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2.
Chest ; 160(1): e39-e44, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34246387

RESUMO

CASE PRESENTATION: A 65-year-old man presented with shortness of breath, gradually worsening for the previous 2 weeks, associated with dry cough, sore throat, and diarrhea. He denied fever, chills, chest pain, abdominal pain, nausea, or vomiting. He did not have any sick contacts or travel history outside of Michigan. His medical history included hypertension, diabetes mellitus, chronic kidney disease, morbid obesity, paroxysmal atrial fibrillation, and tobacco use. He was taking amiodarone, carvedilol, furosemide, pregabalin, and insulin. The patient appeared to be in mild respiratory distress. He was afebrile and had saturation at 93% on 3 L of oxygen, heart rate of 105 beats/min, BP of 145/99 mm Hg, and respiratory rate of 18 breaths/min. On auscultation, there were crackles on bilateral lung bases and chronic bilateral leg swelling with hyperpigmented changes. His WBC count was 6.0 K/cumm (3.5 to 10.6 K/cumm) with absolute lymphocyte count 0.7 K/cumm (1.0 to 3.8 K/cumm); serum creatinine was 2.81 mg/dL (0.7 to 1.3 mg/dL). He had elevated inflammatory markers (serum ferritin, C-reactive protein, lactate dehydrogenase, D-dimer, and creatinine phosphokinase). Chest radiography showed bilateral pulmonary opacities that were suggestive of multifocal pneumonia (Fig 1). Nasopharyngeal swab for SARS-CoV-2 was positive. Therapy was started with ceftriaxone, doxycycline, hydroxychloroquine, and methylprednisolone 1 mg/kg IV for 3 days. By day 3 of hospitalization, he required endotracheal intubation, vasopressor support, and continuous renal replacement. Blood cultures were negative; respiratory cultures revealed only normal oral flora, so antibiotic therapy was discontinued. On day 10, WBC count increased to 28 K/cumm, and chest radiography showed persistent bilateral opacities with left lower lobe consolidation. Repeat respiratory cultures grew Pseudomonas aeruginosa (Table 1). Antibiotic therapy with IV meropenem was started. His condition steadily improved; eventually by day 20, he was off vasopressors and was extubated. However, on day 23, he experienced significant hemoptysis that required reintubation and vasopressor support.


Assuntos
Aspergillus niger/isolamento & purificação , COVID-19 , Hemoptise , Aspergilose Pulmonar Invasiva , Pseudomonas aeruginosa/isolamento & purificação , SARS-CoV-2/isolamento & purificação , Superinfecção , Voriconazol/administração & dosagem , Idoso , Antifúngicos/administração & dosagem , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/fisiopatologia , COVID-19/terapia , Deterioração Clínica , Estado Terminal/terapia , Procedimentos Clínicos , Diagnóstico Diferencial , Hemoptise/diagnóstico , Hemoptise/etiologia , Hemoptise/terapia , Humanos , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/fisiopatologia , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Radiografia Torácica/métodos , Respiração Artificial/métodos , Superinfecção/diagnóstico , Superinfecção/microbiologia , Superinfecção/fisiopatologia , Superinfecção/terapia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
3.
Toxins (Basel) ; 13(5)2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066154

RESUMO

Fusarium graminearum, causal agent of Fusarium head blight (FHB), causes a huge economic loss. No information is available on the activity of quinofumelin, a novel quinoline fungicide, against F. graminearum or other phytopathogens. In this study, we used mycelial growth and spore germination inhibition methods to determine the inhibitory effect of quinofumelin against F. graminearum in vitro. The results indicated that quinofumelin excellently inhibited mycelial growth and spore germination of F. graminearum, with the average EC50 values of 0.019 ± 0.007 µg/mL and 0.087 ± 0.024 µg/mL, respectively. In addition, we found that quinofumelin could significantly decrease deoxynivalenol (DON) production and inhibit the expression of DON-related gene TRI5 in F. graminearum. Furthermore, we found that quinofumelin could disrupt the formation of Fusarium toxisome, a structure for producing DON. Western blot analysis demonstrated that the translation level of TRI1, a marker gene for Fusarium toxisome, was suppressed by quinofumelin. The protective and curative assays indicated that quinofumelin had an excellent control efficiency against F. graminearum on wheat coleoptiles. Taken together, quinofumelin exhibits not only an excellent antifungal activity on mycelial growth and spore germination, but also could inhibit DON biosynthesis in F. graminearum. The findings provide a novel candidate for controlling FHB caused by F. graminearum.


