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1.
Mem Inst Oswaldo Cruz ; 115: e200349, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32997002

RESUMO

BACKGROUND: Essential oils (EO) extracted from Cinnamomum verum has been used as an antimicrobial agents for centuries. The effects of C. verum leaf oil against virulence of microorganisms is not well studied yet. OBJECTIVES: This study evaluates the effect of C. verum leaf oil against three virulence factors of Candida albicans, C. tropicalis and C. dubliniensis and its in-vivo toxicity. METHODS: Chemical composition of EO was determined using gas chromatography-mass spectrometry (GC-MS). Minimum inhibitory concentration (MIC) was determined using clinical and laboratory standards institute (CLSI) M27-A3 broth microdilution. Effect of EO on initial adhesion was quantified using XTT assay after allowing Candida cells to adhere to the polystyrene surface for 2 h. Biofilm formation of Candida in the presence of EO was quantified using XTT viability assay. Efficacy on reduction of germ tube formation was evaluated using standard protocol. Visualisation of biofilm formation and progression under the EO treatment were done using scanning electron microscope (SEM) and Time lapses microscope respectively. In-vivo toxicity of EO was determined using Galleria mellonella larvae. Chlorhexidine digluconate: positive control. RESULTS: Eugenol was the main compound of EO. MIC was 1.0 mg/mL. 50% reduction in initial adhesion was achieved by C. albicans, C. tropicalis and C. dubliniensis with 1.0, > 2.0 and 0.34 mg/mL respectively. 0.5 and 1.0 mg/mL significantly inhibit the germ tube formation. MBIC50 for forming biofilms were ≤ 0.35 mg/mL. 1.0 mg/mL prevent biofilm progression of Candida. SEM images exhibited cell wall damages, cellular shrinkages and decreased hyphal formation. No lethal effect was noted with in-vivo experiment model at any concentration tested. CONCLUSION: C. verum leaf oil acts against virulence factors of Candida and does not show any toxicity.


Assuntos
Candida/efeitos dos fármacos , Cinnamomum zeylanicum/química , Óleos Voláteis , Antifúngicos , Humanos , Fatores de Virulência
2.
J Mycol Med ; 30(3): 101009, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32620497

RESUMO

Chronic renal disease patients under chronic dialysis (CRDD) have a multifactorial immunological deterioration with an increased risk of Candida infections. Incidence of Candida infections is increasing. Choice of suitable antifungal agents is limited due to the resistance of some species to several antifungals. Aim of the present study was to identify the distribution and antifungal susceptibility patterns of oral isolated Candida species from infected and colonized patients, as well as to investigate the risk factors for oral infection in patients on dialysis. Cross-sectional study, approved by the institutional bioethics committees was performed in CRDD patients. Demographic, clinic data, and oral mucosa samples were obtained. Infection diagnosis was established clinically and confirmed with exfoliative cytology, each sample was plated on CHROMagar Candida and incubated at 36°C for 2 days. Yeast species were identified by carbohydrate assimilation ID 32C AUX system and the apiweb database. For the antifungal susceptibility test, the M44 A-3 method (CLSI) using fluconazole (FCZ), miconazole (MCZ), nystatin (NYS), and voriconazole (VCZ). Study included 119 participants, the main cause of CRD was nephropathy due to DM2 (58%), and three-fourths of the patients were under hemodialysis. Candida prevalence was 56.3% of 67 colonized or infected patients, 88 isolates were obtained. Principal identified species were C. albicans (51.1%), C. glabrata (25%), and C. tropicalis (14.8%). C. glabrata showed a reduced response to FCZ in 50% of isolates and C. albicans had a reduced response in 16% of the isolates. Antifungal agent with the least efficacious response or with the lowest susceptibility in the isolates of these patients was MCZ, followed by VCZ and FCZ, whereas NYS induced the best antifungal response.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidíase Bucal/microbiologia , Boca/microbiologia , Insuficiência Renal Crônica/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Candida/classificação , Candidíase Bucal/complicações , Candidíase Bucal/diagnóstico , Candidíase Bucal/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/terapia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/microbiologia , Nefropatias Diabéticas/terapia , Farmacorresistência Fúngica/efeitos dos fármacos , Feminino , Humanos , Masculino , México/epidemiologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Adulto Jovem
3.
J Mycol Med ; 30(3): 101011, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32693980

