1 / 48

Bacterial Vaginosis Gynecologic and Obstetric Considerations

Bacterial Vaginosis Gynecologic and Obstetric Considerations. Reproductive Infectious Disease Seminars March 29, 2005 Natali Aziz, MD, MS Reproductive Infectious Disease and Maternal-Fetal Medicine Fellow Department of Obstetrics, Gynecology and Reproductive Sciences

delores
Download Presentation

Bacterial Vaginosis Gynecologic and Obstetric Considerations

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Bacterial VaginosisGynecologic and Obstetric Considerations Reproductive Infectious Disease Seminars March 29, 2005 Natali Aziz, MD, MS Reproductive Infectious Disease and Maternal-Fetal Medicine Fellow Department of Obstetrics, Gynecology and Reproductive Sciences University of California, San Francisco

  2. Microbiology Pathogenesis Epidemiology Diagnosis Treatment Non-pregnant Pregnant Clinical Associations Gynecologic Obstetric HIV Special Considerations Screening in Pregnancy Treatment in Pregnancy Sexual Transmission Overview www.superscore.com www.fpnotebook.com

  3. Microbiology • Lactobacillus acidophilus • Gardnerella vaginalis • Mycoplasma hominis • Mobiluncus species • Anaerobes • Bacteroides (Porphyromonas) • Peptostreptococcus • Fusobacterium • Prevotella Mobiluncus mulieris www.infek.lu.se Mycoplasma hominis www.ksmed.ru

  4. Pathogenesis • Lactobacilli • Compete with other microorganisms for adherence to epithelial cells • Produce antimicrobial compounds such as organic acids (which lower the vaginal pH), hydrogen peroxide, and bacteriocin-like substances • Mechanism by which floral imbalance occurs and the role of sexual activity in the pathogenesis of bacterial vaginosis are not clear www.ulb.ac.be

  5. Pathogenesis • Marked reduction in lactobacillus • Decreased hydrogen peroxide production • Polymicrobial superficial infection: overgrowth of G. vaginalis and anaerobic bacteria • Lactobacilli predominate after metronidazole treatment • (Spiegel and Holmes 1983) Lactobacillus www002.upp.co-net.ne.jp

  6. Epidemiology • “Nonspecific vaginitis” • Most common vaginal infection in women of childbearing age • Prevalence 5-60% across the world • 35-50% of “vaginitis” • 16% (9-23%) prevalence in pregnant women in US • Higher prevalence (24-37%) in more sexually active women • High prevalence in women who have sex with women, unlike other STIs • Differs by ethnic group • 6% in Asians • 9% in Caucasians • 16 % in Hispanics • 23% % in African Americans CDC 2000, August 2004; Berg 1984; Hillier 1990; Eschenbach 1988; Skinner 1996; Fethers 2000; Joesoef 2001; Morris 2001

  7. Epidemiology • Risk factors • Multiple or new sexual partners • (sexual activity alteration of vaginal pH) • Early age of first sexual intercourse • Douching (Ness 2002, Schwebke 2004) • Cigarette smoking (Joesoef 2001, Morris 2001) • Use of IUD (Joesoef 2001, Morris 2001) *Although sexual activity is a risk factor for the infection, bacterial vaginosis can occur in women who have never had vaginal intercourse (Yen 2003)

  8. Clinical Features • Most cases (50-75%) asymptomatic or mild • Musty or fishy odor of vaginal discharge • Thin, gray-white, non-clumping, homogenous vaginal discharge • Dysuria and dyspareunia rare • Pruritus and inflammation are absent • Absence of inflammation is the basis of the term "vaginosis" rather than vaginitis

  9. Clinical Features Discharge due to bacterial vaginosis has been removed revealing a normal cervix. This discharge associated with BV is from the vagina - not the cervix. www.hc-sc.gc.ca

