Topical Treatment of Infectious Vaginitis: Effects of Antibiotic, Antifungal and Antiseptic Drugs on the Growth of Normal Vaginal Lactobacillus Strains
Affiliation(s)
1 Laboratoire de Bactériologie Clinique, Faculté de Pharmacie, Lille, France. 2 Laboratoire Innotech International, Arcueil, France. 3 Laboratorium voor Farmaceutische Microbiologie, Gent, Belgium.
1 Laboratoire de Bactériologie Clinique, Faculté de Pharmacie, Lille, France. 2 Laboratoire Innotech International, Arcueil, France. 3 Laboratorium voor Farmaceutische Microbiologie, Gent, Belgium.
ABSTRACT
Objectives: The balance of the vaginal ecosystem depends on lactobacilli whose biofilm protectsagainst microorganisms that are not normally present or are subdominant in vaginal flora. Vaginal infection treatments should eliminate pathogens while preserving the Lactobacillus flora to prevent relapse or recurrence. The objective of this study was to determine the sensitivity of lactobacilli to antiseptics, antibiotics and antifungal agents used, alone or in combination, in the topical treatment of infectious vaginitis. Materials and Methods: The minimum inhibitory concentration (MIC) of 15 active ingredients and the minimum inhibitory dilution (MID) of 17 pharmaceuticals products were determined for three main Lactobacillus strains (L. crispatus, L. gasseri and L. jensenii). Results: The MICs of the antibiotics and antifungal agents were above their critical concentrations in the three strains, contrary to the antiseptics. According to their MID, some pharmaceutical products, especially combinations, inhibit the growth of one or more strains at concentrations that can be found in the vaginal mucosa after application at the usual dosage. Conclusions: Certain topical anti-infective drugs may interfere with the growth of lactobacilli, worsening the vaginal flora imbalance. Maintaining vaginal flora balance should be a selection criterion when choosing an anti-infective therapy.
Cite this paper
Neut, C. , Verrière, F. , Nelis, H. and Coenye, T. (2015) Topical Treatment of Infectious Vaginitis: Effects of Antibiotic, Antifungal and Antiseptic Drugs on the Growth of Normal Vaginal Lactobacillus Strains. Open Journal of Obstetrics and Gynecology, 5, 173-180. doi: 10.4236/ojog.2015.53024.
Neut, C. , Verrière, F. , Nelis, H. and Coenye, T. (2015) Topical Treatment of Infectious Vaginitis: Effects of Antibiotic, Antifungal and Antiseptic Drugs on the Growth of Normal Vaginal Lactobacillus Strains. Open Journal of Obstetrics and Gynecology, 5, 173-180. doi: 10.4236/ojog.2015.53024.
References
[1] Reid, G. (2001) Probiotic Agents to Protect the Urogenital Tract against Infection. The American Journal of Clinical Nutrition, 73, 437S-443S. [2] Hyman, R.W., Fukushima, M., Diamond, L., Kumm, J., Giudice, L.C. and Davis, R.W. (2005) Microbes on the Human Vaginal Epithelium. Proceedings of the National Academy of Sciences of the United States of America, 102, 7952-7957.
http://dx.doi.org/10.1073/pnas.0503236102 [3] Hay, P. (2005) Life in the Littoral Zone: Lactobacilli Losing the Plot. Sexually Transmitted Infections, 81, 100-102.
http://dx.doi.org/10.1136/sti.2003.007161 [4] Dover, S.E., Aroutcheva, A.A., Faro, S. and Chikindas, M.L. (2008) Natural Antimicrobials and Their Role in Vaginal Health: A Short Review. International Journal of Probiotics and Prebiotics, 3, 219-230. [5] Boskey, E.R., Telsch, K.M., Whaley, K.J., Moench, T.R. and Cone, R.A. (1999) Acid Production by Vaginal Flora in Vitro Is Consistent with the Rate and Extent of Vaginal Acidification. Infection and Immunity, 67, 5170-5175. [6] Atassi, F. and Servin, A.L. (2010) Individual and Co-Operative Roles of Lactic Acid and Hydrogen Peroxide in the Killing Activity of Enteric Strain Lactobacillus Johnsonii NCC933 and Vaginal Strain Lactobacillus Gasseri KS120.1 against Enteric, Uropathogenic and Vaginose-Associated Pathogens. FEMS Microbiology Letters, 304, 29-38.