RESUMO

INTRODUCTION: Otomycosis, a superficial fungal infection of the external auditory canal (EAC), is a disease with exceptionally high prevalence. AIM: The aim of this study was to determine the prevalence of otomycosis, the distribution of causative species and to evaluate epidemiological characteristics of these infections. METHODOLOGY: The patients' data were collected from record book and database of mycological examinations conducted at Public Health Institute Nis, Serbia. In the period from 2014 to 2018 samples of 1287 patients with symptoms and signs of EAC infection were investigated. Standard mycological methods were used for isolation and determination of fungi. RESULTS: High prevalence of otomycosis was determined in examined patients (22.7%). However, the prevalence rates did not differ significantly in the studied period (p=0.931). The majority of patients were diagnosed with only unilateral EAC infection (82.9%). Considering all patients with otomycosis, mold infections caused by the genus Aspergillus (143/48.9%) were more frequent than Candida spp. ear infections (133/45.6%), with Aspergillus niger and Candida аlbicans being predominant causative agents. Mixed Aspergillus and Candida otomycosis was established in 16 (5.5%) patients. Otomycosis was more common in male subjects (26.8%, p=0.003) who also suffered from Aspergillus otomycosis more frequently (17.5%, p<0.001). The prevalence of these infections increases with age (p=0.005), while they do not show seasonal pattern (p>0.05). CONCLUSION: Noted high prevalence of otomycosis, with both yeasts and non-dermatophyte molds acting as infectious agents which require different treatment, implies the necessity for further epidemiological monitoring of this form of superficial mycoses.


Assuntos
Otomicose/epidemiologia , Otomicose/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/classificação , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/isolamento & purificação , Candida/classificação , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Candidíase/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Técnicas de Tipagem Micológica , Otomicose/tratamento farmacológico , Prevalência , Sérvia/epidemiologia , Adulto Jovem
4.
Mycoses ; 63(8): 771-778, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32609906

RESUMO

BACKGROUND: Emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. Apparently, the novel coronavirus (SARS-CoV-2) is armed by special abilities to spread and dysregulate the immune mechanisms. The likelihood of oropharyngeal candidiasis (OPC) development in COVID-19 patients with a list of attributable risk factors for oral infections has not yet been investigated. OBJECTIVES: We here aim to investigate the prevalence, causative agents and antifungal susceptibility pattern of OPC in Iranian COVID-19 patients. PATIENTS AND METHODS: A total of 53 hospitalised COVID-19 patients with OPC were studied. Relevant clinical data were mined. Strain identification was performed by 21-plex PCR and sequencing of the internal transcribed spacer region (ITS1-5.8S-ITS2). Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, amphotericin B, caspofungin, micafungin and anidulafungin was performed according to the CLSI broth dilution method. RESULTS: In 53 COVID-19 patients with OPC, cardiovascular diseases (52.83%) and diabetes (37.7%) were the principal underlying conditions. The most common risk factor was lymphopaenia (71%). In total, 65 Candida isolates causing OPC were recovered. C albicans (70.7%) was the most common, followed by C glabrata (10.7%), C dubliniensis (9.2%), C parapsilosis sensu stricto (4.6%), C tropicalis (3%) and Pichia kudriavzevii (=C krusei, 1.5%). Majority of the Candida isolates were susceptible to all three classes of antifungal drugs. CONCLUSION: Our data clarified some concerns regarding the occurrence of OPC in Iranian COVID-19 patients. Further studies should be conducted to design an appropriate prophylaxis programme and improve management of OPC in critically ill COVID-19 patients.


