RESUMO
OBJECTIVE: This study aimed to verify oral candidiasis, identify the causative species, and investigate the antifungal susceptibility of yeasts isolated from liver transplant patients. METHODS: A descriptive analysis of 97 patients who underwent liver transplantation was conducted at a hospital. Two clinical examinations (Collections A and B) of the oral cavity were performed. Oral material was collected from all patients, inoculated in Sabouraud Dextrose Agar, and incubated at 35â for 48 hours. Samples were identified by molecular sequencing of the internal trascribed space region of rDNA. RESULTS: An antifungal susceptibility test with fluconazole, amphotericin B, and micafungin was performed using the Clinical and Laboratory Standards Institute yeast broth microdilution method. Among the patients, 15 presented with oral candidiasis: eight in Collection A and seven in Collection B. The primary type of candidiasis was atrophic, followed by pseudomembranous candidiasis. The most prevalent species was Candida albicans (nine), followed by Candida glabrata (three), Candida tropicalis (two), and Candida dubliniensis (one). Regarding susceptibility to fluconazole, of the 15 samples, 11 were susceptible, three were susceptible in a dose-dependent manner, and one was resistant. CONCLUSION: The most commonly identified type of candidiasis was atrophic, with C. albicans and C. glabrata being the most prevalent causative species. One fluconazole-resistant isolate each of C. tropicalis and C. albicans were identified.
Assuntos
Antifúngicos , Candida , Candidíase Bucal , Fluconazol , Transplante de Fígado , Testes de Sensibilidade Microbiana , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Transplante de Fígado/efeitos adversos , Masculino , Candidíase Bucal/microbiologia , Candidíase Bucal/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Candida/efeitos dos fármacos , Candida/classificação , Candida/isolamento & purificação , Fluconazol/farmacologia , Adulto , Anfotericina B/farmacologia , Idoso , Farmacorresistência Fúngica , Micafungina/farmacologia , Micafungina/uso terapêutico , Adulto JovemRESUMO
Species from Candida parapsilosis complex are frequently found in neonatal candidemia. The antifungal agents to treat this infection are limited and the occurrence of low in vitro susceptibility to echinocandins such as micafungin has been observed. In this context, the chaperone Hsp90 could be a target to reduce resistance. Thus, the objective of this research was to identify isolates from the C. parapsilosis complex and verify the action of Hsp90 inhibitors associated with micafungin. The fungal identification was based on genetic sequencing and mass spectrometry. Minimal inhibitory concentrations were determined by broth microdilution method according to Clinical Laboratory and Standards Institute. The evaluation of the interaction between micafungin with Hsp90 inhibitors was realized using the checkerboard methodology. According to the polyphasic taxonomy, C. parapsilosis sensu stricto was the most frequently identified, followed by C. orthopsilosis and C. metapsilosis, and one isolate of Lodderomyces elongisporus was identified by genetic sequencing. The Hsp90 inhibitor geladanamycin associated with micafungin showed a synergic effect in 31.25% of the isolates, a better result was observed with radicicol, which shows synergic effect in 56.25% tested yeasts. The results obtained demonstrate that blocking Hsp90 could be effective to reduce antifungal resistance to echinocandins.
