RESUMO
The urgency surrounding Candida auris as a public health threat is highlighted by both the Center for Disease Control (CDC) and World Health Organization (WHO) that categorized this species as a priority fungal pathogen. Given the current limitations of antifungal therapy for C. auris, particularly due to its multiple resistance to the current antifungals, the identification of new drugs is of paramount importance. Some alkaloids abundant in the venom of the red invasive fire ant (Solenopsis invicta), known as solenopsins, have garnered attention as potent inhibitors of bacterial biofilms, and there are no studies demonstrating such effects against fungal pathogens. Thus, we herein investigated the antibiotic efficacy of solenopsin alkaloids against C. auris biofilms and planktonic cells. Both natural and synthetic solenopsins inhibited the growth of C. auris strains from different clades, including fluconazole and amphotericin B-resistant isolates. Such alkaloids also inhibited matrix deposition and altered cellular metabolic activity of C. auris in biofilm conditions. Mechanistically, the alkaloids compromised membrane integrity as measured by propidium iodide uptake in exposed planktonic cells. Additionally, combining the alkaloids with AMB yielded an additive antifungal effect, even against AMB-resistant strains. Finally, both extracted solenopsins and the synthetic analogues demonstrated protective effect in vivo against C. auris infection in the invertebrate model Galleria mellonella. These findings underscore the potent antifungal activities of solenopsins against C. auris and suggest their inclusion in future drug development. Furthermore, exploring derivatives of solenopsins could reveal novel compounds with therapeutic promise.
Assuntos
Alcaloides , Antifúngicos , Formigas , Biofilmes , Candida auris , Testes de Sensibilidade Microbiana , Animais , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida auris/efeitos dos fármacos , Candida auris/genética , Alcaloides/farmacologia , Alcaloides/química , Formigas/microbiologia , Candidíase/microbiologia , Candidíase/tratamento farmacológico , Venenos de Formiga/farmacologia , Venenos de Formiga/química , Formigas Lava-PésRESUMO
Candida sp. infections are a threat to global health, with high morbidity and mortality rates due to drug resistance, especially in immunocompromised people. For this reason, the search for new alternatives is urgent, and in recent years, a combined therapy with natural compounds has been proposed. Considering the biological potential of isoespintanol (ISO) and continuing its study, the objective of this research was to assess the effect of ISO in combination with the antifungals fluconazole (FLZ), amphotericin B (AFB) and caspofungin (CASP) against clinical isolates of C. tropicalis and to evaluate the cytotoxic effect of this compound in the acute phase (days 0 and 14) and chronic phase (days 0, 14, 28, 42, 56, 70 and 84) in female mice (Mus musculus) of the Balb/c lineage. The results show that ISO can potentiate the effect of FLZ, AFB and CASP, showing synergism with these antifungals. An evaluation of the mice via direct observation showed no behavioral changes or variations in weight during treatment; furthermore, an analysis of the cytokines IFN-γ and TNF in plasma, peritoneal cavity lavage (PCL) and bronchoalveolar lavage (BAL) indicated that there was no inflammation process. In addition, histopathological studies of the lungs, liver and kidneys showed no signs of toxicity caused by ISO. This was consistent with an analysis of oxaloacetic transaminases (GOT) and pyruvic transaminases (GPT), which remained in the standard range. These findings indicate that ISO does not have a cytotoxic effect at the doses evaluated, placing it as a monoterpene of interest in the search for compounds with pharmacological potential.
