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1.
PLoS One ; 15(9): e0238428, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941438

RESUMO

OBJECTIVES: Recurrent vulvovaginal candidiasis (RVVC) causes significant morbidity. Candida albicans is the main pathogen associated with both sporadic and recurrent candidiasis. Due to unsatisfactory treatment effect, the impact of chlorhexidine digluconate and fluconazole alone or in combination on C. albicans and biofilm was investigated. METHODS: Vaginal C. albicans isolates from 18 patients with recurrent candidiasis and commensals from 19 asymptomatic women were isolated by culture. Crystal violet, XTT and colony forming unit assay were used to analyze the effect of chlorhexidine digluconate and fluconazole on growth of C. albicans, formation of new and already established, mature, biofilm. RESULTS: Fluconazole reduced the growth of planktonic C. albicans. However, in established biofilm, fluconazole had no effect on the candida cells and was not able to disperse and reduce the biofilm. By contrast, chlorhexidine digluconate had a direct killing effect on C. albicans grown both planktonically and in biofilm. Chlorhexidine digluconate also dispersed mature biofilm and inhibited formation of new biofilm. No major differences were observed between commensal isolates and candida causing recurrent vulvovaginitis with respect to biofilm or growth after chlorhexidine digluconate treatment. CONCLUSION: Biofilm is a problem in patients with recurrent vulvovaginal candidiasis reducing the effect of antifungal treatment. Development of new treatment strategies are urgently needed to decrease the recurrences. In already established biofilm, chlorhexidine digluconate dispersed the biofilm and was more effective in eradicating candida compared to fluconazole. Future treatment strategy may thus be a combination of chlorhexidine digluconate and fluconazole and prophylactic use of chlorhexidine digluconate to prevent biofilm formation and restrict infections.


Assuntos
Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Clorexidina/análogos & derivados , Adulto , Antifúngicos/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candidíase/tratamento farmacológico , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Clorexidina/metabolismo , Clorexidina/farmacologia , Feminino , Fluconazol/farmacologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Vagina/microbiologia
2.
PLoS One ; 15(8): e0237046, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817677

RESUMO

Candida africana is a pathogenic species within the Candida albicans species complex. Due to the limited knowledge concerning its prevalence and antifungal susceptibility profiles, a comprehensive study is overdue. Accordingly, we performed a search of the electronic databases for literature published in the English language between 1 January 2001 and 21 March 2020. Citations were screened, relevant articles were identified, and data were extracted to determine overall intra-C. albicans complex prevalence, geographical distribution, and antifungal susceptibility profiles for C. africana. From a total of 366 articles, 41 were eligible for inclusion in this study. Our results showed that C. africana has a worldwide distribution. The pooled intra-C. albicans complex prevalence of C. africana was 1.67% (95% CI 0.98-2.49). Prevalence data were available for 11 countries from 4 continents. Iran (3.02%, 95%CI 1.51-4.92) and Honduras (3.03%, 95% CI 0.83-10.39) had the highest values and Malaysia (0%) had the lowest prevalence. Vaginal specimens were the most common source of C. africana (92.81%; 155 out of 167 isolates with available data). However, this species has also been isolated from cases of balanitis, from patients with oral lesions, and from respiratory, urine, and cutaneous samples. Data concerning the susceptibility of C. africana to 16 antifungal drugs were available in the literature. Generally, the minimum inhibitory concentrations of antifungal drugs against this species were low. In conclusion, C. africana demonstrates geographical variation in prevalence and high susceptibility to antifungal drugs. However, due to the relative scarcity of existing data concerning this species, further studies will be required to establish more firm conclusions.


Assuntos
Candida/efeitos dos fármacos , Candida/genética , Candida/metabolismo , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Candidíase Vulvovaginal/microbiologia , Farmacorresistência Fúngica/efeitos dos fármacos , Farmacorresistência Fúngica/genética , Feminino , Humanos , Testes de Sensibilidade Microbiana , Prevalência , Vagina/microbiologia
3.
BMC Infect Dis ; 20(1): 287, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32393342

RESUMO

BACKGROUND: Accurate identification Candida is important for successful therapy and epidemiology study. The aim of research is to study API 20C yeast identification system identification rate by using molecular identification as gold standard and tested the antifungal susceptibility of Candida from patients with vulvovaginal candidiasis (VVC). METHODS: In total, 3574 yeast isolates were obtained from patients with VVC. API 20C yeast identification, molecular identification and in vitro antifungal susceptibility were performed. RESULTS: C. albicans was the predominant Candida species [2748 isolates, 76.9%] in VVC. The isolates from vaginal samples represented 22 species based on molecular identification. The API 20C system identifies only 11 of the species encountered during the study period. Based on the API 20C system, 3273 (91.78%) isolates were correctly identified to the species level. The correct identification rate of the API 20C system for rare yeast was 15.29% (26/170 isolates). Antifungal susceptibility was tested in a total of 1844 isolates of Candida from patients with VVC. C. albicans was susceptible to most of the tested antifungals. The MICs of azoles for C. glabrata were higher than those for C. albicans. The MICs of echinocandins for C. parapsilosis were higher than those for C. albicans. CONCLUSIONS: The API 20C yeast identification system can be used to reliably identify the most common Candida species while molecular methods are necessary for the identification of closely related, emerging, and rare yeast species. The results from this study suggest that much of the previous studies on the epidemiology of VVC should be re-thought. C. albicans was susceptible to most of the tested antifungals.