  10. Diagnostic Methods • Clinical/Microscopic Criteria • Gram Stain (“Gold Standard”) • Pap Smear • Femcard- detect elevated pH and increased amine • Sensitivity 87%; Specificity 92% (Hillier) • *Culture- poor predictive value for G. vaginalis as prevalent in healthy asymptomatic women • *DNA probes- expensive, poor predictive value alone www.hc-sc.gc.ca Courtesy of Abner P. Korn, MD www.superscore.com

  11. Diagnostic Criteria (Amsel’s) Clinical features necessary for diagnosis of BV include 3 of 4 clinical criteria • Clue cells on saline wet mount of vaginal discharge (on >20% cells) • Bacteria adhered to epithelial cells; most reliable single indicator • Vaginal pH > 4.5 • High sensitivity; Poor specificity (false positive with mucus, menses, semen) • Characteristic vaginal discharge: thin, homogeneous, gray-white, and adherent consistency (scant, moderate, profuse) • Positive “whiff” test (Amine Test) • Release of fishy amine odor on addition of 10% KOH to discharge • Also observed in Trichomonas infection www.rnzcgp.org Amsel and Holmes et al, 1983

  12. Diagnosis by Gram Stain

  13. Treatment Considerations • Resolves spontaneously in 1/3 of nonpregnant and pregnant women • Treat • Symptomatic infection • Asymptomatic infection prior to abortion or hysterectomy • 10 -75% reduction in postoperative infectious complications (Larsson 1992, 2000; Crowley2001) • ?Asymptomatic pregnant women with previous preterm birth controversial • *No difference in symptoms with treatment of asymptomatic infection (Shwebke 2000)

  14. Treatment Recommendations • Oral metronidazole 500 mg bid x 7 days ($5) • 84-96% cure rate • Single dose therapy (2g) may be less effective • Oral Clindamycin 300 mg bid x 7 days ($28) • Less effective • Topical treatments (higher recurrence rates) • Metronidazole gel (0.75%) 5 g PV qhs x 5 days ($30) • 70-80% cure rate • Clindamycin cream (2%) 5 g PV qhs x 7 days ($31) • Less effective • May lead to Clindamycin resistant anaerobic bacteria Majeroni 1998

  15. Treatment Refractory/Resistant Cases • Metronidazole 500 mg po bid x 14 days ($10) • Other options • Povidone-iodine (Betadine) gel/supp PV bid x 14-28 days ($59) • *No benefit in treatment of sexual partner • *Future approaches: “Probiotics” • Exogenous lactobacillus (elevated arginine deaminase activity) recolonization with suppositories

  16. Treatment Recurrent Cases • Up to 30% have recurrence in 3 months • Treat as refractory case • Maintenance therapy • Induction: metronidazole gel (0.75%) qhs x 10 days • Maintenance (when no clue cells on wet mount and lower pH): • Metronidazole gel twice weekly x 3 months • Treat concurrent Candida (Fluconazole 150 mg qW)

  17. Treatment RecommendationsPregnancy • First Trimester • Metronidazole 250 mg po tid x 7 days • Clindamycin 300 mg po bid x 7 days • Clindamycin cream PV 5 g PV qhs x 7 days • Metronidazole gel PV bid x 5 days • Other Trimesters • Metronidazole 250 mg po tid x 7 days • Clindamycin 300 mg po bid x 7 days • Erythromycin 333 mg po tid x 14 days • Topical therapy (clindamycin vaginal cream) at 14-26 weeks not as effective in pregnancy • Increased PTD (Joesoef 1995, McGregor 1994)

  18. Safety of Metronidazole in Pregnancy • Hesitation to use oral metronidazole in pregnancy remains, especially in first trimester • Limited studies • Theoretic teratogenicity risk • Meta-analyses report no association between birth defects and use of metronidazole during pregnancy www.accuratepregnancytests.com (Piper 1993, Ledger 1993, Schwebke 1995, Burtin 1995)

