Randomised Clinical Trial in Women with Recurrent Vulvovaginal Candidiasis: Efficacy of Probiotics and Lactoferrin as Maintenance Treatment
Abstract
BACKGROUND: Vulvovaginal candidiasis (VVC) is a recurrent vaginal condition in childbearing women. OBJECTIVES: The aim of this study was to assess the efficacy of an oral formulation containing Lactobacillus acidophilus GLA-14, Lactobacillus rhamnosus HN001 and bovine lactoferrin on symptoms and recurrence of VVC as adjuvant therapy to topical clotrimazole. PATIENTS/METHODS: Forty-eight women positive for C. albicans, symptoms of VVC and documented history of recurrences were randomised into 2 groups receiving verum or placebo (2 capsules/day for 5 days followed by 1 capsule/day for additional 10 days) as adjuvant treatment to clotrimazole (induction phase) followed by a maintenance cycle of 6 months (1 capsule/day verum or placebo for 10 consecutive days each month). Symptoms, overall cure rate and recurrence rate were assessed. RESULTS: After clotrimazole therapy, a significant improvement of symptoms was shown in both groups. However, only women treated with probiotics and lactoferrin showed a significant improvement of itching and discharge at 3 and 6 months. During the six-month follow-up, recurrences were significantly less in the intervention group vs placebo (33.3% vs 91.7% after 3 months and 29.2% vs 100% after 6 months). CONCLUSIONS: The results show that the investigated lactobacilli mixture in combination with lactoferrin represents a safe and effective adjuvant approach for reducing symptoms and recurrences of RVVC.
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A randomized trial from 2019 by Russo et al. showed the effectiveness of a Lactobacilli mixture in combination with lactoferrin in reducing symptoms and preventing RVVC recurrence.
“However, a randomized trial from 2019 by Russo et al. showed the effectiveness of a Lactobacilli mixture in combination with lactoferrin in reducing symptoms and preventing RVVC recurrence [66].”
From Treatment of Vulvovaginal Candidiasis—An Overview of Guidelines and the Latest Treatment Methods (2023) · cites this paper as [66]
Cites
Guidelines for Treatment of Candidiasis
Pappas, P. G., Rex, J. H., Sobel, J. D., Filler, S. G., Dismukes, W. E., Walsh, T. J., & Edwards, J. E. (2004) · Clinical Infectious Diseases · doi:10.1086/380796 · Cited by 1,440 · see citing works
Potential Uses of Probiotics in Clinical Practice
Reid, G., Jaß, J., Sebulsky, M. T., & McCormick, J. K. (2003) · Clinical Microbiology Reviews · doi:10.1128/cmr.16.4.658-672.2003 · Cited by 918 · see citing works
<i>Candida</i> Infections of the Genitourinary Tract
Achkar, J. M., & Fries, B. C. (2010) · Clinical Microbiology Reviews · doi:10.1128/cmr.00076-09 · Cited by 736 · see citing works
Lactoferrin: a general review.
