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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.

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Presentation on theme: "Updates and Controversies in the Management of Common Vulvovaginal Infections January 13, 2009 Eaton Hotel Hongkong Ditas D. Decena, MD, FPOGS, MPH."— Presentation transcript:

1 Updates and Controversies in the Management of Common Vulvovaginal Infections January 13, 2009 Eaton Hotel Hongkong Ditas D. Decena, MD, FPOGS, MPH

2 P HYSIOLOGICAL and T HERAPEUTIC A PROACH TO V AGINAL I NFECTIONS U PDATES AND C ONTROVERSIES Ditas D. Decena, MD, FPOGS, MPH Professor in the Royal and Pontifical University,Faculty of Medicine & Surgery, Professor in the Royal and Pontifical University,Faculty of Medicine & Surgery, University of Santo Tomas, Manila Philippines University of Santo Tomas, Manila Philippines Masters in Public Health, University of the Philippines Masters in Public Health, University of the Philippines Trained in Endoscopic Surgery in India and Maternal Nutrition at the University of Trained in Endoscopic Surgery in India and Maternal Nutrition at the University of California, Davis California, Davis Member, Committee on Residency Training Program, University of Santo Tomas Member, Committee on Residency Training Program, University of Santo Tomas Hospital Inc. Department of Obstetrics and Gynecology Hospital Inc. Department of Obstetrics and Gynecology Author of the study “Metronidazole with Lactacyd vaginal gel in Bacterial Vaginosis” Author of the study “Metronidazole with Lactacyd vaginal gel in Bacterial Vaginosis” published in the Journal of Obstetrics and Gyecology Research 2006 published in the Journal of Obstetrics and Gyecology Research 2006

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4 Points of Discussion Determinants of infectious disease Determinants of infectious disease Common vaginal infections Common vaginal infections Bacterial vaginosis Bacterial vaginosis Trichomoniasis Trichomoniasis Candidiasis Candidiasis Treatment modalities Treatment modalities Specific pharmacotherapy Specific pharmacotherapy Lactic acid, lactoserum wash, douche and gel Lactic acid, lactoserum wash, douche and gel

5 Infectious Disease Result of interactions of microorganisms with host Result of interactions of microorganisms with host Disease = (number of organism X virulence of organism ) host defenses Smith

6 Determinants of Infectious Disease 1. Host’s defenses 2. Properties of microorganisms

7 1. Categories of Host Defenses Anatomical barriers Anatomical barriers Nonspecific cellular and humoral defenses Nonspecific cellular and humoral defenses Immunologically specific cellular and humoral defenses Immunologically specific cellular and humoral defenses Local immunity Local immunity Larsen B. Microbiology 2 nd ed CREOG 1998

8 Anatomical Barriers Performed by intact tissues (skin and mucosa) Performed by intact tissues (skin and mucosa) Normal vaginal flora Normal vaginal flora Endocervical mucus (biochemical impediment) Endocervical mucus (biochemical impediment) Larsen B. Microbiology 2 nd ed CREOG 1998

9 Skin Barrier Homeostasis Acid mantle (ph 4.5 – 5.9) Lactic acid and amino acid (sweat) Lactic acid and amino acid (sweat) Free fatty acids (sebum) Free fatty acids (sebum) Carboxylic and urocranic acid Carboxylic and urocranic acid Rippke F. et al. Stratum Corneum pH in Atopic Dermatitis. Am J. Clin Dermatol 2004; 5 (4):

10 Skin pH (4.5 – 5.9) Varies in different body areas Varies in different body areas Depends on skin moisture content (higher moisture; higher pH) Depends on skin moisture content (higher moisture; higher pH) Changes in pH → “contact & atopic dermatitis” Changes in pH → “contact & atopic dermatitis” Rippke F. et al. Stratum Corneum pH in Atopic Dermatitis. Am J. Clin Dermatol 2004; 5 (4):

11 Vulvar Skin Stratified squamous epithelium Stratified squamous epithelium Contains hair follicles, sebaceous, sweat and apocrine glands Contains hair follicles, sebaceous, sweat and apocrine glands Has a high moisture content Has a high moisture content Subject to both primary and secondary infections Subject to both primary and secondary infections Sensitive to hormonal, metabolic and allergic influences Sensitive to hormonal, metabolic and allergic influences

12 lactobacilli Promotes growth of lactobacilli, inhibits growth of pathogenic bacteria lactic acid estrogen glycogen pH 3.8 – 4.5 Vaginal Ecosystem

13 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:

14 HEALTHY VAGINAL ECOSYSTEM Dominated by certain species of Lactobacillus that control and suppress the growth of other endogenous bacteria through different mechanisms: - Lactic acid - Hydrogen peroxide (H 2 O 2 ) - Bacteriocins