Assuntos
Antifúngicos/farmacologia , Candida/classificação , Candida/efeitos dos fármacos , Candidíase Vulvovaginal/epidemiologia , Candidíase Vulvovaginal/microbiologia , Farmacorresistência Fúngica Múltipla , Adulto , Antifúngicos/uso terapêutico , Candida/genética , Candida/isolamento & purificação , Candidíase Vulvovaginal/tratamento farmacológico , China/epidemiologia , Feminino , Humanos , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Prevalência , Estudos Prospectivos , Adulto Jovem
4.
Sci Rep ; 10(1): 7976, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409699

RESUMO

Vulvovaginal candidosis (VVC) is a common condition with severe symptoms and high recurrence rates. Probiotic lactobacilli are explored as alternatives to azole treatments. Although the vaginal microbiota is generally not depleted in lactobacilli during VVC, studies indicate that the functionality and antimicrobial activity of the lactobacilli is impaired. We selected three strains from the Lactobacillus genus complex (L. rhamnosus GG, L. pentosus KCA1 and L. plantarum WCFS1) based on in vitro evaluation and formulated them in a gel for vaginal application. This gel was evaluated in 20 patients suffering from acute VVC, who were followed for four weeks including a 10-day treatment period. The microbiome was assessed through 16S rRNA (bacteria) and internal transcribed spacer (ITS; fungi) amplicon sequencing, supplemented with quantitative PCR, culture and microscopy for Candida evaluation. 45% of women did not require rescue medication (3×200 mg fluconazole), implying an improvement of their symptoms. These women showed similar end concentrations of fungi as women treated with fluconazole. Moreover, fluconazole appeared to reduce numbers of endogenous lactobacilli. Our study points towards important aspects for future selection of lactobacilli for probiotic use in VVC and the need to investigate possible negative influences of azoles on the vaginal bacterial community.


Assuntos
Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/terapia , Lactobacillus , Microbiota , Probióticos/administração & dosagem , Vagina/microbiologia , Cremes, Espumas e Géis Vaginais , Administração Tópica , Antifúngicos/administração & dosagem , Feminino , Humanos , Probióticos/uso terapêutico , Estudo de Prova de Conceito , Resultado do Tratamento
5.
J Mycol Med ; 30(3): 100966, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32317216

RESUMO

Candida africana has been recovered principally as a causative agent of vulvovaginal candidiasis (VVC) from different countries, which is likely to be misidentified as the typical Candida albicans or Candida dubliniensis. The current study aimed to characterize C. albicans species complex obtained from VVC based on conventional and molecular assays. Furthermore, in vitro antifungal susceptibility testing was performed based on CLSI documents. Additionally, due to low knowledge concerning C. africana infections, we reviewed all published papers from 1991 to 2019. One hundred forty-four out of 287 patients were identified with Candida infection, among whom 151 isolates of Candida were obtained. Candida albicans 109 (72.1%), Candida glabrata 21 (13.9%), Candida krusei 8 (5.2%), Candida tropicalis 5 (3.3%), Candida africana 3 (1.9%), Candida parapsilosis 3 (1.9%) and C. dubliniensis 2 (1.3%) were isolated from patients. MIC results showed that C. africana isolates were susceptible to all tested antifungal drugs. Candida africana infections were more prevalent in Africa. One hundred fifteen (40.6%) of patients with C. africana candidiasis were from seven African countries, and Madagascar and Angola had the majority of cases. The epidemiological data, phenotypic, clinical features, ecologic similarity, and antifungal susceptibility profiles for better understanding of the pathogenic mechanisms and optimal treatment underlying non-CandidaalbicansCandida vulvovaginitis are highly recommended.


Assuntos
Candida/isolamento & purificação , Candidíase Vulvovaginal/epidemiologia , Candidíase Vulvovaginal/microbiologia , África/epidemiologia , Antifúngicos/uso terapêutico , Candida/classificação , Candida/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Feminino , Geografia , História do Século XX , História do Século XXI , Humanos , Madagáscar/epidemiologia , Testes de Sensibilidade Microbiana , Prevalência
6.
Diagn Microbiol Infect Dis ; 97(2): 115024, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32253071

