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Updates and Controversies in the Management of Common Vulvovaginal Infections. January 13, 2009 Eaton Hotel Hongkong. Ditas D. Decena, MD, FPOGS, MPH. P HYSIOLOGICAL and T HERAPEUTIC A PROACH TO V AGINAL I NFECTIONS U PDATES AND C ONTROVERSIES.
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Updates and Controversies in the Management of Common Vulvovaginal Infections January 13, 2009 Eaton Hotel Hongkong Ditas D. Decena, MD, FPOGS, MPH
PHYSIOLOGICAL and THERAPEUTIC APROACH TO VAGINAL INFECTIONSUPDATES AND CONTROVERSIES • Professor in the Royal and Pontifical University,Faculty of Medicine & Surgery, • University of Santo Tomas, Manila Philippines • Masters in Public Health, University of the Philippines • Trained in Endoscopic Surgery in India and Maternal Nutrition at the University of • California, Davis • Member, Committee on Residency Training Program, University of Santo Tomas • Hospital Inc. Department of Obstetrics and Gynecology • Author of the study “Metronidazole with Lactacyd vaginal gel in Bacterial Vaginosis” • published in the Journal of Obstetrics and Gyecology Research 2006 Ditas D. Decena, MD, FPOGS, MPH
Points of Discussion • Determinants of infectious disease • Common vaginal infections • Bacterial vaginosis • Trichomoniasis • Candidiasis • Treatment modalities • Specific pharmacotherapy • Lactic acid, lactoserum wash, douche and gel
Infectious Disease • Result of interactions of microorganisms with host Disease = (number of organism X virulence of organism ) host defenses Smith
Determinants of Infectious Disease • Host’s defenses • Properties of microorganisms
1. Categories of Host Defenses • Anatomical barriers • Nonspecific cellular and humoral defenses • Immunologically specific cellular and humoral defenses • Local immunity Larsen B. Microbiology 2nd ed CREOG 1998
Anatomical Barriers • Performed by intact tissues (skin and mucosa) • Normal vaginal flora • Endocervical mucus (biochemical impediment) Larsen B. Microbiology 2nd ed CREOG 1998
Skin Barrier Homeostasis Acid mantle (ph 4.5 – 5.9) • Lactic acid and amino acid (sweat) • Free fatty acids (sebum) • Carboxylic and urocranic acid Rippke F. et al. Stratum Corneum pH in Atopic Dermatitis. Am J. Clin Dermatol 2004; 5 (4): 217-223
Skin pH (4.5 – 5.9) • Varies in different body areas • Depends on skin moisture content (higher moisture; higher pH) • Changes in pH → “contact & atopic dermatitis” Rippke F. et al. Stratum Corneum pH in Atopic Dermatitis. Am J. Clin Dermatol 2004; 5 (4): 217-223
Vulvar Skin • Stratified squamous epithelium • Contains hair follicles, sebaceous, sweat and apocrine glands • Has a high moisture content • Subject to both primary and secondary infections • Sensitive to hormonal, metabolic and allergic influences
estrogen glycogen lactic acid Vaginal Ecosystem lactobacilli Promotes growth of lactobacilli, inhibits growth of pathogenic bacteria pH 3.8 – 4.5
Endogenous vaginal flora of asymptomatic healthy women • Lactobacillus sp. • Corynebacterium • Diphtheroids • Streptococcus sp. • Staphylococcus epidermidis • Enterococcus faecalis • Escherichia coli • Klebsiella pneumoniae • Proteus vulgaris • Prevotella bivia • P. melaninogenica • Bacteroides fragilis • Fusobacterium nucleatum • Fusobacterium necrophorum Hillier SL. Normal vaginal flora. In: Holmes KK et al., eds. Sexually Transmitted Diseases. 1999:191-204.
