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1.
IDCases ; 36: e01959, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38681078

RESUMEN

Magnusiomyces capitatus (M. capitatus) is an emerging opportunistic yeast in the Mediterranean region typically isolated from immunocompromised patients, usually affected by blood malignancies. We reported a rare case of M. capitatus infection, isolated from a drainage fluid in a patient affected by lung cancer recovered in the University Hospital of Campania "Luigi Vanvitelli", Naples, Italy. The isolate was identified by phenotypic methods, i.e., Gram and Lactophenol cotton blue (LCB) staining, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. We identified M. capitatus on the third day from Sabouraud Dextrose Agar supplemented with chloramphenicol and gentamicin. Antifungal susceptibility test revealed that 5-fluorocytosine was the most active drug against M. capitatus, followed by itraconazole and voriconazole, micafungin, amphotericin B and fluconazole, posaconazole, anidulafungin, and caspofungin. Our data showed the importance of an early cultural and fast microbiology diagnosis based on the characteristic morphologic features observed in Gram-stained smears of blood culture positive bottles, and the validation via MALDI-TOF MS. This dual approach has significant impact in the clinical management of infectious diseases and antibiotic stewardship, by integrating sample processing, fluid handling, and detection for rapid bacterial diagnosis.

2.
J Investig Med High Impact Case Rep ; 12: 23247096241237756, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38462914

RESUMEN

Cases of vulvovaginitis caused by Cryptococcus genus are exceedingly uncommon, with only a handful of instances having been described for this causative species. This report describes a rare case of vulvovaginitis suspected to be caused by Cryptococcus victoriae in a 58-year-old woman residing in an urban area of Hanoi city, Vietnam. The patient with a 10-year history of depression and type 2 diabetes mellitus was admitted to the hospital due to vulvar itching and vaginal discharge. Vaginal swabs confirmed the presence of a yeast infection by direct microscopic examination with 10% KOH and culture on CHROMagar Candida. The yeast was identified as C victoriae using genetic sequencing tools. The patient's treatment plan involved topical clotrimazole and a daily oral dose of 200 mg of itraconazole for 7 days. This comprehensive treatment approach resulted in the patient's full recovery. This is the first reported case of vulvovaginitis attributed to C victoriae in humans worldwide.


Asunto(s)
Basidiomycota , Candidiasis Vulvovaginal , Diabetes Mellitus Tipo 2 , Vulvovaginitis , Femenino , Humanos , Persona de Mediana Edad , Candidiasis Vulvovaginal/diagnóstico , Candidiasis Vulvovaginal/tratamiento farmacológico , Saccharomyces cerevisiae , Vietnam , Vulvovaginitis/tratamiento farmacológico
3.
Photodiagnosis Photodyn Ther ; 46: 104066, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38552814

RESUMEN

Balanoposthitis can affect men in immunocompromised situations, such as HIV infection and diabetes. The main associated microorganism is Candida albicans, which can cause local lesions, such as the development of skin cracks associated with itching. As an alternative to conventional treatment, there is a growing interest in the photodynamic inactivation (PDI). It has been shown that the association of photosensitizers with metallic nanoparticles may improve the effectiveness of PDI via plasmonic effect. We have recently shown that the association of methylene blue (MB), a very known photosensitizer, with silver prismatic nanoplatelets (AgNPrs) improved PDI of a resistant strain of Staphylococcus aureus. To further investigate the experimental conditions involved in PDI improvement, in the present study, we studied the effect of MB concentration associated with AgNPrs exploring spectral analysis, zeta potential measurements, and biological assays, testing the conjugated system against C. albicans isolated from a resistant strain of balanoposthitis. The AgNPrs were synthesized through silver anisotropic seed growth induced by the anionic stabilizing agent poly(sodium 4-styrenesulfonate) and showed a plasmon band fully overlapping the MB absorption band. MB and AgNPrs were conjugated through electrostatic association and three different MB concentrations were tested in the nanosystems. Inactivation using red LED light (660 nm) showed a dose dependency in respect to the MB concentration in the conjugates. Using the highest MB concentration (100 µmol⋅L-1) with AgNPr, it was possible to completely inactivate the microorganisms upon a 2 min irradiation exposure. Analyzing optical changes in the conjugates we suggest that these results indicate that AgNPrs are enhancers of MB photodynamic action probably by a combined mechanism of plasmonic effect and reduction of MB dimerization. Therefore, MBAgNPrs can be considered a suitable choice to be applied in PDI of resistant microorganisms.


