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

2. Ditas D. Decena, MD, FPOGS, MPH
PHYSIOLOGICAL and THERAPEUTIC APROACH TO VAGINAL INFECTIONS UPDATES AND CONTROVERSIES
Ditas D. Decena, MD, FPOGS, MPH
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

4. 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

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

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

7. 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

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

9. 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):

10. 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):

11. 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

12. Vaginal Ecosystem estrogen glycogen lactobacilli lactic acid
Promotes growth of lactobacilli, inhibits growth of pathogenic bacteria
Oral contraceptives may cause an increase in the glycogen and sugar substrate content of the vaginal epithelium eventually leading to decrease in vaginal pH. This will promote yeast proliferation which thrive in a very low pH.
lactic acid
pH 3.8 – 4.5

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 (H2O2)
Bacteriocins

15. 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):

16. 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

17. Vulvar vs. Vaginal Infection
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
Candidiasis
Trichomoniasis BV
Predominant symptom
pruritus
Profuse discharge
Foul odor
Characteristic discharge
Curd like
Frothy
Thin grayish white pH 4 5 6
Gram stain
Pseudo hyphae
(-)
Gram (-) rods
NSS mount
Flagellated protozoa
Clue cells
10% KOH
Hyphae on microscopy
+ amine odor

20. Trichomonas Vaginalis
Bubbly discharge
Pap’s smear showing resemblance of WBCs to nonmotile parasites

21. Vulvovaginal Candidiasis

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

23. Therapeutic Approach to Vaginal Infections

24. 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

25. 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

26. 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

27. 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

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

29. Physiological Approaches to Infections
Feminine wash
Douche
Vaginal gel

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

31. Acidic Wash vs. Soap Soap Acid wash Cross-over Koring et al.1995 pH
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.
10.25
10.00 1 2 3 10 17 24 31 38 45 52 59
9.50
9.75
9.25
9.00
8.75
8.50
8.25
8.00
7.75
7.50
7.25
Days
Propionibacteria/cm2 (log)
Cross-over
4.00
4.25
4.50
4.75
5.00
5.25
5.50 pH
Koring et al.1995
Soap
Acid wash

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

33. Lactoserum and Lactic Acid on External Genitalia in Thai Women
Number and percentage of women on rating the product according to the evaluation criteria
Evaluation criteria
Total number
Number and percentage of satisfaction
P-value
Fragrance free (%)
N = 100
Sweet flora (%)
Spring fresh (%)
Ease of use
Ability to refresh
Scent
Cleansing ability
Overall assessment
300
100 (100)
99 (99)
93 (93)
98 (98)
97 (97)
96 (96)
1.000
0.482
0.331
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 * * * 88
82.1
84.2 *
77.1 * 65
69.8 71
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

36. 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

37. The improvement of functional symptoms
3b. Experience of tenderness relief
100
98.4
100
100
96.8
92.1
98.2 *
94.6
94.6
94.6
92.9 79
80.7
62.5 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

38. 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

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

40. Meta-analysis of studies on vaginal douching and risk of pelvic inflammatory disease
1.0
0.6
0.4
0.2 2 3 4 5 6 7 8 9
Internal
Recent Douching
1-2 times/month
 3 times/month
Control
Random
≥ 3 times/month
≥ 4 times/month
ODDS RATIO
Wolner-Hanssen
Scholes
Pooled RR
Zhang et. Al
1997 

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

42. Meta-analysis of studies on vaginal douching and risk of ectopic pregnancy
Chow
Occasional 
Weekly
Daling
Overall
Once every few months
1/month
Weekly
Chow
Ever douched
Zhang et. Al
1997
Current douching
Phillips
Current douching
Kendrick
Current douching
> 10 years
Pooled RR
Current douching
0.2
0.4
0.6
1.0 2 3 4 5 6 7 8 9
ODDS RATIO

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 <0.001 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: , April, 2006

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

47. 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.

48. Lactic acid for internal hygiene
Adjunct treatment in bacterial vaginosis
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
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

51. Take home messages Vaginal Health Prevention
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.

52. Thank you!