http://dx.doi.org/10.1111/j.1574-6968.2009.01887.x [7] Eschenbach, D.A., Davick, P.R., Williams, B.L., Klebanoff, S.J., Young-Smith, K., Critchlow, C.M. and Holmes, K.K. (1989) Prevalence of Hydrogen Peroxide-Producing Lactobacillus Species in Normal Women and Women with Bacterial Vaginosis. Journal of Clinical Microbiology, 27, 251-256. [8] Mijac, V.D., Duki?, S.V., Opavski, N.Z., Duki?, M.K. and Ranin, L.T. (2006) Hydrogen Peroxide Producing Lactobacilli in Women with Vaginal Infections. The European Journal of Obstetrics & Gynecology and Reproductive Biology, 129, 69-76.
http://dx.doi.org/10.1016/j.ejogrb.2005.11.036 [9] Ravel, J., Gajer, P., Abdo, Z., Schneider, G.M., Koenig, S.S., McCulle, S.L., Karlebach, S., Gorle, R., Russell, J., Tacket, C.O., Brotman, R.M., Davis, C.C., Ault, K., Peralta, L. and Forney, L.J. (2011) Vaginal Microbiome of Reproductive-Age Women. Proceedings of the National Academy of Sciences of the United States of America, 15, 4680-4687.
http://dx.doi.org/10.1073/pnas.1002611107 [10] Martín, R., Soberón, N., Escobedo, S. and Suárez, J.E. (2009) Bacteriophage Induction versus Vaginal Homeostasis: Role of H(2)O(2) in the Selection of Lactobacillus Defective Prophages. International Microbiology, 12, 131-136. [11] Zozaya-Hinchliffe, M., Lillis, R., Martin, D.H. and Ferris, M.J. (2010) Quantitative PCR Assessments of Bacterial Species in Women with and without Bacterial Vaginosis. Journal of Clinical Microbiology, 48, 1812-1829.
http://dx.doi.org/10.1128/JCM.00851-09 [12] Turovskiy, Y., Sutyak Noll, K. and Chikindas, M.L. (2011) The Aetiology of Bacterial Vaginosis. Journal of Applied Microbiology, 110, 1105-1128.
http://dx.doi.org/10.1111/j.1365-2672.2011.04977.x [13] Bohbot, J.M., Sednaoui, P., Verriere, F. and Achhammer, I. (2012) The Etiologic Diversity of Vaginitis. Gynécologie Obstétrique & Fertilité, 40, 578-581.
http://dx.doi.org/10.1016/j.gyobfe.2011.08.001 [14] Spinillo, A., Capuzzo, E., Acciano, S., De Santolo, A. and Zara, F. (1999) Effect of Antibiotic Use on the Prevalence of Symptomatic Vulvovaginal Candidiasis. American Journal of Obstetrics and Gynecology, 180, 14-17.
http://dx.doi.org/10.1016/S0002-9378(99)70141-9 [15] Chen, J.Y., Tian, H. and Beigi, R.H. (2009) Treatment Considerations for Bacterial Vaginosis and the Risk of Recurrence. Journal of Women’s Health, 18, 1997-2004.
http://dx.doi.org/10.1089/jwh.2008.1088 [16] Corsello, S., Spinillo, A., Osnengo, G., Penna, C., Guaschino, S., Beltrame, A., Blasi, N. and Festa, A. (2003) An Epidemiological Survey of Vulvovaginal Candidiasis in Italy. European Journal of Obstetrics & Gynecology and Reproductive Biology, 110, 66-72.
