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1.
Zhonghua Nei Ke Za Zhi ; 59(1): 5-17, 2020 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-31887830

RESUMO

In this consensus we mainly present the etiology, epidemiology, risk factors, microbiology, clinical diagnosis and general principles of treatment, as well as the detailed diagnosis and treatment of common candidiasis. Though mucocutaneous candidiasis such as oral, esophageal and vulvovaginal infections are known as non-invasive diseases, they are included in this consensus, considering their high prevalence and the potential to be the source of systematic infections.In order to be accordant with the practical situation in China, new technologies and drugs that have not been well developed or routinely applied are not recommended in this consensus. As to the differences from foreign guidelines, we address the explanations. Individualized treatment and management should be administrated based on the specific underlying conditions, organism distribution and drug resistance profile of Candida species.


Assuntos
Antifúngicos/uso terapêutico , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Adulto , Antifúngicos/administração & dosagem , Candida/efeitos dos fármacos , China , Consenso , Humanos , Prevalência , Fatores de Risco
2.
Pan Afr Med J ; 33: 280, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692736

RESUMO

Esophageal intramural pseudo-diverticulosis is a rare disease of unknown etiology. It is characterized by multiple pseudodiverticula with segmental or diffuse involvement of the esophagus. We report, the case of a 78-year-old male who suffered from severe dysphagia. Diagnosis of esophageal intramural pseudo-diverticulosis was based on endoscopic and radiologic explorations. Histological analysis of esophageal mucosal biopsies has shown the presence of candida albicans. Antifungal treatment leads to spectacular improvement of dysphasia. Subsequently, the patient presented a cardio-respiratory failure and died despite adequate treatment.


Assuntos
Candida albicans/isolamento & purificação , Candidíase/diagnóstico , Transtornos de Deglutição/diagnóstico , Diverticulose Esofágica/diagnóstico , Idoso , Antifúngicos/administração & dosagem , Candidíase/tratamento farmacológico , Transtornos de Deglutição/tratamento farmacológico , Humanos , Masculino
3.
Pan Afr Med J ; 33: 249, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31692764

RESUMO

Neuromeningeal cryptococcosis is a common and severe opportunistic fungal infection caused by the encapsulated yeast Cryptococcus neoformans. It commonly occurs in immunocompromised patients, in particular in subjects with advanced stage HIV while it is rare in immunocompetent patients. We report 40 cases of neuromeningeal cryptococcosis (NMC) diagnosed at the Mycology-Parasitology Department of the Ibn Sina hospital in Rabat, over a 21-year period (1993-2014). The diagnosis was based on nested-PCR-based assay for the detection of Cryptococcus neoformans after staining with China ink and culture on Sabouraud agar without actidione as well as on the identification of soluble cryptococcal antigens. Thirty-five patients had HIV infection, 2 patients were apparently immunocompetent and 3 were immunocompromised patients without HIV (30 men and 10 women). The average age of patients was 38 years; neuromeningeal cryptococcosis was indicative of HIV infection in 13 cases. In 22 cases it was a complication of AIDS. Twenty-seven patients of our series were treated with fluconazole monotherapy. Amphotericin B was used in 13 patients. Outcome was favorable in 13 patients (32.5%) while 3 patients had complications (7.5%). Eighteen patients died (45%) and 6 were lost to follow-up (15%). The tests to diagnose a Cryptococcus neoformans infection should be performed systematically in patients with neurological signs for early diagnosis.


Assuntos
Antifúngicos/administração & dosagem , Infecções por HIV/epidemiologia , Hospedeiro Imunocomprometido , Meningite Criptocócica/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adulto , Idoso , Anfotericina B/administração & dosagem , Cryptococcus neoformans/isolamento & purificação , Feminino , Fluconazol/administração & dosagem , Infecções por HIV/complicações , Humanos , Masculino , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico , Pessoa de Meia-Idade , Marrocos , Adulto Jovem
4.
Expert Opin Drug Metab Toxicol ; 15(11): 881-895, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31550939