Levay, P., & Viljoen, M. (1995) · PubMed · Cited by 645 · see citing works
Global burden of recurrent vulvovaginal candidiasis: a systematic review
Denning, D. W., Kneale, M., Sobel, J. D., & Rautemaa-Richardson, R. (2018) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(18)30103-8 · Cited by 639 · see citing works
Recurrent vulvovaginal candidiasis
Sobel, J. D. (2016) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2015.06.067 · Cited by 502 · see citing works
Maintenance Fluconazole Therapy for Recurrent Vulvovaginal Candidiasis
Sobel, J. D., Wiesenfeld, H. C., Martens, M., Danna, P., Hooton, T. M., Rompalo, A., Sperling, M., Livengood, C., Horowitz, B., Von Thron, J., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa033114 · Cited by 487 · see citing works
Sobel, J. D. (1997) · New England Journal of Medicine · doi:10.1056/nejm199712253372607 · Cited by 446 · see citing works
Probiotics for prevention of recurrent vulvovaginal candidiasis: a review
Falagas, M. E. (2006) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkl246 · Cited by 248 · see citing works
Recurrent Vulvovaginal Candidiasis
Sobel, J. D. (1986) · New England Journal of Medicine · doi:10.1056/nejm198612043152305 · Cited by 219 · see citing works
Role of Lactobacilli and Lactoferrin in the Mucosal Cervicovaginal Defense
Valenti, P., Rosa, L., Capobianco, D., Lepanto, M. S., Schiavi, E., Cutone, A., Paesano, R., & Mastromarino, P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00376 · Cited by 218 · see citing works
van Schalkwyk, J., Yudin, M. H., Yudin, M. H., Allen, V. M., Bouchard, C., Boucher, M., Boucoiran, I., Caddy, S. C., Castillo, E., Kennedy, V. L., et al. (2015) · Journal of Obstetrics and Gynaecology Canada · doi:10.1016/s1701-2163(15)30316-9 · Cited by 187 · see citing works
Martinez, R. C. R., Franceschini, S. A., Patta, M. C., Quintana, S. M., Candido, R. C., Ferreira, J. C., Martinis, E. C. P. D., & Reid, G. (2009) · Letters in Applied Microbiology · doi:10.1111/j.1472-765x.2008.02477.x · Cited by 187 · see citing works
An Update on the Roles of Non-albicans Candida Species in Vulvovaginitis
Makanjuola, O., Bongomin, F., & Fayemiwo, S. (2018) · Journal of Fungi · doi:10.3390/jof4040121 · Cited by 182 · see citing works
Probiotics as antifungals in mucosal candidiasis
Matsubara, V. H., Bandara, H. M. H. N., Mayer, M. P. A., & Samaranayake, L. P. (2016) · Clinical Infectious Diseases · doi:10.1093/cid/ciw038 · Cited by 151 · see citing works
Kanwar, J. R., Roy, K., Patel, Y., Zhou, S.-F., Singh, M. R., Singh, D., Nasir, M., Sehgal, R., Sehgal, A., Singh, R. S., et al. (2015) · Molecules · doi:10.3390/molecules20069703 · Cited by 136 · see citing works
Probiotics for vulvovaginal candidiasis in non-pregnant women
Xie, H. Y., Feng, D., Wei, D. M., Mei, L., Chen, H., Wang, X., & Fang, F. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010496.pub2 · Cited by 129 · see citing works
Guideline: Vulvovaginal Candidosis (AWMF 015/072), S2k (Excluding Chronic Mucocutaneous Candidosis)
Mendling, W. (2015) · Mycoses · doi:10.1111/myc.12292 · Cited by 117 · see citing works
Treatment of vulvovaginal candidiasis: a review of the literature
Dovnik, A., Golle, A., Novák, D., Arko, D., & Takač, I. (2015) · Acta Dermatovenerologica Alpina Pannonica et Adriatica · doi:10.15570/actaapa.2015.2 · Cited by 107 · see citing works
Pendharkar, S., Brandsborg, E., Hammarström, L. L. G., Marcotte, H., & Larsson, P. (2015) · BMC Infectious Diseases · doi:10.1186/s12879-015-0971-3 · Cited by 99 · see citing works
Odds, F. C., Webster, C. E., Mayuranathan, P., & Simmons, P. D. (1988) · Medical Mycology · doi:10.1080/02681218880000391 · Cited by 98 · see citing works
Seta, F. D., Parazzini, F., Leo, R. D., Banco, R., Maso, G., Santo, D. D., Sartore, A., Stabile, G., Inglese, S., Tonon, M., et al. (2014) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2014.09.018 · Cited by 97 · see citing works
Donders, G. G. G., Babula, O., Bellen, G., Linhares, I. M., & Witkin, S. S. (2008) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2008.01830.x · Cited by 88 · see citing works
Management of Recurrent Vulvo-Vaginal Candidosis as a Chronic Illness
Donders, G. G. G., Bellen, G., & Mendling, W. (2010) · Gynecologic and Obstetric Investigation · doi:10.1159/000314022 · Cited by 83 · see citing works
Lactobacilli at the Front Line of Defense Against Vaginally Acquired Infections
