micafungin and Candidiasis--Vulvovaginal

Chronic recurrent vulvovaginal candidiasis caused by Candida glabrata is still rare in comparison to C. albicans infection, but therapy remains more difficult. Standard agents as fluconazole or itraconazole often fail, as well as the newer systemic triazoles like voriconazole or posaconazole. Micafungin is a new echinocandin drug with a wide antifungal spectrum including rare Candida species. No clinical trials with micafungin in chronic recurrent vulvovaginal candidiasis have been undertaken. We present the initial results employing a new therapy regimen consisting of micafungin in combination with topical ciclopirox olamine. All 14 patients with chronic recurrent vulvovaginal candidiasis caused by C. glabrata were treated successfully.

Topics: Administration, Topical; Antifungal Agents; Candida glabrata; Candidiasis, Cutaneous; Candidiasis, Vulvovaginal; Ciclopirox; Drug Therapy, Combination; Echinocandins; Female; Humans; Lipopeptides; Micafungin; Pyridones; Treatment Outcome

Vulvovaginal candidiasis is a global issue of concern due to its association with economic costs, sexually transmitted infections, and ascending genital tract infection. The aim of this study was to determine species distribution and antifungal susceptibility pattern of Candida species causing vulvovaginal candidiasis.. A cross sectional study was conducted from November 2015 to December 2016 at the Family Guidance Association of Ethiopia. Vaginal swabs collected from study subjects that were clinically diagnosed with vulvovaginal candidiasis were cultured. Yeast identification and antifungal susceptibility testing were determined by the automated VITEK 2 compact system. The association of vulvovaginal candidiasis with possible risk factors was assessed and analyzed using SPSS version 20.. The overall prevalence of vulvovaginal candidiasis was 41.4%. The association of vulvovaginal candidiasis was statistically significant with previous genital tract infection (p = 0.004), number of life-time male sex partners (p = .037), and number of male sex partners in 12 month (p = 0.001). Of 87 Candida isolates recovered, 58.6% were C. albicans while 41.4% were non-albicans Candida species. The highest overall drug resistance rate of Candida species was observed against fluconazole (17.2%), followed by flycytosine (5.7%). All Candida isolates were 100% susceptible to voriconazole, caspofungin, and micafungin. C. albicans, was 100% susceptible to all drugs tested except fluconazole and flycytosine with a resistance rate of 2% each drug. C. krusei, was 100 and 33.3% resistant to fluconazole and flycytosine, respectively.. High prevalence rate of vulvovaginal candidiasis and observation of high prevalence rate of non-albicans Candida species in the present study substantiate, the importance of conducting continuous epidemiological surveys to measure changes in species distribution from C. albicans to non-albicans Candida species in Ethiopia. Although, fluconazole still appeared to be active against all isolates of C. albicans and non-albicans Candida species high resistance rate of C. krusei against the drug may demonstrate a search for alternative antifungal drugs when treating vulvovaginal candidiasis caused by C. krusei.

Topics: Adolescent; Adult; Antifungal Agents; Candida albicans; Candidiasis, Vulvovaginal; Caspofungin; Cross-Sectional Studies; Drug Resistance, Fungal; Ethiopia; Female; Fluconazole; Flucytosine; Humans; Micafungin; Microbial Sensitivity Tests; Middle Aged; Prevalence; Reproductive Tract Infections; Sexual Partners; Voriconazole; Young Adult

Vulvovaginal candidiasis (VVC) is an inflammatory disease of the vulva and vagina caused by different yeasts of the genus Candida which is responsible for infection in pregnant patients who attended Maternidade Escola Januário Cicco, Rio Grande do Norte, Brazil. From 41 samples, 19 yeasts were identified phenotypically as Candida albicans and one as Candida glabrata which is reported as the non-albicans species most frequently isolated from vulvovaginitis. The susceptibility to selected antifungal agents (flucytosine, fluconazole, voriconazole, amphotericin B, caspofungin and micafungin) was determined, and the association between patient-related signs and symptoms aided the construction of an epidemiological profile. Antifungal susceptibility testing performed by automated method showed that all strains were sensitive to the drugs tested, including the C. glabrata specimen despite its known resistance or dose-dependent susceptibility to azole derivatives. Regarding patient signs and symptoms, no statistically significant association between these and the establishment of VVC was found. It can be concluded that the laboratorial diagnosis of VVC is necessary prior to the administration of treatment, since only 48·78% of the patients had VVC but for all of them antifungal therapy were prescribed.. Vulvovaginal candidiasis (VVC) is a problem that affects a significant number of pregnant women worldwide. This type of fungal infection generates great discomfort due to the symptomatology and difficulties of diagnosis and treatment. In view of the scarcity of data in the State of Rio Grande do Norte, Brazil, regarding studies carried out on fungal populations of the genus Candida associated with VVC in pregnant women, this study considered relevant, the phenotypic and genotypic identification of the species, to estimate the prevalence, to determine their susceptibility to the antifungal and to correlate with signs and symptoms.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Brazil; Candida; Candida glabrata; Candidiasis, Vulvovaginal; Echinocandins; Female; Fluconazole; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Pregnancy; Pregnancy Complications; Prevalence; Schools; Young Adult