HEALTHY VAGINALECOSYSTEM • Dominated by certain species of Lactobacillus that control and suppress the growth of other endogenous bacteria through different mechanisms: • - Lactic acid • - Hydrogen peroxide (H2O2) • Bacteriocins
2. Properties of Microorganisms • Virulence • Adhesiveness • Invasiveness • Adaptation • Proliferation • Growth inhibited at acid pH of 5 • Maximal growth at neutral pH • Optimum pH (3.8 – 4.5) growth of Lactobacilli Staphylococcus Larsen B. Microbiology 2nd ed CREOG 1998 Rippke F. et al. Stratum Corneum pH in Atopic Dermatitis. Am J. Clin Dermatol 2004; 5 (4): 217-223
LACTOBACILLUS Lactic Acid As lactobacilli grow, the production of lactic acid increases (~2.5 mg/mL) The production of lactic acid maintains the vaginal pH < 4.5 (creating an inhospitable environment for the growth of most endogenous pathogenic bacteria) Low pH is a primary mechanism for maintaining the equilibrium of a healthy vaginal ecosystem: as the pH of the vagina increases, bacteriocin loses its effectiveness, hydrogen peroxide is degraded, and lactobacilli cannot compete with the other bacteria
Anatomic distribution of symptoms occasionally creates a semantic misinterpretation of the clinical reality First symptom: vulvar pruritus First sign: erythema and edema of vulvar skin Vulvar vs. Vaginal Infection
Excessive vaginal fluid is not appreciated until fluid flows from vagina to vulva Vaginal infections Vulvovaginitis Semantic Compromise
Trichomonas Vaginalis Bubbly discharge Pap’s smear showing resemblance of WBCs to nonmotile parasites
Bacterial Vaginosis Characteristic milky vaginal discharge of BV Clue cells consistent with BV
Standard Treatment of BV • Metronidazole 500 mg twice daily for 7 days • Metronidazole gel 0.75%, 5 g intravaginally once daily for 5 days • Clindamycin cream 5%, 5 g intravaginally hs for 7 days Alternative Regimen • Clindamycin 300 mg twice daily for 7 days • Clindamycin ovules 100 g intravaginally hs for 3 days
Candidiasis Treatment Uncomplicated • Oral: Fluconazole 150 mg p. o. single dose Intravaginal • Butoconazole 2% cream 5g intravaginal X 3 days • Butoconazole 2% cream 5g (sustained release) single intravaginal application CDC 2006
Candidiasis Treatment Intravaginal • Clotrimazole 1% cream 5 g intravaginal X 7 – 14 days • Clotrimazole 100 mg tablet X 7 days • Clotrimazole 100 mg tablet – 2 tablets X 3 days • Clotrimazole 500 mg vaginal tablet – 1 tablet in a single application • Miconazole 2% cream 5 g intravaginal X 7 days • Miconazole 100 mg vaginal suppository X 7 days CDC 2006
Candidiasis Treatment • Miconazole 200 mg vaginal suppository – 1 supp. X 3 days • Nystatin 100,000 units vaginal tablet – 1 tablet X 14 days • Terconazole 0.4% cream 5 g intavaginal X 7 days • Terconazole 80 mg vaginal suppository X 3 days CDC 2006
Trichomonas Treatment • Metronidazole 2g p o single dose • Tinidazole 2g p o single dose Alternative • Metronidazole 500mg BID X 7 days CDC 2006
Physiological Approaches to Infections • Feminine wash • Douche • Vaginal gel
Why prescribe feminine wash? • Hygiene • Relieve vulvar irritation • Postpartum care: cleaning episiotomy wound • Prevention and /or treatment of vulvovaginitis
Cross-over Cross-over 10.25 10.00 5.50 9.75 5.25 9.50 9.25 5.00 9.00 Propionibacteria/cm2 (log) 8.75 pH 4.75 8.50 8.25 4.50 8.00 7.75 4.25 7.50 7.25 4.00 10 1 2 17 24 31 38 45 52 59 3 1 2 3 10 17 38 45 52 24 31 59 Days Days Soap Acid wash Evolution of the propiobacterium counts per square centimeters (1), and of the mean pH value (2) on the subjects foreheads during repeat applications of alkaline soap and acidic syndet in the frame of a comparative crossover trial - = soap first 4 weeks, then syndet for 4 weeks - = syndet first 4 weeks, the soap 4 for weeks. Koring et al.1995 Acidic Wash vs. Soap
Lactic acid for external hygiene • Provides relief of itching and reduces inflammation • Reacidifies the environment alkalinized by pathogens • Fights infections
Lactoserum and Lactic Acid on External Genitalia in Thai Women Number and percentage of women on rating the product according to the evaluation criteria High percentage of satisfaction and tolerability 2005 Tansupasiri et. Al. 2005
