There are many immunologic dysfunctions that predispose to candida infections and there are multiple barrier dysfunctions or exogenous factors, such as diabetes mellitus, that increase occurrence. Specific prevention measures would need to be tailored to the factors that are predisposing your patient to the symptomatic colonization.
Before discussing the potential strategies it is worth emphasizing that the diagnosis should be secure. The definition of recurrent vulvovaginal candidiasis is 4 or more symptomatic episodes per year (Epidemiology and pathogenesis of recurrent vulvovaginal candidiasis (Sobel JD Am J Obstet Gynecol. 1985;152(7 Pt 2):924). I have evaluated women who have recurrent symptoms but the diagnosis of candidiasis is not secure. Occasionally anxiety about symptoms or nonspecific vaginal pruritus or irritant/allergic contact vaginitis is misinterpreted as candidiasis, so it is reasonable to request confirmation of the diagnosis on several occasions. If the vaginal secretions/discharge has a pH greater than 4.5 with increased leukocytes, coexisting bacterial vaginosis is a consideration. Twenty-30% of women with bacterial vaginosis are coinfected with candida (Mixed vaginitis-more than coinfection and with therapeutic implications. Sobel JD, Subramanian C, Foxman B, Fairfax M, Gygax SE Curr Infect Dis Rep. 2013;15(2):104), so failure of treatment for one cause may be due to a second cause. Finally, evidence of candida is not a reason for therapy as 10-20% of women are asymptomatic with vaginal candidiasis and these women do not require therapy.
One option would be to utilize weekly oral fluconazole 150mg therapy for 6 months (Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD, Infectious Diseases Society of America .) Clin Infect Dis. 2009;48(5):503.) . Your question stated that the infection was resistant, but I was not sure if this meant no response to therapy or susceptibility for relapse. Weekly therapy would not be effective for the former. Sensitivity testing of the candida may be helpful as 200 mg fluconazole twice weekly for 6 weeks may be effective if the minimal inhibitory concentration is between 4-8 mcg. However up to 50% of women relapse following such prolonged treatment. Candidal susceptibility to other azoles and subsequent treatment is also a consideration.
If azoles are not an option, additional therapies are of unproven benefit or are poorly tolerated. Probiotics (eg lactobacillus), although very popular, have limited data to support either orally or with topical yogurt. Topical gentian violet may be helpful but can cause mucosal irritation. Topical pH modification with sitz baths containing vinegar is unproven. However for azole resistance boric acid suppositories, 600 mg daily for 2 weeks, may be helpful (Boric acid for recurrent vulvovaginal candidiasis: the clinical evidence. Iavazzo C, Gkegkes ID, Zarkada IM, Falagas ME J Womens Health (Larchmt). 2011 Aug;20(8):1245-55. Epub 2011 Jul 20. ). Of interest to immunologists, candida hypersensitivity has been suggested as a cause of susceptibility to symptomatic candida colonization and candida vaccines have been or are under investigation (Recurrent allergic vulvovaginitis: treatment with Candida albicans allergen immunotherapy. Rigg D, Miller MM, Metzger WJ Am J Obstet Gynecol. 1990 Feb;162(2):332-6. New immunotherapeutic strategies to control vaginal candidiasis; Magliani W, Conti S, Cassone A, De Bernardis F, Polonelli L Trends Mol Med. 2002 Mar;8(3):121-6; Vulvovaginal Candida albicans infections: pathogenesis, immunity and vaccine prospects Cassone A Br J Obstet Gynaecol. 2015;122:785. ). Discussion of a vaccine has been in the literature for over 20 years but there has not been a great deal of progress to my knowledge. Treatment of sexual partners or oral garlic and tea tree oil are not supported by medial literature.
In summary, the most likely effective treatment strategy would be prolonged suppression with an azole if high level of resistance is not an issue. Topical therapy with gentian violet or boric acid are considerations but these may be a source of irritation.
I have copied below a prior question from the Ask the Expert archives which provide some additional information.
I hope this information is of help to you and your practice.
All my best.
Dennis K. Ledford, MD, FAAAAI
9/30/2009: Immunotherapy for vaginal candidiasis
A wife of a colleague has been troubled with recurrent vaginal candidiasis. Eight to ten infections a year for the past 3-4 years. No seasonality. Healthy otherwise. Pt. wondered about the possibility of a trial of immunotherapy with candida to see if this would be helpful. Patient has read that this has been performed at some centers with some success. Any thoughts on this?
Thank you for your recent inquiry.
The literature has been peppered with articles designed to assess any immunologic defect associated with recurrent vaginal candidiasis, and there have been a few articles looking at immunotherapeutic approaches. Not all of these have been concerned with typical "allergen immunotherapy." These articles have looked at a multiplicity of immunotherapeutic approaches.
