Comparison of oral and vaginal metronidazole for treatment of bacterial vaginosis in pregnancy: impact on fastidious bacteria

<p>Abstract</p> <p>Background</p> <p>Bacterial vaginosis (BV) is a common condition that is associated with preterm birth and acquisition of complex communities of vaginal bacteria that include several fastidious species. Treatment of BV in pregnancy has mixed effects on the risk of preterm delivery, which some hypothesize is due to variable antibiotic efficacy for the fastidious bacteria. Both oral and intravaginal metronidazole can be used to treat bacterial vaginosis in pregnancy, but little is known about the impact of different routes of antibiotic administration on concentrations of fastidious vaginal bacteria.</p> <p>Methods</p> <p>This was a sub-study of a larger randomized trial of oral versus vaginal metronidazole for treatment of BV in pregnancy. Fifty-three women were evaluated, including 30 women who received oral metronidazole and 23 who received intravaginal metronidazole. Bacterial taxon-specific quantitative PCR assays were used to measure concentrations of bacterial vaginosis associated bacterium (BVAB) 1, 2, and 3, <it>Gardnerella vaginalis, Atopobium </it>species, <it>Leptotrichia/Sneathia </it>species, <it>Megasphaera </it>species, and <it>Lactobacillus crispatus </it>before and after antibiotic treatment.</p> <p>Results</p> <p>Concentrations of <it>Leptotrichia </it>and <it>Sneathia </it>spp. and the fastidious Clostridia-like bacterium designated BVAB1 decreased significantly with oral (p = .002, p = .02) but not vaginal therapy (p = .141, p = .126). The fastidious bacterium BVAB3 did not significantly decrease with either treatment. Concentrations of <it>Atopobium </it>spp., reportedly resistant to metronidazole <it>in vitro</it>, dropped significantly with oral (p = .002) and vaginal (p = .001) treatment. There was no significant difference in the magnitude of change in bacterial concentrations between oral and vaginal treatment arms for any of the bacterial species. <it>Lactobacillus crispatus </it>concentrations did not change.</p> <p>Conclusion</p> <p>Both oral and vaginal metronidazole therapy in pregnant women result in a significant decrease in concentrations of most BV-associated anaerobic bacteria, with the exception that <it>Leptotrichia, Sneathia </it>and BVAB1 do not significantly decrease with vaginal metronidazole therapy. These data suggest that the route of antibiotic administration has a minor impact on bacterial eradication in pregnant women with BV.</p> <p>Trail Registration</p> <p>This trial is registered with ClinicalTrials.gov, number NCT00153517</p

The vaginal microflora in relation to gingivitis

<p>Abstract</p> <p>Background</p> <p>Gingivitis has been linked to adverse pregnancy outcome (APO). Bacterial vaginosis (BV) has been associated with APO. We assessed if bacterial counts in BV is associated with gingivitis suggesting a systemic infectious susceptibilty.</p> <p>Methods</p> <p>Vaginal samples were collected from 180 women (mean age 29.4 years, SD ± 6.8, range: 18 to 46), and at least six months after delivery, and assessed by semi-quantitative DNA-DNA checkerboard hybridization assay (74 bacterial species). BV was defined by Gram stain (Nugent criteria). Gingivitis was defined as bleeding on probing at ≥ 20% of tooth sites.</p> <p>Results</p> <p>A Nugent score of 0–3 (normal vaginal microflora) was found in 83 women (46.1%), and a score of > 7 (BV) in 49 women (27.2%). Gingivitis was diagnosed in 114 women (63.3%). Women with a diagnosis of BV were more likely to have gingivitis (p = 0.01). Independent of gingival conditions, vaginal bacterial counts were higher (p < 0.001) for 38/74 species in BV+ in comparison to BV- women. Counts of four lactobacilli species were higher in BV- women (p < 0.001). Independent of BV diagnosis, women with gingivitis had higher counts of <it>Prevotella bivia </it>(p < 0.001), and <it>Prevotella disiens </it>(p < 0.001). <it>P. bivia, P. disiens, M. curtisii </it>and <it>M. mulieris </it>(all at the p < 0.01 level) were found at higher levels in the BV+/G+ group than in the BV+/G- group. The sum of bacterial load (74 species) was higher in the BV+/G+ group than in the BV+/G- group (p < 0.05). The highest odds ratio for the presence of bacteria in vaginal samples (> 1.0 × 10⁴cells) and a diagnosis of gingivitis was 3.9 for <it>P. bivia </it>(95% CI 1.5–5.7, p < 0.001) and 3.6 for <it>P. disiens </it>(95%CI: 1.8–7.5, p < 0.001), and a diagnosis of BV for <it>P. bivia </it>(odds ratio: 5.3, 95%CI: 2.6 to 10.4, p < 0.001) and <it>P. disiens </it>(odds ratio: 4.4, 95% CI: 2.2 to 8.8, p < 0.001).</p> <p>Conclusion</p> <p>Higher vaginal bacterial counts can be found in women with BV and gingivitis in comparison to women with BV but not gingivitis. <it>P. bivia </it>and <it>P. disiens </it>may be of specific significance in a relationship between vaginal and gingival infections.</p

