delivery was 12.2% in the clindamycin group and 15.7% in the no treatment group (P=0.78). Birth weight was <2500 g in three and seven babies, respectively, in the two groups (P=0.32). Mean gestational ages at birth were 38.9 and 39.2 (P=0.52), respectively, in the clindamycin and no treatment groups. Conclusions: The results of this study suggest that treating asymptomatic bacterial vaginosis does neither markedly prolong pregnancy nor increase birthweight.     

Bacterial vaginosis: a double-blind randomized trial of the effect of treatment of the sexual partner

In a double-blind randomized controlled trial we assessed the effect of metronidazole treatment of the male partner on the recurrence rate of bacterial vaginosis. Women who fulfilled the diagnostic criteria for bacterial vaginosis were treated with metronidazole given in single doses of 2 g on days 1 and 3. The sexual partners were randomized to receive either the same dosage of metronidazole or a placebo. A total of 107 pairs completed the study. One week after the start of treatment 89% of the women considered themselves improved or cured and 93% no longer had the diagnostic criteria for bacterial vaginosis. At assessment 5 weeks after the treatment, 75% reported that they were cured or improved and the diagnostic criteria were not present in 73%. Treatment of the male partner did not affect subjective symptoms, clinical signs and isolation rates of Gardnerella vaginalis at 1 and 5 weeks after treatment.     

Early postpartum endometritis: the role of bacteria, genital mycoplasmas, and Chlamydia trachomatis

To characterize the flora of early postpartum endometritis and the clinical features of women with specific organisms, endometrial cultures for facultative and anaerobic bacteria, genital mycoplasmas, and Chlamydia trachomatis were taken with a triple-lumen sampling device. More than one organism was recovered from 80% of the women. Over 60% of the women had Gardnerella vaginalis and/or anaerobes associated with bacterial vaginosis isolated from the endometrium; these women were more likely to have severe illness and to develop a wound infection than were other women. Genital mycoplasmas were isolated frequently, but specific antibiotic therapy was not required for clinical cure in the 10% of patients who had Ureaplasma urealyticum only. Chlamydia trachomatis was infrequently isolated, but C trachomatis commonly remained after therapy.     

In vitro antagonistic effect of Lactobacillus on organisms associated with bacterial vaginosis

OBJECTIVE: To assess antagonistic properties of Lactobacillus strains isolated from the vaginas of healthy women as compared to the most common bacterial agents related to vaginosis. STUDY DESIGN: Antagonistic activity of different Lactobacillus strains isolated from the vaginas of healthy women not treated for infections with an antibiotic for the previous three months was screened using an agar slab method. The activity was tested against test organisms associated with bacterial vaginosis and/or urinary tract infections: Staphylococcus aureus, Enterococcus faecalis, Streptococcus agalactiae, Escherichia coli, Gardnerella vaginalis, Peptostreptococcus anaerobius and Prevotella bivia. RESULTS: Many of the 146 Lactobacillus strains tested exerted apparent antagonistic activities against gram-positive aerobic cocci and gram-negative rods, such as S aureus and E coli, and a marked number of Lactobacillus strains inhibited facultative bacteria, such as Gardnerella vaginalis and the anaerobes P anaerobius and P bivia. Only a few lactobacilli were able to inhibit growth of E faecalis and S agalactiae. Indicator bacteria growth inhibition probably relies upon several different complementary mechanisms. The specific indicator bacteria species determines which mechanism predominates. CONCLUSION: Lactobacillus strains taken from normal vaginal flora demonstrated antagonistic activity against a variety of bacteria related to vaginal and urinary tract infections. The specific occurrence rates of active Lactobacillus strains are different, and this difference is dependent on the indicator bacteria species.     

Low-dose secnidazole in the treatment of bacterial vaginosis.

OBJECTIVE: To determine whether bacterial vaginosis could be cured with a single 1-g oral dose of secnidazole. MATERIAL AND METHODS: A total of 80 women were recruited at the outpatient gynecologic clinic of Manuel Noriega Hospital, Maracaibo, Venezuela. Diagnosis and patient enrollment were based on the Amsel criteria. The participants were randomized to 2 groups. In group 1 (n=44) participants received a single 1-g oral dose and in group 2 (n=32) participants received a single 2-g oral dose of secnidazole. Clinical cure was defined as the absence of the characteristic symptoms (a bad odor and a grossly abnormal discharge) and at least 2 of the following: vaginal pH less than 4.5, no fish odor on addition of KOH, and no Gardnerella vaginalis or clue cells on wet-mount examination. Cytologic cure was defined as an absence of G. vaginalis on a Papanicolaou (Pap) smear. RESULTS: Clinical cure was experienced by 95.5% of the women who received the 1-g oral dose and by 97.4% of the women who received the 2-g oral dose of secnidazole. There was no significant difference between the groups in the clinical resolution of bacterial vaginosis. Following treatment, results were negative for G. vaginalis in 94.7% of the women. In group 1, 41 women (93.2%), and in group 2, 31 women (96.9%) had cytologic cure. The Pap smear revealed G. vaginalis in 3 of the women in group 1 and 1 of the women in group 2 (P=0.47). Twenty-seven women (35.5%) reported mild side effects. More women had adverse effects in group 1 (n=16) than in group 2 (n=11) but this difference was not statistically significant. CONCLUSION: This clinical study showed that a single 1-g oral dose of secnidazole is effective to cure bacterial vaginosis associated with G. vaginalis.     