Asunto(s)
Candida albicans , Azul de Metileno , Fotoquimioterapia , Fármacos Fotosensibilizantes , Plata , Candida albicans/efectos de los fármacos , Azul de Metileno/farmacología , Fármacos Fotosensibilizantes/farmacología , Fotoquimioterapia/métodos , Plata/farmacología , Nanopartículas del Metal/uso terapéutico , Nanopartículas del Metal/química , Balanitis/tratamiento farmacológico , Balanitis/microbiología , Humanos
4.
Women Health ; 63(9): 727-735, 2023 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-37771196

RESUMEN

Vulvovaginal candidiasis (VVC) is a fungal infection that is a global issue of women's health due to its association with morbidity, infertility, and economic costs. This study aimed to compare the vitamin D3 levels between women with VVC to healthy controls and determine the species distribution and susceptibility pattern of isolates. Species identification was performed using sequencing of the ITS-rDNA regions and amplification of the HWP1 gene. Antifungal susceptibility testing was determined by the disk diffusion method. Moreover, serum vitamin D3 levels were measured using a commercial ELISA (enzyme-linked immunosorbent assay) kit. Our results indicated that vitamin D3 level in women with VVC was lower than those of healthy women (p-value < .001). Candida albicans complex (62.8 percent) was the most common species, and most species were susceptible to fluconazole, itraconazole, ketoconazole, and nystatin. In conclusion, our study revealed a potential link between vitamin D3 deficiency and VVC in women. Although our findings showed significantly lower vitamin D3 levels in women with VVC, further research is needed to establish a definitive causative relationship between vitamin D3 deficiency and VVC. Nonetheless, our study highlights the potential importance of maintaining adequate levels of vitamin D3 and the need for further exploration in this area.

5.
Nanomedicine (Lond) ; 18(18): 1195-1206, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37724540

RESUMEN

Background: Vulvovaginal candidiasis is primarily caused by Candida albicans (C. albicans). Here, a novel organoselenium compound (G20) was synthesized and evaluated for anti-Candida activity. Methods: Growth-inhibition studies and medium acidification assays to assess the inhibition of the yeast plasma membrane H+-ATPase (Pma1p) were carried out in vitro using G20. A self-nanoemulsifying formulation (SNEP) of G20 was prepared and evaluated for antimycotic activity in a mouse model. Results: G20 inhibited the growth of C. albicans through a mechanism that, at least in part, involves the inhibition of Pma1p. The G20-SNEP formulation significantly reduced vaginal colonization and vaginal inflammation relative to yeast-infected but untreated control mice. Conclusion: G20-SNEP exhibits potent antimycotic activity in a mouse model of vulvovaginal candidiasis.