Assuntos
Antifúngicos/farmacologia , Candida/classificação , Candidíase Bucal/complicações , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Candida/efeitos dos fármacos , Candida/genética , Candidíase Bucal/microbiologia , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Irã (Geográfico) , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pandemias , Fenótipo , Pneumonia Viral/epidemiologia , Fatores de Tempo
5.
J Mycol Med ; 30(3): 101003, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32586733

RESUMO

OBJECTIVE: In order to improve the effect of ketoconazole, poly-lactic acid (PLA) nanoparticles containing ketoconazole were prepared, characterized and tested against dermatophytes and Candida spp planktonic and biofilm cells. METHODS: The ketoconazole-PLA nanoparticles obtained by nanoprecipitation were characterized using dynamic light scattering, scanning electron microscopy, transmission electron microscopy, and differential scanning calorimetry. In addition, quantification of encapsulated ketoconazole and the in vitro release profile were determined. Antifungal susceptibility tests against dermatophytes Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum and yeasts Candida albicans, C. dubliniensis, C. krusei, C. parapsilosis, and C. tropicalis were performed. RESULTS: Spherical nanoparticles, with a mean diameter of 188.5nm and an encapsulation efficiency of 45% ketoconazole, were obtained. The nanoparticles containing ketoconazole had superior antifungal activity against all tested fungi strains than free ketoconazole. Inhibition of yeast biofilm formation was also achieved. CONCLUSION: Ketoconazole-PLA nanoparticles resulted in better antifungal activity of ketoconazole nanoparticles than free drug against dermatophytes and Candida species, indicating a promising tool for the development of therapeutic strategies.


Assuntos
Antifúngicos/administração & dosagem , Arthrodermataceae/efeitos dos fármacos , Candida/efeitos dos fármacos , Portadores de Fármacos , Cetoconazol/administração & dosagem , Nanopartículas/química , Poliésteres/química , Antifúngicos/farmacocinética , Arthrodermataceae/fisiologia , Biofilmes/efeitos dos fármacos , Candida/fisiologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Cetoconazol/farmacocinética , Teste de Materiais , Testes de Sensibilidade Microbiana , Resultado do Tratamento
6.
Biofouling ; 36(3): 319-331, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32410461

RESUMO

Traditional herbal monomers (THMs) are widely distributed in many traditional Chinese formulas (TCFs) and decoctions (TCDs) and are frequently used for the prevention and treatment of fungal infections. The antifungal activities of five common THMs, including sodium houttuyfonate (SH), berberine (BER), palmatine (PAL), jatrorrhizine (JAT) and cinnamaldehyde (CIN), and their potential for inducing cell wall remodeling (CWR), were evaluated against Candida albicans SC5314 and Candida auris 12372. SH/CIN plus BER/PAL/JAT showed synergistic antifungal activity against both Candida isolates. Furthermore, SH-associated combinations (SH plus BER/PAL/JAT) induced stronger exposure of ß-glucan and chitin than their counterparts, while CIN triggered more marked exposure compared with CIN-associated combinations (CIN plus BER/PAL/JAT). Collectively, this study demonstrated the anti-Candida effect and the CWR induction potential of the five THMs and their associated combinations, providing a possibility of their in vivo application against fungal-associated infections.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Acroleína/análogos & derivados , Acroleína/farmacologia , Alcanos/farmacologia , Berberina/análogos & derivados , Berberina/farmacologia , Alcaloides de Berberina/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Sulfitos/farmacologia
7.
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
8.
PLoS One ; 15(5): e0233102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392266

RESUMO

Candida auris, a decade old Candida species, has been identified globally as a significant nosocomial multidrug resistant (MDR) pathogen responsible for causing invasive outbreaks. Biofilms and overexpression of efflux pumps such as Major Facilitator Superfamily and ATP Binding Cassette are known to cause multidrug resistance in Candida species, including C. auris. Therefore, targeting these factors may prove an effective approach to combat MDR in C. auris. In this study, 25 clinical isolates of C. auris from different hospitals of South Africa were used. All the isolates were found capable enough to form biofilms on 96-well flat bottom microtiter plate that was further confirmed by MTT reduction assay. In addition, these strains have active drug efflux mechanism which was supported by rhodamine-6-G extracellular efflux and intracellular accumulation assays. Antifungal susceptibility profile of all the isolates against commonly used drugs was determined following CLSI recommended guidelines. We further studied the role of farnesol, an endogenous quorum sensing molecule, in modulating development of biofilms and drug efflux in C. auris. The MIC for planktonic cells ranged from 62.5-125 mM, and for sessile cells was 125 mM (4h biofilm) and 500 mM (12h and 24h biofilm). Furthermore, farnesol (125 mM) also suppresses adherence and biofilm formation by C. auris. Farnesol inhibited biofilm formation, blocked efflux pumps and downregulated biofilm- and efflux pump- associated genes. Modulation of C. auris biofilm formation and efflux pump activity by farnesol represent a promising approach for controlling life threatening infections caused by this pathogen.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Farneseno Álcool/farmacologia , Anfotericina B/farmacologia , Biofilmes/efeitos dos fármacos , Farmacorresistência Fúngica , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Percepção de Quorum , África do Sul
9.
BMC Infect Dis ; 20(1): 377, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460728

