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1.
Mycopathologia ; 189(3): 44, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734862

RESUMO

A 50-year-old man, previously diagnosed with pulmonary tuberculosis and lung cavities, presented with symptoms including fever, shortness of breath, and cough. A pulmonary CT scan revealed multiple cavities, consolidation and tree-in-bud in the upper lungs. Further investigation through direct examination of bronchoalveolar lavage fluid showed septate hyphae with dichotomous acute branching. Subsequent isolation and morphological analysis identified the fungus as belonging to Aspergillus section Nigri. The patient was diagnosed with probable invasive pulmonary aspergillosis and successfully treated with a three-month oral voriconazole therapy. Phylogenetic analysis based on partial ß-tubulin, calmodulin and RNA polymerase second largest subunit sequences revealed that the isolate represents a putative new species related to Aspergillus brasiliensis, and is named Aspergillus hubkae here. Antifungal susceptibility testing demonstrated that the isolate is resistant to itraconazole but susceptible to voriconazole. This phenotypic and genetic characterization of A. hubkae, along with the associated case report, will serve as a valuable resource for future diagnoses of infections caused by this species. It will also contribute to more precise and effective patient management strategies in similar clinical scenarios.


Assuntos
Antifúngicos , Aspergillus , Aspergilose Pulmonar Invasiva , Testes de Sensibilidade Microbiana , Filogenia , Análise de Sequência de DNA , Voriconazol , Humanos , Masculino , Pessoa de Meia-Idade , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Aspergillus/isolamento & purificação , Aspergillus/genética , Aspergillus/classificação , Aspergillus/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/microbiologia , Análise por Conglomerados , DNA Fúngico/genética , DNA Fúngico/química , Aspergilose Pulmonar Invasiva/microbiologia , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/diagnóstico , Itraconazol/farmacologia , Microscopia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tubulina (Proteína)/genética , Voriconazol/uso terapêutico , Voriconazol/farmacologia
2.
Mycoses ; 67(4): e13724, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38584320

RESUMO

OBJECTIVE: This study aims to assess the clinical characteristics of sporotrichosis in low-endemic areas of China, including the prevalence geography, genotypic traits of patients, clinical manifestations, and strain virulence and drug sensitivities. The objective is to improve the currently used clinical management strategies for sporotrichosis. METHODS: Retrospective data were collected from patients diagnosed with sporotrichosis through fungal culture identification. The isolates from purified cultures underwent identification using CAL (Calmodulin) gene sequencing. Virulence of each strain was assessed using a Galleria mellonella (G. mellonella) larvae infection model. In vitro susceptibility testing against commonly used clinical antifungal agents for sporotrichosis was conducted following CLSI criteria. RESULTS: In our low-endemic region for sporotrichosis, the majority of cases (23) were observed in middle-aged and elderly women with a history of trauma, with a higher incidence during winter and spring. All clinical isolates were identified as Sporothrix globosa (S. globosa). The G. mellonella larvae infection model indicated independent and dose-dependent virulence among strains, with varying toxicity levels demonstrated by the degree of melanization of the G. mellonella. Surprisingly, lymphocutaneous types caused by S. globosa exhibited lower in vitro virulence but were more common in affected skin. In addition, all S.globosa strains displayed high resistances to fluconazole, while remaining highly susceptible to terbinafine, itraconazole and amphotericin B. CONCLUSION: Given the predominance of elderly women engaged in agricultural labour in our region, which is a low-epidemic areas, they should be considered as crucial targets for sporotrichosis monitoring. S. globosa appears to be the sole causative agent locally. However, varying degrees of melanization in larvae were observed among these isolates, indicating a divergence in their virulence. Itraconazole, terbinafine and amphotericin B remain viable first-line antifungal options for treating S.globosa infection.


Assuntos
Sporothrix , Esporotricose , Idoso , Pessoa de Meia-Idade , Humanos , Feminino , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Esporotricose/microbiologia , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Terbinafina/uso terapêutico , Estudos Retrospectivos , Testes de Sensibilidade Microbiana , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Sporothrix/genética , China/epidemiologia
3.
Molecules ; 29(8)2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38675589