Assuntos
Antifúngicos , Sinergismo Farmacológico , Camundongos Endogâmicos BALB C , Animais , Antifúngicos/farmacologia , Camundongos , Feminino , Monoterpenos/farmacologia , Testes de Sensibilidade Microbiana , Anfotericina B/farmacologia , Anfotericina B/toxicidade , Candidíase/tratamento farmacológico , Candida tropicalis/efeitos dos fármacos , Fluconazol/farmacologia , Citocinas/metabolismo , Citocinas/sangue , Caspofungina/farmacologiaRESUMO
OBJECTIVES: The Fluconazole pharmacokinetic-pharmacodynamic relationship was investigated in a few clinical settings and only limited studies regarding burned patients are available. Thus, the authors aimed to investigate fluconazole pharmacokinetics changes and its impact on antifungal therapy coverage against dose-dependent Candida spp. applying the PK/PD approach in critically ill severely burned patients. METHODS: Fluconazole was administered as a one-hour intravenous infusion of 200 mg q12h. Doses were increased according to the coverage based on the PK/PD approach. Blood samples were collected at the end of the infusion (1st hour), two hours after (3rd hour), and before the next dose (12th or 24th hour). Serum concentrations were obtained by HPLC-UV. Pharmacokinetic parameters were estimated by noncompartmental analysis and compared with data described in healthy subjects. The effectiveness predictive index was based on the AUCss0-24h/MIC ratio, with a target above 25. RESULTS: Every pharmacokinetic parameter was reduced throughout all three sets of the study. Compared to healthy subjects, the volume of distribution was decreased about 3â7 times, biological half-life was 2â3 times shorter and total body clearance was slightly altered but statistically significant. Both half-life and total body clearance were correlated to the volume of distribution. Consequently, an increase in fluconazole daily dose was necessary to improve empiric coverage. CONCLUSIONS: Fluconazole pharmacokinetics is altered in critically ill severely burned patients, mainly related to the volume of distribution. Doses higher than usual may be necessary to reach the PK/PD target and guarantee antifungal coverage against dose-dependent Candida spp. up to MIC 32 mg/L.
Assuntos
Antifúngicos , Queimaduras , Estado Terminal , Fluconazol , Humanos , Fluconazol/farmacocinética , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Fluconazol/administração & dosagem , Queimaduras/tratamento farmacológico , Antifúngicos/farmacocinética , Antifúngicos/uso terapêutico , Antifúngicos/administração & dosagem , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Testes de Sensibilidade Microbiana , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Infusões Intravenosas , Área Sob a Curva , Fatores de Tempo , Idoso , Adulto Jovem , Resultado do Tratamento , Relação Dose-Resposta a Droga , Valores de ReferênciaRESUMO
INTRODUCTION: Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing. METHOD: This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance. RESULTS: Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1. DISCUSSION: The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections.
Assuntos
Antifúngicos , Candida auris , Farmacorresistência Fúngica , Fluconazol , Humanos , Farmacorresistência Fúngica/genética , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Virulência/genética , Candida auris/genética , Candida auris/efeitos dos fármacos , Candida auris/patogenicidade , Testes de Sensibilidade Microbiana , Mutação , Pequim , Simulação de Acoplamento Molecular , Candidíase/microbiologia , Candidíase/tratamento farmacológico , Sequenciamento Completo do Genoma , Ásia MeridionalRESUMO
Candida albicans invasive candidiasis is considered a global health problem. In such cases, biofilm formation on implanted devices represents a therapeutic challenge and the presence of metabolically inactive persistent cells (PCs) in these communities increases their tolerance to fungicidal drugs. This study investigated the influence of amoxicillin, AMX; cefepime, CEF; gentamicin, GEN; amikacin, AMK; vancomycin, VAN; and ciprofloxacin, CIP; on the production of PCs in biofilms of C. albicans bloodstream isolates. 48 h-mature biofilms (n = 6) grown in RPMI-1640 supplemented with antibiotics were treated with 100 µg ml-1 amphotericin B and then evaluated for PCs. Biofilms grown in the presence of antibiotics produced more PCs, up to 10×, when exposed to AMX and CIP; 5 × to CEF; and 6 × to GEN and VAN. The results indicate that antibiotics can modulate PC production in C. albicans biofilms. This scenario may have clinical repercussions in immunocompromised patients under broad-spectrum antibiotic therapy.
Biofilms are microbial communities tolerant to antifungals. Our research showed that antibiotics stimulate the formation of persistent cells within Candida albicans biofilms. These are dormant, metabolically silent cells that resist to therapy and can be related to metastatic and recalcitrant infections.