Partner- and partnership-related risk factors for preterm birth among low-income women in Lima, Peru

A woman's partner and the characteristics of their partnership can play an important role in the health of her pregnancy. Yet, with the notable exception of intimate partner violence, there has been little previous research addressing the associations between partner- or partnership-related factors and birth outcomes. This analysis tested the hypothesis that risk factors related specifically to partner or partnership characteristics increased the risk for preterm birth. Between 2003 and 2005, a total of 580 preterm cases (20-36 weeks gestational age at delivery) and 633 term controls (>=37 weeks) were selected from women delivering at an obstetric hospital in Lima, Peru. Each woman completed a confidential, structured interview and provided biological specimens within 48 h after delivery. Multivariable logistic regression was used to assess associations between partner and partnership characteristics and preterm birth. After adjustment for behavioral, demographic, and obstetric risk factors, ever having had a partner with a history of drug use (aOR = 1.91, 95% CI 1.22-2.99), ever having had anal sex (aOR = 1.40, 95% CI 1.07-1.84), having a current partner with a history of visiting prostitutes (aOR = 1.69, 95% CI 1.22-2.33), and perceiving one's current partner as a "womanizer" (aOR = 1.34, 95% CI 1.02-1.77) were significantly associated with an elevated risk of preterm birth when tested in separate models. These four factors were then used to create a composite partnership risk score, which showed an increasing dose-response relationship with preterm birth risk (per additional partner risk factor: aOR = 1.31, 95% CI 1.16-1.49). These results highlight the importance of considering a broader set of risk factors for preterm birth, specifically those related to a woman's partner and partnership characteristics. Further research could clarify the specific mechanisms through which these partner and partnership characteristics may increase the risk of preterm birth.Peru Preterm birth Risk Sexually transmitted infections Partner and partnership factors Women

Effect of Semen on Vaginal Fluid Cytokines and Secretory Leukocyte Protease Inhibitor

The presence of semen in vaginal fluid, as identified by an acid phosphatase spot test, does not influence vaginal proinflammatory cytokine concentrations. Objective: determine whether semen, as detected by acid phosphatase, influences vaginal cytokines or secretory leukocyte protease inhibitor concentrations. Methods: 138 pregnant women had vaginal fluid collected for Gram stain, acid phosphatase detection by colorimetric assay, and interleukin 1-Beta, interleukin-6, interleukin-8, and secretory leukocyte protease inhibitor measurement by enzyme immunoassay. Results for women with and without acid phosphatase were compared by Mann-Whitney test. Results: of 138 subjects, 28 (20%) had acid phosphatase detected; of these, only 19 (68%) reported recent intercourse and 3 (11%) had sperm seen on Gram stain. There were no significant differences in proinflammatory cytokine concentrations; however, secretory leukocyte protease inhibitor concentrations were significantly higher among women with acid phosphatase. Conclusions: proinflammatory cytokine measurement does not appear to be affected by the presence of semen, but secretory leukocyte protease inhibitor is significantly higher when semen is present. Detection of semen by acid phosphatase was associated with higher vaginal SLPI concentrations, however, the presence of semen did not appear to influence vaginal proinflammatory cytokine concentrations

Associations Between Genital Tract Infections, Genital Tract Inflammation, and Cervical Cytobrush HIV-1 DNA in US Versus Kenyan Women