RESUMO

BACKGROUND: It is commonly stated that Candida in the vagina prefers a low pH to develop infection. However, mixed infections of Candida with bacterial vaginosis (BV) and aerobic vaginitis (AV) are rather common and may challenge the rule that Candida should only be looked for in low vaginal pH settings. In this study we tested whether the vaginal pH in acute vaginal candidosis is lower than in women successfully treated to prevent Candida recurrences. METHODS: Vaginal pH and microscopy findings of vaginal microbiota were recorded during 12 visits over 1.5 years in 117 patients medically monitored during a degressive fluconazole maintenance regimen for proven recurrent vulvovaginal candidosis (ReCiDiF trial). The fluctuation of the mean pH of and microscopic findings of the vaginal smears were studied before, during and after the treatment. RESULTS: The mean vaginal pH of women with acute infection before or after ending maintenance treatment was (4.7±0.8 and 4.8 ±1.0, respectively, p>0.05). During maintenance treatment with fluconazole, the pH dropped significantly to 4.5±0.8 (p=0.01). Depression of Lactobacilli spp. (increased lactobacillary grades) was more frequent during the acute, pre-treatment period (30.0%) than during the treatment period (23.1%, p=0.03). Aerobic vaginitis type flora was also more prevalent pre-treatment than during treatment (30.0% vs 22.2%, OR=0.7 (95%CI 0.5-0.9), p=0.01). DISCUSSION: In women with RVVC, acute vaginal Candida infection is associated with an increased pH, and disturbed vaginal bacterial microbiota. During fluconazole maintenance treatment, the pH drops to normal levels and the lactobacillary grade improves. CONDENSATION: Acute Candida vulvovaginitis can be associated with a disturbance of the vaginal microbiota. In patients with recurrent vulvovaginal candidosis, decrease of pH, and increase of Lactobacilli spp. were observed during fluconazole maintenance treatment. This pH drop was seen in all response groups. This contradicts the common belief that active vaginal Candida infection is related to low pH.


Assuntos
Antifúngicos/uso terapêutico , Candidíase Vulvovaginal/prevenção & controle , Fluconazol/uso terapêutico , Microbiota/efeitos dos fármacos , Vagina/efeitos dos fármacos , Vagina/microbiologia , Doença Aguda , Adolescente , Adulto , Bactérias/efeitos dos fármacos , Candida/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Disbiose , Feminino , Humanos , Concentração de Íons de Hidrogênio , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Recidiva , Vagina/química , Adulto Jovem
7.
Int J Med Microbiol ; 310(3): 151414, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32173268

RESUMO

Vulvovaginal candidiasis (VVC) caused by Candida albicans is a common disease worldwide. A very important C. albicans virulence factor is its ability to form biofilms on epithelium and/or on intrauterine devices promoting VVC. It has been shown that VVC has a hormonal dependency and that progesterone affects virulence traits of C. albicans cells. To understand how the acidic environment (pH 4) and progesterone (either alone and in combination) modulate C. albicans response during formation of biofilm, a transcriptomic analysis was performed together with characterization of the biofilm properties. Compared to planktonic cells, acidic biofilm-cells exhibited major changes in their transcriptome, including modifications in the expression of 286 genes that were not previously associated with biofilm formation in C. albicans. The vast majority of the genes up-regulated in the acidic biofilm cells (including those uniquely identified in our study) are known targets of Sfl1, and consistently, Sfl1 deletion is herein shown to impair the formation of acidic biofilms (pH 4). Under the acidic conditions used, the presence of progesterone reduced C. albicans biofilm biomass and structural cohesion. Transcriptomic analysis of biofilms developed in the presence of progesterone led to the identification of 65 down-regulated genes including, among others, the regulator Tec1 and several of its target genes, suggesting that the function of this transcription factor is inhibited by the presence of the hormone. Additionally, progesterone reduced the susceptibility of biofilm cells to fluconazole, consistent with an up-regulation of efflux pumps. Overall, the results of this study show that progesterone modulates C. albicans biofilm formation and genomic expression under acidic conditions, which may have implications for C. albicans pathogenicity in the vaginal environment.


Assuntos
Ácidos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Perfilação da Expressão Gênica , Progesterona/farmacologia , Antifúngicos/farmacologia , Candidíase Vulvovaginal/microbiologia , Feminino , Fluconazol/farmacologia , Proteínas Fúngicas/genética , Humanos , Concentração de Íons de Hidrogênio , Transcriptoma , Virulência/efeitos dos fármacos
8.
Am J Obstet Gynecol ; 223(3): 406.e1-406.e16, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32135142