RESUMO

Introduction: Therapeutic drug monitoring (TDM) has been shown to optimize the management of invasive fungal infections (IFIs), particularly for select antifungal agents with a well-defined exposure-response relationship and an unpredictable pharmacokinetic profile or a narrow therapeutic index. Select triazoles (itraconazole, voriconazole, and posaconazole) and flucytosine fulfill these criteria, while the echinocandins, fluconazole, isavuconazole, and amphotericin B generally do not do so. Given the morbidity and mortality associated with IFIs and the challenges surrounding the use of currently available antifungal agents, TDM plays an important role in therapy.Areas covered: This review seeks to describe the rationale for TDM of antifungal agents, summarize their pharmacokinetic and pharmacodynamic properties, identify treatment goals for efficacy and safety, and provide recommendations for optimal dosing and therapeutic monitoring strategies.Expert opinion: Several new antifungal agents are currently in development, including compounds from existing antifungal classes with enhanced pharmacokinetic or safety profiles as well as agents with novel targets for the treatment of IFIs. Given the predictable pharmacokinetics of these newly developed agents, use of routine TDM is not anticipated. However, expanded knowledge of exposure-response relationships of these compounds may yield a role for TDM to improve outcomes for adult and pediatric patients.


Assuntos
Antifúngicos/administração & dosagem , Monitoramento de Medicamentos/métodos , Infecções Fúngicas Invasivas/tratamento farmacológico , Adulto , Antifúngicos/farmacocinética , Antifúngicos/farmacologia , Criança , Desenvolvimento de Medicamentos , Humanos , Infecções Fúngicas Invasivas/microbiologia
5.
Medicina (B Aires) ; 79(4): 287-290, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31487250

RESUMO

Histoplasmosis and leishmaniasis are neglected and endemic diseases in Argentina, and generally are found associated with immunosuppression. We report the case of an immunocompetent 16-years-old man with simultaneous occurrence of central nervous system histoplasmosis and cutaneous leishmaniasis. Upon admission, the patient showed a one-month old skin lesion in a leg and mild paraparesis. Imaging studies detected thickening and edema in the spinal cord and the cerebrospinal fluid analysis was within normal range. The case was diagnosed as a demyelinating disorder and treated with high-dose short-term steroids. Seventy-two hours later the patient showed severe paraparesis and nuclear magnetic resonance imaging revealed nodular lesions in the spinal cord. Histoplasma capsulatum belonging to the phylogenetic species LamB was isolated from cerebrospinal fluid samples. The patient received intravenous antifungal therapy with amphotericin B for 30 days, followed by oral fluconazole and itraconazole for one year. Three months after initiation of antifungal treatment, the cutaneous lesion recrudesced and Leishmania amastigotes were observed on microscopic examination. The cutaneous leishmaniasis was treated with intramuscular meglumine antimoniate. The patient's outcome was favorable after treatment for both diseases.


Assuntos
Infecções Fúngicas do Sistema Nervoso Central/complicações , Histoplasmose/complicações , Leishmaniose Cutânea/complicações , Adolescente , Antibacterianos/administração & dosagem , Antifúngicos/administração & dosagem , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Humanos , Imunocompetência , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Masculino
6.
BMC Infect Dis ; 19(1): 707, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399065

RESUMO

BACKGROUND: Talaromyces marneffei is a thermally dimorphic fungus endemic in south-east Asia. It predominantly occurs in both immunocompromised and immunosuppressed patients and can be fatal if diagnosis and treatment are delayed. The clinical manifestations of T. marneffei infection are nonspecific and rapid diagnosis of T. marneffei infection remains challenging. CASE PRESENTATION: A 24-year-old man came to our outpatient department with the sign of common skin lesions. The lesions were cuticolor follicular papules with or without central umbilication, nodules and acne-like lesions, which are common in syringoma, steatocystoma multiplex and trichoepithelioma. A dermatoscopy examination was performed to differentiate these skin lesions. The dermatoscopic images revealed circular or quasi-circular whitish amorphous structure with a central brownish keratin plug, providing the diagnostic clues of T. marneffei infection. Therefore, a skin scrapings culture, skin biopsy and serological detection for human immunodeficiency virus (HIV) were performed. The final diagnosis of this patient was T. marneffei and HIV co-infection. CONCLUSION: Rapid diagnosis of T. marneffei infection is clinically challenging since presenting clinical manifestations are nonspecific with significant overlap with other common conditions. This case highlights that dermatoscopy is a promising tool for the rapid diagnosis of T. marneffei infection in patients with nonspecific skin lesions, assisting clinicians to avoid delayed diagnosis or misdiagnosis.