Spurbeck, R. R., & Arvidson, C. G. (2011) · Future Microbiology · doi:10.2217/fmb.11.36 · Cited by 77 · see citing works
Linhares, I. M., Witkin, S. S., Miranda, S. D., da Fonseca, Â. M., Pinotti, J. A., & Ledger, W. J. (2001) · Infectious Diseases in Obstetrics and Gynecology · doi:10.1155/s1064744901000369 · Cited by 76 · see citing works
Recurrent allergic vulvovaginitis: Treatment with Candida albicans allergen immunotherapy
Rigg, D., Miller, M. M., & Metzger, W. J. (1990) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(90)90380-p · Cited by 75 · see citing works
Morici, P., Fais, R., Rizzato, C., Tavanti, A., & Lupetti, A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0167470 · Cited by 70 · see citing works
Recurrent vulvovaginal candidiasis: A review of guideline recommendations
Matheson, A., & Mazza, D. (2017) · Australian and New Zealand Journal of Obstetrics and Gynaecology · doi:10.1111/ajo.12592 · Cited by 68 · see citing works
Russo, R., Edu, A., & Seta, F. D. (2018) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-018-4771-z · Cited by 68 · see citing works
Self-citationPalma, C., Cassone, A., Serbousek, D., Pearson, C. A., & Djeu, J. Y. (1992) · Infection and Immunity · doi:10.1128/iai.60.11.4604-4611.1992 · Cited by 62 · see citing works
Spear, G. T., Kendrick, S. R., Chen, H. Y., Thomas, T. T., Bahk, M., BALDERAS, R. S., Ghosh, S. K., Weinberg, A., & LANDAY, A. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019560 · Cited by 57 · see citing works
Alberti, D. D., Russo, R., Terruzzi, F., Nobile, V., & Ouwehand, A. C. (2015) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-015-3711-4 · Cited by 57 · see citing works
Self-citationMurina, F., Graziottin, A., Vicariotto, F., & Seta, F. D. (2014) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000000225 · Cited by 56 · see citing works
Prevention and Treatment of Vulvovaginal Candidiasis Using Exogenous Lactobacillus
Jeavons, H. S. (2003) · Journal of Obstetric, Gynecologic & Neonatal Nursing · doi:10.1177/0884217503253439 · Cited by 51 · see citing works
Treatment of vaginal Candida infections
Sobel, J. D. (2002) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.3.8.1059 · Cited by 50 · see citing works
Pino, A., Giunta, G., Randazzo, C. L., Caruso, S., Caggia, C., & Cianci, A. (2017) · Microbial Ecology in Health and Disease · doi:10.1080/16512235.2017.1357417 · Cited by 49 · see citing works
Effects of lactoferrin in 6 patients with refractory bacterial vaginosis
Otsuki, K., & Imai, N. (2016) · Biochemistry and Cell Biology · doi:10.1139/bcb-2016-0051 · Cited by 48 · see citing works
Probiotics. Some evidence of their effectiveness.
Reid, G., & Hammond, J.-A. (2005) · Europe PMC (PubMed Central) · Cited by 46 · see citing works
Sex Hormones Coordinate Neutrophil Immunity in the Vagina by Controlling Chemokine Gradients
Lasarte, S., Samaniego, R., Salinas-Muñoz, L., Guia-Gonzalez, M. A., Weiss, L. A., Mercader, E., Ceballos-García, E., Navarro-González, T., Moreno-Ochoa, L., Perez-Millan, F., et al. (2015) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiv402 · Cited by 45 · see citing works
Effect of progesterone on Candida albicans vaginal pathogenicity
Alves, C. T., Silva, S. M., Pereira, L., Williams, D. W., Azeredo, J., & Henriques, M. (2014) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2014.07.004 · Cited by 40 · see citing works
Hammad, N., ELBadawy, N. E., Refaie, A. N., Ghramh, H. A., & Kady, L. M. A. (2018) · BioMed Research International · doi:10.1155/2018/7648152 · Cited by 37 · see citing works
Candida vulvovaginitis: A store with a buttery and a show window
Donders, G. G. G., & Sobel, J. D. (2016) · Mycoses · doi:10.1111/myc.12572 · Cited by 27 · see citing works
Management of chronic vulvovaginal candidiasis: a long term retrospective study
Nguyen, Y., Lee, A. C.-Y., & Fischer, G. O. (2016) · Australasian Journal of Dermatology · doi:10.1111/ajd.12497 · Cited by 16 · see citing works
Naidu, A. S., Chen, J., Martinez, C., et al. (2004) · PubMed · Cited by 15 · see citing works
Komatsu, A., Satoh, T., Wakabayashi, H., & Ikeda, F. (2013) · Odontology · doi:10.1007/s10266-013-0135-0 · Cited by 14 · see citing works
Ventolini, G., & Baggish, M. S. (2004) · Maturitas · doi:10.1016/j.maturitas.2004.08.012 · Cited by 13 · see citing works
Recurrent vulvovaginal candidiasis.