RESUMO

BACKGROUND: Vulvodynia (idiopathic vulvar pain) affects up to 8% of women by age 40 years, has a poorly understood etiology, and has variable treatment efficacy. Several risk factors are associated with vulvodynia from a history of yeast infections to depression and allergies. Recent work suggests an altered immune inflammatory mechanism plays a role in vulvodynia pathophysiology. Because the vaginal microbiome plays an important role in local immune-inflammatory responses, we evaluated the vaginal microbiome among women with vulvodynia compared with controls as 1 component of the immune system. OBJECTIVE: The objective of the study was to characterize the vaginal microbiome in women with clinically confirmed vulvodynia and age-matched controls and assess its overall association with vulvodynia and how it may serve to modify other factors that are associated with vulvodynia as well. STUDY DESIGN: We conducted a case-control study of 234 Minneapolis/Saint Paul-area women with clinically confirmed vulvodynia and 234 age-matched controls clinically confirmed with no history of vulvar pain. All participants provided vulvovaginal swab samples for culture-based and non-culture (sequencing)-based microbiological assessments, background and medical history questionnaires on demographic characteristics, sexual and reproductive history, and history of psychosocial factors. Vaginal microbiome diversity was assessed using the Shannon alpha diversity Index. Data were analyzed using logistic regression. RESULTS: Culture and molecular-based analyses of the vaginal microbiome showed few differences between cases and controls. However, among women with alpha diversity below the median (low), there was a strong association between increasing numbers of yeast infections and vulvodynia onset, relative to comparable time periods among controls (age-adjusted odds ratio, 8.1, 95% confidence interval, 2.9-22.7 in those with 5 or more yeast infections). Also among women with low-diversity microbiomes, we observed a strong association between moderate to severe childhood abuse, antecedent anxiety, depression, and high levels of rumination and vulvodynia with odds ratios from 1.83 to 2.81. These associations were not observed in women with high-diversity microbiomes. CONCLUSION: Although there were no overall differences in microbiome profiles between cases and controls, vaginal microbiome diversity influenced associations between environmental and psychosocial risk factors and vulvodynia. However, it is unclear whether vaginal diversity modifies the association between the risk factors and vulvodynia or is altered as a consequence of the associations.


Assuntos
Microbiota/fisiologia , Vagina/microbiologia , Vulvodinia/microbiologia , Adolescente , Adulto , Bactérias/classificação , Bactérias/genética , Candidíase Vulvovaginal/epidemiologia , Candidíase Vulvovaginal/microbiologia , Estudos de Casos e Controles , Contraceptivos Hormonais , Feminino , Humanos , Minnesota/epidemiologia , Psicologia , RNA Ribossômico 16S/análise , Parceiros Sexuais , Vulvodinia/epidemiologia , Adulto Jovem
10.
Sci Rep ; 10(1): 3615, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32107396

RESUMO

Vulvovaginal candidiasis causes sufferers much discomfort. Phytotherapy with garlic has been reported to be a possible alternative form of treatment; however, it is unknown why patients report varying success with this strategy. Fresh garlic extract has been shown to down-regulate the putative virulence gene, SIR2 in C. albicans. Our study aimed to see if previous observations were reproducible for the gene responsible for Candidalysin (ECE1). Two clinical strains from patients with reported variable efficacy of using garlic for the treatment of vulvovaginal candidiasis were compared through biofilm assays and antimicrobial susceptibility. Real-time PCR was used to assess changes in gene expression when exposed to garlic. Treatment with fresh garlic extract and pure allicin (an active compound produced in cut garlic) resulted in a decrease in SIR2 expression in all strains. In contrast, ECE1 expression was up-regulated in a reference strain and an isolate from a patient unresponsive to garlic therapy, while in an isolate from a patient responsive to garlic therapy, down-regulation of ECE1 occurred. Future studies that investigate the effectiveness of phytotherapies should take into account possible varying responses of individual strains and that gene expression may be amplified in the presence of serum.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/microbiologia , Proteínas Fúngicas/genética , Alho/química , Extratos Vegetais/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/genética , Candida albicans/metabolismo , Candidíase Vulvovaginal/tratamento farmacológico , Feminino , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Humanos , Ácidos Sulfínicos/farmacologia , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
11.
J Dermatol ; 47(4): 385-389, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32030818

RESUMO

Anogenital skin care for the elderly remains an umbrella term concerning protective and non-interventional regimens, particularly for ordinary diaper users. Our recent investigation has demonstrated the preventive effect of daily anogenital washing with miconazole nitrate-containing soap to the development of diaper candidiasis. We extended this work to cover our hypothesis as to whether the miconazole soap has a therapeutic benefit in genital candidiasis. The study outline includes: (i) the enrollment of 21 bedridden inpatients (84 ± 9 years; eight men and 13 women) who were diagnosed clinically and mycologically with genital candidiasis, and who had never received topical and/or systemic antifungal agents; (ii) administration of anogenital washing with 0.75% miconazole-containing soap once daily for 4 weeks; and (iii) assessment of clinical symptoms and detection of Candida materials by culture and microscopic examination. As assessed by clinical symptom scoring for incontinence-associated dermatitis (IAD), the ratio of patients with severe to moderate symptoms dramatically decreased by 2 weeks and 10 of 21 patients became symptom-free at 4 weeks. The IAD clinical severity score was significantly decreased at 4 weeks. Compared with the baseline positivity, both microscopic and cultured Candida-positive rates were significantly decreased at 4 weeks after washing. All culture-detected fungi were Candida albicans. Severe adverse events did not occur in all participants. Individual medical and risk factors had no significant correlation with clinical severity and duration of candidiasis on variance analysis. In conclusion, topical washing with miconazole soap is a safe and reliable non-medical approach for soothing diaper-associated genital candidiasis in bedridden inpatients in whom it is difficult to perform prompt medical examination.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Cutânea/terapia , Candidíase Vulvovaginal/terapia , Dermatite das Fraldas/terapia , Higiene da Pele/métodos , Sabões/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Candida/isolamento & purificação , Candidíase Cutânea/diagnóstico , Candidíase Cutânea/microbiologia , Candidíase Vulvovaginal/diagnóstico , Candidíase Vulvovaginal/microbiologia , Dermatite das Fraldas/diagnóstico , Dermatite das Fraldas/microbiologia , Fraldas para Adultos/efeitos adversos , Feminino , Humanos , Masculino , Miconazol/administração & dosagem , Estudos Prospectivos , Índice de Gravidade de Doença , Sabões/química , Resultado do Tratamento , Incontinência Urinária/terapia
12.
Ann Clin Microbiol Antimicrob ; 19(1): 5, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992328