RESUMO

BACKGROUND: Candida diddensiae, a yeast found in olive oil, is considered non-pathogenic to humans. Here, we describe the first case of fungemia caused by C. diddensiae in a hospitalized patient with underlying diseases. CASE PRESENTATION: A 62-year-old woman was admitted because of multiple contusions due to repeated falls and generalized weakness. She presented with chronic leukopenia due to systemic lupus erythematosus, and multiple cranial nerve neuropathies due to a recurring chordoma. She was given a lipid emulsion containing total parenteral nutrition (TPN) starting on the day of admission. Broad-spectrum antibiotics had been administered during her last hospital stay and from day 8 of this hospitalization. However, no central venous catheter was used during this hospital stay. Blood cultures obtained on hospital days 17, 23, and 24 yielded the same yeast, which was identified as C. diddensiae via sequence analyses of the internal transcribed spacer region and D1/D2 regions of the 26S ribosomal DNA of the rRNA gene. In vitro susceptibility testing showed that the minimum inhibitory concentration of fluconazole for all isolates was 8 µg/mL. On day 23, TPN was discontinued and fluconazole therapy was started. Blood cultures obtained on day 26 were negative. The fluconazole therapy was replaced with micafungin on day 26 and the patient exhibited improvements. CONCLUSION: The use of lipid TPN may potentially contribute to the occurrence of nosocomial fungemia by C. diddensiae, an unusual Candida species.


Assuntos
Infecção Hospitalar/microbiologia , Fungemia/microbiologia , Antibacterianos , Antifúngicos/administração & dosagem , Candida/efeitos dos fármacos , Candida/genética , Candida/isolamento & purificação , Candida/fisiologia , Cateteres Venosos Centrais , Infecção Hospitalar/tratamento farmacológico , DNA Ribossômico/genética , Feminino , Fluconazol/administração & dosagem , Fungemia/tratamento farmacológico , Hospitais , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Nutrição Parenteral Total
10.
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
11.
J Mycol Med ; 30(2): 100940, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32201243

RESUMO

Despite the use of conventional antifungal drugs, Candida spp resistance, especially mediated by biofilms formation remains recurrent. Therefore, new drugs to treat fungal infections are urgently needed. In this line, our study aimed to determine the anticandidal activity and the synergistic effect of essential oil fractions from Syzygium aromaticum, Cymbopogon citratus and Aeollanthus heliotropioides harvested in Cameroon using a combination approach. Essential oils have been obtained by hydrodistillation and their chemical composition was analysed by GC/MS. Antifungal activity was evaluated by the determination of minimum inhibitory concentration (MIC) using a micro-dilution method. The sorbitol and ergosterol binding ability and anti-biofilm activity were also assessed in order to evaluate the mode of action. The crude essential oils showed a good anticandidal activity, most probably due to the eugenol, linalool and citral content. The combination of two fractions F7 and F10 showed an improved growth inhibition of Candida spp compared to the crude essential oils. The inhibitory effect could be related with the presence of γ-dodecalactone and citronellol as main compounds. The best synergistic combination F7F10 inhibited biofilm formation at ten time reduced combination MIC. The active fractions targeted different fungal cell structures, including cell wall and membrane. Our study showed that the combination of selected essential oils fractions exhibited an increased antifungal activity against Candida spp compared to the crude essential oils. The combination approach of inner compound groups may be used as a promising strategy for the development of efficient recombined micro-essential oils as antifungal agents to face Candida resistance.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Cymbopogon/química , Lamiaceae/química , Óleos Voláteis/farmacologia , Syzygium/química , Antifúngicos/isolamento & purificação , Biofilmes/efeitos dos fármacos , Camarões , Candida/fisiologia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Fracionamento Químico , Sinergismo Farmacológico , Humanos , Testes de Sensibilidade Microbiana , Óleos Voláteis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Óleos Vegetais/isolamento & purificação , Óleos Vegetais/farmacologia
12.
Medicine (Baltimore) ; 99(11): e19494, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176090