Assuntos
Antibacterianos , Biofilmes , Candida albicans , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Antibacterianos/farmacologia , Humanos , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana , Ciprofloxacina/farmacologia , Gentamicinas/farmacologia , Amoxicilina/farmacologia , Vancomicina/farmacologia , Amicacina/farmacologia , Cefepima/farmacologia , Anfotericina B/farmacologia , Cefalosporinas/farmacologia , Candidíase/microbiologia , Candidíase/tratamento farmacológicoRESUMO
Introduction. The development of new antifungal drugs has become a global priority, given the increasing cases of fungal diseases together with the rising resistance to available antifungal drugs. In this scenario, drug repositioning has emerged as an alternative for such development, with advantages such as reduced research time and costs.Gap statement. Propafenone is an antiarrhythmic drug whose antifungal activity is poorly described, being a good candidate for further study.Aim. This study aims to evaluate propafenone activity against different species of Candida spp. to evaluate its combination with standard antifungals, as well as its possible action mechanism.Methodology. To this end, we carried out tests against strains of Candida albicans, Candida auris, Candida parapsilosis, Candida tropicalis, Candida glabrata and Candida krusei based on the evaluation of the MIC, minimum fungicidal concentration and tolerance level, along with checkerboard and flow cytometry tests with clinical strains and cell structure analysis by scanning electron microscopy (SEM).Results. The results showed that propafenone has a 50% MIC ranging from 32 to 256 µg ml-1, with fungicidal activity and positive interactions with itraconazole in 83.3% of the strains evaluated. The effects of the treatments observed by SEM were extensive damage to the cell structure, while flow cytometry revealed the apoptotic potential of propafenone against Candida spp.Conclusion. Taken together, these results indicate that propafenone has the potential for repositioning as an antifungal drug.
Assuntos
Antifúngicos , Candida , Testes de Sensibilidade Microbiana , Propafenona , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Propafenona/farmacologia , Humanos , Itraconazol/farmacologia , Sinergismo Farmacológico , Farmacorresistência Fúngica/efeitos dos fármacos , Candidíase/microbiologia , Candidíase/tratamento farmacológico , Reposicionamento de MedicamentosRESUMO
BACKGROUND: Tuberculosis (TB), one of the leading causes of death worldwide, has a higher incidence among indigenous people. Albeit uncommon, autoimmune hemolytic anemia (AIHA) has been deemed a risk condition to develop mycobacterial infection, as a result of the immunosuppressive treatments. TB, in turn, can be a predisposing factor for secondary infections. CASE PRESENTATION: Here we present a case of a 28-year-old indigenous woman from Colombia, previously diagnosed with AIHA and pulmonary TB. Despite various treatments, therapies and medical interventions, the patient died after severe medullary aplasia of multiple causes, including secondary myelotoxicity by immunosuppressive therapy and secondary disseminated infections, underlining infection by Staphylococcus aureus, Klebsiella pneumoniae and Candida glabrata, which were identified as drug-resistant microorganisms. Together, this led to significant clinical complications. Invasive aspergillosis was diagnosed at autopsy. CONCLUSIONS: This report presents a rarely finding of AIHA followed by TB, and highlights the great challenges of dealing with co-infections, particularly by drug resistant pathogens. It also aims to spur governments and public health authorities to focus attention in the prevention, screening and management of TB, especially among vulnerable communities, such as indigenous people.
Assuntos
Anemia Hemolítica Autoimune , Coinfecção , Humanos , Feminino , Adulto , Coinfecção/microbiologia , Evolução Fatal , Anemia Hemolítica Autoimune/complicações , Colômbia , Klebsiella pneumoniae/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , Candida glabrata/isolamento & purificação , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/microbiologia , Infecções Estafilocócicas/microbiologia , Povos Indígenas , Candidíase/tratamento farmacológico , Candidíase/microbiologiaRESUMO
Aim: The objective of this study was to evaluate the clinical and epidemiological aspects of Candida infections. Methods: The study relied on the analysis of electronic medical records. Results: Among 183 patients with positive fungal infections, 57 were from the community and 126 from hospitals. Females predominated in both groups (82.4% in the community, 54.7% in hospitals). Non-albicans Candida spp. accounted for 62.8% of cases. Antifungal therapy was prescribed for 67 patients, with a 55.6% mortality rate. Conclusion: The increasing prevalence of non-albicans Candida species highlights the need for better candidiasis monitoring and control, especially concerning antifungal use amidst rising antimicrobial resistance, particularly in empirical therapy scenarios.
Fungal infections, particularly those caused by a group of yeasts called Candida, are a major concern. This study looks at clinical laboratory and medical records. We found that certain species of Candida not previously associated with human disease are common. We also noted the inappropriate use of antifungal medication, highlighting the need for healthcare workers to carefully diagnose patients and make appropriate decisions when treating fungal infections.