http://dx.doi.org/10.1016/S0301-2115(03)00096-4 [17] Razzak, M.S., Al-Charrakh, A.H. and Al-Greitty, B.H. (2011) Relationship between Lactobacilli and Opportunistic Bacterial Pathogens Associated with Vaginitis. North American Journal of Medical Sciences, 3, 185-192. [18] Agnew, K.J. and Hillier, S.L. (1995) The Effect of Treatment Regimens for Vaginitis and Cervicitis on Vaginal Colonization by Lactobacilli. Sexually Transmitted Diseases, 22, 269-273.
http://dx.doi.org/10.1097/00007435-199509000-00001 [19] Soussy, C.J. (2012) Antibiogram Committee of the French Society for Microbiology, Recommendations. http://www.sfm-microbiologie.org/UserFiles/files/casfm/CASFM_2012.pdf [20] Odds, F.C. and MacDonald, F. (1981) Persistence of Miconazole in Vaginal Secretions after Single Applications. Implications for the Treatment of Vaginal Candidosis. British Journal of Venereal Diseases, 57, 400-401. [21] Mendling, W. and Plempel, M. (1982) Vaginal Secretion Levels after 6 Days, 3 Days and 1 Day of Treatment with 100, 200 and 500 mg Vaginal Tablets of Clotrimazole and Their Therapeutic Efficacy. Chemotherapy, 28, 43-47.
http://dx.doi.org/10.1159/000238151 [22] Houang, E.T. and Lawrence, A.G. (1985) Systemic Absorption and Persistence of Tioconazole in Vaginal Fluid after Insertion of a Single 300-mg Tioconazole Ovule. Antimicrobial Agents and Chemotherapy, 27, 964-965.
http://dx.doi.org/10.1128/AAC.27.6.964 [23] Jones, R.N., Bale, M.J., Hoban, D. and Erwin, M.E. (1993) In Vitro Antimicrobial Activity of Tioconazole and Its Concentrations in Vaginal Fluids Following Topical (Vagistat-1 6.5%) Application. Diagnostic Microbiology and Infectious Disease, 17, 45-51.
http://dx.doi.org/10.1016/0732-8893(93)90069-J [24] Eriksson, K., Larsson, P.G., Nilsson, M. and Forsum, U. (2011) Vaginal Retention of Locally Administered Clindamycin. APMIS, 119, 373-376.
http://dx.doi.org/10.1111/j.1600-0463.2011.02742.x [25] Aroutcheva, A., Simoes, J.A., Shott, S. and Faro, S. (2001) The Inhibitory Effect of Clindamycin on Lactobacillus in Vitro. Infectious Diseases in Obstetrics and Gynecology, 9, 239-244.
http://dx.doi.org/10.1155/S1064744901000394 [26] Simoes, J.A., Aroutcheva, A.A., Shott, S. and Faro S. (2001) Effect of Metronidazole on the Growth of Vaginal Lactobacilli in Vitro. Infectious Diseases in Obstetrics and Gynecology, 9, 41-45.
http://dx.doi.org/10.1155/S1064744901000072 [27] Agence Nationale de Sécurité du Médicament (2011) Guidelines for the Appropriate Use of Antibiotics.
http://ansm.sante.fr/Activites/Publicite-pour-les-medicaments/Recommandations-pour-la-publicite-aupres-des-professionnels-de-sante/Recommandations-pour-la-publicite-aupres-des-professionnels-de-sante/Antibiotiques
[1] Reid, G. (2001) Probiotic Agents to Protect the Urogenital Tract against Infection. The American Journal of Clinical Nutrition, 73, 437S-443S. [2] Hyman, R.W., Fukushima, M., Diamond, L., Kumm, J., Giudice, L.C. and Davis, R.W. (2005) Microbes on the Human Vaginal Epithelium. Proceedings of the National Academy of Sciences of the United States of America, 102, 7952-7957.
http://dx.doi.org/10.1073/pnas.0503236102 [3] Hay, P. (2005) Life in the Littoral Zone: Lactobacilli Losing the Plot. Sexually Transmitted Infections, 81, 100-102.