RESUMO

Recurrent vulvovaginal infections (RVVI) has not only become an epidemiological and clinical problem but also include large social and psychological consequences. Understanding the mechanisms of both commensalism and pathogenesis are necessary for the development of efficient diagnosis and treatment strategies for these enigmatic vaginal infections. Through this review, an attempt has been made to analyze vaginal microbiota (VMB) from scratch and to provide an update on its current understanding in relation to health and common RVVI i.e. bacterial vaginosis, vulvovaginal candidiaisis and Trichomoniasis, making the present review first of its kind. For this, potentially relevant studies were retrieved from data sources and critical analysis of the literature was made. Though, culture-independent methods have greatly unfolded the mystery regarding vaginal bacterial microbiome, there are only a few studies regarding the composition and diversity of vaginal mycobiome and different Trichomonas vaginalis strains. This scenario suggests a need of further studies based on comparative genomics of RVVI pathogens to improve our perceptive of RVVI pathogenesis that is still not clear (Fig. 5). Besides this, the review details the rationale for Lactobacilli dominance and changes that occur in healthy VMB throughout a women's life. Moreover, the list of possible agents continues to expand and new species recognised in both health and VVI are updated in this review. The review concludes with the controversies challenging the widely accepted dogma i.e. "VMB dominated with Lactobacilli is healthier than a diverse VMB". These controversies, over the past decade, have complicated the definition of vaginal health and vaginal infections with no definite conclusion. Thus, further studies on newly recognised microbial agents may reveal answers to these controversies. Conversely, VMB of women could be an answer but it is not enough to just look at the microbiology. We have to look at the woman itself, as VMB which is fine for one woman may be troublesome for others. These differences in women's response to the same VMB may be determined by a permutation of behavioural, cultural, genetic and various other anonymous factors, exploration of which may lead to proper definition of vaginal health and disease.


Assuntos
Candidíase Vulvovaginal , Microbiota , Vaginite por Trichomonas , Vagina/microbiologia , Vaginose Bacteriana , Biofilmes/crescimento & desenvolvimento , Candida/isolamento & purificação , Candida/metabolismo , Candida albicans/isolamento & purificação , Candida albicans/metabolismo , Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/patologia , Candidíase Vulvovaginal/transmissão , Coinfecção/microbiologia , Coinfecção/parasitologia , Feminino , Gardnerella vaginalis/isolamento & purificação , Interações entre Hospedeiro e Microrganismos , Humanos , Lactobacillus/isolamento & purificação , Lactobacillus/metabolismo , Interações Microbianas , Microbiota/fisiologia , Recidiva , Vaginite por Trichomonas/parasitologia , Vaginite por Trichomonas/patologia , Vaginite por Trichomonas/transmissão , Trichomonas vaginalis/isolamento & purificação , Trichomonas vaginalis/metabolismo , Vagina/parasitologia , Vaginose Bacteriana/microbiologia , Vaginose Bacteriana/patologia , Vaginose Bacteriana/transmissão , Fatores de Virulência/metabolismo
13.
BMC Infect Dis ; 20(1): 32, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931738

RESUMO

BACKGROUND: Vaginal candidiasis is frequent in pregnant women and is associated with sepsis and adverse neonatal outcomes. This study determined the prevalence of candida species in symptomatic pregnant women and evaluated the antifungal susceptibility profile of the isolated Candida strains. It also aimed to explore whether Candida species predicts gestational complications and adverse neonatal outcomes. METHODS: A total of 258 pregnant women with vaginal discharge at 35 to 37 week of gestation participated in this study. Vaginal swabs from these patients were collected at various obstetrics and gynecology clinics in Lebanon for a period of 14 months. Candida isolates were identified at species level and antifungal susceptibility of Candida albicans to fluconazole (FCZ), amphotericin B (AMB), itraconazole (ICZ) and voriconazole (VCZ) was determined by the agar-based E-test method. RESULTS: Among 258 women tested, 100 (39%) were positive for Candida species. C. albicans, C. glabrata and C. krusei were isolated from 42, 41 and 17% of the women, respectively. C. albicans was significantly associated only with gestational diabetes while C. krusei or C. glabrata had significant positive associations with other gestational complications. The antifungal susceptibility tests of C. albicans isolates revealed 97.5, 90, 87.5 and 97.5% susceptibility to AMB, FCZ, ICZ and VCZ, respectively. CONCLUSION: The current study revealed high incidence of both C. albicans and non-C. albicans Candida strains causing vulvovaginitis among pregnant women in Beirut, Lebanon. Candida screening as antenatal follow up is advised to minimize the risk of adverse neonatal outcome or gestational complications.