Assuntos
Antifúngicos , Candida , Candidíase , Farmacorresistência Fúngica , Humanos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Feminino , Masculino , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Pessoa de Meia-Idade , Candidíase/epidemiologia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Candidíase/mortalidade , Idoso , Adulto , Idoso de 80 Anos ou mais , Prevalência , Adulto Jovem , Adolescente , Criança , Estudos Retrospectivos , Pré-EscolarRESUMO
Candida spp. can be found in the human microbiome. However, immunocompromised patients are likely to develop invasive Candida infections, with mortality rates higher than 50%. The discovery of C. auris, a species that rapidly acquire antifungal resistance, increased the concern about Candida infections. The limited number of antifungal agents and the high incidence of resistance to them make imperative the development of new antifungal drugs. ß-lapachone is a biological active naphthoquinone that displays antifungal activity against C. albicans and C. glabrata. The aim of this study was to evaluate if this substance affects C. auris growth and elucidate its mechanism of action. A fluconazole-resistant C. auris isolate was used in this study. The antifungal activity of ß-lapachone was determined through microbroth dilution assays, and its mechanism of action was evaluated using fluorescent probes. Interaction with fluconazole and amphotericin B was assessed by disk diffusion assay and checkerboard. ß-lapachone inhibited planktonic C. auris cell growth by 92.7%, biofilm formation by 84.9%, and decrease the metabolism of preformed biofilms by 87.1% at 100 µg/ml. At 100 µg/ml, reductions of 30% and 59% of Calcofluor White and Nile red fluorescences were observed, indicating that ß-lapachone affects cell wall chitin and neutral lipids content, respectively. Also, the ratio 590 nm/529 nm of JC-1 decreased 52%, showing that the compound affects mitochondria. No synergism was observed between ß-lapachone and fluconazole or amphotericin B. Data show that ß-lapachone may be a promising candidate to be used as monotherapy to treat C. auris resistant infections.
Assuntos
Antifúngicos , Biofilmes , Candida auris , Farmacorresistência Fúngica , Fluconazol , Testes de Sensibilidade Microbiana , Naftoquinonas , Naftoquinonas/farmacologia , Antifúngicos/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Fluconazol/farmacologia , Biofilmes/efeitos dos fármacos , Humanos , Candida auris/efeitos dos fármacos , Candida auris/genética , Anfotericina B/farmacologia , Candidíase/microbiologia , Candidíase/tratamento farmacológicoRESUMO
Candida albicans is a polymorphic human fungal pathogen and the prime etiological agent responsible for candidiasis. The main two aspects of C. albicans virulence that have been suggested are yeast-to-hyphal (Y-H) morphological transitions and biofilm development. Anti-fungal agents targeting these virulence attributes enhances the antifungal drug development process. Repositioning with other non-fungal drugs offered a one of the new strategies and a potential alternative option to counter the urgent need for antifungal drug development. In the current study, an antiviral drug ganciclovir was screened as an antifungal agent against ATCC 90028, 10231 and clinical isolate (C1). Ganciclovir at 0.5 mg/ml concentration reduced 50% hyphal development on a silicon-based urinary catheter and was visualized using scanning electron microscopy. Ganciclovir reduced ergosterol biosynthesis in both strains and C1 isolate of C. albicans in a concentration-dependent manner. Additionally, a gene expression profile study showed that ganciclovir treatment resulted in upregulation of hyphal-specific repressors MIG1, TUP1, and NRG1 in C. albicans. Additionally, an in vivo study on the Bombyx mori silkworm model further evidenced the virulence inhibitory ability of ganciclovir (0.5 mg/ml) against C. albicans. This is the first report that explore the novel anti-morphogenic activities of ganciclovir against the pathogenic C. albicans strains, along with clinical isolates. Further, ganciclovir may be considered for therapeutic purpose after combinations with standard antifungal agents.