Asunto(s)
Candidiasis Vulvovaginal , Femenino , Humanos , Ratones , Animales , Candidiasis Vulvovaginal/tratamiento farmacológico , Isoindoles , Azoles/farmacología , Azoles/uso terapéutico , Candida albicans , Antifúngicos/farmacología , Antifúngicos/uso terapéutico
6.
Mycoses ; 66(11): 992-1002, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37515448

RESUMEN

BACKGROUND: Trichosporon is an emerging yeast that causes invasive infections in immunocompromised patients experiencing prolonged hospitalisation, indwelling venous catheters and neutropenia. METHODS: This retrospective observational cohort study analysed invasive Trichosporon infections (ITIs) occurring between January 2005 and December 2022 at three tertiary hospitals and compared the clinical characteristics and prognostic factors of ITIs caused by Trichosporon asahii and non-T. asahii spp. After evaluating 1067 clinical isolates, we identified 46 patients with proven ITIs, defined as cases in which Trichosporon was isolated from blood, cerebrospinal fluid, or sterile tissues. RESULTS: The patients were separated into T. asahii and non-T. asahii groups containing 25 and 21 patients, respectively, all of which except one were immunocompromised. During this period, both the number of clinical isolates and patients with ITIs (mainly T. asahii) increased; whereas, cases involving non-T. asahii spp. decreased. Compared with the non-T. asahii group, the T. asahii group had more patients with multiple catheters (84% vs. 33%, p = .001) and those receiving renal replacement therapy (48% vs. 14%, p = .005). The all-cause 28-day mortality rate after ITI in the T. asahii group (44%) was significantly higher than in the non-T. asahii group (10%, Log-rank p = .014). The multivariate Cox regression model revealed that T. asahii (reference, non-T. asahii spp.; aHR = 4.3; 95% CI = 1.2-15.2, p = .024) and neutropenia for 5 days or more (aHR = 2.2, 95% CI = 1.5-3.6, p = .035) were independent factors in the 28-day mortality after ITI. CONCLUSION: The proven ITIs due to T. asahii produced more unfavourable outcomes compared with ITIs caused by non-T. asahii spp.


Asunto(s)
Neutropenia , Trichosporon , Tricosporonosis , Humanos , Tricosporonosis/tratamiento farmacológico , Antifúngicos/uso terapéutico , Estudios Retrospectivos , Neutropenia/tratamiento farmacológico
7.
Obstet Gynecol Clin North Am ; 50(2): 311-326, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37149312

RESUMEN

Vulvovaginitis occurs in mostly reproductive aged women. Recurrent vaginitis affects overall quality of life, with a large financial burden on the patient, family, and health system. This review discusses a clinician's approach to vulvovaginitis with specific attention to the 2021 updated Center for Disease Control and Prevention guidelines. The authors discuss the role of the microbiome in vaginitis and evidence-based approaches for diagnosis and treatment of vaginitis. This review also provides updates on new considerations, diagnosis, management, and treatment of vaginitis. Desquamative inflammatory vaginitis and genitourinary syndrome of menopause are discussed as differential diagnosis of vaginitis symptoms.


Asunto(s)
Microbiota , Vaginitis , Vaginosis Bacteriana , Vulvovaginitis , Femenino , Humanos , Adulto , Vaginosis Bacteriana/diagnóstico , Vaginosis Bacteriana/terapia , Calidad de Vida , Vulvovaginitis/diagnóstico , Vulvovaginitis/terapia , Vaginitis/diagnóstico , Vaginitis/terapia
8.
Prev Nutr Food Sci ; 28(1): 1-9, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37066035

RESUMEN

We previously reported that breast milk from women with (W) or without (WO) vaginal yeast infection during pregnancy differs in its immunological and antimicrobial properties, especially against pathogenic vaginal Candida sp.. Here, we investigated the differences in microbiota profiles of breast milk from these groups. Seventy-two breast milk samples were collected from lactating mothers (W, n=37; WO, n=35). The DNA of bacteria was extracted from each breast milk sample for microbiota profiling by 16S rRNA gene sequencing. Breast milk from the W-group exhibited higher alpha diversity than that from the WO-group across different taxonomic levels of class (P=0.015), order (P=0.011), family (P=0.020), and genus (P=0.030). Compositional differences between groups as determined via beta diversity showed marginal differences at taxonomic levels of phylum (P=0.087), family (P=0.064), and genus (P=0.067). The W-group showed higher abundances of families Moraxellaceae (P=0.010) and Xanthomonadaceae (P=0.008), and their genera Acinetobacter (P=0.015), Enhydrobacter (P=0.015), and Stenotrophomonas (P=0.007). Meanwhile, the WO-group showed higher abundances of genus Staphylococcus (P=0.046) and species Streptococcus infantis (P=0.025). This study shows that, although breast milk composition is affected by vaginal infection during pregnancy, this may not pose a threat to infant growth and development.