Assuntos
Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/epidemiologia , Farmacorresistência Fúngica/efeitos dos fármacos , Descarga Vaginal/microbiologia , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Candida albicans/isolamento & purificação , Candida glabrata/efeitos dos fármacos , Candida glabrata/isolamento & purificação , Candidíase Vulvovaginal/microbiologia , Estudos Transversais , Feminino , Fluconazol/uso terapêutico , Seguimentos , Humanos , Incidência , Recém-Nascido , Itraconazol/uso terapêutico , Líbano/epidemiologia , Testes de Sensibilidade Microbiana , Gravidez , Prevalência , Voriconazol/uso terapêutico
14.
Int J Biol Macromol ; 148: 1053-1060, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31982527

RESUMO

Vulvovaginal candidiasis (VVC) is one of the most common infections in women. The purpose of this study was to evaluate the ability of a water-soluble ß-glucan salecan to protect against Candida albicans (C. albicans) vaginal infection. The model was reproduced with intravaginal inoculation of yeast blastoconidia in pseudoestrus mice. We found that mice that received salecan (0.5 mg per mouse) after infection had 85% fewer CFU than infected mice given saline. Compared with the C.albicans group, salecan reduced the migration of polymorphonuclear neutrophils (PMNs) in the vagina, decreased mRNA levels of cytokines IL23, IL22, IL17a, and IL17f, anti-candidal genes S100a8 and S100a9 and C.albicans pattern recognition receptor Dectin1. The analysis for vaginal microbial community composition at different taxa levels revealed that the bacterial flora composition in the vagina of the salecan-treated mice was similar to that of the uninfected mice, and distinguished from the infected mice. The vaginal lavages from the salecan treated group had more Enterococcus and its metabolite lactate. Our results suggest salecan might be a potential therapeutic agent for vaginal infection of C.albicans.


Assuntos
Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Candidíase Vulvovaginal/microbiologia , beta-Glucanas/farmacologia , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Candidíase Vulvovaginal/tratamento farmacológico , Contagem de Colônia Microbiana , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação Fúngica da Expressão Gênica , Ácido Láctico , Camundongos , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , RNA Mensageiro/genética , Receptores de Reconhecimento de Padrão/genética , Receptores de Reconhecimento de Padrão/metabolismo , Vagina/microbiologia , beta-Glucanas/química
15.
Eur J Contracept Reprod Health Care ; 25(2): 120-125, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31990231

RESUMO

Objectives: The aim of the study was to investigate the effect of copper-bearing intrauterine device (IUD) use on the virulence of Candida species causing vulvovaginal candidiasis (VVC). The in vitro ability of Candida species to produce proteinase and phospholipase enzymes was studied, together with their antifungal susceptibility.Methods: Vaginal swabs from women with VVC were cultured and Candida species were identified. Participants comprised 132 women with culture-confirmed VVC, of whom 65 were using a copper-bearing IUD and 67 were not. Candida isolates were tested for their ability to produce proteinase and phospholipase as well as for their susceptibility to fluconazole and nystatin.Results: Proteinase production was higher in non-albicans Candida (NAC) isolates of IUD users compared with non-users (p = 0.017). IUD use was significantly associated with antifungal resistance of NAC isolates to fluconazole (p = 0.013) and nystatin (p = 0.018). By contrast, IUD use seemed to significantly reduce the production of proteinase by C. albicans (p = 0.041), with no effect on its antifungal susceptibility. There was a significant negative correlation between proteinase production in both C. albicans and NAC as well as sensitivity to fluconazole (r= -0.383, p < 0.05 and r= -0.497, p < 0.05, respectively).Conclusion: IUD use enhanced the virulence (proteinase production and antifungal resistance) of NAC but not C. albicans, indicating a variation in virulence between Candida species in response to IUD use. C. albicans responded better to fluconazole, whereas NAC isolates were more sensitive to nystatin.


Assuntos
Candidíase Vulvovaginal/microbiologia , Farmacorresistência Fúngica/efeitos dos fármacos , Dispositivos Intrauterinos de Cobre/efeitos adversos , Adulto , Candida/metabolismo , Estudos Transversais , Egito , Feminino , Humanos , Peptídeo Hidrolases/biossíntese , Fosfolipases/biossíntese , Virulência
16.
J Low Genit Tract Dis ; 24(1): 48-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31860575