To date, however, I know of no well constructed therapeutic trial that would offer us any evidence that immunotherapy is effective in this condition, and thus any treatment of vaginal candidiasis with classical allergen immunotherapy would be done only in a speculative manner.
Even considering the data contained in the abstracts listed below, as stated above, the use of allergen immunotherapy for this disorder remains at this time unproven, and the decision to institute it as a form of therapy will of course simply be based on your perspective after looking at the available data. There is no documentation with large placebo controlled trials of its efficacy in this disorder.
Thank you again for your inquiry and we hope this response is helpful to you.
Rev Iberoam Micol. 2002 Sep;19(3):144-8.
New strategies for treatment of Candida vaginal infections.
Magliani W, Conti S, Salati A, Arseni S, Frazzi R, Ravanetti L, Polonelli L.
Dipartimento di Patologia e Medicina di Laboratorio, Sezione di Microbiologia, Universita degli Studi di Parma, Viale Gramsci 14, 43100 Parma, Italy.
New strategies for treatment of vaginal candidiasis have been recently exploited, due to widespread occurrence of this disease, in particular as recurrent infections, limitations of safe and efficacious antifungals as well as the lack of reliable preventative approaches. In this review new chemotherapeutic and immunotherapeutic strategies, based on the improved understanding of the immunopathogenesis of this prevalent human infection, will be discussed. The role of killer antibodies (or their molecular derivatives), i.e. antibodies that show antibiotic activity bearing the internal image of a yeast killer toxin (KT), characterized by a wide spectrum of microbicidal activity, and of the specific cell wall KT receptor as putative new therapeutic agents and preventative or therapeutic vaccines, respectively, will be particularly outlined.
Trends Mol Med. 2002 Mar;8(3):121-6.
New immunotherapeutic strategies to control vaginal candidiasis.
Magliani W, Conti S, Cassone A, De Bernardis F, Polonelli L.
Microbiology Section, Dept of Pathology and Laboratory Medicine, University of Parma, Viale Gramsci 14, 43100 Parma, Italy. firstname.lastname@example.org
The widespread occurrence of mucosal infections caused by Candida, in particular recurrent vulvovaginal candidiasis among fertile-age women, together with the paucity of safe candidacidal antimycotics, have prompted a great number of investigations into the immunotherapy of candidal vaginitis. This article will discuss three different experimental approaches demonstrated to be potentially transferable to human disease: (1) the use of antibodies against well-defined cell-surface adhesins or enzymes; (2) the generation of yeast killer-toxin-like candidacidal anti-idiotypic antibodies and their engineered molecular derivatives (e.g. single chains, peptides); and (3) the generation of therapeutic vaccines and immunomodulators.
Int J Gynaecol Obstet. 2007 Feb;96(2):130. Epub 2007 Jan 18.
Candida autovaccination in the treatment of vulvovaginal Candida infections.
Rusch K, Schwiertz A.
Background: Recurrent vaginal candidiasis (RVC) is an important health problem with unknown pathogenesis. Although impairment of the T-cell response is associated with persistent or recurrent candidiasis, data on immunologic responses in patients with RVC are controversial. Objectives: To evaluate the T-cell response in patients with RVC and the ability of cytokines and cytokine antagonists to modulate IFN-γ production in cultures stimulated with Candida albicans antigens. Methods: Participants in the study included 13 patients with RVC and 7 control women with sporadic candidiasis. Cytokines were determined by ELISA in supernatants of mononuclear cells with C albicans , purified protein derivative, or tetanus toxoid antigen. Results: IFN-γ production was absent or low in 11 of 13 women (84.6%) with RVC. Absent or low IFN-γ production was specific to C albicans antigens (189 ± 389 pg/mL), because high IFN-γ levels were found in cultures stimulated with purified protein derivative (739 ± 774 pg/mL) or tetanus toxoid antigens (1085 ± 546 pg/mL). Monoclonal antibody anti-IL-10 enhanced IFN-γ levels (750 ± 753 pg/mL), and IL-10 suppressed this cytokine production in patients with sporadic candidiasis. Conclusions: Mononuclear cells from patients with RVC stimulated with C albicans antigen have low or absent IFN-γ production. IL-10 plays an important role in downregulation of the T-cell response in these patients. (J Allergy Clin Immunol 2002;109:102-5.)
Ann Allergy. 1979 Oct;43(4):250-3.
Hyposensitisation in the management of recurring vaginal candidiasis.
Rosedale N, Browne K.
Hyposensitisation with a commercially available antigen has been attempted in the treatment of women suffering from recurring monilial vaginitis. Ten women entered the trial, each being used as her own control. Eight of them showed undoubted improvement and the average interval between relapses increased from 5.1 to 15.7 months (p. less than .01). Reasons are given for believing that allergic reactions play a part in recurrent vaginal thrush.
Phil Lieberman, M.D.