MacNeill, C., & Jc, C. (2001) · PubMed · Cited by 13 · see citing works
Lactobacilli and lactoferrin: Biotherapeutic effects for vaginal health
Bertuccini, L., Russo, R., Iosi, F., & Superti, F. (2018) · Journal of Functional Foods · doi:10.1016/j.jff.2018.03.033 · Cited by 10 · see citing works
Self-citation
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Cited by
Sorted by citations
Guideline: Vulvovaginal Candidosis (AWMF 015/072, Level S2k)
Farr, A., Effendy, I., Frey Tirri, B., Hof, H., Mayser, P., Petricevic, L., Ruhnke, M., Schaller, M., Schaefer, A. P. A., Sustr, V., et al. (2021) · Mycoses · doi:10.1111/myc.13248 · Cited by 184 · see citing works
Treatment of Vulvovaginal Candidiasis—An Overview of Guidelines and the Latest Treatment Methods
Satora, M., Grunwald, A., Zaremba, B., Frankowska, K., Żak, K., Tarkowski, R., & Kułak, K. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12165376 · Cited by 84 · see citing works
Treatment for recurrent vulvovaginal candidiasis (thrush)
Cooke, G., Watson, C., Deckx, L., Pirotta, M., Smith, J., & van Driel, M. L. (2022) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009151.pub2 · Cited by 48 · see citing works
Mollazadeh-Narestan, Z., Yavarikia, P., Homayouni-Rad, A., Samadi Kafil, H., Mohammad-Alizadeh-Charandabi, S., Gholizadeh, P., & Mirghafourvand, M. (2023) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-022-09997-3 · Cited by 29 · see citing works
- Authors
- Russo, R., Superti, F., Karadja, E., & De Seta, F.
- Affiliations
- Giellepi SpA (Italy) (IT)
- Istituto Superiore di Sanità (IT)
- Spitalul Clinic Judeţean de Urgenţă "Pius Brînzeu" Timişoara (RO)
- Department of Medical Science University of Trieste Trieste Italy
- Corresponding author
- Russo, Rosario
- Venue
- Mycoses
- Publisher
- Wiley
- Published
- 2019-02-20
- Volume
- 62
- Issue
- 4
- Pages
- 328-335
- ISSN
- 0027-5557 (ISSN-L)
- 0933-7407
- 1439-0507
- OpenAlex
- W2904888642
- Cited by
- 94
- References
- 49
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 12 · 2023: 22 · 2022: 14 · 2021: 14 · 2020: 9 · 2019: 4
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Mycoses (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Giellepi S.p.A.
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- recurrent vulvovaginal candidiasis, probiotics, lactoferrin, Lactobacillus rhamnosus HN001, clotrimazole, adjuvant therapy, maintenance therapy, Candida albicans, recurrence prevention, vaginal symptoms
- MeSH terms
- Adolescent, Adult, Animals, Anti-Infective Agents, Candidiasis, Vulvovaginal, Clotrimazole, Double-Blind Method, Female, Humans, Lactoferrin, Middle Aged, Placebos, Prospective Studies, Treatment Outcome, Probiotics, Secondary Prevention, Young Adult, Chemoradiotherapy, Adjuvant, Maintenance Chemotherapy
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