Assuntos
Dermoscopia/métodos , Micoses/diagnóstico , Talaromyces/patogenicidade , Anfotericina B/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , China , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Itraconazol/administração & dosagem , Itraconazol/uso terapêutico , Masculino , Micologia/métodos , Micoses/tratamento farmacológico , Adulto Jovem
7.
BMC Infect Dis ; 19(1): 710, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405376

RESUMO

BACKGROUND: Pulmonary Cryptococcosis (PC) is diagnosed with increasing incidence in recent years, but it does not commonly involve the pleural space. Here, we report a HIV-negative case with advanced stage IIIB non-small cell lung cancer (NSCLC) treated with radiation therapy presented with dyspnea, a new PET-positive lung mass and bilateral pleural effusion suspecting progressive cancer. However, the patient has been diagnosed as pulmonary cryptococcal infection and successfully treated with oral fluconazole therapy. CASE PRESENTATION: A 77-year-old male with advanced stage non-small cell lung cancer treated with combined chemo-radiation therapy who presented with progressive dyspnea, a new PET-positive left lower lobe lung mass and bilateral pleural effusions. Initial diagnostic thoracentesis and bronchoscopy yielded no cancer, but instead found yeast forms consistent with cryptococcal organisms in the transbronchial biopsies of the left lower lobe lung mass. Subsequent to this, the previously collected pleural fluid culture showed growth of Cryptococcus neoformans. The same sample of pleural effusion was tested and was found to be positive for crytococcal antigen (CrAg) by a lateral flow assay (LFA). The patient has been treated with oral fluconazole therapy resulting in gradual resolution of the nodular infiltrates. CONCLUSION: PC should be considered in immunosuppressed cancer patients. Additionally, concomitant pleural involvement in pulmonary cryptococcal infections may occur. The incidence of false positive 18FDG-PET scans in granulomatous infections and the use of CrAg testing in pleural fluid to aid in diagnosis are reviewed.


Assuntos
Criptococose/diagnóstico por imagem , Criptococose/microbiologia , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/microbiologia , Derrame Pleural/microbiologia , Administração Oral , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Criptococose/tratamento farmacológico , Cryptococcus neoformans/patogenicidade , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/tratamento farmacológico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/radioterapia , Masculino , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/etiologia , Tomografia por Emissão de Pósitrons
8.
BJOG ; 126(13): 1546-1552, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31446677

RESUMO

BACKGROUND: Oral fluconazole is used to treat vulvovaginal candidiasis during pregnancy. However, there are concerns regarding the pregnancy outcomes following exposure to fluconazole. OBJECTIVES: To evaluate the pregnancy outcomes associated with exposure to oral fluconazole during the first trimester of pregnancy. SEARCH STRATEGY: A systematic literature search was conducted to identify relevant studies published from inception until April 2019. SELECTION CRITERIA: Relevant English-language citations using the terms oral fluconazole and pregnancy in humans. DATA COLLECTION: Two reviewers independently abstracted data and assessed study quality. MAIN RESULTS: Oral fluconazole use during the first trimester of pregnancy was marginally associated with an increased risk of congenital malformations (odds ratio [OR] 1.09, 95% CI 0.99-1.2, P = 0.088; n = 6 studies), whereas in the subgroup analysis, this association existed only for high-dose users (>150 mg) (OR 1. 19, 95% CI 1.01-1.4, P = 0.039; n = 2). Exposure to fluconazole also increased the risk of heart malformations (OR 1.31, 95% CI 1.09-1.57, P = 0.003; n = 4), cardiac septal defects (OR 1.3, 95% CI 1.1-1.67, P = 0.047; n = 3), and tetralogy of Fallot (OR 3.39 95% CI 1.71-6.74, P < 0.001; n = 2) in the offspring. In addition, exposure to fluconazole was significantly associated with an increased risk of spontaneous abortion (OR 1.99, 95% CI 1.38-2.88, P < 0.001; n = 3). CONCLUSIONS: Oral fluconazole use during the first trimester of pregnancy appears to be associated with heart malformations and spontaneous abortion, but a causal link cannot be proven. TWEETABLE ABSTRACT: Oral fluconazole during the first trimester of pregnancy may be associated with unfavourable pregnancy outcomes.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Vulvovaginal/tratamento farmacológico , Anormalidades Craniofaciais/induzido quimicamente , Fluconazol/administração & dosagem , Anormalidades Induzidas por Medicamentos , Administração Oral , Antifúngicos/efeitos adversos , Feminino , Fluconazol/efeitos adversos , Humanos , Segurança do Paciente , Gravidez , Primeiro Trimestre da Gravidez
9.
AAPS PharmSciTech ; 20(7): 297, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444661