Cervical shedding of HIV-1 DNA may influence HIV-1 sexual transmission. HIV-1 DNA was detected in 250 (80%) of 316 and 207 (79%) of 259 cervical cytobrush specimens from 56 US and 80 Kenyan women, respectively. Plasma HIV-1 RNA concentration was associated with increased HIV-1 DNA shedding among US and Kenyan women. Kenyan women had higher cervicovaginal concentrations of proinflammatory interleukins (IL)-1β, IL-6, IL-8, and anti-inflammatory secretory leukocyte protease inhibitor compared with US women (all P &lt; 0.01). HIV-1 DNA shedding was associated with increased concentrations of IL-1β and IL-6 and lower secretory leukocyte protease inhibitor among US women but not Kenyan women

Interaction Between Lactobacilli, Bacterial Vaginosis-Associated Bacteria, and HIV Type 1 RNA and DNA Genital Shedding in U.S. and Kenyan Women

Bacterial vaginosis has been associated with genital HIV-1 shedding; however, the effect of specific vaginal bacterial species has not been assessed. We tested cervicovaginal lavage from HIV-1-seropositive women for common Lactobacillus species: L. crispatus, L. jensenii, and seven BV-associated species: BVAB1, BVAB2, BVAB3, Leptotrichia, Sneathia, Megasphaera, and Atopobium spp. using quantitative PCR. We used linear and Poisson regression to evaluate associations between vaginal bacteria and genital HIV-1 RNA and DNA. Specimens from 54 U.S. (310 visits) and 50 Kenyan women (137 visits) were evaluated. Controlling for plasma viral load, U.S. and Kenyan women had similar rates of HIV-1 RNA (19% of visits vs. 24%; IRR=0.95; 95% CI 0.61, 1.49) and DNA shedding (79% vs. 76%; IRR=0.90; 0.78, 1.05). At visits during antiretroviral therapy (ART), the likelihood of detection of HIV-1 RNA shedding was greater with BVAB3 (IRR=3.16; 95% CI 1.36, 7.32), Leptotrichia, or Sneathia (IRR=2.13; 1.02, 4.72), and less with L. jensenii (IRR=0.39; 0.18, 0.84). At visits without ART, only L. crispatus was associated with a lower likelihood of HIV-1 RNA detection (IRR=0.6; 0.40, 0.91). Vaginal Lactobacillus species were associated with lower risk of genital HIV-1 shedding, while the presence of certain BV-associated species may increase that risk

Cervicovaginal Shedding of HIV Type 1 Is Related to Genital Tract Inflammation Independent of Changes in Vaginal Microbiota

We examined the relationship of proinflammatory vaginal cytokines and secretory leukocyte protease inhibitor (SLPI) with genital HIV-1 shedding after controlling for genital coinfections. Fifty-seven HIV-1-infected women in Seattle, WA (n = 38) and Rochester, NY (n = 19) were followed every 3–4 months for a total of 391 visits. At each visit, plasma and cervicovaginal lavage (CVL) were tested for HIV-1 RNA using qPCR. Vaginal samples were tested for bacterial vaginosis, yeast, hydrogen peroxide-producing Lactobacillus colonization, Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis, CMV, and HSV shedding. CVL interleukins (IL)-1β, IL-6, IL-8, and SLPI were measured using ELISA. Linear regression with generalized estimating equations examined effects of cytokine concentrations on CVL HIV-1 RNA, adjusted for plasma HIV RNA, and measured coinfections. CVL IL-1β and IL-8 were significantly associated with CVL HIV-1 RNA. This persisted after adjusting for plasma HIV-1 RNA. Higher levels of IL-1β were associated with higher concentrations of HIV-1 RNA in CVL (β = 0.25, 95% CI 0.09, 0.42), as were higher levels of IL-8 (β = 0.34, 95% CI 0.17, 0.50). Adjusting for the presence of the coinfections described, this relationship was attenuated for IL-1β (β = 0.16; 95% CI –0.01, 0.33) but still significant for IL-8 (β = 0.29; 95% CI 0.13, 0.45). The proinflammatory cytokines IL-1β and IL-8 are associated with higher cervicovaginal HIV-1 RNA concentrations, even after controlling for plasma viral load and vaginal microbial cofactors. This association suggests that there may be additional, noninfectious causes of inflammation that increase cervicovaginal HIV-1 shedding