Assuntos
Antifúngicos , Candida albicans , Proteínas Fúngicas , Ganciclovir , Hifas , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Candida albicans/crescimento & desenvolvimento , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Antifúngicos/farmacologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ganciclovir/farmacologia , Animais , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candidíase/microbiologia , Candidíase/tratamento farmacológico , Testes de Sensibilidade Microbiana , Neuregulina-1/genética , Neuregulina-1/metabolismo , Virulência/efeitos dos fármacos , Humanos , Morfogênese/efeitos dos fármacos , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismoRESUMO
Candida species have been responsible for a high number of invasive infections worldwide. In this sense, Rottlerin has demonstrated a wide range of pharmacological activities. Therefore, this study aimed to evaluate the antifungal, antibiofilm and antivirulence activity of Rottlerin in vitro against Candida spp. and its toxicity and antifungal activity in vivo. Rottlerin showed antifungal activity against all yeasts evaluated, presenting Minimum Inhibitory and Fungicidal Concentration (MIC and MFC) values of 7.81 to > 1000 µg/mL. Futhermore, it was able to significantly inhibit biofilm production, presenting Biofilm Inhibitory Concentration (MICB50) values that ranged from 15.62 to 250 µg/mL and inhibition of the cell viability of the biofilm by 50% (IC50) from 2.24 to 12.76 µg/mL. There was a considerable reduction in all hydrolytic enzymes evaluated, with emphasis on hemolysin where Rottlerin showed a reduction of up to 20%. In the scanning electron microscopy (SEM) analysis, Rottlerin was able to completely inhibit filamentation by C. albicans. Regarding in vivo tests, Rottlerin did not demonstrate toxicity at the therapeutic concentrations demonstrated here and was able to increase the survival of C. elegans larvae infected. The results herein presented are innovative and pioneering in terms of Rottlerin's multipotentiality against these fungal infections.
Assuntos
Acetofenonas , Antifúngicos , Benzopiranos , Biofilmes , Testes de Sensibilidade Microbiana , Biofilmes/efeitos dos fármacos , Antifúngicos/farmacologia , Benzopiranos/farmacologia , Animais , Acetofenonas/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candida albicans/efeitos dos fármacosRESUMO
The incidence of Candida species resistant to traditional antifungal drugs is increasing globally. This issue significantly impacts patients' lives and increases healthcare expenses, confirming the need to develop novel therapeutic strategies. Recently, a thermostable trypsin inhibitor named ShTI (11.558 kDa), which has antibacterial effects on Staphylococcus aureus, was isolated from Salvia hispanica L. (chia) seeds. This study aimed to assess the antifungal effect of ShTI against Candida species and its synergism with fluconazole and to evaluate its mode of action. Preliminary toxicological studies on mouse fibroblasts were also performed. ShTI exhibited antifungal effects against C. parapsilosis (ATCC® 22,019), C. krusei (ATCC® 6258), and six clinical fluconazole-resistant strains of C. albicans (2), C. parapsilosis (2), and C. tropicalis (2). The minimum inhibitory concentration (MIC) values were 4.1 µM (inhibiting 50% of the isolates) and 8.2 µM (inhibiting 100% of the isolates). Additionally, when combined with fluconazole, ShTI had a synergistic effect on C. albicans, altering the morphological structure of the yeast. The mode of action of ShTI against C. krusei (ATCC® 6258) and C. albicans involves cell membrane permeabilization, the overproduction of reactive oxygen species, the formation of pseudohyphae, pore formation, and consequently, cell death. In addition, ShTI (8.65 and 17.3 µM) had noncytotoxic and nongenotoxic effects on L929 mouse fibroblasts. These findings suggest that ShTI could be a promising antimicrobial candidate, but further research is necessary to advance its application as a novel antifungal agent.
Assuntos
Antifúngicos , Candida , Farmacorresistência Fúngica , Fluconazol , Testes de Sensibilidade Microbiana , Salvia , Sementes , Inibidores da Tripsina , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Fluconazol/farmacologia , Fluconazol/toxicidade , Candida/efeitos dos fármacos , Salvia/química , Sementes/química , Animais , Camundongos , Inibidores da Tripsina/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Fibroblastos/efeitos dos fármacos , Sinergismo Farmacológico , Candidíase/microbiologia , Candidíase/tratamento farmacológicoRESUMO
Introduction: Candida auris is a relatively novel pathogen first described in 2009 in Japan. It has increased its presence worldwide, becoming a public health concern due to its innate resistance to antifungals and outbreak potential. Methods: We performed a query using the word "Candida auris" from the Scopus database, further performing a bibliometric analysis with the open-source R package Bibliometrix. Results: 907 original articles were retrieved, allowing us to map the principal authors, papers, journals, and countries involved in this yeast research, as well as analyze current and future trends and the number of published articles. Conclusion: C. auris will continue to be a pivotal point in fungal resistance research, either for a better understanding of its resistance and pathogenic mechanisms or for developing novel drugs.