  19. PID Post-induced abortion (Eschenbach 1993) Plasma cell endometritis 15x higher in women with BV (Korn 1995) Post-surgical Infection Post hyst cuff cellulitis (Larsson 1991) ?CIN (Boyle 1999, Frega1997) More common in women with PID BUT… Not independently responsible for PID (Soper 1994, Ness 2004) Clinical Associations Gynecologic www.uptodate.com Courtesy of Jack Sobel, MD

  20. Clinical Associations Obstetric • Approximately 15-20% of pregnant women in US have BV • Preterm Delivery • BV association with PTD: 1.8 and 2.2 pooled OR from meta-analyses (Flynn 1999, Leitich 2003) • Flynn- 19 studies • Pooled aOR yielded 60% increase in PTD in presence of BV • Leitich- 18 studies (over 20,000 patients) • Two-fold increase in PTD with BV (OR 2.2) • Early Dx and Tx may be more effective in prevention of PTD than late second trimester management • BV dx < 16 weeks: PTD OR 7.55 (1.80-31.65) • BV dx < 20 weeks: PTD OR 4.20 (2.11-8.39) • SAB OR 9.91 (1.99-49.34) • Maternal Infection OR 2.53 (1.26-5.08) (Hillier 1995, Meis 1995, Hauth 1995)

  21. Clinical Associations Obstetric • Potential Mechanism of BV association with PTL/PTD • Genetic polymorphism in regulation of cytokine production/TNF-2 with greater pro-inflammatory immune response to infectious stimuli (BV) (Macones 2004, Romero 2003) • “Susceptible” genotype (TNf-2 allele) and BV yielded OR 6.1of PTD vs. OR 2.7 in setting of TNF-2 allele alone (Macones 2004) • Enhanced cytokine induction possibly leading to PTL or PPROM • Women with altered vaginal flora developed elevated IL-1beta and subsequently are at higher risk of PTB than women with similar altered flora but no IL-1beta elevation • Sensitivity of 78%; specificity 51% (Genc 1995)

  22. Clinical Associations Obstetric • Chorioamnionitis • (Eschenbach 1989, Hillier 1988) • Amniotic fluid infection • OR 1.85 (1.16-2.9) (Newton 1997) • Spontaneous abortions • Increased risk of 1st trimester SAB in IVF aOR 2.03 (1.09-3.78) • Diagnosed more frequently in women w/ h/o late miscarriage (Llahi-Camp 1995) • Associated with 2nd trimester loss (McGregor 1995, Hay 199$) • 2nd trimester loss AB OR 9.91 (1.99-49.34) (Leitich 2003) • PPROM: • OR 7.3 (McGregor 19993) • Postpartum Endometritis • OR 2.53 (1.26-5.08) (Leitich 2003) • PP endometritis post c/section: RR 1.4 (Newton); aOR 5.8 (Watts 1990) • PP endometritis post VD: RR 14.2 (Newton 1990)

  23. Clinical Associations Pediatric • Low-birth weight • In setting of PTD (Hillier 1995) • ?Neonatal Infections

  24. ConsiderationsScreening/Treatment in Pregnancy • Studies do not show reduction of PTD or other adverse prenatal outcomes with treatment of asymptomatic BV in pregnant women (McDonald 2003, Carey 2000, McDonald1997) • Cochrane Review 2003: • 10 trials/>4200 patients • Abx therapy effective in eradicating infection • No significant reduction of PTB at < 37 weeks, at < 34 weeks, or <32 weeks (McDonald 2003) • Screening and treating all pregnant women with asymptomatic bacterial vaginosis to prevent PTD NOT RECOMMENDED • (McDonald 2003)