RESUMO

Miconazole nitrate (MZ) is a BCS class II antifungal poorly water-soluble drug with limited dissolution properties and gastrointestinal side effects. Self-nanoemulsifying delivery system-based gel of MZ can improve both solubility and oral mucosal absorption with enhanced antifungal activity. The study aims to formulate MZ self-nanoemulsion (MZ-NE) and combine it within hyaluronic acid-based gel. MZ solubility in various oils, surfactants, and cosurfactant used in NE formulations were evaluated. Mixture design was implemented to optimize the levels of NE components as a formulation variable to study their effects on the mean globule size and antifungal inhibition zones. Further, the optimized MZ-NE was loaded into a hyaluronic acid gel base. Rheological behavior of the prepared gel was assessed. Ex vivo permeability of optimized formulation across buccal mucous of sheep and inhibition against Candida albicans were examined. Mixture design was used to optimize the composition of MZ-NE formulation as 22, 67, and 10% for clove oil, Labrasol, and propylene glycol, respectively. The optimized formulation indicated globule size of 113 nm with 29 mm inhibition zone. Pseudoplastic flow with thixotropic behavior was observed, which is desirable for oral gels. The optimized formulation exhibited higher ex vivo skin permeability and enhanced antifungal activity by 1.85 and 2.179, respectively, compared to MZ-SNEDDS, and by 1.52 and 1.72 folds, respectively, compared to marketed gel. Optimized MZ-NE hyaluronic acid-based oral gel demonstrated better antifungal activity, indicating its potential in oral thrush pharmacotherapy.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Bucal/tratamento farmacológico , Química Farmacêutica/métodos , Ácido Hialurônico/administração & dosagem , Miconazol/administração & dosagem , Nanocápsulas/administração & dosagem , Administração Oral , Animais , Antifúngicos/síntese química , Antifúngicos/farmacocinética , Candidíase Bucal/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Emulsões/administração & dosagem , Emulsões/síntese química , Emulsões/farmacocinética , Ácido Hialurônico/síntese química , Ácido Hialurônico/farmacocinética , Hidrogéis/administração & dosagem , Hidrogéis/síntese química , Hidrogéis/farmacocinética , Miconazol/síntese química , Miconazol/farmacocinética , Nanocápsulas/química , Ovinos
10.
J Dermatol ; 46(10): 911-913, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342551

RESUMO

A 73-year-old healthy woman noticed black pigmentation on both thumbnails for 6 years. Upon her visit to our clinic, she had pigmented onychomycosis with onycholysis in the distal area. There was no evidence of paronychia. Direct microscopy using Zoomblue™ and histopathological examination showed aggregated blastoconidia. Fontana-Masson staining confirmed fungal melanin production. A combination of morphological features and genetic testing identified the isolates as Candida parapsilosis. Fungal melanonychia due to C. parapsilosis is rare, with only six cases reported since 1979. The minimum inhibitory concentration of the isolates was 0.25 µg/mL for itraconazole, less than 0.03 µg/mL for ravuconazole and 2.0 µg/mL for terbinafine. Both oral terbinafine treatment and itraconazole pulse therapy performed for 6 months were unsuccessful. The disease was ultimately cured with a 3-month treatment of oral fosravuconazole.