Assuntos
Candida , Candidíase , Humanos , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Candidíase/microbiologia , Candida auris , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Surtos de Doenças , Saccharomyces cerevisiae , Testes de Sensibilidade MicrobianaRESUMO
Essential oils are a complex mixture of aromatic substances whose pharmacological actions, including antimicrobial, antioxidant, anticancer, and anti-inflammatory activities, have been widely reported. This study aimed to evaluate the anti-Candida and dermal anti-inflammatory activity of essential oils from native and cultivated Ecuadorian plants. Essential oils from Bursera graveolens, Dacryodes peruviana, Mespilodaphne quixos, and Melaleuca armillaris were isolated by hydrodistillation and were characterized physically and chemically. Its tolerance was analyzed by in vitro and in vivo studies. The antifungal activity was studied against Candida albicans, Candida glabrata, and Candida parapsilosis, whereas the anti-inflammatory effect was evaluated by a mouse ear edema model. The main compounds were limonene, α-phellandrene, (E)-methyl cinnamate, and 1,8-cineole, respectively. All essential oils showed high tolerability for skin application, antifungal activity against the three Candida strains, and anti-inflammatory efficacy by decreasing edema and overexpression of pro-inflammatory cytokines. Dacryodes peruviana essential oil showed the highest antifungal activity. On the other hand, Dacryodes peruviana and Melaleuca armillaris showed the greatest anti-inflammatory potential, decreasing edema by 53.3% and 65.25%, respectively, and inhibiting the overexpression of TNF-α, IL-8, IL-17A, and IL-23. The results suggest that these essential oils could be used as alternative therapies in the treatment of both cutaneous candidiasis and dermal inflammation.
Assuntos
Candidíase , Óleos Voláteis , Camundongos , Animais , Óleos Voláteis/química , Antifúngicos/química , Óleos de Plantas/química , Equador , Candida , Candida albicans , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Anti-Inflamatórios/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Invasive Candida infections threaten human health due to the increasing incidence of resistance to the currently available antifungal agents. Amphotericin B (AMB) is the gold standard therapy to treat these infections. Nevertheless, the use of such substance in the clinic is aggravated by its toxicity. Since AMB binds to membrane sterols, it forms pores on human plasma membranes, mainly in kidney cells, leading to nephrotoxicity. The combination of this drug to a second substance could allow for the use of smaller concentrations of AMB, consequently lowering the probability of adverse effects. This mini-review summarizes information regarding an array of substances that enhance AMB antifungal activity. It may be noticed that several of these compounds target plasma membrane. Interestingly, substances approved for human use also presented combinatory anti-Candida activity with AMB. These data reinforce the potential of associating AMB to another drug as a promising therapeutical alternative to treat Candida infections. Further studies, regarding mechanism of action, pharmacokinetics and toxicity parameters must be conducted to confirm the role of these substances as adjuvant agents in candidiasis therapy.
Assuntos
Candidíase , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Anfotericina B/farmacologia , Candida , Antifúngicos/farmacologia , Candidíase/tratamento farmacológico , Adjuvantes ImunológicosAssuntos
Candidíase , Doenças da Unha , Recém-Nascido , Humanos , Unhas , Pele , Candidíase/diagnóstico , Candidíase/tratamento farmacológicoRESUMO
BACKGROUND: Candida bloodstream infection (CBSI) is a growing problem among patients with cancer. AIM: To describe the main clinical and microbiological characteristics in patients with cancer who suffer CBSI. METHODS: We reviewed the clinical and microbiological characteristics of all patients with CBSI diagnosed between January 2010 and December 2020, at a tertiary-care oncological hospital. Analysis was done according to the Candida species found. Multivariate logistic regression analysis was used to determine the risk factors associated with 30-day mortality. RESULTS: There were 147 CBSIs diagnosed, 78 (53%) in patients with hematologic malignancies. The main Candida species identified were Candida albicans (n=54), Candida glabrata (n=40) and Candida tropicalis (n=29). C. tropicalis had been mainly isolated from patients with hematologic malignancies (79.3%) who had received chemotherapy recently (82.8%), and in patients with severe neutropenia (79.3%). Seventy-five (51%) patients died within the first 30 days, and the multivariate analysis showed the following risk factors: severe neutropenia, a Karnofsky Performance Scale score under 70, septic shock, and not receiving appropriate antifungal treatment. CONCLUSIONS: Patients with cancer who develop CBSI had a high mortality related with factors associated with their malignancy. Starting an empirical antifungal therapy the soonest is essential to increase the survival in these patients.
