Sharon L. Hillier

Diagnosis and clinical manifestations of bacterial vaginosis

Among 640 randomly selected women who were attending a sexually transmitted disease clinic and did not have trichomoniasis, 33% had bacterial vaginosis as defined by a composite of four clinical criteria: (1) Vaginal discharge was homogeneous; (2) vaginal discharge had a pH greater than or equal to 4.7; (3) vaginal discharge had an amine-like odor when mixed with 10% potassium hydroxide; (4) vaginal discharge contained clue cells representing greater than or equal to 20% of vaginal epithelial cells. Previously published Gram stain criteria for bacterial vaginosis correlated better than results of semiquantitative cultures for Gardnerella vaginalis with presence or absence of clue cells and with composite clinical criteria. Of 293 women with bacterial vaginosis by Gram stain criteria, 65% had symptoms of increased vaginal discharge and/or vaginal malodor, while 74% had signs of characteristic homogeneous vaginal discharge or amine-like odor. Elevated vaginal pH was the least specific and amine-like odor the least sensitive sign of bacterial vaginosis. Gram stain criteria for bacterial vaginosis were not associated with the concentrations of endocervical or vaginal inflammatory cells but were significantly associated with a clinical diagnosis of pelvic inflammatory disease. After adjusting for coinfection, sexual behavior, and other variables, bacterial vaginosis remained associated with adnexal tenderness (odds ratio = 9.2, p = 0.04). Bacterial vaginosis, previously implicated as a risk factor for obstetric infections, may be a risk factor for pelvic inflammatory disease.

The relationship of hydrogen peroxide-producing lactobacilli to bacterial vaginosis and genital microflora in pregnant women.

Lactobacilli provide an important microbial defense against genital colonization by pathogens. The role of hydrogen peroxide (H2O2) in the control of genital microflora was explored in a cross-sectional study of 275 women in the second trimester of pregnancy. Vaginal cultures were obtained for detec

Diagnostic microbiology of bacterial vaginosis

Bacterial vaginosis is characterized microbiologically by replacement of the Lactobacillus-predominant vaginal flora by Gardnerella vaginalis, Bacteroides species, Mobiluncus species, and genital mycoplasmas. A standardized, laboratory-based diagnostic test for bacterial vaginosis is desirable in those instances in which a microscope is unavailable in the clinic or when the evaluator of the wet mount examination is inexperienced at recognizing clue cells. Vaginal cultures have excellent sensitivity for the diagnosis of bacterial vaginosis, but because the predictive value of a positive G. vaginalis culture is less than 50%, cultures are not recommended. Vaginal Gram smears are objective and reproducible, have 62% to 100% sensitivity, and have a positive predictive value of 76% to 100%. Diagnosis of bacterial vaginosis with use of Papanicolaou-stained smears has been reported, but standardized criteria have not been widely adopted. A rapid, office-based oligonucleotide probe test for high concentrations of G. vaginalis has been developed and may be useful when direct microscopy is unavailable or confidence in microscopic examination is low. Laboratory tests that detect microbial products unique to the vaginal fluid of women with bacterial vaginosis include detection of amines (putrescine, cadaverine, and trimethylamine), measurement of the relative levels of succinate and lactate in the vaginal fluid by gas chromatography, detection of proline aminopeptidase by colorimetric assay, or detection of sialidases in the vaginal fluid. Although these tests are not yet applicable to routine use, these research tests could be adapted for wider use in office laboratories. Vaginal Gram stains are more useful than culture for laboratory confirmation of bacterial vaginosis.

Intravaginal clindamycin treatment for bacterial vaginosis: Effects on preterm delivery and low birth weight☆