Assuntos
Antifúngicos/farmacologia , Fusarium/efeitos dos fármacos , Tricotecenos/metabolismo , Antifúngicos/administração & dosagem , Relação Dose-Resposta a Droga , Fusarium/genética , Genes Fúngicos/efeitos dos fármacos , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Esporos Fúngicos/efeitos dos fármacos
4.
Mycoses ; 64(8): 817-822, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34091966

RESUMO

OBJECTIVES: To investigate the occurrence of Trichosporon asahii fungemia among critically ill COVID-19 patients. METHODS: From 1 July to 30 September 2020, cases of T asahii fungemia (TAF) in a Brazilian COVID-19 referral centre were investigated. The epidemiology and clinical courses were detailed, along with a mycological investigation that included molecular species identification, haplotype diversity analysis and antifungal susceptibility testing. RESULTS: Five critically ill COVID-19 patients developed TAF in the period. All five patients had common risk conditions for TAF: central venous catheter at fungemia, previous exposure to broad-spectrum antibiotics, prior echinocandin therapy and previous prolonged corticosteroid therapy. The average time of intensive care unit hospitalisation previous to the TAF episode was 23 days. All but one patient had voriconazole therapy, and TAF 30-day mortality was 80%. The five T asahii strains from the COVID-19 patients belonged to 4 different haplotypes, mitigating the possibility of skin origin and cross-transmission linking the 5 reported episodes. The antifungal susceptibility testing revealed low minimal inhibitory concentrations for azole derivatives. CONCLUSIONS: Judicious prescription of antibiotics, corticosteroids and antifungals needs to be discussed in critically ill COVID-19 patients to prevent infections by hard-to-treat fungi like T asahii.


Assuntos
Corticosteroides/administração & dosagem , Antifúngicos/administração & dosagem , Basidiomycota/isolamento & purificação , COVID-19/complicações , Superinfecção/complicações , Tricosporonose/complicações , Corticosteroides/farmacologia , Idoso , Antifúngicos/farmacologia , Basidiomycota/classificação , Basidiomycota/efeitos dos fármacos , Basidiomycota/genética , Brasil/epidemiologia , COVID-19/epidemiologia , Candidemia/complicações , Feminino , Fungemia/complicações , Haplótipos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Filogenia , Fatores de Risco , Superinfecção/epidemiologia , Tricosporonose/epidemiologia
5.
Transplant Proc ; 53(5): 1583-1588, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33962777

RESUMO

Tacrolimus, an immunosuppressant prescribed to reduce the risk of organ rejection, is metabolized by cytochrome P450 and is a substrate for P-glycoprotein. Many medications affect tacrolimus concentrations, making it difficult to maintain exposure within its narrow therapeutic index. Clotrimazole troches, prescribed to posttransplant recipients immediately for the first 30 days for oral candidiasis prevention, are considered nonsystemic. However, data suggest a potential drug interaction, affecting tacrolimus exposure. To assess the magnitude of the effect of clotrimazole on tacrolimus trough levels, 97 kidney transplant recipients, on a stable dose of tacrolimus, were retrospectively evaluated. Tacrolimus trough concentrations were analyzed 7 and 14 days before and after discontinuation of clotrimazole. The median change in tacrolimus trough level was -1.3 ng/mL (confidence interval, -2.5, -1.0; P < .001) at day 7 and -2.8 ng/mL (confidence interval, -3.3, -1.6; P < .001) at day 14 after clotrimazole discontinuation, from a median baseline of 8.9 ng/mL. Overall, a reduction in tacrolimus level was observed in 60% of patients after discontinuation of clotrimazole. When assessing the effect of race and sex, no influence was found on the degree of change in tacrolimus level after clotrimazole discontinuation. In conclusion, clotrimazole exerts a significant interaction on tacrolimus where close monitoring of tacrolimus trough levels after discontinuation of clotrimazole is warranted.


Assuntos
Antifúngicos/administração & dosagem , Clotrimazol/administração & dosagem , Imunossupressores/sangue , Transplante de Rim/efeitos adversos , Tacrolimo/sangue , Adulto , Idoso , Interações Medicamentosas , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Micoses/prevenção & controle , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Adulto Jovem
6.
Cochrane Database Syst Rev ; 5: CD009289, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34033120