Assuntos
Candidemia , Candidíase , Neoplasias Hematológicas , Neoplasias , Neutropenia , Humanos , Candida , Antifúngicos/uso terapêutico , Estudos Retrospectivos , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Candidemia/microbiologia , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Candida tropicalis , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neutropenia/complicações , Neutropenia/tratamento farmacológico , Neoplasias Hematológicas/complicações , Fatores de RiscoRESUMO
Candida spp. infections are a serious health problem, especially in patients with risk factors. The acquisition of resistance, often associated with biofilm production, makes treatment more difficult due to the reduced effectiveness of available antifungals. Drug repurposing is a good alternative for the treatment of infections by Candida spp. biofilms. The present study evaluated the in vitro antibiofilm activity of sertraline in reducing the cell viability of forming and matured biofilms, in addition to elucidating whether effective concentrations are safe. Sertraline reduced biofilm cell viability by more than 80â% for all Candida species tested, acting at low and safe concentrations, both on mature biofilm and in preventing its formation, even the one with highest virulence. Its preventive mechanism seemed to be related to binding with ALS3. These data indicate that sertraline is a promising drug with anticandidal biofilm potential in safe doses. However, further studies are needed to elucidate the antibiofilm mechanism and possible application of pharmaceutical forms.
Assuntos
Candida , Candidíase , Humanos , Sertralina/farmacologia , Sertralina/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Biofilmes , Testes de Sensibilidade Microbiana , Candida albicansRESUMO
OBJECTIVE: The main objective was to assess the clinical characteristics, associated factors, and outcomes of patients admitted to the ICU for candidemia. The secondary objective was to examine the relationship of candidemia with the length of stay and mortality. METHODS: The analysis was a retrospective single-center cohort study addressing the effect of invasive candidemia on outcomes. This study was performed in a medical-surgical ICU located in a tertiary private hospital in São Paulo, Brazil. Data was collected through the review of the hospital database. RESULTS: In total, 18,442 patients were included in our study, including 22 patients with candidemia. The median age was similar in patients with and without candidemia [67 (56-84) vs. 67 (51-80)]. Most patients were male, and the proportion of men was higher among patients with candidemia (77% vs. 55.3%). The rates of renal replacement therapy (40.9% vs. 3.3%), mechanical ventilation (63.6% vs. 29.6%), and parenteral nutrition (40.9% vs. 4.8%) were higher in patients with candidemia than in those without candidemia. The mortality rate (77.3% vs. 11.9%) and length of hospital stay [42 days (23.0-78.8) vs. 8 days (5.0-17.0)] were significantly higher in patients with candidemia. CONCLUSIONS: Patients with candidemia are prone to longer hospital stay and mortality. In addition, we found associations of candidemia with the use of invasive mechanical ventilation, renal replacement therapy, and parenteral nutrition.
Assuntos
Candidemia , Candidíase , Humanos , Masculino , Feminino , Candida , Candidemia/epidemiologia , Candidemia/tratamento farmacológico , Estudos Retrospectivos , Estudos de Coortes , Brasil/epidemiologia , Candidíase/epidemiologia , Candidíase/tratamento farmacológico , Fatores de Risco , Unidades de Terapia Intensiva , Centros de Atenção Terciária , Antifúngicos/uso terapêuticoRESUMO
Polymeric films containing pomegranate peel extract (PPE) can act as a drug-delivery platform for topical treatment of candidiasis. The composition, mechanical resistance, and in vitro antifungal activity of a polymeric film containing PPE at 1.25 mg.mL-1 were investigated. Films were prepared using a solvent casting technique. The incorporation of PPE in the polymeric matrix gave rise to homogeneous, smooth, shiny, and yellowish-brown films. FTIR spectra of the film containing PPE showed differences without compromising the stability of the extract and the matrix. SEM analysis showed the existence of interruptions in the continuity of the films with extract, which promoted a reduction in the mechanical parameters without significantly changing the tensile strength and elongation at break. Films showed adequate mechanical properties and antifungal activity against Candida albicans, C. glabrata, C. krusei and C. tropicalis.