OBJECTIVE Our goal was to evaluate whether treatment of bacterial vaginosis during pregnancy with 2% clindamycin vaginal cream reduces the incidence of either preterm delivery or low birth weight or of both. STUDY DESIGN A multicenter, double-blind, randomized, placebo-controlled trial in Indonesia compared a 2% clindamycin vaginal cream with a placebo cream. Women seeking prenatal care at 14 to 26 weeks of gestational age who had bacterial vaginosis (Gram stain score > 6 and pH of vaginal fluid > 4.5) were invited to participate. Of the 745 women enrolled, 681 (91.4%) women were followed up through delivery. RESULTS Clindamycin vaginal cream was an effective treatment for bacterial vaginosis. Two weeks after completion of the treatment, 85.5% of the women were cured. The rate of preterm delivery (< 37 weeks) was 15.0% for clindamycin patients and 13.5% for placebo patients (odds ratio 1.1, 95% confidence interval 0.7 to 1.7). The rate of low birth weight was 9.0% for clindamycin patients and 6.8% for placebo patients (odds ratio 1.3, 95% confidence interval 0.8 to 2.4). CONCLUSIONS Treatment of bacterial vaginosis with clindamycin vaginal cream did not reduce preterm delivery or low birth weight. Although clindamycin vaginal cream is an effective treatment for bacterial vaginosis, intravaginal treatment would not be effective against bacterial vaginosis-associated microorganisms harbored in the upper genital tract. Systemic treatment may be required to eradicate upper tract infection to reduce preterm delivery.

Antenatal microbiologic and maternal risk factors associated with prematurity.

In a prospective study of 202 women (gestational age 24 +/- 4 weeks), we evaluated possible influences of lower genital tract infection or bacterial conditions on obstetric outcomes, including preterm labor, preterm premature rupture of membranes, and preterm birth. The presence of bacterial vaginosis (18.7%) was associated with an increased risk of preterm labor (relative risk, 2.6; 95% confidence interval, 1.08 to 6.46). For women with bacterial vaginosis who also had Mobiluncus species morphotypes identified on Gram stain, the relative risk of preterm labor was 3.8 (95% confidence interval, 1.32 to 11.5). Presence of vaginal Mycoplasma hominis (10.8% of patients) was associated with both preterm labor (relative risk, 1.8; 95% confidence interval, 0.77 to 4.4) and preterm birth (relative risk, 5.1; 95% confidence interval, 1.45 to 17.9). Recovery of Staphylococcus aureus (3.0%) was associated with preterm labor (relative risk, 3.1; 95% confidence interval 1.12 to 8.7). Identification of two or more bacterial-linked abnormalities was also associated with preterm labor (relative risk, 3.3; 95% confidence interval, 1.44 to 7.58). An increased level of vaginal wash protease (greater than or equal to 10 trypsin units) (16%) was associated with preterm labor and was noted in 50% of women with preterm premature rupture of membranes. A history of prior preterm birth was the single best historical predictor of both preterm labor (relative risk, 3.6; 95% confidence interval, 1.92 to 6.83) and preterm birth (relative risk, 6.7; 95% confidence interval, 2.2 to 20.4). History of three or more abortions, antenatal urinary tract infection, and occurrence of medical complications during pregnancy also correlated with increased risk of preterm labor. These findings affirm and refine associations of various maternal reproductive tract infections with preterm labor, premature rupture of membranes, and birth, allowing for controlled treatment trials aimed at prevention of preterm birth.

Broad-Spectrum Bacterial rDNA Polymerase Chain Reaction Assay for Detecting Amniotic Fluid Infection Among Women in Premature Labor

We amplified bacterial 16S rRNA encoding DNA (rDNA) with the polymerase chain reaction (PCR) to detect amniotic fluid infection in 69 women in premature labor whose membranes were intact. Bacterial rDNA was detected by PCR in samples from 15 (94%) of 16 patients with positive amniotic fluid cultures. Bacteria were detected by PCR in samples from 5 (36%) of 14 patients with negative cultures and elevated interleukin (IL)-6 levels vs. 1 (3%) of 39 patients with negative cultures and IL-6 levels of < or = 2,000 pg/mL (P < .01). The median amniotic fluid cytokine levels and the pregnancy outcomes were similar for patients with positive amniotic fluid cultures and those with negative cultures and positive rDNA PCR assays. The association between amniotic fluid infection and premature labor may be underestimated on the basis of amniotic fluid culture results. The broad-spectrum bacterial 16S rDNA PCR assay may prove useful for diagnosing amniotic fluid infection.