RESUMO

BACKGROUND: Otomycosis is a fungal infection of the outer ear, which may be treated with topical antifungal medications. There are many types, with compounds belonging to the azole group ('azoles') being among the most widely used. OBJECTIVES: To evaluate the benefits and harms of topical azole treatments for otomycosis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The search date was 11 November 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults and children with otomycosis comparing any topical azole antifungal with: placebo, no treatment, another type of topical azole or the same type of azole but applied in different forms. A minimum follow-up of two weeks was required. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) clinical resolution as measured by the proportion of participants with complete resolution at between two and four weeks after treatment (however defined by the authors of the studies) and 2) significant adverse events. Secondary outcomes were 3) mycological resolution and 4) other less serious adverse effects. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included four studies with 559 participants from Spain, Mexico and India. Three studies included children and adults; one included only adults. The duration of symptoms was not always explicitly stated. Mycological resolution results were only reported in one study. The studies assessed two comparisons: one type of topical azole versus another and the same azole but administered in different forms (cream versus solution). A. Topical azoles versus placebo None of the studies assessed this comparison. B. Topical azoles versus no treatment None of the studies assessed this comparison. C. One type of topical azole versus another type of topical azole i) Clotrimazole versus other types of azoles (eberconazole, fluconazole, miconazole) Three studies examined clotrimazole versus other types of azoles. The evidence is very uncertain about the difference between clotrimazole and other types of azole in achieving complete clinical resolution at four weeks (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.07; 3 studies; 439 participants; very low-certainty evidence). The anticipated absolute effects are 668 per 1000 for clotrimazole versus 835 per 1000 for other azoles. One study planned a safety analysis and reported no significant adverse events in either group. The evidence is therefore very uncertain about any differences between clotrimazole and other types of azole (no events in either group; 1 study; 174 participants; very low-certainty evidence). Clotrimazole may result in little or no difference in mycological resolution at two weeks follow-up (RR 1.01, 95% CI 0.96 to 1.06; 1 study; 174 participants; low-certainty evidence) or in other (less serious) adverse events at two weeks follow-up (36 per 1000, compared to 45 per 1000, RR 0.79, 95% CI 0.18 to 3.41; 1 study; 174 participants; very low-certainty evidence). ii) Bifonazole cream versus bifonazole solution One study compared bifonazole 1% cream with solution. Bifonazole cream may have little or no effect on clinical resolution at two weeks follow-up when compared to solution, but the evidence is very uncertain (RR 1.07, 95% CI 0.73 to 1.57; 1 study; 40 ears; very low-certainty evidence). Bifonazole cream may achieve less mycological resolution compared to solution at two weeks after the end of therapy, but the evidence for this is also very uncertain (RR 0.53, 95% CI 0.29 to 0.96; 1 study; 40 ears; very low-certainty evidence). Five out of 35 patients sustained severe itching and burning from the bifonazole solution but none with the bifonazole cream (very low-certainty evidence). AUTHORS' CONCLUSIONS: We found no studies that evaluated topical azoles compared to placebo or no treatment. The evidence is very uncertain about the effect of clotrimazole on clinical resolution of otomycosis, on significant adverse events or other (non-serious) adverse events when compared with other topical azoles (eberconazole, fluconazole, miconazole). There may be little or no difference between clotrimazole and other azoles in terms of mycological resolution. It may be difficult to generalise these results because the range of ethnic backgrounds of the participants in the studies is limited.


Assuntos
Antifúngicos/administração & dosagem , Otomicose/tratamento farmacológico , Administração Tópica , Adulto , Antifúngicos/efeitos adversos , Viés , Criança , Clotrimazol/administração & dosagem , Clotrimazol/efeitos adversos , Cicloeptanos/administração & dosagem , Cicloeptanos/efeitos adversos , Fluconazol/administração & dosagem , Fluconazol/efeitos adversos , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Miconazol/administração & dosagem , Miconazol/efeitos adversos , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
7.
Pan Afr Med J ; 38: 178, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995784

RESUMO

Candidiasis is an acute or subacute fungal infection caused by fungi that belongs to candida genus, with Candida albicansbeing the most frequent causative agent. Candida kefyr is a rare cause of candidiasis which has been reported in systemic candidiasis and deep infections. However, to date, it has never been reported as a cause in dermatophytosis. We report a case of candidiasis caused by Candida kefyr in a 72-year-old woman with a chief complaint of pruritic erythematous rash on the back from one day prior to admission. Diagnosis was established based on clinical features, direct microscopic examination with 10% potassium hydroxide solution, gram staining. The fungal species was determined by carbohydrate fermentation test which showed a positive result for Candida kefyr. The patient was treated with miconazole cream and fusidic cream and showed significant clinical improvement.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Cutânea/diagnóstico , Kluyveromyces/isolamento & purificação , Idoso , Candidíase Cutânea/tratamento farmacológico , Candidíase Cutânea/microbiologia , Eritema/microbiologia , Feminino , Ácido Fusídico/administração & dosagem , Humanos , Miconazol/administração & dosagem , Prurido/microbiologia , Resultado do Tratamento
8.
Dtsch Med Wochenschr ; 146(9): 603-607, 2021 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-33931838