Assuntos
Antifúngicos , Candida parapsilosis , Candidemia , Proteínas de Choque Térmico HSP90 , Micafungina , Humanos , Recém-Nascido , Antifúngicos/farmacologia , Benzoquinonas/farmacologia , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/isolamento & purificação , Candida parapsilosis/genética , Candidemia/microbiologia , Farmacorresistência Fúngica , Sinergismo Farmacológico , Equinocandinas/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/genética , Lactamas Macrocíclicas/farmacologia , Lipopeptídeos/farmacologia , Micafungina/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Fungi are becoming increasingly resistant, especially the new strains. Therefore, this work developed nanoemulsions (NE) containing micafungin (MICA), in order to improve its action against infections caused by Candida auris. The NEs were composed of the surfactants polyoxyethylene (20) cetyl ether (Brij 58®)/soy phosphatidylcholine at 10%, sunflower oil/cholesterol at 10%, and 80% PBS. The NEs were characterized by Dynamic Light Scattering (DLS). For the microbiological in vitro evaluation the determination of the minimum inhibitory concentration (MIC), ergosterol/sorbitol, time kill and biofilms tests were performed. Additionally, the antifungal activity was also evaluated in a Galleria mellonella model. The same model was used in order to evaluate acute toxicity. The NE showed a size of â¼ 42.12 nm, a polydispersion index (PDI) of 0.289, and a zeta potential (ZP) of -3.86 mV. NEM had an average size of 41.29 nm, a PDI of 0.259, and a ZP of -4.71 mV. Finally, both nanoemulsions showed good stability in a storage period of 3 months. Although NEM did not show activity in planktonic cells, it exhibited action against biofilm and in the in vivo infection model. In the alternative in vivo model assay, it was possible to observe that both, NEM and free MICA at 0.2 mg/l, was effective against the infection, being that NEM presented a better action. Finally, NEM and free MICA showed no acute toxicity up to 4 mg/l. NEM showed the best activities in in vitro in mature antibiofilm and in alternative in vivo models in G. mellonella. Although, NEs showed to be attractive for MICA transport in the treatment of infections caused by C. auris in vitro and in vivo studies with G. mellonella, further studies should be carried out, in mice, for example.
Candida auris is a fungus that can cause infections in the human body. As it is a microorganism with a high potential for resistance, it is extremely important to develop new therapeutic alternatives. Thus, nanotechnology, the science that studies materials with extremely small sizes, can be considered a promising method in the treatment of these infections.
Assuntos
Antifúngicos , Ergosterol , Animais , Camundongos , Micafungina/farmacologia , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana/veterinária , BiofilmesRESUMO
Candida auris is an emerging global public health threat. It is an opportunistic yeast that usually affects critically ill patients in healthcare settings and is characterized by reduced susceptibility to multiple antifungal classes. Combination therapy with antifungals and repurposed drugs is a feasible alternative to overcome this problem. The aim of this study was to examine the in vitro interactions and potential synergy of micafungin (MFG) and voriconazole (VRC) plus the antidepressant sertraline (SRT) against clinical isolates of C. auris. Conventional antifungal testing was first performed with the three drugs according to the CLSI methodology. Drug interactions were determined by the checkerboard microdilution assay using the fractional inhibitory concentration (FIC) index. Synergistic interactions were noted with the combination of MFG and SRT plus VRC with FIC values of 0.37 to 0.49 for some strains. Indifferent interactions were observed when MFG was combined with SRT with just one exception (FIC 0.53). No antagonism was observed for any combination. The combination of VRC with MCF or SRT may be relevant for treating C. auris infections.
Assuntos
Antifúngicos , Sertralina , Humanos , Voriconazol/farmacologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Micafungina/farmacologia , Sertralina/farmacologia , Candida auris , Candida , Testes de Sensibilidade MicrobianaRESUMO
Background Fungal spondylodiscitis is not common but should be suspected in some cases. Candida tropicalis infections are being more frequently diagnosed due to some factors related to the microorganism. Case Description A C. tropicalis spondylodiscitis is described in a 72-year-old man who was treated with a combination of echinocandin (micafungin) and surgery. Conclusion The presence of some risk factors should promptly raise the suspicion of fungal spondylodiscitis. Treatment should be instituted as early as possible for the best outcome for the patient.