Bacteria in the prostate tissue of men with idiopathic prostatic inflammation

PURPOSE Although antibiotics represent the first line of treatment for prostatitis syndromes, physicians can document infection in remarkably few cases. We examined the relationship of genitourinary infection to inflammatory prostatitis in 85 subjects without bacteriuria. MATERIALS AND METHODS Evaluation consisted of cultures of urethra, urine and transperineal prostate biopsies, specifically for commensal and fastidious organisms, and leukocyte counts of expressed prostatic secretions. RESULTS Men with inflamed expressed prostatic secretions (25) were more likely to have any bacterial isolation (p = 0.01), positive cultures for anaerobic bacteria (p = 0.03), higher total bacterial counts (p = 0.02) and more bacteria, species isolated (p = 0.02) in prostate biopsy cultures than men without expressed prostatic secretion inflammation (60). CONCLUSIONS Bacterial colonization/invasion of the prostate may be associated with inflammatory prostatitis in some cases.

Rectal applications of nonoxynol-9 cause tissue disruption in a monkey model

Background Efforts to develop topical microbicide products have all but ignored evaluation for rectal use. Goal The goal of this study was to assess the effects of multiple rectal applications of Conceptrol (containing 4% nonoxynol-9) on flora and mucosal tissues in the pig-tailed macaque model. Study Design Monkeys (8 per group) received daily rectal applications of Conceptrol, placebo gel, or no product, for 3 days. At each visit, a preapplication rectal lavage specimen and swab specimen for microbiology and pH determination were collected. Conceptrol or placebo gel (2.5 ml) was then administered intrarectally. Fifteen minutes after application, samples were again collected. Results Gross observation of rectal lavage indicated sheets of epithelium 15 minutes after application of the nonoxynol-9 product. Histopathology of these samples revealed epithelial sheets with stroma attached. The presence of H2O2-producing lactobacilli remained relatively constant, whereas that of H2O2-producing viridans streptococci diminished in all nonoxynol-9-exposed animals in which these organisms were detected at baseline. Conclusions Repeated applications of nonoxynol-9 disrupts the rectal mucosa of the pig-tailed macaque. The disruption of these tissues could have serious implications for an increase in likelihood of acquisition of sexually transmitted infection/HIV in humans.

Distribution of genital Lactobacillus strains shared by female sex partners.

The prevalence of bacterial vaginosis among lesbians is high. We assessed whether unique Lactobacillus strains were shared by female sex partners. Cultures of vaginal and rectal specimens for detection of Lactobacillus organisms were performed for women who reported having had sex with women. Lactobacilli were identified on the basis of DNA homology and were typed and fingerprinted by repetitive element sequence-based polymerase chain reaction (rep-PCR). Of 237 women, Lactobacillus crispatus was detected in 98% and Lactobacillus gasseri in 21%. Detection of L. gasseri was associated with recent receptive digital-vaginal sex (P = .04) and increased bacterial vaginosis risk (odds ratio, 4.2; 95% confidence interval, 1.4-13.4). Of 31 couples monogamous for >3 months, rep-PCR fingerprints were identical in both members in 23 (77%).

Randomized treatment of mucopurulent cervicitis with doxycycline or amoxicillin

A randomized trial of doxycycline versus amoxicillin was performed to treat mucopurulent cervicitis. Chlamydia trachomatis , the most common single agent associated with mucopurulent cervicitis, was isolated from 30 (47%) and Neisseria gonorrhoeae from five (8%) of 64 patients. Patients were followed up for 3 months, and the effect of treatment was assessed by clinical (presence of endocervical mucopus, cervicitis severity score, and number of polymorphonuclear leukocytes on Gram-stained smears of endocervical secretions) and microbiologic criteria. Doxycycline and amoxicillin were equally effective for treating chlamydial and nonchlamydial cervicitis. However; endocervical mucopus was still present in 18% of the patients in both treatment groups after 2 months and in 23% of the doxycycline group and 33% of the amoxicillin group after 3 months of therapy. The cause of persistent/recurrent mucopus after antimicrobial treatment was not explained by relapse or reinfection with Chlamydia trachomatis , Neisseria gonorrhoeae , genital mycoplasmas, or Gardnerella vaginalis , but persistence was associated with the degree of cervical ectopy.