RESUMO

HISTORY AND CLINICAL FINDINGS: A 68-year-old male patient with psorias and a bullous pemphigoid as an underlying disease developed bilateral groundglass opacities on chest CT under longer-term, higher-dose immunosuppressive therapy with methylprednisolone with clinical symptoms of dry cough, progressive dyspnea and fever. DIAGNOSIS AND THERAPY: After the exclusion of COVID-19, Pneumocystis jirovecii pneumonia (PCP) was detected and a corresponding high-dose therapy with trimethoprim-sulfamethoxazole was initiated promptly. COURSE: Nonetheless, a complicated course with bacterial superinfection and pulmonary aspergillosis as well as ARDS developed. DISCUSSION AND CONCLUSION: In contrast to COVID-19, the typical course, diagnosis and therapy of Pneumocystitis jirovecii pneumonia are discussed. It is particularly emphasized that not all ground glass infiltrates in the CT chest image can be traced back to a COVID-19, even in a pandemic situation. Possible differential diagnoses should always be considered and taken into account in the diagnosis.


Assuntos
Pneumocystis carinii , Pneumonia por Pneumocystis , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , COVID-19 , Diagnóstico Diferencial , Humanos , Masculino , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/patologia , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
9.
J Wound Care ; 30(Sup4): S24-S27, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33856927

RESUMO

OBJECTIVE: The primary goals of managing incontinence-associated dermatitis (IAD) are to control the incontinence and to stop the progress of dermatitis. This study evaluated the effectiveness of using a combination of topical antibiotic and topical antifungal medication to manage IAD. METHOD: Patients with grade 2 IAD treated with a combination of topical antibiotic Biomycin (CBC Biotechnological and Pharmaceutical, Taiwan) and antifungal clotrimazole (Sinphar Group, Taiwan) between January 2017 and January 2019 were included in this retrospective study. Data collected included patients' age, sex, diagnosis, body mass index, comorbidities and surface area involved. Patients were reviewed fortnightly until the wounds had healed, the patient was discharged or had died. RESULTS: A total of 76 patients were included. There were 39 men and 37 women with a mean age of 74 years. In 58 (76%) patients, the surface area involved was >50cm2, in 13 (17%) patients the involved area was 20-50cm2 and in five (7%) patients the area involved was <20cm2. The mean number of days treated was 10.3 (range: 1-53). A total of 46 (61%) patients showed total healing of their IAD, 17 (22%) patients showed improvement of >50% of the involved area, seven (9%) patients showed improvement of 0-50%, five (7%) patients showed no improvement and one (1%) patient showed an increase in the area involved. CONCLUSION: This combination of treatment was effective in the management of IAD. It was cheap, easy to apply, easy to remove and easily accessible. It could be used efficiently by the hospital staff and the patient's family.


Assuntos
Antifúngicos/uso terapêutico , Dermatite/tratamento farmacológico , Incontinência Fecal/complicações , Idoso , Antibacterianos/uso terapêutico , Antifúngicos/administração & dosagem , Dermatite/etiologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Higiene da Pele
10.
Clin Drug Investig ; 41(6): 539-548, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33891293

RESUMO

BACKGROUND: Solid tumors are a common predisposing factor for invasive candidiasis (IC) or candidemia due to IC. OBJECTIVES: Post hoc analysis of patient-level efficacy and safety data from six studies of anidulafungin (with similar protocols/endpoints) in adults with IC/candidemia summarized by past or recent diagnosis of solid tumors. PATIENTS/METHODS: Patients received a single intravenous (IV) dose of anidulafungin 200 mg, followed by 100 mg once daily. After ≥ 5 to ≥ 10 days of IV treatment, switch to oral voriconazole/fluconazole was permitted in all but one study. Time of solid tumor diagnosis was defined as past, ≥ 6; and recent, < 6 months prior to study entry. Primary endpoint: global response of success (GRS) rate at the end of IV therapy (EOIVT). Secondary endpoints included the GRS rate at the end of all therapy (EOT), all-cause mortality, and safety. RESULTS: The GRS rate in the overall population was 73.4% at EOIVT and 65.5% at EOT. Past or recent solid tumor diagnosis did not affect GRS at EOIVT or EOT (past: 75.5% and 71.4%; recent: 72.2% and 62.2%, respectively). All-cause mortality was 14.4% on day 14 and 20.1% at day 28. Most treatment-emergent adverse events were mild/moderate in severity (81.6%). CONCLUSIONS: Treatment of IC was effective regardless of the time of solid tumor diagnosis. TRIAL REGISTRATION: Data were pooled from six studies: NCT00496197 (first posted on ClinicalTrials.gov on July 4, 2007); NCT00548262 (first posted on ClinicalTrials.gov on October 23, 2007); NCT00537329 (first posted on ClinicalTrials.gov on October 1, 2007); NCT00689338 (first posted on ClinicalTrials.gov on June 3, 2008); NCT00806351 (first posted on ClinicalTrials.gov on December 10, 2008); NCT00805740 (first posted on ClinicalTrials.gov on December 10, 2008).


