Nystatin-Neomycin-Polymyxin B Combination: Efficacy and Tolerance as 1st-Line Local Treatment of Infectious Vaginitis

Jean-Marc Bohbot, Patrice Sednaoui, François Verriere

Institut Alfred Fournier, Paris, France.
Laboratoire Innotech International, Arcueil, France.

DOI: 10.4236/ojog.2014.47065                

Abstract

Objective: To evaluate the efficacy and tolerance of a local treatment combining two antibacterials and one antifungal in patients with a clinical presentation suggesting infectious vaginitis. Patients and methods: 169 patients presenting with clinical criteria for vaginitis were included in an open, multicenter trial. Vaginal samples were taken for microbiological analyses and a triple-combination product of nystatin, neomycin and polymyxin B was then started as local treatment, without waiting for the test results. The treatment was continued with the usual dosage (1 vaginal capsule at bedtime for 12 days) for vaginal infections in the scope of the combination product with approved labeling. A second vaginal sample was performed at the end of the treatment. The main efficacy criterion was the clinical success rate (cure or improvement of the clinical signs and symptoms) according to the investigator.Results: 93 patients were included in the efficacy population. Non-exclusively fungal vaginitis (strictly bacterial or bacterial + fungal) represented 31.2% of the cases. The clinical success rate was 97.8% according to the investigator and 95.7% according to the patients. The microbiological success rate was 81.3%, with no differences between etiologies (Candida spp., bacteria or both). The combination product was well-tolerated, despite the local inflammation before treatment. Discussion and conclusion: Given the etiological diversity of vaginitis, this trial supports the efficacy of a triple-combination product (nystatin, neomycin, polymyxin B) as a first-line local treatment of Candida, bacterial or mixed vaginitis.

Keywords

Candidiasis, Mixed Vaginitis, Bacterial Vaginitis, Nystatin Neomycin, Polymyxin B, Empirical Therapy