Assessment of the effectiveness and tolerability of Lactacyd FH when used as adjunctive external vaginal wash to standard treatment of Bacterial vaginosis Nguyen Thi Ngoc Phuong et al. Vietnam Gyne-OB Association Journal, 2005
The improvement of functional symptoms Experience of malodor relief * * 88 * 84.2 82.1 * 77.1 * 65 71 69.8 63.5 59.7 28.9 40.2 N=96 n=103 8 18.6 4.8 D1 D2 D3 D4 D5 D6 D7 (*) p< 0.05 Lactacyd FH use (n=96) Non-Lactacyd FH use (n=103) Nguyen Thi Ngoc Phuong et al. Vietnam OB Gyne Association 2005
The improvement of functional symptoms Experience of pruritus relief * * * * 100 98.6 98.6 98.6 * 91.7 90.3 91.2 89.7 89.7 88.2 89.7 66.7 75.0 57.4 D1 D2 D3 D4 D5 D6 D7 (*) p < 0.05 Lactacyd FH use (n=96) Non-Lactacyd FH use (n=103) Nguyen Thi Ngoc Phuong et al. Vietnam OB Gyne Association 2005
Conclusion • Adding Lactacyd FH as external vaginal wash to standard regimen (Metronidazole) in Bacterial vaginosis is useful in relieving symptoms. Nguyen Thi Ngoc Phuong et al. Vietnam OB Gyne Association 2005
Types of Douching Solution • Plain water • Water with acetic acid (acidic solution) • Betel • Povidone iodine • Lactic acid; lactoserum
Recent Douching Internal Wolner-Hanssen 1-2 times/month Control Random Control 1-2 times/month ≥ 3 times/month Scholes Recent Douching 3 times/month ≥ 4 times/month Recent Douching Pooled RR 1.0 2 0.2 0.4 0.6 3 4 5 6 7 8 9 Zhang et. Al 1997 ODDS RATIO Meta-analysis of studies on vaginal douching and risk of pelvic inflammatory disease
Possible factors for douching and PID • Pressure douching • Timing of douching during menstrual cycle • Frequency Zhang, Thomas 1997
Meta-analysis of studies on vaginal douching and risk of ectopic pregnancy Chow Occasional Weekly Overall Daling Once every few months 1/month Weekly Ever douched Chow Zhang et. Al 1997 Current douching Phillips Current douching Kendrick Current douching > 10 years Current douching Pooled RR 1.0 2 0.2 0.4 0.6 3 4 5 6 7 8 9 ODDS RATIO
Metronidazole with Lactacyd Vaginal gel in BVOpen-labeled, randomized, 3-arm comparative study
Effect of Treatment on Lactobacilli Colony Count* *Repeated Measures ANOVA: p<0.001 across visits; p=0.0045 at day 8 between lactic acid gel group and metronidazole group; p=0.0002 at day 14 between combination arm and metronidazole arm and between LVG arm and metronidazole arm. Decena, Sison, Manalastas, Padolina, Palaypayon, Co, Dancel, Lelis, J.Obstet.Gynaecol.Res Vol 32, No. 2:243-251, April, 2006
Effect of Treatment on Vaginal pH* Figure 2: Frequency of patients with Vaginal pH <4.7 across time *Cochran’s Q test: p <0.001 across visits; 2 test: p>0.05 across treatment groups Decena, Sison, Manalastas, Padolina, Palaypayon, Co, Dancel, Lelis, J.Obstet.Gynaecol.Res Vol 32, No. 2:243-251, April, 2006
Frequency of Recurrent* Foul-smelling Vaginal Discharge Recurrence of Foul-Smelling Vaginal Discharge at Day 56 4/28 (14.3%) Decena et. Al 2005 2/30 (6.7%) No. of Patients 1/28 (3.6%) *Fisher’s exact test: p=0.4965 across treatment groups.
Study Conclusion • Lactacyd vaginal gel (LVG) is safe and as efficacious as metronidazole in the treatment of bacterial vaginosis. • There is evidence that Lactacyd vaginal gel (LVG), when combined with metronidazole, is superior to metronidazole alone in promoting lactobacilli colonization • Lactacyd vaginal gel (LVG) as an adjunct to metronidazole appears to result to a better long-term treatment effect on BV.
Lactic acid for internal hygiene • Adjunct treatment in bacterial vaginosis • Promotes the growth of Lactobacilli
Physiological Therapeutic Approaches in Vaginal Infections Summary • Anatomical barriers as the acid mantle in the skin and normal vaginal flora are important host’s defenses • Lactic acid wash in combination with standard regimen is effective in relieving symptoms of Bacterial vaginosis • Lactic acid vaginal gel (LVG) is safe and as efficacious as metronidazole in the treatment of bacterial vaginosis. • Specific pharmacotherapy for vaginal infections is still the mainstay of treatment
Take home messages Vaginal Health The vaginal microflora does not consist of a static population but, rather, a dynamic one (types and concentrations continuously fluctuate in accordance with the changing environment). Prevention Lactic acid wash and gel has been shown to be tolerated and efficacious in prevention and treatment of vulvovaginal infections.