Assuntos
Anidulafungina/uso terapêutico , Candidíase Invasiva/tratamento farmacológico , Neoplasias/complicações , Administração Intravenosa , Antifúngicos/administração & dosagem , Candidemia/induzido quimicamente , Fluconazol/administração & dosagem , Humanos , Resultado do Tratamento , Voriconazol/uso terapêutico
11.
Int J Infect Dis ; 107: 59-61, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33872781

RESUMO

We report this rare case of cerebral phaeohyphomycosis in a previously healthy Chinese boy, who was found to have caspase recruitment domain family member 9 (CARD9) deficiency. Initial radiological features suggested a neoplastic cerebral lesion, while histopathological examination supplemented by internal transcribed sequencing (ITS) of cerebral tissue confirmed the diagnosis of phaeohyphomycosis. He was treated with intravenous (IV) liposomal amphotericin B and voriconazole, guided by plasma and cerebrospinal fluid (CSF) level monitoring at drug initiation. At the 1 year follow-up, the patient demonstrated near complete neurological and radiological recovery.


Assuntos
Candidíase Mucocutânea Crônica/diagnóstico , Feoifomicose Cerebral/diagnóstico , Administração Intravenosa , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Proteínas Adaptadoras de Sinalização CARD/genética , Candidíase Mucocutânea Crônica/tratamento farmacológico , Feoifomicose Cerebral/tratamento farmacológico , Feoifomicose Cerebral/microbiologia , Feoifomicose Cerebral/cirurgia , Criança , China , Humanos , Masculino , Mutação de Sentido Incorreto , Radiografia/métodos , Resultado do Tratamento , Voriconazol/administração & dosagem
12.
J Laryngol Otol ; 135(5): 442-447, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33827722

RESUMO

OBJECTIVE: To study the possible association between invasive fungal sinusitis (mucormycosis) and coronavirus disease. METHODS: A prospective observational study was conducted at a tertiary care centre over four months, involving all patients with mucormycosis of the paranasal sinuses suffering from or having a history of coronavirus disease infection. RESULTS: Twenty-three patients presented with mucormycosis, all had an association with coronavirus disease 2019. The ethmoids (100 per cent) were the most common sinuses affected. Intra-orbital extension was seen in 43.47 per cent of cases, while intracranial extension was only seen in 8.69 per cent. Diabetes mellitus was present in 21 of 23 cases, and was uncontrolled in 12 cases. All patients had a history of steroid use during their coronavirus treatment. CONCLUSION: New manifestations of coronavirus disease 2019 are appearing over time. The association between coronavirus and mucormycosis of the paranasal sinuses must be given serious consideration. Uncontrolled diabetes and over-zealous use of steroids are two main factors aggravating the illness, and both of these must be properly checked.


Assuntos
COVID-19/microbiologia , Mucorales/isolamento & purificação , Mucormicose/microbiologia , Seios Paranasais/microbiologia , Administração Intravenosa , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/virologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/microbiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mucorales/efeitos dos fármacos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/etiologia , Pandemias , Seios Paranasais/diagnóstico por imagem , Estudos Prospectivos , SARS-CoV-2 , Sinusite/diagnóstico , Sinusite/microbiologia , Esteroides/efeitos adversos , Esteroides/uso terapêutico
13.
J Zoo Wildl Med ; 52(1): 300-305, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827189

RESUMO

Batrachochytrium dendrobatidis (Bd) is an important fungal pathogen present in wild hellbender (Cryptobranchus alleganiensis) populations that appears to cause disease during novel exposure and acute stress. Hellbender repatriation efforts are ongoing to combat declining populations, but mortality by chytridiomycosis (disease from Bd) after release has been reported. The goal was to determine whether a safe antifungal agent could be administered and provide prolonged plasma concentrations without repeated handling. A subcutaneous implant impregnated with 24.5 mg of terbinafine was tested in three juvenile eastern hellbenders (C. a. alleganiensis) raised in human care, and plasma terbinafine concentrations were recorded from weekly to biweekly for 141 days. Plasma concentrations were variable, with peak plasma concentrations of 1,610, 112, and 66 ng/ml between 28 and 56 days postimplant. Although all hellbenders achieved plasma concentrations above the published minimum inhibitory concentration for terbinafine against Bd zoospores (63 ng/ml) at several time points, only one individual remained above this threshold for more than two consecutive time intervals. Results show the potential for these implants as a prophylaxis for chytridiomycosis in captive-to-wild hellbender releases. However, further investigation will be needed to determine the plasma concentrations required to achieve prophylaxis in vivo and implant reliability.