RESUMO

As detection rates of non-albicans Candida species are increasing, determining their pathogen profiles and antifungal susceptibilities is important for antifungal treatment selection. We identified the antifungal susceptibility patterns and predictive factors for mortality in candidemia.A multicenter retrospective analysis of patients with at least 1 blood culture positive for Candida species was conducted. Candida species were classified into 3 groups (group A, Candia albicans; group B, Candida tropicalis, and Candida parasilosis; group C, Candida glabrata and Candida krusei ) to analyze the susceptibility patterns, first-line antifungal administered, and mortality. Univariate and multivariate comparisons between outcomes were performed to identify mortality risk factors.In total, 317 patients were identified, and 136 (42.9%) had recorded mortality. Echinocandin susceptibility was higher for group A than group B (111/111 [100%] vs 77/94 [81.9%], P < .001). Moreover, group A demonstrated higher fluconazole susceptibility (144/149 [96.6%] vs 39/55 [70.9%], P < .001) and lower mortality (68 [45.3%] vs 34 [61.8%], P = .036) than those of group C. In the multivariate analysis, the sequential organ failure assessment score (odds ratio OR 1.351, 95% confidence interval 1.067-1.711, p = 0.013) and positive blood culture on day 7 of hospitalization (odds ratio 5.506, 95% confidence interval, 1.697-17.860, P = .004) were associated with a higher risk of mortality.Patients with higher sequential organ failure assessment scores and sustained positive blood cultures have an increased risk of mortality.


Assuntos
Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidemia/tratamento farmacológico , Farmacorresistência Fúngica , Fluconazol/uso terapêutico , Idoso , Antifúngicos/farmacologia , Candidemia/mortalidade , Feminino , Fluconazol/farmacologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Valor Preditivo dos Testes , República da Coreia , Estudos Retrospectivos , Fatores de Risco
13.
Pol J Microbiol ; 69(1): 73-84, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32189482

RESUMO

The contribution of fluconazole-resistant Candida spp. isolates to urinary tract infections in Egypt has become a nationwide problem. A recent approach to overcome such disaster is combining conventional antifungals with non-antifungals. This study investigated the interaction of amikacin with fluconazole against resistant Candida strains isolated from the urine culture of patients admitted to Alexandria Main University Hospital. Among the collected Candida spp. isolates, 42.9% were resistant to fluconazole with MICs ranging between 128 and 1,024 µg/ml. The resistance-modifying activity of amikacin (4,000 µg/ml) was studied against fluconazole-resistant isolates where amikacin sensitized 91.7 % of resistant Candida spp. isolates to fluconazole with a modulation factor ranging between 32 and 256. The rhodamine efflux assay was performed to examine the impact of amikacin on efflux pump activity. After 120 minutes of treatment, amikacin affected the efflux pump activity of the isolates tested with a percentage of reduction in the fluorescence intensity of 8.9%. Quantitative real-time PCR was applied to assess the amikacin effect on the expression of the efflux pump genes MDR1, CDR1, and CDR2. The downregulatory effect of amikacin on the expression of the studied genes caused a percentage of reduction in the expression level ranging between 42.1 and 94%. In conclusion, amikacin resensitized resistant Candida spp. isolates to fluconazole and could be used in combination in the management of candiduria with a higher efficiency or at lower administration doses. To the best of our knowledge, this is the first study evaluating the enhancement of fluconazole activity in combination with amikacin against Candida spp.The contribution of fluconazole-resistant Candida spp. isolates to urinary tract infections in Egypt has become a nationwide problem. A recent approach to overcome such disaster is combining conventional antifungals with non-antifungals. This study investigated the interaction of amikacin with fluconazole against resistant Candida strains isolated from the urine culture of patients admitted to Alexandria Main University Hospital. Among the collected Candida spp. isolates, 42.9% were resistant to fluconazole with MICs ranging between 128 and 1,024 µg/ml. The resistance-modifying activity of amikacin (4,000 µg/ml) was studied against fluconazole-resistant isolates where amikacin sensitized 91.7 % of resistant Candida spp. isolates to fluconazole with a modulation factor ranging between 32 and 256. The rhodamine efflux assay was performed to examine the impact of amikacin on efflux pump activity. After 120 minutes of treatment, amikacin affected the efflux pump activity of the isolates tested with a percentage of reduction in the fluorescence intensity of 8.9%. Quantitative real-time PCR was applied to assess the amikacin effect on the expression of the efflux pump genes MDR1, CDR1, and CDR2. The downregulatory effect of amikacin on the expression of the studied genes caused a percentage of reduction in the expression level ranging between 42.1 and 94%. In conclusion, amikacin resensitized resistant Candida spp. isolates to fluconazole and could be used in combination in the management of candiduria with a higher efficiency or at lower administration doses. To the best of our knowledge, this is the first study evaluating the enhancement of fluconazole activity in combination with amikacin against Candida spp.