RESUMO

The aim of this study was to develop cholic-acid-stabilized itraconazole nanosuspensions (ITZ-Nanos) with the objective of enhancing drug dissolution and oral absorption. A laboratory-scale microprecipitation-high-pressure homogenization method was employed for the preparation of the ITZ-Nanos, while dynamic light scattering, transmission electron microscope analysis, X-ray diffraction, differential scanning calorimetry, and high-performance liquid chromatography analysis were utilized to evaluate their physicochemical properties. The absorption and bioavailability of the ITZ-Nanos were assessed using Caco-2 cells and rats, with Sporanox® pellets as a comparison. Prior to lyophilization, the particle size of the ITZ-Nanos measured approximately 225.7 nm. Both X-ray diffraction and differential scanning calorimetry confirmed that the ITZ remained crystalline within the nanocrystals. Compared to the pellets, the ITZ-Nanos exhibited significantly higher levels of supersaturation dissolution and demonstrated enhanced drug uptake by the Caco-2 cells. The AUC(0-t) value for the ITZ-Nanos in rats was 1.33-fold higher than that observed for the pellets. These findings suggest that cholic acid holds promise as a stabilizer for ITZ nanocrystals, as well as potentially other nanocrystals.


Assuntos
Itraconazol , Nanopartículas , Solubilidade , Tensoativos , Itraconazol/química , Itraconazol/farmacocinética , Itraconazol/administração & dosagem , Nanopartículas/química , Humanos , Células CACO-2 , Animais , Ratos , Administração Oral , Tensoativos/química , Masculino , Disponibilidade Biológica , Tamanho da Partícula , Difração de Raios X , Varredura Diferencial de Calorimetria , Ácido Cólico/química
4.
Mycopathologia ; 189(2): 30, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578519

RESUMO

OBJECTIVE: To study the distribution of pathogenic Aspergillus strains of otomycosis in central China and the identification of their antifungal sensitivity. METHODS: We collected external ear canal secretions clinically diagnosed as otomycosis from April 2020 to January 2023 from the Department of Otolaryngology-Head and Neck Surgery in central China. The pathogenic Aspergillus strains were identified through morphological examination and sequencing. The antifungal sensitivity was performed using the broth microdilution method described in the Clinical Laboratory Standard Institute document M38-A3. RESULTS: In the 452 clinical strains isolated from the external ear canal, 284 were identified as Aspergillus terreus (62.83%), 92 as Aspergillus flavus (20.35%), 55 as Aspergillus niger (12.17%). In antifungal susceptibility tests the MIC of Aspergillus strains to bifonazole and clotrimazole was high,all the MIC90 is > 16 ug/mL. However, most Aspergillus isolates show moderate greatly against terbinafine, itraconazole and voriconazole. CONCLUSION: A. terreus is the most common pathogenic Aspergillus strain in otomycosis in central China. The selected topical antifungal drugs were bifonazole and clotrimazole; the drug resistance rate was approximately 30%. If the infection is persistent and requires systemic treatment, terbinafine and itraconazole can be used. The resistance of Aspergillus in otomycosis to voriconazole should be screened to avoid the systemic spread of infection in immunocompromised people and poor compliance with treatment. However, the pan-azole-resistant strain of Aspergillus should be monitored, particularly in high-risk patients with otomycosis.


Assuntos
Aspergilose , Otomicose , Humanos , Antifúngicos/farmacologia , Otomicose/epidemiologia , Otomicose/microbiologia , Itraconazol , Voriconazol , Terbinafina , Clotrimazol/farmacologia , Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergillus , Testes de Sensibilidade Microbiana
5.
Int J Biol Macromol ; 267(Pt 2): 131404, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582466

RESUMO

Chitosan has received much more attention as a functional biopolymer with applications in pharmaceuticals, agricultural, drug delivery systems and cosmetics. The objectives of present investigation were to carry out modification of chitosan for enhancement of aqueous solubility, which will impart increased solubility and dissolution rate of poorly soluble drug itraconazole (ITZ) and also evaluate the modified chitosan for soyabean seed germination studies. The modification of chitosan was accomplished through the antisolvent precipitation method; employing five carboxylic acids. The resulting products were assessed for changes in molecular weight, degree of deacetylation, solubility and solid state characterization. Subsequently, the modified chitosan was complexed with itraconazole using the co-grinding technique. The prepared formulations were evaluated for solubility, FTIR (Fourier-transform infrared spectroscopy), PXRD (Powder X-ray diffraction), in-vitro dissolution studies. Furthermore the effect of modified chitosan has been evaluated on soybean seed germination. Results demonstrated that, modified chitosan improves self and solubility of itraconazole by six folds. As there was increased degree of deacetylation of chitosan leads to improvement in solubility. The results of FTIR showed the slight shifting of peaks in co-grind formulations of itraconazole. Formulations showed reduction in crystallinity of drug which leads to enhancement in dissolution rate as compared to pure itraconazole. Retention of property of seed germination was observed with modified chitosan at optimum concentration of 3 % w/v, with benefit of enhanced aqueous solubility of chitosan. This positive result paves the way for the advancement of pharmaceutical and agrochemical products employing derivatives of chitosan.