Assuntos
Antifúngicos/uso terapêutico , Batrachochytrium , Micoses/veterinária , Terbinafina/uso terapêutico , Urodelos , Animais , Antifúngicos/administração & dosagem , Antifúngicos/sangue , Implantes de Medicamento , Micoses/prevenção & controle , Absorção Subcutânea , Terbinafina/administração & dosagem , Terbinafina/sangue
14.
BMC Infect Dis ; 21(1): 375, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882845

RESUMO

BACKGROUND: Cryptococcal meningitis (CM) is a common HIV-associated opportunistic-infection worldwide. Existing literature focusses on hospital-based outcomes of induction treatment. This paper reviews outpatient management in integrated primary care clinics in Yangon. METHOD: This retrospective case note review analyses a Myanmar HIV-positive patient cohort managed using ambulatory induction-phase treatment with intravenous amphotericin-B-deoxycholate (0.7-1.0 mg/kg) and oral fluconazole (800 mg orally/day). RESULTS: Seventy-six patients were diagnosed between 2010 and 2017. The median age of patients diagnosed was 35 years, 63% were male and 33 (45%) were on concurrent treatment for tuberculosis. The median CD4 count was 60 at the time of diagnosis. Amphotericin-B-deoxycholate infusions precipitated 56 episodes of toxicity, namely hypokalaemia, nephrotoxicity, anaemia, febrile reactions, phlebitis, observed in 44 patients (58%). One-year survival (86%) was higher than existing hospital-based treatment studies. CONCLUSION: Ambulation of patients in this cohort saved 1029 hospital bed days and had better survival outcomes when compared to hospital-based studies in other resource constrained settings.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Cryptococcus neoformans/imunologia , Ácido Desoxicólico/administração & dosagem , Fluconazol/administração & dosagem , HIV , Meningite Criptocócica/complicações , Meningite Criptocócica/tratamento farmacológico , Atenção Primária à Saúde , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Administração Intravenosa , Administração Oral , Adolescente , Adulto , Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Cryptococcus neoformans/isolamento & purificação , Ácido Desoxicólico/efeitos adversos , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Fluconazol/efeitos adversos , Humanos , Masculino , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/microbiologia , Pessoa de Meia-Idade , Mianmar/epidemiologia , Flebite/induzido quimicamente , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Molecules ; 26(6)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809569

RESUMO

The incorporation of permeation enhancers in topical preparations has been recognized as a simple and valuable approach to improve the penetration of antifungal agents into toenails. In this study, to improve the toenail delivery of efinaconazole (EFN), a triazole derivative for onychomycosis treatment, topical solutions containing different penetration enhancers were designed, and the permeation profiles were evaluated using bovine hoof models. In an in vitro permeation study in a Franz diffusion cell, hydroalcoholic solutions (HSs) containing lipophilic enhancers, particularly prepared with propylene glycol dicaprylocaprate (Labrafac PG), had 41% higher penetration than the HS base. Moreover, the combination of hydroxypropyl-ß-cyclodextrin with Labrafac PG further facilitated the penetration of EFN across the hoof membrane. In addition, this novel topical solution prepared with both lipophilic and hydrophilic enhancers was physicochemically stable, with no drug degradation under ambient conditions (25 °C, for 10 months). Therefore, this HS system can be a promising tool for enhancing the toenail permeability and therapeutic efficacy of EFN.


Assuntos
Portadores de Fármacos/química , Casco e Garras/efeitos dos fármacos , Casco e Garras/metabolismo , Permeabilidade/efeitos dos fármacos , Triazóis/administração & dosagem , Triazóis/química , Administração Tópica , Animais , Antifúngicos/administração & dosagem , Antifúngicos/química , Bovinos , Difusão , Sistemas de Liberação de Medicamentos/métodos , Onicomicose/tratamento farmacológico , Propilenoglicol/química
16.
AAPS PharmSciTech ; 22(2): 74, 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33586022