Assuntos
Amicacina/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Fluconazol/farmacologia , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Regulação para Baixo , Proteínas Fúngicas/genética , Humanos , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
14.
BMC Infect Dis ; 20(1): 231, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32188422

RESUMO

BACKGROUND: The spectrum of yeasts and their antifungal susceptibility profile are poorly known and treatment of fungal disease has remained empirical. The aim of this study is to determine the spectrum and antifungal susceptibility profile of yeasts particularly of Candida species. METHODS: A descriptive study on the composition of Candida species and antifungal susceptibility profile were conducted from January 2018 to September 2018. Clinical samples collected from different sites were cultured on Sabouraud dextrose agar and incubated for an appropriate time. Identification of yeast isolates and their antifungal susceptibility profile were determined by the VITEK 2 compact system. Descriptive statistics such as frequency and percentage of Candida species were calculated using SPSS version 20. RESULTS: Of 209 yeasts recovered, 104(49.8%), 90 (43.1%), 15(7.2%) were C. albicans, non albicans Candida species, and other yeasts, respectively. Among non albicans Candida species, Candida krusei was the commonest isolate. Of other yeast groups, 66.7% was represented by Cryptococcus laurentii. Regardless of Candida species identified, 85.6, 3.9, and 10.5% of the isolates were susceptible, intermediate, and resistant to fluconazole, respectively. C krusei was 100% resistant to the drug. Voriconazole demonstrated the greatest antifungal activity against Candida isolates in which 99.4% of Candida isolates were susceptible. The susceptibility and the resistance rate of Candida isolate to both caspofungin and micafungin were the same being 96 and 4% respectively. However, micafungin was more potent than caspofungin. The susceptibility, resistant, and intermediate rates of yeasts against flucytosine were, 86.2, 6.6, and 7.2%, respectively. CONCLUSIONS: The present study demonstrated the distribution of Candida species in different clinical specimens where the isolation rate of non-albicans Candida species was comparable to Candida albicans. The high resistance rate of C. krusei to fluconazole and flucytosine may demonstrate that the treatment of candidiasis empirically is questionable.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidíase/microbiologia , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Caspofungina/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Etiópia , Humanos , Micafungina/farmacologia , Testes de Sensibilidade Microbiana
15.
Med Mycol J ; 61(1): 1-5, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115443

RESUMO

Effects of the type of microplates and solvent for preparation of caspofungin (CPFG) on antifungal susceptibility testing of CPFG against clinical isolates of Candida albicans, Candida glabrata, and Candida krusei (20 strains each) by broth microdilution method according to the Clinical and Laboratory Standards Institute were evaluated. When CPFG was dissolved in water, MICs against the three Candida species decreased 3.1-6.0-fold in surface-untreated microplates compared to those in treated microplates. When CPFG was dissolved in dimethyl sulfoxide, MICs against the three Candida species decreased 1.3-2.5-fold in surface-untreated microplates compared to those in treated microplates. Differences in MICs according to the type of solvent did not exceed the difference for one dilution interval (0.5-2-fold MIC ratio) regardless of whether the microplate surface was treated or not. These findings suggest that differences in CPFG MICs may depend mainly on the type of surface treatment of assay microplates.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Caspofungina/farmacologia , Técnicas Microbiológicas/métodos , Solventes , Farmacorresistência Fúngica
16.
Nat Rev Microbiol ; 18(6): 319-331, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32047294