http://dx.doi.org/10.1136/sti.2003.007161 [4] Dover, S.E., Aroutcheva, A.A., Faro, S. and Chikindas, M.L. (2008) Natural Antimicrobials and Their Role in Vaginal Health: A Short Review. International Journal of Probiotics and Prebiotics, 3, 219-230. [5] Boskey, E.R., Telsch, K.M., Whaley, K.J., Moench, T.R. and Cone, R.A. (1999) Acid Production by Vaginal Flora in Vitro Is Consistent with the Rate and Extent of Vaginal Acidification. Infection and Immunity, 67, 5170-5175. [6] Atassi, F. and Servin, A.L. (2010) Individual and Co-Operative Roles of Lactic Acid and Hydrogen Peroxide in the Killing Activity of Enteric Strain Lactobacillus Johnsonii NCC933 and Vaginal Strain Lactobacillus Gasseri KS120.1 against Enteric, Uropathogenic and Vaginose-Associated Pathogens. FEMS Microbiology Letters, 304, 29-38.
http://dx.doi.org/10.1111/j.1574-6968.2009.01887.x [7] Eschenbach, D.A., Davick, P.R., Williams, B.L., Klebanoff, S.J., Young-Smith, K., Critchlow, C.M. and Holmes, K.K. (1989) Prevalence of Hydrogen Peroxide-Producing Lactobacillus Species in Normal Women and Women with Bacterial Vaginosis. Journal of Clinical Microbiology, 27, 251-256. [8] Mijac, V.D., Duki?, S.V., Opavski, N.Z., Duki?, M.K. and Ranin, L.T. (2006) Hydrogen Peroxide Producing Lactobacilli in Women with Vaginal Infections. The European Journal of Obstetrics & Gynecology and Reproductive Biology, 129, 69-76.
http://dx.doi.org/10.1016/j.ejogrb.2005.11.036 [9] Ravel, J., Gajer, P., Abdo, Z., Schneider, G.M., Koenig, S.S., McCulle, S.L., Karlebach, S., Gorle, R., Russell, J., Tacket, C.O., Brotman, R.M., Davis, C.C., Ault, K., Peralta, L. and Forney, L.J. (2011) Vaginal Microbiome of Reproductive-Age Women. Proceedings of the National Academy of Sciences of the United States of America, 15, 4680-4687.
http://dx.doi.org/10.1073/pnas.1002611107 [10] Martín, R., Soberón, N., Escobedo, S. and Suárez, J.E. (2009) Bacteriophage Induction versus Vaginal Homeostasis: Role of H(2)O(2) in the Selection of Lactobacillus Defective Prophages. International Microbiology, 12, 131-136. [11] Zozaya-Hinchliffe, M., Lillis, R., Martin, D.H. and Ferris, M.J. (2010) Quantitative PCR Assessments of Bacterial Species in Women with and without Bacterial Vaginosis. Journal of Clinical Microbiology, 48, 1812-1829.
http://dx.doi.org/10.1128/JCM.00851-09 [12] Turovskiy, Y., Sutyak Noll, K. and Chikindas, M.L. (2011) The Aetiology of Bacterial Vaginosis. Journal of Applied Microbiology, 110, 1105-1128.
http://dx.doi.org/10.1111/j.1365-2672.2011.04977.x [13] Bohbot, J.M., Sednaoui, P., Verriere, F. and Achhammer, I. (2012) The Etiologic Diversity of Vaginitis. Gynécologie Obstétrique & Fertilité, 40, 578-581.
http://dx.doi.org/10.1016/j.gyobfe.2011.08.001 [14] Spinillo, A., Capuzzo, E., Acciano, S., De Santolo, A. and Zara, F. (1999) Effect of Antibiotic Use on the Prevalence of Symptomatic Vulvovaginal Candidiasis. American Journal of Obstetrics and Gynecology, 180, 14-17.