RESUMO

The current study aimed to load terconazole (TCZ), an antifungal agent with low permeability characteristics, into highly deformable bilosomes (HBs) for augmenting its topical delivery. HBs contain edge activator in addition to the constituents of traditional bilosomes (Span 60, cholesterol, and bile salts). More elasticity is provided to the membrane of vesicles by the existence of edge activator and is expected to increase the topical permeation of TCZ. HBs were formulated using ethanol injection technique based on 24 complete factorial design to inspect the impact of various formulation variables (bile salt type and amount, edge activator type, and sonication time) on HBs characteristics (entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP)). The optimum formula (HB14) was decided based on Design-Expert® software and was utilized for further explorations. HB14 exhibited EE% = 84.25 ± 0.49%, PS = 400.10 ± 1.69 nm, PDI = 0.23 ± 0.01, and ZP = - 56.20 ± 0.00 mV. HB14 showed spherical vesicles with higher deformability index (9.94 ± 1.91 g) compared to traditional bilosomal formula (3.49 ± 0.49 g). Furthermore, HB14 showed superior inhibition of Candida albicans growth relative to TCZ suspension using XTT (2,3-bis(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reduction assay. Moreover, in vivo skin deposition studies revealed superior TCZ deposition inside the skin from HB14 compared to traditional bilosomal formula and TCZ suspension. Moreover, histopathological examination in rats assured the safety of HB14 for topical use. Concisely, the obtained outcomes confirmed the pronounced efficacy of HBs for topical delivery of TCZ.


Assuntos
Antifúngicos/administração & dosagem , Lipossomos/administração & dosagem , Pele/metabolismo , Triazóis/administração & dosagem , Administração Tópica , Animais , Masculino , Ratos , Ratos Wistar , Suspensões , Triazóis/farmacocinética
17.
Lancet ; 397(10273): 499-509, 2021 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549194

RESUMO

BACKGROUND: Voriconazole has been recommended as primary treatment for patients with invasive aspergillosis. Intravenous and tablet formulations of posaconazole that have improved systemic absorption could be an effective alternative to voriconazole. We aimed to assess non-inferiority of posaconazole to voriconazole for the primary treatment of invasive aspergillosis. METHODS: We did a randomised, prospective, double-blind, double-dummy, controlled trial comparing posaconazole (intravenous or oral posaconazole 300 mg twice on day 1, followed by 300 mg once a day for days 2-84) with voriconazole (6 mg/kg intravenous or 300 mg oral twice on day 1 followed by 4 mg/kg intravenously or 200 mg orally twice a day for days 2-84) for 12 weeks or less in the primary treatment of invasive aspergillosis. Participants were from 91 study sites in 26 countries, were aged 13 years or older, weighed at least 40 kg, and met criteria for proven, probable, or possible fungal disease. Participants were randomly assigned (1:1) via a computer-generated randomisation schedule with stratification by risk status. The primary endpoint was cumulative all-cause mortality up until day 42 in the intention-to-treat (ITT) population (defined as randomly assigned participants who received ≥1 dose of study drug), with a 10% non-inferiority margin. The ITT population was also evaluated for safety. This study is registered with ClinicalTrials.gov, NCT01782131, and EudraCT, 2011-003938-14. FINDINGS: Between Oct 25, 2013, and Sept 10, 2019, of 653 individuals assessed for eligibility, 575 ITT participants were randomly assigned and received one or more doses of study drug (n=288 [50%] posaconazole, n=287 [50%] voriconazole). Mortality up until day 42 was 15% (44 of 288) in the posaconazole group and 21% (59 of 287) in the voriconazole group (treatment difference -5·3% [95% CI -11·6 to 1·0]; p<0·0001). Mortality up until day 42 in the full-analysis-set subpopulation (ITT participants with proven or probable invasive aspergillosis) supported this conclusion: 31 (19%) of 163 participants in the posaconazole group and 32 (19%) of 171 participants in the voriconazole group (treatment difference 0·3% [95% CI -8·2 to 8·8]). The most frequently reported treatment-related adverse events (incidence >3%) were increased aspartate aminotransferase (AST) or alanine aminotransferase (ALT), nausea, hypokalaemia, and vomiting in the posaconazole group and increased ALT, AST, or alkaline phosphatase, hallucination, increased γ-glutamyltransferase peptidase, nausea, and blurred vision in the voriconazole group. The overall incidence of treatment-related adverse event rates in the ITT population was 30% for posaconazole and 40% for voriconazole (treatment difference -10·2% [95% CI -17·9 to -2·4]). INTERPRETATION: Posaconazole was non-inferior to voriconazole for all-cause mortality up until day 42 in participants with invasive aspergillosis. Posaconazole was well tolerated, and participants had fewer treatment-related adverse events than in the voriconazole group. This study supports the use of posaconazole as a first-line treatment for the condition. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc.