9.
Drug Des Devel Ther ; 17: 363-367, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36785761

RESUMEN

Vulvovaginal candidiasis (VVC) is experienced by an estimated 75% of women at least once in their lifetime and is recurrent, defined as three or more infections per year (RVVC) in 5-9%. Candida albicans is the most common causative agent, but up to 19% of infections may be related to non-albicans species. Available treatment options for VVC have consisted of oral and topical azoles (except for topical nystatin, a polyene). Oral polyenes are not absorbed and therefore not effective for VVC. Fluconazole is the only oral medication FDA approved for VVC. None of these treatments are FDA approved for RVVC. Ibrexafungerp, a triterpenoid fungicidal agent, was FDA approved in 2021, becoming the first oral non-azole agent for VVC. Ibrexafungerp reaches concentrations up to 9-fold higher in vaginal tissues versus plasma. In Phase 2 clinical trials, ibrexafungerp had a clinical cure rate comparable to fluconazole at day 10, but significantly better at day 25. In Phase 3 clinical trials, ibrexafungerp had both a higher clinical and mycologic cure rate versus placebo at both days 10 and 25. In December 2022, Ibrexafungerp received FDA approval for once monthly dosing to decrease the incidence of RVVC. This approval was based on data from the CANDLE STUDY, which showed 65.4% resolution of symptoms and culture negative success through week 24, compared to 53.1% of placebo. Ibrexafungerp provides an alternative oral option for treatment of acute, severe VVC. It is the only FDA approved antifungal for RVVC. Currently, the population likely to benefit from this drug are those with azole allergy, non-albicans or azole resistant albicans species, or other azole contraindications such as drug interactions (like statins or tricyclics). Side effects are mostly gastrointestinal and mild in nature. Ibrexafungerp, like fluconazole, should be used with caution in women who are or may become pregnant.


Asunto(s)
Candidiasis Vulvovaginal , Triterpenos , Embarazo , Femenino , Humanos , Candidiasis Vulvovaginal/tratamiento farmacológico , Candidiasis Vulvovaginal/diagnóstico , Candidiasis Vulvovaginal/microbiología , Fluconazol/farmacología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Triterpenos/uso terapéutico , Triterpenos/farmacología , Candida albicans , Azoles/farmacología , Azoles/uso terapéutico , Polienos/farmacología , Polienos/uso terapéutico
11.
Anal Chim Acta ; 1239: 340658, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36628751

RESUMEN

Invasive fungal infection serves as a great threat to human health. Discrimination between fungal and bacterial infections at the earliest stage is vital for effective clinic practice; however, traditional culture-dependent microscopic diagnosis of fungal infection usually requires several days, meanwhile, culture-independent immunological and molecular methods are limited by the detectable type of pathogens and the issues with high false-positive rates. In this study, we proposed a novel culture-independent phenotyping method based on single-cell Raman spectroscopy for the rapid discrimination between fungal and bacterial infections. Three Raman biomarkers, including cytochrome c, peptidoglycan, and nucleic acid, were identified through hierarchical clustering analysis of Raman spectra across 12 types of most common yeast and bacterial pathogens. Compared to those of bacterial pathogens, the single cells of yeast pathogens demonstrated significantly stronger Raman peaks for cytochrome c, but weaker signals for peptidoglycan and nucleic acid. A two-step protocol combining the three biomarkers was established and able to differentiate fungal infections from bacterial infections with an overall accuracy of 94.9%. Our approach was also used to detect ten raw urinary tract infection samples. Successful identification of fungi was achieved within half an hour after sample obtainment. We further demonstrated the accurate fungal species taxonomy achieved with Raman-assisted cell ejection. Our findings demonstrate that Raman-based fungal identification is a novel, facile, reliable, and with a breadth of coverage approach, that has a great potential to be adopted in routine clinical practice to reduce the turn-around time of invasive fungal disease (IFD) diagnostics.