  25. ConsiderationsScreening/Treatment in Pregnancy • Cochrane Review 2003 (McDonald 2003) • Subgroup analysis of women with a history of >1 prior preterm births • Detection and treatment of asymptomatic bacterial vaginosis in this population appeared to markedly reduce the rate of PPROM (OR 0.14, 95% CI 0.05-0.38) and low birth weight (OR 0.31, 95% CI 0.13-0.75) • No significant affect on risk of subsequent preterm birth (OR 0.83, 95% CI 0.59-1.17) • Lack of reduction in preterm birth was largely due to data from the largest (n = 1953) trial of screening and treatment of bacterial vaginosis in pregnant women, which reported an absence of benefit in both average risk women and in the subgroup of women at high risk of preterm birth (n = 210) (Carey 2000)

  26. ConsiderationsScreening/Treatment in Pregnancy • US Preventive Services Task Force (7 RTC)

  27. ConsiderationsScreening/Treatment in Pregnancy • USPSTF

  28. ConsiderationsScreening/Treatment in Pregnancy • US PSTF

  29. ConsiderationsScreening/Treatment in Pregnancy • Recommendation *Screening and treatment of bacterial vaginosis could be considered in women with a previous preterm birth in order to lower the rate of preterm premature rupture of membranes and low birth weight, as these conditions are associated with maternal and neonatal morbidity *But still not recommended as standard of care for women with prior PTD -Cochrane Review -Centers for Disease Control and Prevention -United States Preventive Services Task Force

  30. ConsiderationsScreening/Treatment in Pregnancy • Still Unclear • Optimal choice of therapy • Time of therapy initiation • Therapy duration

  31. First three trials demonstrating reduction in preterm birth in high risk patients had screened patients in the second trimester Women with positive test results were treated with oral metronidazole or oral metronidazole and erythromycin (Morales 1994, Hauth 1995, McDonald 1997) Seven days of treatment may be more effective than two day regimens (Leitich 2003) Oral clindamycin (300 mg twice daily for five days) or clindamycin cream (daily per vagina for three to seven days) given early in pregnancy were effective alternatives (Ugwumadu 2004, Kiss 2004, Ugwumadu 2003, Lamont 2003) ConsiderationsScreening/Treatment in Pregnancy

  32. ConsiderationsScreening/Treatment in Pregnancy • CDC If women with prior PTD is screened in subsequent pregnancy • Perform at first PNV • Initiate treatment at that time if BV diagnosed • F/U evaluation in 1 month after completion of therapy CDCP; STD Treatment Guidelines 2002

  33. ConsiderationsScreening/Treatment in Pregnancy

  34. Clinical Associations HIV www.vpul.upenn.edu • BV more prevalent and more persistent in HIV-infected women • Prospective cohort study • Patients followed over 5 years; exams Q6 months • Adjusted analyses • HIV+ women more likely than HIV- women to have prevalence of BV aOR 1.29 (1.08-1.55) • HIV+ women more likely than HIV- women to have persistent BV aOR 1.49 (1.18-1.89) • HIV+/CD4<200 more likely than HIV+/CD4 >500 to have prevalence of BV aOR1.29 (1.03-1.60); persistent BV aOR 1.38 (1.01-1.91); more severe BV aOR 1.50 (1.12-2.0) Jamieson 2001

  35. Clinical Associations HIV • BV-associated microflora isolated from female genital tract activates HIV-1 expression (Al-Harthi 1999; Hashemi 1999; Hashemi 2000) • Possible risk factor for HIV acquisition and transmission

  36. Clinical Associations HIV • BV independently associated with HIV seroprevalence • Cross sectional study • 144 female commercial sex workers • Tested for gonorrhea, Chlamydia, syphilis, Candida, Trichomonas, HIV, BV (clinical criteria and Gram stain) • BV association with HIV OR 2.7 (1.3-5.0) by clinical criteria • BV association with HIV aOR 4.0 (1.7-9.4) • Relationship: ?HIV promotion of abnormal vaginal flora or does BV increase susceptibility of HIV sexual transmission • OR intervening variables: BV marker or cofactor of HIV transmission Cohen 1995