Assuntos
Antifúngicos/administração & dosagem , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Triazóis/administração & dosagem , Voriconazol/administração & dosagem , Administração Intravenosa , Administração Oral , Adolescente , Adulto , Antifúngicos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Aspergilose Pulmonar Invasiva/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Triazóis/efeitos adversos , Voriconazol/efeitos adversos , Adulto Jovem
18.
Medicine (Baltimore) ; 100(6): e24630, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578579

RESUMO

RATIONALE: Mucormycosis is a rare fungal infection that typically occurs in immunosuppressed patients following chemotherapy or hematopoietic stem cell transplantation. PATIENT CONCERNS: An 11-year-old child with newly developed acute lymphoblastic leukemia suffered from the paroxysmal left chest pain, fever, and hemoptysis. DIAGNOSES: We made a histopathologic diagnosis aided by bronchoscopy techniques, which indicated invasive fungal hyphae that are characteristic of mucormycosis. INTERVENTIONS: The patient was treated with oral posaconazole and repeated bronchoscopy interventions for 4 months. OUTCOMES: The patient's clinical signs and symptoms and signs were no longer present. The prior lung lesions were also no longer observable using radiologic methods, and a 3-month follow-up with the patient showed no signs of mucormycosis recurrence. Finally, the patient was cured, when the cancer chemotherapy was stopped. Close follow-up for another 2 years showed no evidence of recurrence. LESSONS: Mucormycosis diagnosis is difficult as clinical and imaging findings vary. This case demonstrates that posaconazole monotherapy combined with bronchoscopy interventions may be a safe and effective treatment option for pediatric pulmonary mucormycosis.


Assuntos
Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/diagnóstico , Mucormicose/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Administração Oral , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Criança , Diagnóstico Diferencial , Febre/etiologia , Humanos , Pneumopatias Fúngicas/complicações , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/patologia , Masculino , Mucormicose/complicações , Mucormicose/tratamento farmacológico , Mucormicose/patologia , Triazóis/administração & dosagem , Triazóis/uso terapêutico
19.
Isr Med Assoc J ; 23(2): 116-120, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33595218

RESUMO

BACKGROUND: Extremely preterm infants are at high risk for mortality and morbidity including neurodevelopmental impairment from invasive Candida infections. Prophylactic antifungal therapy has been shown to reduce both colonization and invasive candidemia in high-risk preterm infants. Prophylactic treatment should be started in the first 48 to 72 hours after birth to extremely low birth weight (ELBW) infants (weighing ≤ 1000 grams at birth) or below 27 weeks gestation age with risk factors, or in any NICU with moderate (5-10%) or high (≥ 10%) rates of invasive candidiasis. Studies demonstrated the benefits of fluconazole prophylaxis regarding its safety of the short-term and long-term without the development of fungal resistance. Empiric antifungal therapy may lower mortality and improve outcomes.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Invasiva/prevenção & controle , Doenças do Prematuro/prevenção & controle , Antifúngicos/efeitos adversos , Candidíase Invasiva/mortalidade , Farmacorresistência Fúngica , Fluconazol/administração & dosagem , Fluconazol/efeitos adversos , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/microbiologia , Doenças do Prematuro/mortalidade , Unidades de Terapia Intensiva Neonatal , Seleção de Pacientes
20.
Int J Nanomedicine ; 16: 119-132, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33447031

RESUMO

Purpose: This manuscript aimed at encapsulating an antifungal terconazole (TCZ) into innovative novasomes for improving its penetration into the skin and clinically modulating its therapeutic efficacy. Methods: Novasomes containing free fatty acid (FFA) as a penetration enhancer were formulated using ethanol injection technique based on 24 full factorial design to explore the impact of various formulation variables on novasomes characteristics regarding entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum formulation was chosen using Design-Expert® software and utilized for further explorations. Results: The chosen formulation (N15; including 100 mg lipid components and Span 80 to oleic acid in a ratio of 2:1 (w/w)) exhibited an EE% = 99.45 ± 0.78%, PS = 623.00 ± 2.97 nm, PDI = 0.40 ± 0.04, and ZP = -73.85 ± 0.64 mV. N15 showed spherical vesicles with a higher deformability index (DI) (9.62 ± 0.15 g) compared to traditional niosomal formulation (0.92 ± 0.12 g). Further, N15 showed superior inhibition of Candida albicans growth relative to TCZ suspension using XTT (2,3-bis-(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reduction assay. Moreover, in vivo skin deposition tests revealed a superior TCZ deposition inside the skin from N15 in comparison to traditional niosomal formulation and TCZ suspension. Furthermore, histopathological examination for rats assured the safety of N15 for topical use. A clinical study conducted on infants suffering from napkin candidiasis proved the superiority of N15 to placebo in providing a complete cure of such fungal infections. Conclusion: Concisely, the obtained outcomes confirmed the pronounced efficacy of N15 to successfully treat skin fungal infections.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Triazóis/administração & dosagem , Administração Tópica , Animais , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Análise Fatorial , Humanos , Lactente , Lipossomos , Masculino , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/microbiologia , Pele/patologia , Absorção Cutânea/efeitos dos fármacos , Eletricidade Estática , Suspensões , Triazóis/farmacologia , Triazóis/uso terapêutico
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