Asunto(s)
Infecciones Bacterianas , Saccharomyces cerevisiae , Humanos , Espectrometría Raman/métodos , Citocromos c , Peptidoglicano , Bacterias
12.
BMC Pregnancy Childbirth ; 23(1): 70, 2023 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-36703111

RESUMEN

BACKGROUND: The primary aim was to evaluate the association between gestational diabetes and blood glucose levels and vulvovaginal yeast infections in pregnancy. Secondly, we clarified the possible associations between maternal and prenatal factors, and birth outcomes and yeast infections. METHODS: Three thousand nine hundred sixty-five pregnant women of the Kuopio Birth Cohort Study (KuBiCo) reported vulvovaginal yeast infections during pregnancy, via electronic questionnaires. Maternal and prenatal data, as well as clinical obstetric and early neonatal outcomes were registered during and after birth. The oral glucose tolerance test was performed on 3,079 women during pregnancy. Logistic regression analysis evaluated the possible multivariable associations between yeast infections, gestational diabetes and other prenatal and maternal factors. RESULTS: No association was detected between gestational diabetes or blood glucose levels and vulvovaginal yeast infections during pregnancy. In multivariable analysis, women with yeast infections were more often multiparous, with higher education and had used more often antibiotics during pregnancy compared to others. No significant associations were detected in multivariable analysis between infections, the mode of delivery, preterm birth, birth weight or Apgar scores. CONCLUSIONS: Women with reported vulvovaginal yeast infections managed generally well during pregnancy. They had no more gestational diabetes or higher blood glucose levels and their newborns managed equally well during early neonatal period.


Asunto(s)
Diabetes Gestacional , Nacimiento Prematuro , Embarazo , Recién Nacido , Femenino , Humanos , Diabetes Gestacional/epidemiología , Resultado del Embarazo/epidemiología , Saccharomyces cerevisiae , Glucemia , Estudios de Cohortes , Peso al Nacer
13.
J Mycol Med ; 33(1): 101351, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36413850

RESUMEN

The incidence of invasive candidiasis in pediatric patients is increasing and is associated with significant morbidity and mortality. C. pelliculosa has been rarely reported as a human pathogen, however, it has been associated with serious nosocomial infections and clonal outbreaks with poor clinical outcomes in immunocompromised children were reported. Here, we describe the first case of candidemia due to Candida pelliculosa in a 5-year-old immunocompromised male suffered from Griscelli syndrome with hemophagocytic syndrome hospitalized in the pediatric intensive care unit (PICU), Tehran, Iran. In addition, the history of reported cases or case-series due to C. pelliculosa is reviewed.


Asunto(s)
Candidemia , Infección Hospitalaria , Fungemia , Saccharomycetales , Humanos , Niño , Masculino , Preescolar , Fungemia/diagnóstico , Fungemia/tratamiento farmacológico , Fungemia/epidemiología , Candida , Irán , Candidemia/epidemiología , Infección Hospitalaria/epidemiología , Antifúngicos/uso terapéutico
14.
Ann Pharmacother ; 57(1): 99-106, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35502451