Assuntos
Candida parapsilosis/isolamento & purificação , Dermatoses da Mão/tratamento farmacológico , Melanose/tratamento farmacológico , Onicomicose/tratamento farmacológico , Tiazóis/administração & dosagem , Triazóis/administração & dosagem , Administração Oral , Idoso , Antifúngicos/administração & dosagem , Feminino , Dermatoses da Mão/diagnóstico , Dermatoses da Mão/microbiologia , Humanos , Melanose/diagnóstico , Melanose/microbiologia , Onicomicose/diagnóstico , Onicomicose/microbiologia , Pró-Fármacos/administração & dosagem , Resultado do Tratamento
11.
Emerg Microbes Infect ; 8(1): 895-908, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223062

RESUMO

The Prp8 intein is one of the most widespread eukaryotic inteins, present in important pathogenic fungi, including Cryptococcus and Aspergillus species. Because the processed Prp8 carries out essential and non-redundant cellular functions, a Prp8 intein inhibitor is a mechanistically novel antifungal agent. In this report, we demonstrated that cisplatin, an FDA-approved cancer drug, significantly arrested growth of Prp8 intein-containing fungi C. neoformans and C. gattii, but only poorly inhibited growth of intein-free Candida species. These results suggest that cisplatin arrests fungal growth through specific inhibition of the Prp8 intein. Cisplatin was also found to significantly inhibit growth of C. neoformans in a mouse model. Our results further showed that cisplatin inhibited Prp8 intein splicing in vitro in a dose-dependent manner by direct binding to the Prp8 intein. Crystal structures of the apo- and cisplatin-bound Prp8 inteins revealed that two degenerate cisplatin molecules bind at the intein active site. Mutation of the splicing-site residues led to loss of cisplatin binding, as well as impairment of intein splicing. Finally, we found that overexpression of the Prp8 intein in cryptococcal species conferred cisplatin resistance. Overall, these results indicate that the Prp8 intein is a novel antifungal target worth further investigation.


Assuntos
Antifúngicos/administração & dosagem , Cisplatino/administração & dosagem , Criptococose/microbiologia , Cryptococcus neoformans/efeitos dos fármacos , Proteínas Fúngicas/genética , Inteínas , Proteínas de Ligação a RNA/genética , Sequência de Aminoácidos , Animais , Antifúngicos/química , Cisplatino/química , Cryptococcus neoformans/genética , Cryptococcus neoformans/crescimento & desenvolvimento , Cryptococcus neoformans/metabolismo , Feminino , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Alinhamento de Sequência
12.
Ann Hematol ; 98(9): 2081-2088, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31240471

RESUMO

Few reports analyze the incidence and clinical outcome of invasive fungal disease (IFD) in patients with newly diagnosed acute myeloid leukemia (AML) undergoing intensive chemotherapy, and thus the impact of different antifungal prophylactic regimens remains unclear. We analyze the incidence and clinical outcome of IFD in a large series of adult AML patients undergoing front-line intensive induction and consolidation chemotherapy between 2004 and 2015 in a single institution. Three antifungal prophylaxis regimens were given (2004-2005 oral fluconazole, 2006-2012 intravenous itraconazole, and 2013-2015 voriconazole). Overall, 285 patients and 589 intensive chemotherapy episodes were assessed (47%) (induction courses 47% and consolidation 53%). The median age was 51 years (range, 17-65). We observed 56 (10%) episodes of IFD. According to the EORTC 2008 criteria, IFD was classified as possible (29, 52%), probable (17, 30%), and proven (10, 18%). Possible/probable/proven IFD rate was significantly lower during HiDAC consolidation as compared to any anthracycline-containing chemotherapy courses (2% vs. 11%, P = 0.001), and under voriconazole prophylaxis as compared to itraconazole and fluconazole (6% vs. 11% vs. 15%, P = 0.007), and the multivariate analysis showed that they were independent risk factors. Patients under voriconazole prophylaxis had shorter hospitalization duration and less frequent use of empirical or directed antifungal therapy. In conclusion, IFD was a frequent complication during upfront intensive chemotherapy courses for adult AML patients. This retrospective study shows that voriconazole prophylaxis was feasible and associated with a lower risk of IFD compared with intravenous itraconazole or oral fluconazole schedules.


