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Incidence & Predictors of Treatment Failure for Bacterial Vaginosis. JM Marrazzo , KK Thomas, K Ringwood, T Fiedler, DN Fredricks University of Washington & Fred Hutchinson Cancer Research Center, Seattle WA jmm2@u.washington.edu. Background. Most common
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Incidence & Predictors of Treatment Failure for Bacterial Vaginosis JM Marrazzo, KK Thomas, K Ringwood, T Fiedler, DN Fredricks University of Washington & Fred Hutchinson Cancer Research Center, Seattle WA jmm2@u.washington.edu
Background • Most common • Cause of vaginal symptoms prompting medical evaluation for vaginitis • Cause of vaginitis • >10% of women experience BV • May cause 11% of preterm deliveries in U.S. • Etiology not understood, but associated with douching, new male partner, unprotected sex in heterosexual women, sex between women • Frequently persists after treatment (15% - 20%) • Very frequently recurs after successful treatment (30% - 60%) • History of BV, regular partner throughout follow-up, and female partner implicated Sobel 2006; Bradshaw 2006
Background • Traditionally defined asovergrowth of commensal anaerobic flora (classically G. vaginalis, Prevotella, Mobiluncus, M. hominis) relative to H2O2+ lactobacilli • Molecular (cultivation-independent) approaches have recently expanded spectrum of BV microbiology • Some bacteria highly specific for BV in recent studies • Some with known high-level resistance to metronidazole • Atopobium vaginae • “New” bacteria not yet incorporated into prospective analyses for BV persistence or recurrence Verstraelen 2004, Ferris 2004, Fredricks 2005
BV-associated bacteria (BVAB 1, 2, 3) and their relationship to bacteria in the Clostridium phylum BVAB1 Clostridium Cluster XIVa BVAB3 BVAB2
Methods • Subjects recruited to research clinic • 16-29 years • Sex with woman (prior year) • Recruited through ads (self-referred) and partners • Underwent computer-assisted self-interview (CASI) at enrollment • BV diagnosed by Amsel criteria and treated with vaginal metronidazole • BV confirmed by Nugent criteria (later) • Vaginal fluid collected with polyurethane foam swab and saline lavage (0.5 cc)
Methods • All women with BV asked to return at 1 month for repeat procedures (CASI, vaginal fluid collection) • BV persistence = Nugent >6 • Abnormal vaginal flora = Nugent >3 • All women asked to return at 3 months • BV recurrence defined by Nugent score >6 among women whose baseline BV was cured at 1 month
Methods Vaginal Fluid Collected at All Visits: • Traditional culture • Used to define H2O2 production by lactobacilli • Typical panel of anaerobic flora • Bacterium-specific PCR assays based on cloned 16s rDNA sequences derived from earlier analysis of clones by RFLP, sequencing; all positive results sequence-confirmed
Characteristics: Median age 25 y Nonwhite: 25% Sex with male last 3 mos: 28% Douche last 3 mos: 6.4% BV N = 12 / 72 (17%) BV @ baseline N = 66 (28%) No BV N = 173 (72%) New BV during study N = 6 239 women enrolled No BV N = 60 / 72 (83%) ResultsBaseline and Persistent BV + At 1 month 72 women with BV • 28% had BV at baseline • Overall f/u at 1 month = 90% • 83% responded to vaginal MTZ • Persistent BV incidence: 17%
ResultsFactors Associated with BV Persistence Demographics Incidence of BV Recurrence (%) OR (95% CI) Age 26-33 y 3.9 (0.9, 16.4) Black race 7.0 (3.9, 12.4) P=0.03 P=0.06 Baseline Vaginal Microbiology (PCRs) OR (95% CI) BVAB1 2.3 (0.8, 6.5)) BVAB2 2.2 (0.3, 15.5) BVAB3 4.4 (1.5, 13.4) P=0.009 P=0.15 P=0.67
ResultsAdditionalFactors Associated with Persistence of Abnormal Flora (N = 22) Incidence of BV Recurrence (%) P=0.05 P=0.05 P=0.02 P=0.09 OR (95% CI) BVAB1 2.6 (1.3, 5.2) Adherence 0.36 (0.2, 0.7) Any sex 4.1 (0.6, 28) Vaginal sex 2.1 (1.1, 4.2) *Intercourse with male partner
BV N = 12 / 72 (17%) BV @ baseline N = 66 (28%) No BV N = 173 (72%) New BV during study N = 6 239 women enrolled No BV N = 60 / 72 (83%) Recurrent BV N = 8 / 53 (15%) ResultsBaseline and Persistent BV + At 1 month 72 women with BV • 15% who initially responded to MTZ had BV recurrence
Conclusions • Distinct risks predict BV persistence • Demographics • Black women consistently at high risk for BV • Reasons unclear; not related to douching in our study • Older age • Vaginal microbiology • BVAB3, possibly BVAB1 • Sex • Vaginal fluid exchange, intercourse with men [Sanchez 2004, Bradshaw 2006] • Further study needed • Additional accrual of subjects to substantiate preliminary trends and assess risks for BV recurrence • Cultivation of BVAB to assess pathogenicity and antibiotic susceptibilities
Limitations • Small number of subjects who were self-referred or referred by partners • Limits on reproducibility, generalizability • However, excellent retention and diverse sexual practices • Development of bacterium-specific PCRs directed by initial clone analysis • May not include all relevant species
Study personnel Nancy Dorn Dana Varon Lauren Asaba Susan Heideke Corey Fish Kathy Agnew Becca Hutcheson Acknowledgements Support • Dave Eschenbach • Sharon Hillier • King Holmes • Larry Corey
Associations Between Bacteria Detected and BV Bacterium-specific PCR assays for vaginal fluid samples from 40 subjects with BV and 65 without BV. ORs adjusted for age, site of enrollment, vaginal symptoms, report of sex with men