RESUMO

Systemic fungal infections pose a serious clinical problem. Treatment options are limited, and antifungal drug resistance is increasing. In addition, a substantial proportion of patients do not respond to therapy despite being infected with fungi that are susceptible to the drug. The discordance between overall treatment outcome and low levels of clinical resistance may be attributable to antifungal drug tolerance. In this Review, we define and distinguish resistance and tolerance and discuss the current understanding of the molecular, genetic and physiological mechanisms that contribute to those phenomena. Distinguishing tolerance from resistance might provide important insights into the reasons for treatment failure in some settings.


Assuntos
Antifúngicos/farmacologia , Farmacorresistência Fúngica , Candida/efeitos dos fármacos , Tolerância a Medicamentos , Humanos , Testes de Sensibilidade Microbiana
17.
PLoS One ; 15(2): e0228864, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32092072

RESUMO

The integration of metallic or ceramic nanoparticles in polymer matrices has improved the antimicrobial and antifungal behavior, resulting in the search for composites with increased bactericidal and antimycotic properties. A polycaprolactone fibers with copper oxide nanoparticles was prepared. Polycaprolactone-copper fibers (PCL- CuONPs) were prepared into two major steps in situ method: (a) Synthesis of CuO particles, then (b) incorporation of polycaprolactone to electrospun process. The first step is the reduction of Cu+2 ions by gallic acid in N,N-dimethylformamide and tetrahydrofuran solution with the simple addition of polycaprolactone in the solution for the second electrospun step. Raman spectra provide information about the nature of the copper oxide synthesized. There are three Raman peaks in the sample, at 294 and 581 cm-1 and a very broad band from 400 to 600 cm-1 which are characteristics bands for CuO. Scanning electron microscopy (TEM) revealed copper oxide nanoparticles with semispherical shapes with diameter 35 ±11 nm. Dynamic light scattering (DLS) analysis showed uniform CuONPs in a range of 88±11 nm. Scanning electron microscopy (SEM) of PCL-CuONps reveled fibers with diameters ranging from 925 to 1080 nm were successfully obtained by electrospinning technique. Orientation, morphology and diameter were influenced by the increment on CuONPs concentration, with the smaller diameter present in samples prepared from low concentrated solutions. The antimycotic applicability of the composite was evaluated to determine the antifungal activity in three species of the genus Candida (Candida albicans, Candida glabrata and Candida tropicalis). PCL-CuONPs exhibit a considerable antifungal effect on all species tested. The preparation of PCL-CuONPs was simple, fast and low-cost for practical application as an antifungal dressing.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Cobre/farmacologia , Antifúngicos/administração & dosagem , Antifúngicos/química , Candida/ultraestrutura , Cobre/administração & dosagem , Cobre/química , Humanos , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Nanotecnologia , Poliésteres/química , Análise Espectral Raman
18.
Int J Antimicrob Agents ; 55(3): 105901, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31954831

RESUMO

Antifungal combination is an interesting approach for the treatment of several fungal infections but there is currently little evidence to support combined therapy in Candida auris infections. The antibacterial colistin has recently been shown to interact synergistically with antifungals against Candida spp., including azole-resistant isolates. The current study evaluated the in vitro interaction between colistin and either caspofungin or micafungin against 15 C. auris isolates by a checkerboard methodology based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference method. Results were analysed by two approaches: calculation of the fractional inhibitory concentration index (FICI) and response surface analysis based on the Bliss model. The minimum inhibitory concentration (MIC) range (geometric mean [Gmean]) of caspofungin and micafungin was 0.25 to 1 µg/mL (0.691 µg/mL) and 0.03 to 0.125 µg/mL (0.114 µg/mL), respectively. No activity was observed for colistin alone with MIC of >64 µg/mL for all the isolates. When colistin was combined with caspofungin, synergistic interactions were observed for all strains with FICI values of 0.08 to 0.14. In contrast, indifferent interactions were observed for the combination of colistin with micafungin with FICI values of 0.51 to 1.01. Synergy was also demonstrated using the Bliss model against all isolates for the colistin-caspofungin combination and in 60% of isolates for the colistin-micafungin combination. Antagonism was not observed for any combination.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Colistina/farmacologia , Equinocandinas/farmacologia , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Caspofungina/farmacologia , Caspofungina/uso terapêutico , Colistina/uso terapêutico , Sinergismo Farmacológico , Equinocandinas/uso terapêutico , Humanos , Micafungina/farmacologia , Micafungina/uso terapêutico
19.
Chem Biodivers ; 17(2): e1900580, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31913571