RESUMEN

OBJECTIVE: To review the pharmacology, efficacy, and safety of ibrexafungerp in the management of vulvovaginal candidiasis (VVC). DATA SOURCES: Literature was sought using PubMed (1966-February 2022) and EMBASE (1973-February 2022), and clinicaltrials.gov. Search terms included ibrexafungerp, SCY-078, and VVC. STUDY SELECTION AND DATA EXTRACTION: All studies including humans and published in English with data assessing the efficacy and safety of ibrexafungerp for the treatment of VVC were evaluated. DATA SYNTHESIS: A phase 2 dose-finding study found ibrexafungerp had similar efficacy to fluconazole in the clinical cure of VVC (51.9% vs 58.3%, respectively). Two phase 3 clinical trials demonstrated ibrexafungerp had statistical superiority over placebo for clinical cure in moderate to severe VVC (P < 0.001 and P = 0.023, respectively). The most frequently reported adverse reactions in the clinical trials were gastrointestinal-related symptoms. To date, data comparing efficacy of ibrexafungerp and topical imidazoles in the treatment of VVC are nonexistent. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Topical imidazoles and oral fluconazole are effective for the treatment of uncomplicated VVC. Due to increased resistance, limited fluconazole coverage for non-Candida albicans species, and potential for significant drug interactions associated with fluconazole use, alternative treatments for VVC are needed. Ibrexafungerp is a new oral triterpenoid antifungal agent indicated for the treatment of VVC. Additional clinical trials are needed to evaluate long-term safety data as well as efficacy and safety in specialty populations. CONCLUSION: Ibrexafungerp, a recently approved triterpenoid antifungal agent, is an effective and well-tolerated option for the treatment of VVC.


Asunto(s)
Candidiasis Vulvovaginal , Triterpenos , Femenino , Humanos , Candidiasis Vulvovaginal/tratamiento farmacológico , Fluconazol/efectos adversos , Antifúngicos/efectos adversos , Triterpenos/uso terapéutico , Imidazoles/uso terapéutico
15.
Telemed J E Health ; 29(5): 738-743, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36251960

RESUMEN

Objective: Compare demographics, treatment, and follow-up rates for patients with complaints of vulvovaginitis suggestive of candida infection evaluated via e-visit, face-to-face (F2F) visits, or nurse-administered phone protocol. Methods: Manual review of 150 vaginitis visits of each visit type (e-visit, F2F, and phone protocol) completed between May 5, 2018 through January 31, 2020 by Mayo Clinic patients residing in Minnesota. Outcomes: Comparison between the three visit types of patient characteristics, treatment rates, type of treatment, follow-up rates, and types of follow-up. Results: Patients utilizing phone visits were significantly older than those seeking care via e-visit (p < 0.0001) or F2F (p = 0.001) and were more likely to be treated with oral fluconazole than those treated by e-visit (p < 0.0001) or F2F (p < 0.0001) encounters. Patients were significantly less likely to receive fungal directed treatment at a F2F visit than an e-visit (p < 0.0001) or phone encounter (p < 0.0001). There was no significant difference in follow-up rates between the three groups. Conclusion: Virtual visits (non-F2F) for suspected vulvovaginal candidiasis are unlikely to result in more follow-up visits than F2F encounters; however, prescriptions for antifungals are significantly higher with virtual visits.


Asunto(s)
Candidiasis Vulvovaginal , Telemedicina , Femenino , Humanos , Candidiasis Vulvovaginal/diagnóstico , Candidiasis Vulvovaginal/tratamiento farmacológico , Prescripciones , Teléfono , Instituciones de Atención Ambulatoria , Minnesota , Telemedicina/métodos
16.
Am J Obstet Gynecol ; 227(6): 880.e1-880.e11, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35863457