The novel echinocandin CD101 has stability properties amenable to topical formulation for use in the treatment of acute vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). CD101 has demonstrated potent antifungal activity at pH 7, but assessment of its activity at the physiological pH of the vaginal environment is needed.. To evaluate the antifungal activity of CD101 against clinical VVC isolates of Candida spp., including azole-resistant strains, at pH 4.. MIC values of CD101 and comparators (fluconazole, itraconazole, micafungin, caspofungin and anidulafungin) were assessed via broth microdilution. MIC assays were conducted at pH 7 and 4 after 24 and 48 h against a 108 VVC isolate panel of Candida spp., including Candida albicans ( n  =   60), Candida glabrata ( n  =   21), Candida parapsilosis ( n  =   14) and Candida tropicalis ( n  =   13).. Overall, MIC values of all drugs were slightly higher at pH 4 versus 7 and at 48 versus 24 h of incubation. CD101 MIC values typically exhibited ∼4-fold shifts at pH 4 and were not affected by azole susceptibility. C. parapsilosis susceptibility was the least affected at pH 4 and did not increase for most drugs.. CD101 had potent activity against all Candida isolates tested, including azole-resistant strains. Although there was some reduction in activity at pH 4 versus 7, the resulting MIC values were still well below the intravaginal CD101 drug concentrations anticipated to be present following topical administration. These results support continued development of topical CD101 for the treatment of VVC/RVVC.

Topics: Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Candida tropicalis; Candidiasis, Vulvovaginal; Caspofungin; Drug Resistance, Fungal; Echinocandins; Female; Humans; Hydrogen-Ion Concentration; Lipopeptides; Micafungin; Microbial Sensitivity Tests

There is concern about the rise of antifungal drug resistance, but little is known about comparative biological properties and pathogenicity of drug-resistant strains. We generated fluconazole (FLC; CO23 RFLC)- or micafungin (FK; CO23 RFK)-resistant strains of Candida albicans by treating a FLC- and FK-susceptible strain of this fungus (CO23 S) with stepwise-increasing concentrations of either drug. Molecular analyses showed that CO23 RFLC had acquired markedly increased expression of the drug-resistance efflux pump encoded by the MDR1 gene, whereas CO23 RFK had a homozygous mutation in the FSK1 gene. These genetic modifications did not alter to any extent the growth capacity of the drug-resistant strains in vitro, either at 28 degrees C or at 37 degrees C, but markedly increased their experimental pathogenicity in a systemic mouse infection model, as assessed by the overall mortality and target organ invasion. Interestingly, no apparent increase in the vaginopathic potential of the strains was observed with an estrogen-dependent rat vaginal infection. The increased pathogenicity of drug-resistant strains for systemic infection was associated with a number of biochemical and physiological changes, including (i) marked cellular alterations associated with a different expression and content of major cell wall polysaccharides, (ii) more rapid and extensive hypha formation in both liquid and solid media, and (iii) increased adherence to plastic and a propensity for biofilm formation. Overall, our data demonstrate that experimentally induced resistance to antifungal drugs, irrespective of drug family, can substantially divert C. albicans biology, affecting in particular biological properties of potential relevance for deep-seated candidiasis.

Topics: Animals; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Candidiasis, Vulvovaginal; Cell Adhesion; Drug Resistance, Fungal; Echinocandins; Female; Fluconazole; Fungal Proteins; Host-Pathogen Interactions; Humans; Lipopeptides; Lipoproteins; Male; Micafungin; Mice; Mice, Inbred BALB C; Microscopy, Electron, Scanning; Phenotype; Rats; Rats, Wistar; Virulence