RESUMO

Developing effective and eco-friendly antimicrobials and pesticides has become a highly important issue. The repellent, insecticidal and antimicrobial activity of essential oils (EOs) isolated by hydrodistillation from dried leaves of the three Eucalyptus species (E. cloeziana, E. umbellata and E. benthamii) were investigated. During GC/MS analysis, α-pinene (47.36 %), 1,8-cineol (38.53 %) and α-pinene (35.31 %) were identified as major components of E. cloeziana, E. umbellata and E. benthamii, respectively. The EOs from E. cloeziana exhibited the longest effective protection time (465 min, at 50.0 % w/w) for humans among the EOs studied. The effective protection time was 30 min and 300 min at concentrations of 12.5 % (w/w) and 25.0 % (w/w), respectively. Fumigating insecticidal activity of EOs from three Eucalyptus species was tested by airtight fumigation in conical flask, which indicated that essential oils had a highly and rapidly insecticidal activity on Culex pipiens quinquefasciatus. The antimicrobial activity of EOs was evaluated by using disc diffusion and agar dilution methods. There was no significant difference in the antibacterial activity of EOs from E. cloeziana and E. umbellate and they had the same MICs (20 mL/L) on Staphylococcus aureus, Salmonella typhi, Bacillus subtilis and Escherichia coli. E. benthamii had the worst microbial inhibitory effect among the three Eucalyptus essential oils and the MIC value for the test species is 40 mL/L except for Rhodotorula Harrison (10 mL/L).


Assuntos
Anti-Infecciosos/química , Eucalyptus/química , Repelentes de Insetos/química , Inseticidas/química , Óleos Voláteis/química , Folhas de Planta/metabolismo , Animais , Anti-Infecciosos/farmacologia , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Culex/efeitos dos fármacos , Eucalyptus/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Repelentes de Insetos/farmacologia , Testes de Sensibilidade Microbiana , Óleos Voláteis/análise , Óleos Voláteis/farmacologia , Folhas de Planta/química
20.
J Enzyme Inhib Med Chem ; 35(1): 398-403, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31899979

RESUMO

(2-(2,4-Dichlorophenyl)-3-(1H-indol-1-yl)-1-(1,2,4-1H-triazol-1-yl)propan-2-ol (8 g), a new 1,2,4-triazole-indole hybrid molecule, showed a broad-spectrum activity against Candida, particularly against low fluconazole-susceptible species. Its activity was higher than fluconazole and similar to voriconazole on C. glabrata (MIC90 = 0.25, 64 and 1 µg/mL, respectively), C. krusei (MIC90 = 0.125, 64 and 0.125 µg/mL, respectively) and C. albicans (MIC90 = 0.5, 8 and 0.25 µg/mL, respectively). The action mechanisms of 8 g were also identified as inhibition of ergosterol biosynthesis and phospholipase A2-like activity. At concentration as low as 4 ng/mL, 8g inhibited ergosterol production by 82% and induced production of 14a-methyl sterols, that is comparable to the results obtained with fluconazole at higher concentration. 8 g demonstrated moderate inhibitory effect on phospholipase A2-like activity being a putative virulence factor. Due to a low MRC5 cytotoxicity, this compound presents a high therapeutic index. These results pointed out that 8 g is a new lead antifungal candidate with potent ergosterol biosynthesis inhibition.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Indóis/farmacologia , Triazóis/farmacologia , Animais , Antifúngicos/química , Candida/enzimologia , Candida/metabolismo , Linhagem Celular , Ergosterol/antagonistas & inibidores , Ergosterol/biossíntese , Feminino , Humanos , Indóis/química , Camundongos , Testes de Sensibilidade Microbiana , Especificidade da Espécie , Triazóis/química
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