  37. Clinical Associations HIV • Association between BV and HIV-1 among pregnant and post-natal women • Prospective cohort • BV associated with antenatal seroconversion aOR 3.7 • BV associated with postnatal HIV seroconversion aOR 2.3 • Increased risk of HIV seroconversion with increasing severity of vaginal disturbance • Attributable risk of BV alone for HIV seroconversion • Antenatal 23% • Postnatal 14% Taha 1998

  38. Clinical Associations HIV • Increased HIV-1 infection in women with abnormal vaginal flora (Sewankambo 1997) • Prospective cohort study (Martin 1999) • Absence of vaginal lactobacilli per culture associated with increase risk acquisition HIV-1, HR 2.0 (1.2-3.5); gonorrhea, HR 1.7 (1.2-2.6) • Presence of abnormal vaginal flora on Gram stain associated with increased risk acquisition HIV-1, HR 1.9 (1.1-3.1); Trichomonas, HR 1.8, (1.3-2.4) • Controlled for identified RF using multivariate models

  39. Clinical Associations HIV Martin et al, 1999

  40. Clinical Associations HIV www.wooster.edu • Bacterial vaginosis associated with HIV-1 RNA expression in female genital tract of HIV-infected women • Cross sectional cohort study • Assessed for effect of lower GTI on HIV-1 RNA levels • 108 HIV infected women (136 paired plasma and cervicovaginal lavage specimens) • Assessed by BV (Amsel’s), Trichomonas (culture), Candida (culture and clinical criteria) • Defined threshold HIV-1 RNA levels >400 copies/ml • Logistic regression adjusting for plasma VL, ARV, and CD4 count Cu-Uvin et al, 2001

  41. Clinical Associations HIV Detectable HIV-1 RNA Cu-Uvin et al, 2001

  42. Clinical Associations HIV Proportion of women with plasma HIV type 1 (HIV-1) RNA level >400 copies/mL from whom cervicovaginal lavage (CVL) samples were obtained that had an HIV-1 RNA level >400 copies/mL, stratified by genital tract infection status and receipt of highly active antiretroviral therapy (HAART). Vertical bars represent 95% CIs for the estimated proportions. Neg, negative results of tests for infection; Pos, positive results of tests for infection. Cu-Uvin et al, 2001

  43. Clinical Associations HIV Cu-Uvin et al, 2001

  44. Clinical Associations HIV • Conclusion: Cu-Uvin et al, 2001 • BV associated with increased expression of HIV-1 RNA levels in female genital tract • Limitation of small sample size of women with genital tract infections other than BV • BV may be surrogate marker for other nonspecific inflammatory states or behavioral/clinical factors increasing risk of HIV RNA expression • Plausibility of BV as RF for HIV acquisition and transmission • BV-associated microflora isolated from female genital tract activates HIV expression (Al-Harthi 1999; Hashemi 1999; Hashemi 2000) • In vitro evidence for increased pro-inflammatory cytokines (TNF-alpha and IL-1) in patients with BV; ?thereby increased risk for HIV susceptibility associated with BV (Sturm-Ramirez 2000)

  45. Future ConsiderationsHIV Control • Studies investigating treatment/control of BV effect on reduction of HIV viral load in genital tract and ultimately HIV sexual/perinatal transmission • Development and evaluation of vaginal microbicides consisting of naturally occurring Lactobacillus

  46. ConsiderationsSexual Transmission • Controversy remains • Occurs more commonly in women with more than one sexual partner • BUT can also occur in women not yet sexually active • No difference in BV rates between sexually active and not yet sexually active groups (Bump 1988, Yen 2003) • Treatment of male partner: no improvement in cure rates or reduced rate of recurrence (Moi 1989) • Treatment of sexual partner not recommended • Variable Co-infection rates • Chlamydia and gonorrhea increased • No difference in syphilis or Trichomonas • Not exclusively STI

More Related