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	ACOG Practice Bulletin (2006) Clinical Management Guidelines for Obstetrician—Gynecologists. American Journal of Obstetrics and Gynecology, 107, 1195-1206.
[2]	Egan, M.E. and Lipsky, M.S. (2000) Diagnosis of Vaginitis. American Family Physician, 62, 1095-1104.
[3]	Sobel, J.D. (1997) Vaginitis. The New England Journal of Medicine, 337, 1896-1903. http://dx.doi.org/10.1056/NEJM199712253372607
[4]	Donders, G.G., Vereecken, A., Bosmans, E., Dekeersmaecker, A., Salembier, G. and Spitz, B. (2002) Definition of a Type of Abnormal Vaginal Flora That Is Distinct from Bacterial Vaginosis: Aerobic Vaginitis. BJOG: An International Journal of Obstetrics & Gynaecology, 109, 34-43. http://dx.doi.org/10.1111/j.1471-0528.2002.00432.x
[5]	Landers, D.V., Wiesenfeld, H.C., Heine, R.P., Krohn, M.A. and Hillier, S.L. (2004) Predictive Value of the Clinical Diagnosis of Lower Genital Tract Infection in Women. American Journal of Obstetrics & Gynecology, 190, 1004-1008. http://dx.doi.org/10.1016/j.ajog.2004.02.015
[6]	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
[7]	Eckert, L.O. (2006) Clinical Practice. Acute Vulvovaginitis. The New England Journal of Medicine, 355, 1244-1252. http://dx.doi.org/10.1056/NEJMcp053720
[8]	Libalova, Z., Cepicky, P., Malina, J., Stanslicky, K., Kuzelova, M., Medalova, Z., et al. (2007) Vulvovaginitis. Occurrence and Importance of Mixed and Unclassifiable Pictures. Ceská Gynekologie, 72, 32-37.
[9]	Thulkar, J., Kriplani, A., Agarwal, N. and Vishnubhatla, S. (2010) Aetiology & Risk Factors of Recurrent Vaginitis & Its Association with Various Contraceptive Methods. Indian Journal of Medical Research, 131, 83-87.
[10]	Kalkanci, A., Ciftci, B., Biri, A., Kustimur, S. and Güner, H. (2005) Distribution of the Pathogens According to Vaginal Culture Results of the Patients with Vaginitis. Türkiye Klinikleri Jinekoloji Obstetrik Ozel Dergisi, 15, 137-139.
[11]	Ozturk, C.E., Ozdemir, I., Yavuz, T., Kaya, D. and Behcet, M. (2006) Etiologic Agents of Cervicovaginitis in Turkish Women. Saudi Medical Journal, 27, 1503-1507.
[12]	Fidel Jr., P.L., Vazquez, J.A. and Sobel, J.D. (1999) Candida Glabrata: Review of Epidemiology, Pathogenesis, and Clinical Disease with Comparison to C. albicans. Clinical Microbiology Reviews, 12, 80-96.
[13]	Richter, S.S., Galask, R.P., Messer, S.A., Hollis, R.J., Diekema, D.J. and Pfaller, M.A. (2005) Antifungal Susceptibilities of Candida Species Causing Vulvovaginitis and Epidemiology of Recurrent Cases. Journal of Clinical Microbiology, 43, 2155-2162. http://dx.doi.org/10.1128/JCM.43.5.2155-2162.2005
[14]	Wiesenfeld, H.C., et al. (1999) The Infrequent Use of Office-Based Diagnostic Tests for Vaginitis. American Journal of Obstetrics & Gynecology, 181, 39-41. http://dx.doi.org/10.1016/S0002-9378(99)70433-3
[15]	Larsen, B. (1993) Vaginal Flora in Health and Disease. Clinical Obstetrics & Gynecology, 36, 107-121. http://dx.doi.org/10.1097/00003081-199303000-00016
[16]	Schaaf, V.M., Perez-Stable, E.J. and Borchardt, K. (1990) The Limited Value of Symptoms and Signs in the Diagnosis of Vaginal Infections. Archives of Internal Medicine, 150, 1929-1933. http://dx.doi.org/10.1001/archinte.1990.00390200111021
[17]	Lurie, S., Woliovitch, I., Rotmensch, S., Sadan, O. and Glezerman, M. (2001) Value of Vaginal Culture in Management of Acute Vaginitis. Archives of Gynecology and Obstetrics, 265, 187-189. http://dx.doi.org/10.1007/s004040000157
[18]	González, I.D.C., González, F.G., Cuesta, T.S., Fernández, J.M., Rodríguez, J.M.D.A., Ferrairo, R.A.E., et al. (2011) Patient Preferences and Treatment Safety for Uncomplicated Vulvovaginal Candidiasis in Primary Health Care. BMC Public Health, 11, 63. http://dx.doi.org/10.1186/1471-2458-11-63
[19]	Jacquetin, B. and Wattiez, A. (1986) Intérêt de l’utilisation de Polygynax sans acétarsol dans le traitement de l’infection génitale basse. Revue de Médecine de Clermont-Ferrand, 15, 32-36.
[20]	Marhic, C. and Charles, G. (1986) Traitement local des vaginites microbiennes par une association nystatine, néomycine, polymyxine B. Gazette médicale de France, 93, 83-84.
[21]	Blanc, B. (1987) Le traitement des infections cervico-vaginales par Polygynax sans acetarsol. Méditerranée Médicale, 15, 33-35.
[22]	Bruhat, M.A. (1992) Use of a Local Antibiotic Combination in the Treatment of Mycotic Vaginitis and Mixed Vaginitis. Revue Francaise de Gynecologie et d Obstetrique, 87, 161-168.
[23]	Goran, D., Vesna, A., Adela, S., Biljana, T.K. and Snezana, M. (2004) Polygynax in the Treatment of Fungal and Non Specific Vaginitis. Akusherstvo i Ginekologiia (Sofiia), 43, 23-26.
[24]	Verriere, F. (2011) Effectiveness of Polygynax in the Treatment of Vaginitis: A Prospective Multicentre Study. Bulgarian Society of Obstetrics and Gynecology, 50, 32-37.
[25]	Schwartz, D. (1996) Méthodes statistiques à l'usage des médecins et biologistes. 4ème édition. Collection statistique en biologie et en médecine, Médecine-Science Flammarion.
[26]	Achkar, J.M. and Fries, B.C. (2010) Candida Infections of the Genitourinary Tract. Clinical Microbiology Reviews, 23, 253-273. http://dx.doi.org/10.1128/CMR.00076-09
[27]	Danby, C.S., Boikov, D., Rautemaa-Richardson, R. and Sobel, J.D. (2012) Effect of pH on in Vitro Susceptibility of Candida glabrata and Candida albicans to 11 Antifungal Agents and Implications for Clinical Use. Antimicrobial Agents and Chemotherapy, 56, 1403-1406. http://dx.doi.org/10.1128/AAC.05025-11
[28]	Fan, S.R., Liu, X.P. and Li, J.W. (2008) Clinical Characteristics of Vulvovaginal Candidiasis and Antifungal Susceptibilities of Candida Species Isolates among Patients in Southern China from 2003 to 2006. Journal of Obstetrics and Gynaecology Research, 34, 561-566. http://dx.doi.org/10.1111/j.1447-0756.2008.00817.x
[29]	Fan, S.R. and Liu, X.P. (2011) In Vitro Fluconazole and Nystatin Susceptibility and Clinical Outcome in Complicated Vulvovaginal Candidosis. Mycoses, 54, 501-505. http://dx.doi.org/10.1111/j.1439-0507.2010.01887.x
[30]	Choukri, F., Benderdouche, M. and Sednaoui, P. (in press) In Vitro Susceptibility Profile of 200 Recent Clinical Isolates of Candida spp. to Topical Antifungal Treatments of Vulvovaginal Candidiasis, the Azoles and Nystatin Agents. Journal of Medical Mycology.
[31]	Bornstein, J., Lakovsky, Y., Lavi, I., Bar-Am, A. and Abramovici, H. (2001) The Classic Approach to Diagnosis of Vulvovaginitis: A Critical Analysis. Infectious Diseases in Obstetrics and Gynecology, 9, 105-111. http://dx.doi.org/10.1155/S1064744901000187
[32]	Schwiertz, A., Taras, D., Rusch, K. and Rusch, V. (2006) Throwing the Dice for the Diagnosis of Vaginal Complaints? Annals of Clinical Microbiology and Antimicrobials, 5, 4. http://dx.doi.org/10.1186/1476-0711-5-4
[33]	Nurbhai, M., Grimshaw, J., Watson, M., Bond, C., Mollison, J. and Ludbrook, A. (2007) Oral versus Intra-Vaginal Imidazole and Triazole Anti-Fungal Treatment of Uncomplicated Vulvovaginal Candidiasis (Thrush). Cochrane Database of Systematic Reviews, 17, Published Online.
[34]	Neut, C., Nelis, H.J. and Coenye, T. (2012) Treatment of Infectious Vaginitis: Antimicrobial Drugs Effects on Lactobacillus strains of the Normal Vaginal Flora. Internal Study Report.