Assuntos
Antifúngicos/administração & dosagem , Quimioterapia de Consolidação , Infecções Fúngicas Invasivas , Leucemia Mieloide Aguda , Adolescente , Adulto , Idoso , Feminino , Humanos , Incidência , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/prevenção & controle , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
13.
Rev Inst Med Trop Sao Paulo ; 61: e31, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31241660

RESUMO

Chromoblastomycosis is a chronic fungal infection. Itraconazole and terbinafine are the most recommended antifungal drugs for chromoblastomycosis, while amphotericin B is not usually recommended. A patient with chromoblastomycosis in our hospital showed poor clinical responses to itraconazole and terbinafine. The fungus isolated from the lesions of this patient was identified as Fonsecaea nubica and numbered zssy0803. In vitro antifungal susceptibilities of F. nubica zssy0803 to terbinafine, amphotericin B, itraconazole, voriconazole and caspofungin were evaluated, as well as the combinations of terbinafine with the other four antifungals. The combined effect of terbinafine and amphotericin B on other 20 clinical F. nubica strains was also evaluated. The minimal inhibitory concentrations of terbinafine, amphotericin B, itraconazole, voriconazole and caspofungin on F. nubica zssy0803 were 0.25 µg/mL, 2 µg/mL, 1 µg/mL, 4 µg/mL and 8 µg/mL, respectively. The combination of terbinafine and amphotericin B showed the lowest fractional inhibitory concentration index of 0.28 to F. nubica zssy0803 in comparison with combinations of terbinafine and the other four antifungal drugs. The combination of terbinafine and amphotericin B was also synergistic for all the other 20 F. nubica strains. Then, the combination of oral terbinafine (500 mg/day) and intralesional injections of amphotericin B (1 mg/mL) was used to treat this patient. After this combined therapy for 25 weeks and terbinafine monotherapy for additional 12 weeks, the patient was cured. These findings indicate for the first time that terbinafine and amphotericin B are synergistic in killing F. nubica both in vitro and in vivo.


Assuntos
Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Ascomicetos/efeitos dos fármacos , Cromoblastomicose/tratamento farmacológico , Terbinafina/administração & dosagem , Ascomicetos/isolamento & purificação , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade
14.
PLoS Negl Trop Dis ; 13(6): e0007441, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31163021

RESUMO

Paracoccidioidomycosis (PCM) is a neglected disease present in Latin America with difficulty in treatment and occurrence of serious sequelae. Thus, the development of alternative therapies is imperative. In the current work, two oxadiazole compounds (LMM5 and LMM11) presented fungicidal activity against Paracoccidioides spp. The minimum inhibitory and fungicidal concentration values ranged from 1 to 32 µg/mL, and a synergic effect was observed for both compounds when combined with Amphotericin B. LMM5 and LMM11 were able to reduce CFU counts (≥2 log10) on the 5th and 7th days of time-kill curve, respectively. The fungicide effect was confirmed by fluorescence microscopy (FUN-1/FUN-2). The hippocratic screening and biochemical analysis were performed in Balb/c male mice that received a high dose of each compound, and the compounds showed no in vivo toxicity. The treatment of experimental PCM with the new oxadiazoles led to significant reduction in CFU (≥1 log10). Histopathological analysis of the groups treated exhibited control of inflammation, as well as preserved lung areas. These findings suggest that LMM5 and LMM11 are promising hits structures, opening the door for implementing new PCM therapies.


Assuntos
Antifúngicos/farmacologia , Oxidiazóis/farmacologia , Paracoccidioides/efeitos dos fármacos , Anfotericina B/farmacologia , Animais , Antifúngicos/administração & dosagem , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Sinergismo Farmacológico , Histocitoquímica , Pulmão/microbiologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Oxidiazóis/administração & dosagem , Paracoccidioidomicose/tratamento farmacológico , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/patologia , Resultado do Tratamento
16.
AAPS PharmSciTech ; 20(5): 215, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31172376