RESUMO

OBJECTIVES: This study evaluated use of long-term fluconazole beyond an initial 6-month course of weekly fluconazole in premenopausal patients with idiopathic recurrent vulvovaginal candidiasis (RVVC) due to Candida albicans. MATERIALS AND METHODS: A retrospective chart review was performed of women seen in Wayne State University Vaginitis Clinic with culture-confirmed idiopathic RVVC due to Candida albicans during a 10-year period (January 2006 to December 2015). Only patients without risk factors for secondary VVC and who initiated a 6-month course of weekly fluconazole therapy were selected. Data included long-term use of fluconazole therapy, treatment efficacy, and development of fluconazole resistance. Questionnaires were mailed to evaluate patient's experience after fluconazole therapy. RESULTS: Of 883 patients with RVVC based on clinical records, 191 with culture positive idiopathic RVVC due to C. albicans were started on the maintenance fluconazole regimen, and 147 (77.0%) completed 6 months of therapy. Of these, 107 (72.8%) continued or received maintenance past 6 months. The most common reason for additional fluconazole therapy was culture-confirmed VVC recurrence (55.1%), unconfirmed but possible VVC recurrence (16.8%), and patient preference (10.3%). The mean duration of fluconazole maintenance was 35.7 (range = 7-288) months. Fluconazole resistance emerged in 7.5% completing 6-month therapy. Upon questionnaire follow-up, 93.6% of 51 respondents reported benefit during maintenance regimen; however, 80.9% described relapse after discontinuing weekly therapy. CONCLUSIONS: Fluconazole suppression therapy was highly effective in preventing VVC symptoms but was rarely curative and VVC relapse occurred frequently after discontinuation of maintenance therapy. The development of drug resistance in C. albicans isolates after long-term fluconazole maintenance therapy although uncommon is a previously unrecognized complication.


Assuntos
Antifúngicos/administração & dosagem , Candida albicans/isolamento & purificação , Candidíase Vulvovaginal/tratamento farmacológico , Fluconazol/administração & dosagem , Adolescente , Adulto , Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/patologia , Farmacorresistência Fúngica , Feminino , Humanos , Michigan , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
17.
BJOG ; 127(2): 287-299, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31299136

RESUMO

BACKGROUND: Vaginal probiotics claiming to cure and/or prevent bacterial and/or fungal vaginal dysbiosis are available on the market but, until recently, did not have to be approved as drugs for human use. OBJECTIVES: We evaluated the impact of vaginal probiotics on bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) cure and/or recurrence, as well as vaginal microbiota (VMB) composition and vaginal detection of probiotic strains. SEARCH STRATEGY: We performed a systematic literature search in MEDLINE and Embase up to 15 January 2019. SELECTION CRITERIA: There were no restrictions in probiotic strains/formulations, study populations, and designs. BV had to be diagnosed by Nugent or Ison-Hay Gram stain scoring, VVC by culture, wet mount or PCR, and VMB composition/detection by molecular techniques. DATA COLLECTION AND ANALYSIS: The authors independently extracted data. MAIN RESULTS: All 22 vaginal probiotics evaluated in the 34 eligible studies contained Lactobacillus strains, and some contained additional active ingredients. The probiotics hold promise for BV cure and prevention, but much less so for VVC cure and prevention. No major safety concerns were reported in any of the studies. Vaginal detection of probiotic strains never lasted long beyond the dosing period, suggesting that they did not colonise the vagina. However, findings are not definitive because heterogeneity was high and the quality of most studies suboptimal. CONCLUSIONS: Availability of vaginal probiotics for vaginal health indications will likely decline in 2020 because of regulatory changes. We urge the field to invest in clinical evidence-based product development and to conduct future trials more rigorously. TWEETABLE ABSTRACT: Lactobacilli-containing vaginal probiotics hold promise for bacterial vaginosis cure and prevention, but not for vulvovaginal candidiasis.


Assuntos
Candidíase Vulvovaginal , Disbiose/prevenção & controle , Disbiose/terapia , Lactobacillus , Microbiota , Probióticos/administração & dosagem , Vagina/microbiologia , Vaginose Bacteriana , Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/prevenção & controle , Candidíase Vulvovaginal/terapia , Disbiose/microbiologia , Feminino , Humanos , Resultado do Tratamento , Vaginose Bacteriana/microbiologia , Vaginose Bacteriana/prevenção & controle , Vaginose Bacteriana/terapia
18.
Med Mycol ; 58(3): 341-350, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31254346

RESUMO

Vulvovaginal candidiasis (VVC) is an infection usually caused by Candida albicans and increasingly by Candida glabrata, which has an intrinsically high resistance to commonly used antifungals. Candida species possess virulence factors that contribute to VVC development, as the ability to form biofilms in vaginal walls and intrauterine devices. It is known that VVC is promoted by conditions that increase the hormones levels, during pregnancy, however, the effects of hormones on Candida cells are poorly studied, especially in C. glabrata. Thus, the influence of progesterone and ß-estradiol, at normal cycle and pregnancy concentrations, on biofilm formation and resistance of C. albicans and C. glabrata vaginal isolates, was analyzed using acidic conditions (pH 4). Biofilms of C. albicans developed in the presence of hormones presented reduced biomass (up to 65%) and impaired cells ability to produce filamentous forms. On the other hand, C. glabrata presented high adaptation to the presence of hormones, which did not affect its biofilm formation. Additionally, hormones impaired the susceptibility of C. albicans and C. glabrata cells to azoles, with potential clinical significance in the presence of pregnancy hormone levels. A similar result was obtained for the susceptibility to hydrogen peroxide, a biological vaginal barrier against Candida growth. Overall, the results of this study suggest that hormones may act as environmental cues promoting Candida protection from vaginal defenses and harmful conditions, what may have implications in Candida vaginal pathogenicity and treatment of VVC, especially in C. glabrata infections due to its high adaptability to vaginal conditions.