Evaluation of the Gram stain as a screening tool for maternal carriage of group B beta-hemolytic streptococci. The Vaginal Infections and Prematurity Study Group.

To determine the usefulness of the vaginal Gram stain as a screen for maternal group B streptococcal carriage, we compared the presence of gram-positive cocci on Gram stain with a cervicovaginal culture in 7755 women at 23-26 weeks' gestation and in 1452 women at delivery. Group B streptococci were isolated from 18.4% of women at 23-26 weeks and 14.9% of women at delivery. The sensitivity, specificity, positive predictive value, and negative predictive value of the Gram stain were 28, 69, 17, and 81%, respectively, in mid-gestation and 34, 72, 18, and 86%, respectively, at delivery. The presence of gram-positive cocci on Gram stain was strongly associated with the isolation of Gardnerella vaginalis and with the presence of bacterial vaginosis. We conclude that most gram-positive cocci seen on Gram stain are probably anaerobes or micrococci and that the vaginal Gram stain is neither sensitive nor specific enough to be of use as a tool in the diagnosis of maternal group B streptococcal carriage.     

Randomised treatment trial of bacterial vaginosis to prevent post-abortion complication

OBJECTIVE: To evaluate the efficacy of metronidazole to reduce post-abortion complications among women with bacterial vaginosis. DESIGN: A randomised, double-blind placebo-controlled trial. SETTING: An American outpatient abortion facility between April 1999 and June 2000. SAMPLE: Women presenting for surgical abortion were screened for bacterial vaginosis using a pH and amines card test. METHODS: Women positive for elevated pH and amines on a self-collected vaginal discharge sample were randomised to 1000 mg oral metronidazole before abortion followed by 500 mg twice daily or placebo. All randomised women were also dispensed 100 mg doxycycline to take twice daily for seven days. MAIN OUTCOME MEASURES: Data were collected by phone, daily diary or visit and scored from 0 to 7 for post-abortion complications. Intention-to-treat analyses were completed prior to unblinding. RESULTS: Of 1764 women screened by card test, 638 (36%) were positive. Of these, 393 were randomised. Follow up data were available for 253 (64%) of these women. A complication score of 3 or more occurred in 21% of women assigned to metronidazole, compared with 19% in those assigned placebo (RR 1.1, 95% CI 0.7-1.9). Among 153 women with Gram stain confirmation for bacterial vaginosis, there was a similar lack of benefit with treatment (RR 1.6, 95% CI 0.9-3.0). No individual symptom or sign was statistically different between groups even for second trimester procedures. CONCLUSION: Among women undergoing abortion and diagnosed with bacterial vaginosis, oral metronidazole, in conjunction with doxycycline, did not reduce post-abortion complications.     

Bacterial vaginosis and trichomoniasis vaginitis are risk factors for cuff cellulitis after abdominal hysterectomy

To assess the relationship between either bacterial vaginosis or trichomoniasis vaginitis and posthysterectomy infection, preoperative evaluation of the vaginal secretions was performed in 161 women undergoing abdominal hysterectomy. Thirty-two patients (19.9%) and 27 patients (16.8%), respectively, met the diagnostic criteria for bacterial vaginosis and trichomoniasis vaginitis. Patients with either bacterial vaginosis or trichomoniasis vaginitis were more likely than control subjects to have cuff cellulitis, cuff abscess, or both (relative risk 3.2, 95% confidence interval 1.5 to 6.7 for bacterial vaginosis; relative risk 3.4, 95% confidence interval 1.6 to 7.1 for trichomoniasis vaginitis). Preoperative vaginitis had no effect with respect to the incidence of postoperative wound infection, urinary tract infection, or intravenous line phlebitis. Bacteroides sp., Peptostreptococcus sp., and/or Gardnerella vaginalis ("bacterial vaginosis organisms") were isolated from the vaginal cuff in the majority of patients with postoperative cuff cellulitis. Bacterial vaginosis and trichomoniasis vaginitis are risk factors for the development of posthysterectomy cuff cellulitis.