http://dx.doi.org/10.1016/S0002-9378(99)70141-9 [15] Chen, J.Y., Tian, H. and Beigi, R.H. (2009) Treatment Considerations for Bacterial Vaginosis and the Risk of Recurrence. Journal of Women’s Health, 18, 1997-2004.
http://dx.doi.org/10.1089/jwh.2008.1088 [16] Corsello, S., Spinillo, A., Osnengo, G., Penna, C., Guaschino, S., Beltrame, A., Blasi, N. and Festa, A. (2003) An Epidemiological Survey of Vulvovaginal Candidiasis in Italy. European Journal of Obstetrics & Gynecology and Reproductive Biology, 110, 66-72.
http://dx.doi.org/10.1016/S0301-2115(03)00096-4 [17] Razzak, M.S., Al-Charrakh, A.H. and Al-Greitty, B.H. (2011) Relationship between Lactobacilli and Opportunistic Bacterial Pathogens Associated with Vaginitis. North American Journal of Medical Sciences, 3, 185-192. [18] Agnew, K.J. and Hillier, S.L. (1995) The Effect of Treatment Regimens for Vaginitis and Cervicitis on Vaginal Colonization by Lactobacilli. Sexually Transmitted Diseases, 22, 269-273.
http://dx.doi.org/10.1097/00007435-199509000-00001 [19] Soussy, C.J. (2012) Antibiogram Committee of the French Society for Microbiology, Recommendations. http://www.sfm-microbiologie.org/UserFiles/files/casfm/CASFM_2012.pdf [20] Odds, F.C. and MacDonald, F. (1981) Persistence of Miconazole in Vaginal Secretions after Single Applications. Implications for the Treatment of Vaginal Candidosis. British Journal of Venereal Diseases, 57, 400-401. [21] Mendling, W. and Plempel, M. (1982) Vaginal Secretion Levels after 6 Days, 3 Days and 1 Day of Treatment with 100, 200 and 500 mg Vaginal Tablets of Clotrimazole and Their Therapeutic Efficacy. Chemotherapy, 28, 43-47.
http://dx.doi.org/10.1159/000238151 [22] Houang, E.T. and Lawrence, A.G. (1985) Systemic Absorption and Persistence of Tioconazole in Vaginal Fluid after Insertion of a Single 300-mg Tioconazole Ovule. Antimicrobial Agents and Chemotherapy, 27, 964-965.
http://dx.doi.org/10.1128/AAC.27.6.964 [23] Jones, R.N., Bale, M.J., Hoban, D. and Erwin, M.E. (1993) In Vitro Antimicrobial Activity of Tioconazole and Its Concentrations in Vaginal Fluids Following Topical (Vagistat-1 6.5%) Application. Diagnostic Microbiology and Infectious Disease, 17, 45-51.
http://dx.doi.org/10.1016/0732-8893(93)90069-J [24] Eriksson, K., Larsson, P.G., Nilsson, M. and Forsum, U. (2011) Vaginal Retention of Locally Administered Clindamycin. APMIS, 119, 373-376.
http://dx.doi.org/10.1111/j.1600-0463.2011.02742.x [25] Aroutcheva, A., Simoes, J.A., Shott, S. and Faro, S. (2001) The Inhibitory Effect of Clindamycin on Lactobacillus in Vitro. Infectious Diseases in Obstetrics and Gynecology, 9, 239-244.
http://dx.doi.org/10.1155/S1064744901000394 [26] Simoes, J.A., Aroutcheva, A.A., Shott, S. and Faro S. (2001) Effect of Metronidazole on the Growth of Vaginal Lactobacilli in Vitro. Infectious Diseases in Obstetrics and Gynecology, 9, 41-45.
http://dx.doi.org/10.1155/S1064744901000072 [27] Agence Nationale de Sécurité du Médicament (2011) Guidelines for the Appropriate Use of Antibiotics.
http://ansm.sante.fr/Activites/Publicite-pour-les-medicaments/Recommandations-pour-la-publicite-aupres-des-professionnels-de-sante/Recommandations-pour-la-publicite-aupres-des-professionnels-de-sante/Antibiotiques