Assuntos
Azóis/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida glabrata/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Progesterona/farmacologia , Antifúngicos/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida albicans/fisiologia , Candida glabrata/fisiologia , Candidíase Vulvovaginal/microbiologia , Estradiol/farmacologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Vagina/microbiologia
19.
Lett Appl Microbiol ; 70(2): 95-101, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31705810

RESUMO

Candida albicans is an opportunistic fungus, which causes vulvovaginal candidiasis (VVC). The aim of this study was to evaluate Mrr2 mutation and its expression levels and Candida drug resistance 1 (Cdr1) in C. albicans associated with fluconazole (FCA) resistance. We identified 80 isolates of C. albicans from 155 vaginal secretions and performed FCA drug sensitivity tests, using M27-A3 micro-broth dilution. We extracted DNA, sequenced Mrr2, and performed reverse transcriptase-quantitative PCR polymerase chain reaction (RT-qPCR) to detect mRNA expression levels of Mrr2 and Cdr1. In total, 40 isolates were sensitive, 10 were dose-dependently sensitive, and 30 were resistant to FCA. Mrr2 mutation occurred in 56·67% isolates, which was significantly higher than that in the FCA sensitive group (26·08%, P < 0·05). The mRNA expression level of Cdr1 in the FCA resistant group was significantly higher than that in the sensitive group Cdr1 (0·42 ± 0·294 vs 0·25 ± 0·289, P < 0·05). The odds ratio of FCA-resistant occurrence in C. albicans with Mrr2 mutation and high expression levels was 47·5 times higher than C. albicans without Mrr2 mutation and low expression levels. The results may provide new insights for improving VVC treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Significance and Impact of the Study: Candida albicans is an opportunistic fungus, which causes vulvovaginal candidiasis (VVC). Fluconazole (FCA) is the most widely used drug in VVC infection. However, the widespread use of FCA has severely increased the incidence of FCA-resistant fungus. Therefore, the mechanism underlying FCA resistance in C. albicans must be elucidated urgently. This study demonstrated that high expression of Cdr1 and Mrr2 may directly be linked to C. albicans resistance to FCA, and high expression of Mrr2 may promote high expression of Cdr1 and mediate resistance of C. albicans to FCA. The results may provide new insights for improving VVC treatment.


Assuntos
Antifúngicos/uso terapêutico , Candida albicans/genética , Candidíase Vulvovaginal/tratamento farmacológico , Farmacorresistência Fúngica/genética , Fluconazol/uso terapêutico , Adulto , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candidíase Vulvovaginal/microbiologia , Feminino , Humanos , Testes de Sensibilidade Microbiana , Mutação , Ativação Transcricional , Regulação para Cima
20.
Gynecol Obstet Invest ; 85(1): 88-93, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31694024

RESUMO

OBJECTIVES: The aim of this work is to evaluate the susceptibility profile of the isolates against antifungal drugs and the level of virulent genes and resistant genes mRNA expression of Candida nivariensis. METHODS: We analyzed a collection of 9 C. nivariensis isolates from clinical isolates of Candida glabrata complex isolated from patients with vulvovaginal candidiasis (VVC). Antifungal susceptibilities of the isolates were assayed by using the broth microdilution method. The level of virulent genes and resistant genes mRNA expression was determined by using real-time PCR. RESULTS: At day 7-14 and day 30-35 follow-up, mycological cure of VVC caused by C. nivariensis was 5 in 9 and 4 in 9 cases. The minimum inhibitory concentration geometric means of caspofungin, fluconazole, itraconazole, and amphotericin B in C. nivariensis isolates were higher than those in Candida albicans ATCC90028 (0.340, 1.852, 0.367, and 1.587 vs. 0.124, 0.140, 0.030, and 0.891 µg/mL; p < 0.05). The level of resistant genes ERG11, CDR1, and CDR2 and virulent genes YPS1, AWP3, and EPA1 mRNA expression was higher in C. nivariensis isolates than that of C. glabrata (2.58 ± 0.78, 9.31 ± 5.19, 11.10 ± 0.76, 13.57 ± 0.54, 11.96 ± 2.93, and 14.40 ± 0.61 vs. 1.05 ± 1.19, 2.22 ± 0.27, 0.85 ± 0.48, 0.30 ± 0.37, 1.90 ± 0.43, and 2.40 ± 0.65). CONCLUSION: We conclude that patients infected with C. nivariensis were symptomatic and with a low mycological cure rate when treated with commonly used antifungal agents. Compared with C. albicans, C. nivariensis is more antifungal resistant and virulent.


Assuntos
Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Adulto , Candida glabrata/isolamento & purificação , Candidíase Vulvovaginal/microbiologia , Farmacorresistência Fúngica , Feminino , Humanos , Testes de Sensibilidade Microbiana
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