Assuntos
Humanos , Masculino , Idoso , Discite/cirurgia , Candida tropicalis/patogenicidade , Micafungina/uso terapêutico , Vértebras Lombares/cirurgia , Candidíase/diagnóstico , Candidíase/terapia , Discite/diagnóstico por imagem , Laminectomia/métodosRESUMO
Candida albicans and Staphylococcus aureus are pathogens commonly isolated from bloodstream infections worldwide. While coinfection by both pathogens is associated with mixed biofilms and more severe clinical manifestations, due to the combined expression of virulence and resistance factors, effective treatments remain a challenge. In this study, we evaluated the activity of echinocandins, especially caspofungin, against mixed biofilms of C. albicans and methicillin-resistant (MRSA) or methicillin-susceptible S. aureus (MSSA) and their effectiveness in vivo using the Galleria mellonella coinfection model. Although caspofungin (CAS) and micafungin (MFG) inhibited the mixed biofilm formation, with CAS exhibiting inhibitory activity at lower concentrations, only CAS was active against preformed mixed biofilms. CAS significantly decreased the total biomass of mixed biofilms at concentrations of ≥2 µg/ml, whereas the microbial viability was reduced at high concentrations (32 to 128 µg/ml), leading to fungus and bacterium cell wall disruption and fungal cell enlargement. Notably, CAS (20 or 50 mg/kg of body weight) treatment led to an increased survival and improved outcomes of G. mellonella larvae coinfected with C. albicans and MRSA, since a significant reduction of fungal and bacterial burden in larval tissues was achieved with induction of granuloma formation. Our results reveal that CAS can be a therapeutic option for the treatment of mixed infections caused by C. albicans and S. aureus, supporting additional investigation. IMPORTANCE Infections by microorganisms resistant to antimicrobials is a major challenge that leads to high morbidity and mortality rates and increased time and cost with hospitalization. It was estimated that 27 to 56% of bloodstream infections by C. albicans are polymicrobial, with S. aureus being one of the microorganisms commonly coisolated worldwide. About 80% of infections are associated with biofilms by single or mixed species that can be formed on invasive medical devices, e.g., catheter, and are considered a dissemination source. The increased resistance to antimicrobials in bacterial and fungal cells when they are in biofilms is the most medically relevant behavior that frequently results in therapeutic failure. Although there are several studies evaluating treatments for polymicrobial infections associated or not with biofilms, there is still no consensus on an effective antimicrobial therapy to combat the coinfection by bacteria and fungi.
Assuntos
Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Caspofungina/farmacologia , Coinfecção/tratamento farmacológico , Larva/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Equinocandinas/farmacologia , Micafungina/farmacologia , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Mariposas , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacosRESUMO
Micafungin is characterized as one of the most active available drugs for candidemia treatment; however, their use is also associated in prophylaxis protocols in cases of invasive fungal infections. The use of this drug is widely appreciated in the medical field due to be the most active echinocandin available for invasive fungal infections. In order to provide important parameters related to the chemical, physical, biological and therapeutic characteristics, this review article gathers important research results that demonstrate the biological potential of this drug, as well as to present analytical methods that can be used to determine the antifungal potential and a monitoring of administered dosages. Important studies about the methods most commonly used in biological activity evaluation and determination/quantification by analytical methods are provided in this review article. With the data provided, the scientific community will have the possibility to choose the analytical methods and biological that can be employed in clinical and scientific research to provide greater safety and reliability of the results to be found.
Assuntos
Antifúngicos/análise , Antifúngicos/metabolismo , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Micafungina/análise , Micafungina/metabolismo , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Aspergillus fumigatus/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Farmacorresistência Fúngica , Equinocandinas/farmacologia , Eletroforese Capilar , Humanos , Micafungina/administração & dosagem , Micafungina/efeitos adversos , Solubilidade , Espectrometria de Massas em Tandem , Resultado do TratamentoRESUMO
OBJECTIVE: To determine micafungin plasma levels and pharmacokinetic behavior in patients treated with extracorporeal membrane oxygenation. METHODS: The samples were taken through an access point before and after the membrane in two tertiary hospitals in Spain. The times for the calculation of pharmacokinetic curves were before the administration of the drug and 1, 3, 5, 8, 18 and 24 hours after the beginning of the infusion on days one and four. The area under the curve, drug clearance, volume of distribution and plasma half-life time with a noncompartmental pharmacokinetic data analysis were calculated. RESULTS: The pharmacokinetics of the values analyzed on the first and fourth day of treatment did not show any concentration difference between the samples taken before the membrane (Cin) and those taken after the membrane (Cout), and the pharmacokinetic behavior was similar with different organ failures. The area under the curve (AUC) before the membrane on day 1 was 62.1 (95%CI 52.8 - 73.4) and the AUC after the membrane on this day was 63.4 (95%CI 52.4 - 76.7), p = 0.625. The AUC before the membrane on day 4 was 102.4 (95%CI 84.7 - 142.8) and the AUC was 100.9 (95%CI 78.2 - 138.8), p = 0.843. CONCLUSION: The pharmacokinetic parameters of micafungin were not significantly altered.