RESUMEN

BACKGROUND: Recurrent vulvovaginal candidiasis affects nearly 138 million women globally each year. In the United States, fluconazole is considered the standard of care for acute vulvovaginal candidiasis, but until recently there was no US Food and Drug Administration-approved drug for the treatment of recurrent vulvovaginal candidiasis. Oteseconazole is a novel oral selective inhibitor of fungal lanosterol demethylase (sterol 14α-demethylase cytochrome P450, an enzyme required for fungal growth) approved for the treatment of recurrent vulvovaginal candidiasis. OBJECTIVE: This study was conducted to evaluate the efficacy and safety of oral oteseconazole (VT-1161) in the prevention of recurrent culture-verified acute vulvovaginal candidiasis episodes through 50 weeks in participants with recurrent vulvovaginal candidiasis and to compare the efficacy of oteseconazole and fluconazole in the treatment of the presenting acute vulvovaginal candidiasis episode. STUDY DESIGN: Women and postmenarcheal girls aged ≥12 years with a history of recurrent vulvovaginal candidiasis (N=219) were enrolled at 38 US sites. Eligible participants presenting with an active vulvovaginal candidiasis infection entered an induction phase in which they were randomly assigned 2:1 to receive 600 mg oral oteseconazole on day 1 and 450 mg on day 2, with matching placebo capsules, or to 3 sequential 150-mg oral doses (once every 72 hours) of fluconazole, with matching placebo capsules. Following the 2-week induction phase, the 185 participants with resolved acute vulvovaginal candidiasis infection (a clinical signs and symptoms score of <3) entered the maintenance phase and received 150 mg of oteseconazole or placebo weekly for 11 weeks. Participants were observed for an additional 37 weeks. RESULTS: In the induction phase, oteseconazole was noninferior to fluconazole in the proportion of participants in the intent-to-treat population with resolved acute vulvovaginal candidiasis infection at the week 2 (day 14) test-of-cure visit, with 93.2% of participants on oteseconazole vs 95.8% on fluconazole achieving resolution. In the maintenance phase, oteseconazole was superior to placebo in the proportion of participants in the intent-to-treat population with ≥1 culture-verified acute vulvovaginal candidiasis episode through 50 weeks, 5.1% compared with 42.2%, respectively (P<.001). Overall, treatment-emergent adverse event rates were similar in both groups: 54% for participants who received oteseconazole in the induction and maintenance phases vs 64% for participants who received fluconazole in the induction phase and placebo in the maintenance phase. Most treatment-emergent adverse events in each group were mild or moderate, with 3.4% of treatment-emergent adverse events graded as severe or higher in the OTESECONAZOLE/oteseconazole group vs 4.2% in FLUCONAZOLE/placebo group. CONCLUSION: In participants with recurrent vulvovaginal candidiasis, oteseconazole was safe and efficacious in the treatment and prevention of recurrent acute vulvovaginal candidiasis episodes and was noninferior to vulvovaginal candidiasis standard-of-care fluconazole in the treatment of the presenting acute vulvovaginal candidiasis infection.


Asunto(s)
Candidiasis Vulvovaginal , Infecciones , Femenino , Humanos , Candidiasis Vulvovaginal/tratamiento farmacológico , Candidiasis Vulvovaginal/inducido químicamente , Fluconazol/uso terapéutico , Fluconazol/efectos adversos , Administración Oral , Antifúngicos/efectos adversos
17.
J Fungi (Basel) ; 7(9)2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34575799

RESUMEN

This single-center retrospective study of invasive fungal disease (IFD) enrolled 251 adult patients undergoing induction chemotherapy for newly diagnosed acute myeloid leukemia (AML) from 2014-2019. Patients had primary AML (n = 148, 59%); antecedent myelodysplastic syndrome (n = 76, 30%), or secondary AML (n = 27, 11%). Seventy-five patients (30%) received an allogeneic hematopoietic cell transplant within the first year after induction chemotherapy. Proven/probable IFD occurred in 17 patients (7%). Twelve of the 17 (71%) were mold infections, including aspergillosis (n = 6), fusariosis (n = 3), and mucomycosis (n = 3). Eight breakthrough IFD (B-IFD), seven of which were due to molds, occurred in patients taking antifungal prophylaxis. Patients with proven/probable IFD had a significantly greater number of cumulative neutropenic days than those without an IFD, HR = 1.038 (95% CI 1.018-1.059), p = 0.0001. By cause-specific proportional hazards regression, the risk for IFD increased by 3.8% for each day of neutropenia per 100 days of follow up. Relapsed/refractory AML significantly increased the risk for IFD, HR = 7.562 (2.585-22.123), p = 0.0002, and Kaplan-Meier analysis showed significantly higher mortality at 1 year in patients who developed a proven/probable IFD, p = 0.02. IFD remains an important problem among patients with AML despite the use of antifungal prophylaxis, and development of IFD is associated with increased mortality in these patients.

