Long-Term Outcomes of Women With Recurrent Vulvovaginal Candidiasis After a Course of Maintenance Antifungal Therapy

Crouss, Tess; Sobel, Jack D.; Smith, K.; Nyirjesy, Paul

doi:10.1097/lgt.0000000000000413

Cited by 17 publications

(10 citation statements)

References 11 publications

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“…More than 70% of women worldwide suffer from VVCs (with maximum incidence between 20 and 40 years old) and around 5% experience recurrent infections (RVVCs), defined as four or more episodes per year (13)(14)(15)(16). RVVCs require antifungal therapy to avoid recurrence and its overuse involves antimycotic resistances (17)(18)(19). Both RUTIs and RVVCs markedly diminish quality of life in women, with a negative impact at work and social life (20,21).…”

Section: Introductionmentioning

confidence: 99%

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A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections

et al. 2021

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Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems with high socio-economic impact worldwide. Antibiotic and antifungal prophylaxis remain the gold standard treatments for RUTIs and RVVCs, contributing to the massive rise of antimicrobial resistance, microbiota alterations and co-infections. Therefore, the development of novel vaccine strategies for these infections are sorely needed. The sublingual heat-inactivated polyvalent bacterial vaccine MV140 shows clinical efficacy for the prevention of RUTIs and promotes Th1/Th17 and IL-10 immune responses. V132 is a sublingual preparation of heat-inactivated Candida albicans developed against RVVCs. A vaccine formulation combining both MV140 and V132 might well represent a suitable approach for concomitant genitourinary tract infections (GUTIs), but detailed mechanistic preclinical studies are still needed. Herein, we showed that the combination of MV140 and V132 imprints human dendritic cells (DCs) with the capacity to polarize potent IFN-γ– and IL-17A–producing T cells and FOXP3+ regulatory T (Treg) cells. MV140/V132 activates mitogen-activated protein kinases (MAPK)-, nuclear factor-κB (NF-κB)- and mammalian target of rapamycin (mTOR)-mediated signaling pathways in human DCs. MV140/V132 also promotes metabolic and epigenetic reprogramming in human DCs, which are key molecular mechanisms involved in the induction of innate trained immunity. Splenocytes from mice sublingually immunized with MV140/V132 display enhanced proliferative responses of CD4+ T cells not only upon in vitro stimulation with the related antigens contained in the vaccine formulation but also upon stimulation with phytohaemagglutinin. Additionally, in vivo sublingual immunization with MV140/V132 induces the generation of IgG and IgA antibodies against all the components contained in the vaccine formulation. We uncover immunological mechanisms underlying the potential mode of action of a combination of MV140 and V132 as a novel promising trained immunity-based vaccine (TIbV) for GUTIs.

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Section: Introductionmentioning

confidence: 99%

“…Both RUTIs and RVVCs markedly diminish quality of life in women, with a negative impact at work and social life (20,21). Therefore, there is an urgent need to develop novel strategies for concomitant and recurrent genitourinary tract infections (GUTIs), including RUTIs and RVVCs (1,4,(16)(17)(18)22).…”

Section: Introductionmentioning

confidence: 99%

A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections

et al. 2021

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“…Among the conventional antifungals recommended by CDC, imidazoles (including clotrimazole, miconazole and econazole), the polyene nystatin, and fluconazole have been on the market for more than 35 years and still remain effective against acute VVC. Their effectiveness for RVVC, however, are suboptimal, as recurrence of infection is common after an initial course of fluconazole or clotrimazole and ongoing antifungal maintenance therapy is often required (Tapia et al, 2017; Crouss et al, 2018). This is possibly due to the low efficacy of conventional antifungals in eradicating biotic biofilms and persister cells that have grown on vaginal epithelia and in underlying tissues.…”

Section: Discussionmentioning

confidence: 99%

RAFT-Derived Polymethacrylates as a Superior Treatment for Recurrent Vulvovaginal Candidiasis by Targeting Biotic Biofilms and Persister Cells

Zhang

et al. 2019

Front. Microbiol.

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BackgroundVulvovaginal candidiasis (VVC) is a common infection in need of more effective treatment. Formation of epithelium-associated Candida biofilms and the presence of persister cells are among the major contributing factors to the recurrence of this condition. We have previously developed RAFT-derived polymethacrylates that are effective in killing C. albicans biofilms in vitro. This study aimed to examine the clinical potential of polymethacrylates as antifungals for treatment of recurrent VVC (RVVC).MethodsA mouse model of VVC was used to establish vaginal epithelium-associated biofilms, using C. albicans isolates from VVC/RVVC patients. A comparison was made of the efficacies of polymethacrylates and conventional antifungals, clotrimazole and nystatin, in killing Candida in epithelium-associated biofilms in vivo. Ex vivo biofilms were used for Candida population profiling and to quantify persister cells in vaginal epithelia. The potency of polymethacrylates and conventional antifungals against persister cells, either as sole agents or in combination, was assessed.ResultsPolymethacrylates showed negligible local toxicity, resistance to vaginal acidity, and outstanding in vivo activity against vaginal epithelium-associated C. albicans biofilms. In vivo tests polymethacrylates outperformed the conventional antifungals, nystatin and clotrimazole at concentrations 50 times below the over-the-counter concentrations. Using polymethacrylates was associated with fewer persister cells, and better eradication of persister cells pre-selected by conventional antifungals.ConclusionThis study systematically assessed the clinical potential of RAFT-derived polymethacrylates as an effective treatment for VVC/RVVC in a mouse model. Polymethacrylates effectively killed vaginal epithelium-related C. albicans in vivo by specially targeting biotic biofilms and persister cells. Treatment presented negligible local toxicity.

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“…Studies have shown that women with recurrent vulvovaginal candidiasis can find relief with fluconazole but then experience recurrences. These patients may find relief with maintenance fluconazole for suppression [8].…”

Section: Discussionmentioning

confidence: 99%

Candida glabrata Fungemia Following Robotic Total Laparoscopic Hysterectomy and Bilateral Salpingo-oophorectomy in a Patient with Recurrent Vulvovaginitis: A Case Report

Mikdachi

Spann

2019

Cureus

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Vulvovaginal candidiasis is a common gynecologic diagnosis that can be treated empirically with fluconazole. We present a patient that developed post-operative Candida glabrata ( C. glabrata ) fungemia after being empirically treated for vulvuovaginal candidiasis with fluconazole multiple times throughout the year prior to robotic total laparoscopic hysterectomy and bilateral salpingo-oophorectomy. C. glabrata is becoming increasingly resistant to azole antimycotic therapy. It is likely that this patient had undertreated fluconazole-resistant C. glabrata vulvovaginitis prior to surgery, and that the pelvic infection was the source of fungemia.

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Long-Term Outcomes of Women With Recurrent Vulvovaginal Candidiasis After a Course of Maintenance Antifungal Therapy

Abstract: Although RVVC can be controlled, relapse is common after an initial course of maintenance fluconazole. Ongoing maintenance remains the most effective treatment option.

Cited by 17 publications

References 11 publications

A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections

A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections

RAFT-Derived Polymethacrylates as a Superior Treatment for Recurrent Vulvovaginal Candidiasis by Targeting Biotic Biofilms and Persister Cells

Candida glabrata Fungemia Following Robotic Total Laparoscopic Hysterectomy and Bilateral Salpingo-oophorectomy in a Patient with Recurrent Vulvovaginitis: A Case Report

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