15 2. Properties of Microorganisms Virulence Virulence Adhesiveness Adhesiveness Invasiveness Invasiveness Adaptation Adaptation Proliferation Proliferation Growth inhibited at acid pH of 5 Growth inhibited at acid pH of 5 Maximal growth at neutral pH Maximal growth at neutral pH Optimum pH (3.8 – 4.5) growth of Lactobacilli Optimum pH (3.8 – 4.5) growth of Lactobacilli Staphylococcus Larsen B. Microbiology 2 nd ed CREOG 1998 Rippke F. et al. Stratum Corneum pH in Atopic Dermatitis. Am J. Clin Dermatol 2004; 5 (4):

16 LACTOBACILLUS As lactobacilli grow, the production of lactic acid increases (~2.5 mg/mL) Lactic Acid 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

17 Vulvar vs. Vaginal Infection Anatomic distribution of symptoms occasionally creates a semantic misinterpretation of the clinical reality 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

18 Semantic Compromise Excessive vaginal fluid is not appreciated until fluid flows from vagina to vulva Vaginal infections Vulvovaginitis

19 Common Vaginal Infections CandidiasisTrichomoniasisBV Predominant symptom pruritus Profuse discharge Foul odor Characteristic discharge Curd like Frothy Thin grayish white pH456 Gram stain Pseudo hyphae (-) Gram (-) rods NSS mount Pseudo hyphae Flagellated protozoa Clue cells 10% KOH Hyphae on microscopy (-) + amine odor

20 Trichomonas Vaginalis Bubbly dischargePap’s smear showing resemblance of WBCs to nonmotile parasites

21 Vulvovaginal Candidiasis

22 Characteristic milky vaginal discharge of BV Clue cells consistent with BV Bacterial Vaginosis

23 Therapeutic Approach to Vaginal Infections

24 Standard Treatment of BV Metronidazole 500 mg twice daily for 7 days Metronidazole 500 mg twice daily for 7 days Metronidazole gel 0.75%, 5 g intravaginally once daily for 5 days Metronidazole gel 0.75%, 5 g intravaginally once daily for 5 days Clindamycin cream 5%, 5 g intravaginally hs for 7 days Clindamycin cream 5%, 5 g intravaginally hs for 7 days Alternative Regimen Clindamycin 300 mg twice daily for 7 days Clindamycin 300 mg twice daily for 7 days Clindamycin ovules 100 g intravaginally hs for 3 days Clindamycin ovules 100 g intravaginally hs for 3 days

25 Candidiasis Treatment Uncomplicated Oral: Fluconazole 150 mg p. o. single dose Oral: Fluconazole 150 mg p. o. single doseIntravaginal Butoconazole 2% cream 5g intravaginal X 3 days Butoconazole 2% cream 5g intravaginal X 3 days Butoconazole 2% cream 5g (sustained release) single intravaginal application Butoconazole 2% cream 5g (sustained release) single intravaginal application CDC 2006

26 Candidiasis Treatment Intravaginal Clotrimazole 1% cream 5 g intravaginal X 7 – 14 days Clotrimazole 1% cream 5 g intravaginal X 7 – 14 days Clotrimazole 100 mg tablet X 7 days Clotrimazole 100 mg tablet X 7 days Clotrimazole 100 mg tablet – 2 tablets X 3 days Clotrimazole 100 mg tablet – 2 tablets X 3 days Clotrimazole 500 mg vaginal tablet – 1 tablet in a single application Clotrimazole 500 mg vaginal tablet – 1 tablet in a single application Miconazole 2% cream 5 g intravaginal X 7 days Miconazole 2% cream 5 g intravaginal X 7 days Miconazole 100 mg vaginal suppository X 7 days Miconazole 100 mg vaginal suppository X 7 days CDC 2006

27 Candidiasis Treatment Miconazole 200 mg vaginal suppository – 1 supp. X 3 days Miconazole 200 mg vaginal suppository – 1 supp. X 3 days Nystatin 100,000 units vaginal tablet – 1 tablet X 14 days Nystatin 100,000 units vaginal tablet – 1 tablet X 14 days Terconazole 0.4% cream 5 g intavaginal X 7 days Terconazole 0.4% cream 5 g intavaginal X 7 days Terconazole 80 mg vaginal suppository X 3 days Terconazole 80 mg vaginal suppository X 3 days CDC 2006

28 Trichomonas Treatment Metronidazole 2g p o single dose Metronidazole 2g p o single dose Tinidazole 2g p o single dose Tinidazole 2g p o single doseAlternative Metronidazole 500mg BID X 7 days Metronidazole 500mg BID X 7 days CDC 2006

29 Physiological Approaches to Infections Feminine wash Feminine wash Douche Douche Vaginal gel Vaginal gel

30 Why prescribe feminine wash? 1. Hygiene 2. Relieve vulvar irritation 3. Postpartum care: cleaning episiotomy wound 4. Prevention and /or treatment of vulvovaginitis