18.
Bioelectrochemistry ; 142: 107921, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34419917

RESUMEN

Wireless electroceutical dressing (WED) fabric kills bacteria and disrupts bacterial biofilm. This work tested, comparing with standard of care topical antibiotic ketoconazole, whether the weak electric field generated by WED is effective to manage infection caused by ketoconazole-resistant yeast Candida albicans. WED inhibited Candida albicans biofilm formation and planktonic growth. Unlike ketoconazole, WED inhibited yeast to hyphal transition and downregulated EAP1 curbing cell attachment. In response to WED-dependent down-regulation of biofilm-forming BRG1 and ROB1, BCR1 expression was markedly induced in what seems to be a futile compensatory response. WED induced NRG1 and TUP1, negative regulators of filamentation; it down-regulated EFG1, a positive regulator of hyphal pathway. Consistent with the anti-hyphal properties of WED, the expression of ALS3 and HWP1 were diminished. Ketoconazole failed to reproduce the effects of WED on NRG1, TUP1 and EFG1. WED blunted efflux pump activity; this effect was in direct contrast to that of ketoconazole. WED exposure compromised cellular metabolism. In the presence of ketoconazole, the effect was synergistic. Unlike ketoconazole, WED caused membrane depolarization, changes in cell wall composition and loss of membrane integrity. This work presents first evidence that weak electric field is useful in managing pathogens which are otherwise known to be antibiotic resistant.


Asunto(s)
Vendajes/microbiología , Biopelículas/crecimiento & desarrollo , Candida albicans/metabolismo , Candidiasis/terapia , Farmacorresistencia Microbiana/efectos de los fármacos , Técnicas Electroquímicas/métodos
20.
Nanomedicine ; 37: 102428, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34217850

RESUMEN

Vulvovaginal candidiasis (VVC), caused by Candida albicans, is a common infection in women affecting their quality of life. Standard antifungal drugs (e.g., fluconazole, itraconazole) are typically fungistatic or rendered ineffective due to drug resistance indicating an urgent need to build an arsenal of novel antifungal agents. To surmount this issue, we tested the hypothesis that the organoselenium compound ebselen (EB) possesses antifungal efficacy in a mouse model of VVC. EB is a poorly water-soluble drug and DMSO as a vehicle has the potential to exhibit cytotoxic effects when administered in vivo. EB loaded self-nanoemulsifying preconcentrate (EB-SNEP) was developed, characterized in vitro, and tested in a mouse model of VVC. In vivo studies carried out with EB-SNEP (12.5 mg/kg) showed a remarkable decrease in infection by ~562-fold compared to control (infected, untreated animals). Taken together, EB nanoemulsion proved to be an effective and promising antifungal agent.


Asunto(s)
Candidiasis Vulvovaginal/tratamiento farmacológico , Emulsiones/farmacología , Isoindoles/farmacología , Nanopartículas/química , Compuestos de Organoselenio/farmacología , Animales , Antifúngicos/química , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Candida albicans/patogenicidad , Candidiasis Vulvovaginal/patología , Modelos Animales de Enfermedad , Emulsiones/química , Femenino , Fluconazol/farmacología , Humanos , Isoindoles/química , Ratones , Pruebas de Sensibilidad Microbiana , Compuestos de Organoselenio/química
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