RESUMO

There has been a great interest towards transungual delivery systems due to limited drug penetration for the treatment of nail diseases. More important, antifungal oral medicaments used may cause serious side effects including liver damage. Therefore, we propose non-oral dissolvable microneedle (MN) patch to strike the poor permeability of the nail. We report the design of MN patch mould using a laser-cutting machine and solvent casting of several hydrophilic polymers to fabricate these MN patches. Formulations were evaluated for their in vitro release and penetration properties and selected based on physical characterization for compatibility (differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD)), dimension repeatability and drug content uniformity. A 72-array of cone-shaped MN patch mould was successfully constructed on polymethylmethacrylate sheets. Interval and frequency of laser exposure were pivotal to determine the needle sharpness, attained unexpectedly at a low level of circa 30 µm. F1 platform of polyvinyl alcohol, kollicoat IR®, ethylene glycol and gelatin showed circa 74% penetration of methylhydroxy-4-benzoate (F1(A)) over 24 h, whereas F2 (same as F1-A with the addition of poloxamer 338) resulted in an almost 42% of this drug retention in the bovine hoof (24 h). Both formulations are likely to be useful for onychomycosis treatment. F1 polymers also afford enhanced permeability (almost 73.5% after 24 h) of terbinafine hydrochloride into the hoof (F1(B)). However, F3 (chitosan, gelatin and ethylene glycol) presents the prospect of developing MN patch for this drug with almost complete hoof penetration (circa 96.3% after 24 h). All medicated formulations have shown similar mechanical properties after ageing for 1 year under dry conditions.


Assuntos
Antifúngicos/uso terapêutico , Unhas/química , Agulhas , Onicomicose/tratamento farmacológico , Animais , Antifúngicos/administração & dosagem , Humanos , Permeabilidade , Solubilidade
17.
Yakugaku Zasshi ; 139(6): 917-922, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31155536

RESUMO

The use of a drug administration plan and therapeutic drug monitoring (TDM) based on pharmacokinetic-pharmacodynamic (PK-PD) analysis is important for the effective use of antimicrobial agents to treat infections. We focused on the use of beta-lactam agents, anti-methicillin-resistant Staphylococcus aureus (MRSA) agents, and an antifungal agent as antimicrobial agents and examined their efficacy in patients under special clinical conditions from the viewpoint of safety and TDM. Our PK-PD analysis of the use of an administration plan to set an optimum serum level for beta-lactam agents or anti-MRSA drugs for the treatment of pneumonia, acute renal failure during continuous hemodialysis filtration, febrile neutropenia, or malignant tumors confirmed the necessity of managing the optimal serum level. PK-PD analysis was also useful for TDM of voriconazole and intubation administration in long-term use from the viewpoint of preventing the onset of side effects. PK-PD analysis appears to be a useful tool in antibiotic therapy and TDM for developing a pharmacokinetic "individual difference" for "individualization therapy" under special clinical conditions. PK-PD analysis utilizes the restrictive information that is obtained by a clinic to the maximum and allows coordination with the mission of hospital pharmacists to provide adequate antibiotic therapy.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Monitoramento de Medicamentos , Medicina de Precisão , Antibacterianos/efeitos adversos , Antifúngicos/efeitos adversos , Neutropenia Febril , Humanos , Neoplasias , Diálise Renal
18.
J Dermatol ; 46(8): 641-651, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31206779

RESUMO

We evaluated the efficacy of efinaconazole 10% topical solution in long-term use, for up to 72 weeks, for onychomycosis, including severe cases. Among 605 participants, 219 patients diagnosed as having onychomycosis were evaluated for the efficacy of efinaconazole. The treatment success rate (<10% clinical involvement of the target toenail) at the final assessment time point was 56.6%, the complete cure rate was 31.1% and the mycological cure rate was 61.6%, all of which increased over time, demonstrating that continuous application contributed to the improvement of cure rate. Even in severe cases, reduction of the affected nail area was observed, showing the potential efficacy of the treatment. Responses to a quality of life questionnaire among patients with onychomycosis, OnyCOE-t, suggested that efinaconazole treatment improved the patients' quality of life. The incidence of adverse drug reaction in the patients eligible for the assessment was 6.3%, and this developed only in the administration site in all cases. No systemic adverse event was observed. In addition, no increase in the incidence of adverse drug reaction due to long-term use was found. Efinaconazole therapy was proved to exhibit excellent balance between efficacy and safety, and thus may serve as a useful treatment option for onychomycosis.