Assuntos
Antifúngicos/farmacocinética , Oxigenação por Membrana Extracorpórea , Micafungina/farmacocinética , Adulto , Idoso , Antifúngicos/administração & dosagem , Área Sob a Curva , Feminino , Meia-Vida , Humanos , Masculino , Micafungina/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Centros de Atenção Terciária , Distribuição TecidualRESUMO
RESUMO Objetivo: Determinar os níveis plasmáticos e o comportamento farmacocinético da micafungina em pacientes tratados com oxigenação por membrana extracorpórea. Métodos: As amostras foram colhidas por meio de pontos de acesso antes e depois da membrana, em dois hospitais espanhóis de nível terciário. Os momentos para o cálculo das curvas farmacocinéticas foram antes da administração do fármaco, e 1, 3, 5, 8, 18 e 24 horas após o início da infusão nos dias 1 e 4 de tratamento. Calcularam-se a área sob a curva, a depuração do fármaco, o volume de distribuição e a meia-vida plasmática por meio de análise farmacocinética não compartimental. Resultados: Os valores farmacocinéticos analisados no primeiro e quarto dias de tratamento não mostram qualquer diferença de concentração entre amostras colhidas antes da membrana e após a membrana, e o comportamento farmacocinético foi similar na vigência de diferentes falências de órgãos. A área sob a curva antes da membrana no dia 1 foi de 62,1 (IC95% 52,8 - 73,4) e a área sob a curva após a membrana nesse mesmo dia foi de 63,4 (IC95% 52,4 - 76,7), com p = 0,625. A área sob a curva antes da membrana no dia 4 foi de 102,4 (IC95% 84,7 - 142,8), enquanto a área sob a curva após a membrana nesse mesmo dia foi de 100,9 (IC95% 78,2 - 138,8), com p = 0,843. Conclusão: Os parâmetros farmacocinéticos da micafungina não foram alterados significantemente.
ABSTRACT Objective: To determine micafungin plasma levels and pharmacokinetic behavior in patients treated with extracorporeal membrane oxygenation. Methods: The samples were taken through an access point before and after the membrane in two tertiary hospitals in Spain. The times for the calculation of pharmacokinetic curves were before the administration of the drug and 1, 3, 5, 8, 18 and 24 hours after the beginning of the infusion on days one and four. The area under the curve, drug clearance, volume of distribution and plasma half-life time with a noncompartmental pharmacokinetic data analysis were calculated. Results: The pharmacokinetics of the values analyzed on the first and fourth day of treatment did not show any concentration difference between the samples taken before the membrane (Cin) and those taken after the membrane (Cout), and the pharmacokinetic behavior was similar with different organ failures. The area under the curve (AUC) before the membrane on day 1 was 62.1 (95%CI 52.8 - 73.4) and the AUC after the membrane on this day was 63.4 (95%CI 52.4 - 76.7), p = 0.625. The AUC before the membrane on day 4 was 102.4 (95%CI 84.7 - 142.8) and the AUC was 100.9 (95%CI 78.2 - 138.8), p = 0.843. Conclusion: The pharmacokinetic parameters of micafungin were not significantly altered.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Oxigenação por Membrana Extracorpórea , Micafungina/farmacocinética , Antifúngicos/farmacocinética , Distribuição Tecidual , Estudos Prospectivos , Área Sob a Curva , Centros de Atenção Terciária , Micafungina/administração & dosagem , Meia-Vida , Antifúngicos/administração & dosagemRESUMO
Candida rugosa (recently reclassified Diutina rugosa) is an emerging pathogen affecting humans and animals. Candida resistance to existing drugs is an important factor to be monitored, as well as the need of researching alternatives to conventional antifungals. Here, we evaluated the in vitro effects of some antifungals and major components of essential oils by the broth microdilution method (CLSI M27-A3) against fifteen C. rugosa strains from animals isolated and molecular identificated. The results showed MIC90 of: 0.125µg/mL to ketoconazole and voriconazole, 0.25µg/mL to micafungin, 0.5µg/mL to anidulafungin, 1µg/mL to caspofungin, 2µg/mL to amphotericin B, itraconazole and flucytosin, 8µg/mL to fluconazole, 16µg/mL to nystatin and >128µg/mL to terbinafine. The compounds carvacrol (MIC90 320µg/mL), thimol (MIC90 320µg/mL) and cinnamaldehyde (MIC90 160µg/mL) demonstrated antifungal activity against the samples tested.