31 Acidic Wash vs. Soap 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 Days Propionibacteria/cm 2 (log) Cross-over Days pH Cross-over Koring et al.1995 Soap Acid wash

32 Lactic acid for external hygiene Provides relief of itching and reduces inflammation Provides relief of itching and reduces inflammation Reacidifies the environment alkalinized by pathogens Reacidifies the environment alkalinized by pathogens Fights infections Fights infections

33 Lactoserum and Lactic Acid on External Genitalia in Thai Women Evaluation criteria Total number Number and percentage of satisfaction P- value Fragrance free (%) N = 100 Sweet flora (%) N = 100 Spring fresh (%) N = Ease of use 2. Ability to refresh 3. Scent 4. Cleansing ability 5. Overall assessment (100) 99 (99) 93 (93) 98 (98) 100 (100) 99 (99) 100 (100) 97 (97) 100 (100) 99 (99) 100 (100) 96 (96) 100 (100) 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

34 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

35 The improvement of functional symptoms Experience of malodor relief D1D2D3D4D5D6D7 Lactacyd FH use (n=96) Non-Lactacyd FH use (n=103) * * * * * (*) p< 0.05 N=96 n=103 Nguyen Thi Ngoc Phuong et al. Vietnam OB Gyne Association 2005

36 Experience of pruritus relief D1D2D3D4D5D6D7 Lactacyd FH use (n=96)Non-Lactacyd FH use (n=103) * *** (*) p < 0.05 * The improvement of functional symptoms Nguyen Thi Ngoc Phuong et al. Vietnam OB Gyne Association 2005

37 3b. Experience of tenderness relief D1D2D3D4D5D6D7 Lactacyd FH use (n=96)Non-Lactacyd FH use (n=103) (*) p< 0.05 * The improvement of functional symptoms Nguyen Thi Ngoc Phuong et al. Vietnam OB Gyne Association 2005

38 Conclusion Adding Lactacyd FH as external vaginal wash to standard regimen (Metronidazole) in Bacterial vaginosis is useful in relieving symptoms. 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

39 Types of Douching Solution Plain water Plain water Water with acetic acid (acidic solution) Water with acetic acid (acidic solution) Betel Betel Povidone iodine Povidone iodine Lactic acid; lactoserum Lactic acid; lactoserum

40 Meta-analysis of studies on vaginal douching and risk of pelvic inflammatory disease Internal Recent Douching 1-2 times/month  3 times/month Control Random Recent Douching Control 1-2 times/month ≥ 3 times/month ≥ 4 times/month Recent Douching ODDS RATIO Wolner-Hanssen Scholes Pooled RR Zhang et. Al 1997        

41 Possible factors for douching and PID Pressure douching Pressure douching Timing of douching during menstrual cycle Timing of douching during menstrual cycle Frequency Frequency Zhang, Thomas 1997

42 Meta-analysis of studies on vaginal douching and risk of ectopic pregnancy Occasional Weekly 1/month Overall Once every few months             Weekly Ever douched Current douching > 10 years ODDS RATIO Chow Daling Chow Phillips Kendrick Pooled RR Zhang et. Al 1997

43 Metronidazole with Lactacyd Vaginal gel in BV Open-labeled, randomized, 3-arm comparative study

44 Effect of Treatment on Lactobacilli Colony Count* *Repeated Measures ANOVA: p<0.001 across visits; p= at day 8 between lactic acid gel group and metronidazole group; p= 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: , April, 2006

45 Effect of Treatment on Vaginal pH* Figure 2: Frequency of patients with Vaginal pH <4.7 across time *Cochran’s Q test: p 0.05 across treatment groups Decena, Sison, Manalastas, Padolina, Palaypayon, Co, Dancel, Lelis, J.Obstet.Gynaecol.Res Vol 32, No. 2: , April, 2006

46 Recurrence of Foul-Smelling Vaginal Discharge at Day 56 Frequency of Recurrent* Foul-smelling Vaginal Discharge *Fisher’s exact test: p= across treatment groups. No. of Patients 2/30 (6.7%) 4/28 (14.3%) 1/28 (3.6%) Decena et. Al 2005

47 Study Conclusion Lactacyd vaginal gel (LVG) is safe and as efficacious as metronidazole in the treatment of bacterial vaginosis. 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 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. Lactacyd vaginal gel (LVG) as an adjunct to metronidazole appears to result to a better long- term treatment effect on BV.

48 Lactic acid for internal hygiene Adjunct treatment in bacterial vaginosis Adjunct treatment in bacterial vaginosis Promotes the growth of Lactobacilli Promotes the growth of Lactobacilli

49 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 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 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. 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 Specific pharmacotherapy for vaginal infections is still the mainstay of treatment

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51 Take home messages 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). 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). Lactic acid wash and gel has been shown to be tolerated and efficacious in prevention and treatment of vulvovaginal infections.

52 Thank you!


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