Assuntos
Antifúngicos/administração & dosagem , Dermatoses do Pé/tratamento farmacológico , Onicomicose/tratamento farmacológico , Triazóis/administração & dosagem , Administração Tópica , Idoso , Antifúngicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Dermatoses do Pé/diagnóstico , Humanos , Incidência , Assistência de Longa Duração/métodos , Masculino , Pessoa de Meia-Idade , Onicomicose/diagnóstico , Qualidade de Vida , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Triazóis/efeitos adversos
19.
BMC Infect Dis ; 19(1): 558, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242860

RESUMO

BACKGROUND: Amphotericin-induced phlebitis is a common infusion-related reaction in patients managed for cryptococcal meningitis. High-quality nursing care is critical component to successful cryptococcosis treatment. We highlight the magnitude and main approaches in the management of amphotericin-induced phlebitis and the challenges faced in resource-limited settings. METHODS: We prospectively determined the incidence of amphotericin-induced phlebitis during clinical trials in Kampala, Uganda from 2013 to 2018. We relate practical strategies and challenges faced in clinical management of phlebitis. RESULTS: Overall, 696 participants were diagnosed with HIV-related cryptococcal meningitis. Participants received 7-14 doses of intravenous (IV) amphotericin B deoxycholate 0.7-1.0 mg/kg/day for induction therapy through peripheral IV lines at a concentration of 0.1 mg/mL in 5% dextrose. Overall, 18% (125/696) developed amphotericin-induced phlebitis. We used four strategies to minimize/prevent the occurrence of phlebitis. First, after every dose of amphotericin, we gave one liter of intravenous normal saline. Second, we rotated IV catheters every three days. Third, we infused IV amphotericin over 4 h. Finally, early ambulation was encouraged to minimize phlebitis. To alleviate phlebitis symptoms, warm compresses were used. In severe cases, treatment included topical diclofenac gel and oral anti-inflammatory medicines. Antibiotics were used only when definite signs of infection developed. Patient/caregivers' education was vital in implementing these management strategies. Major challenges included implementing these interventions in participants with altered mental status and limited access to topical and oral anti-inflammatory medicines in resource-limited settings. CONCLUSIONS: Amphotericin-induced phlebitis is common with amphotericin, yet phlebitis is a preventable complication even in resource-limited settings. TRIAL REGISTRATION: The ASTRO-CM trial was registered prospectively. ClincalTrials.gov : NCT01802385 ; Registration date: March 1, 2013; Last verified: February 14, 2018.


Assuntos
Anfotericina B/efeitos adversos , Infecções por HIV/tratamento farmacológico , Meningite Criptocócica/tratamento farmacológico , Flebite/induzido quimicamente , Flebite/terapia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adulto , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Ácido Desoxicólico/administração & dosagem , Ácido Desoxicólico/efeitos adversos , Combinação de Medicamentos , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Recursos em Saúde/economia , Humanos , Incidência , Infusões Intravenosas , Masculino , Meningite Criptocócica/complicações , Meningite Criptocócica/epidemiologia , Flebite/epidemiologia , Áreas de Pobreza , Uganda/epidemiologia
20.
J Med Microbiol ; 68(7): 1047-1052, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31169488

RESUMO

INTRODUCTION: Miramistin is a topical antiseptic with broad antimicrobial activity that was developed in the Soviet Union during the Cold War. AIM: To investigate the antifungal activity of miramistin against clinically relevant drug-resistant fungi. METHODOLOGY: The in vitro activity of miramistin was determined following Clinical and Laboratory Standards Institute (CLSI) guidelines. Mammalian cell toxicity was tested using a McCoy cell line and topical and systemic tolerability, and in vivo efficacy was tested using Galleria mellonella models. RESULTS: The minimal inhibitory concentration (MIC) range against fungi was 1.56-25 mg l-1 (GM 3.13 mg l-1 ). In the G. mellonella model, miramistin provided potent survival benefits for Candida albicans and Aspergillus fumigatus infection. Miramistin was tolerated by McCoy cell lines at concentrations up to 1000 mg l-1 and was systemically safe in G. mellonella at 2000 mg kg-1. Topical administration at 32 000 mg l-1 was well tolerated with no adverse effects. CONCLUSION: These findings support further investigation of miramistin and suggest its possible use for treatment of superficial fungal infections.


Assuntos
Antifúngicos/farmacologia , Compostos de Benzalcônio/farmacologia , Fungos/efeitos dos fármacos , Animais , Antifúngicos/administração & dosagem , Antifúngicos/toxicidade , Compostos de Benzalcônio/administração & dosagem , Compostos de Benzalcônio/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Farmacorresistência Fúngica , Camundongos , Testes de Sensibilidade Microbiana , /efeitos dos fármacos
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