Assuntos
Agroquímicos , Quitosana , Itraconazol , Solubilidade , Quitosana/química , Agroquímicos/química , Agroquímicos/farmacologia , Itraconazol/química , Itraconazol/farmacologia , Glycine max/química , Germinação/efeitos dos fármacos , Sementes/química , Sementes/efeitos dos fármacos , Fenômenos Químicos , Espectroscopia de Infravermelho com Transformada de Fourier , Peso Molecular , Difração de Raios X
6.
Mar Drugs ; 22(4)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38667795

RESUMO

This open-label, two-part, phase Ib drug-drug interaction study investigated whether the pharmacokinetic (PK) and safety profiles of lurbinectedin (LRB), a marine-derived drug, are affected by co-administration of itraconazole (ITZ), a strong CYP3A4 inhibitor, in adult patients with advanced solid tumors. In Part A, three patients were sequentially assigned to Sequence 1 (LRB 0.8 mg/m2, 1-h intravenous [IV] + ITZ 200 mg/day oral in Cycle 1 [C1] and LRB alone 3.2 mg/m2, 1 h, IV in Cycle 2 [C2]). In Part B, 11 patients were randomized (1:1) to receive either Sequence 1 (LRB at 0.9 mg/m2 + ITZ in C1 and LRB alone in C2) or Sequence 2 (LRB alone in C1 and LRB + ITZ in C2). Eleven patients were evaluable for PK analysis: three in Part A and eight in Part B (four per sequence). The systemic total exposure of LRB increased with ITZ co-administration: 15% for Cmax, area under the curve (AUC) 2.4-fold for AUC0-t and 2.7-fold for AUC0-∞. Co-administration with ITZ produced statistically significant modifications in the unbound plasma LRB PK parameters. The LRB safety profile was consistent with the toxicities described in previous studies. Co-administration with multiple doses of ITZ significantly altered LRB systemic exposure. Hence, to avoid LRB overexposure when co-administered with strong CYP3A4 inhibitors, an LRB dose reduction proportional to CL reduction should be applied.


Assuntos
Carbolinas , Inibidores do Citocromo P-450 CYP3A , Interações Medicamentosas , Compostos Heterocíclicos de 4 ou mais Anéis , Itraconazol , Neoplasias , Humanos , Itraconazol/farmacocinética , Itraconazol/administração & dosagem , Itraconazol/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Neoplasias/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Inibidores do Citocromo P-450 CYP3A/farmacocinética , Inibidores do Citocromo P-450 CYP3A/farmacologia , Carbolinas/farmacocinética , Carbolinas/administração & dosagem , Carbolinas/efeitos adversos , Adulto , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Área Sob a Curva , Antineoplásicos/farmacocinética , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem
7.
BMJ Case Rep ; 17(3)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38458767

RESUMO

Eumycetoma, a subcutaneous infection caused by various fungi with pathognomonic discharging grain, is rarely reported in Malaysia. This case concerns a eumycetoma infection in an immunocompetent man who presented with progressive left foot swelling complicated with pustules, sinuses and pale grain discharge for the past year after recurrent thorn pricks. Histological findings of the grain and tissue showed foci of septate fungal hyphae. Tissue culture yielded no growth. Amplification and sequencing of the rDNA internal transcribed spacer 1 (ITS1), ITS4 and large subunit regions of the tissue identified the causative agent as Fusarium falciforme, highlighting the role of molecular diagnostic method in identifying fungal species in eumycetoma. The patient was treated with surgical excision and oral itraconazole with excellent improvement. However, he presented again with recurrence after defaulting therapy. F. falciforme has been implicated in causing diseases in crops and sea turtles. Therefore, the One Health approach should be adopted to manage this emerging species.


Assuntos
Fusarium , Micetoma , Masculino , Humanos , Micetoma/diagnóstico , Micetoma/tratamento farmacológico , Doenças Negligenciadas , Itraconazol/uso terapêutico
8.
BMJ Case Rep ; 17(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38471698

RESUMO

Abdominal masses clubbed with weight loss in the paediatric age group can raise hairs, especially since malignancy is a differential. We present the case of an early adolescent male who presented with abdominal pain and was found to have a mass mimicking a malignancy. The resected surgical specimen revealed entomophthoromycosis of the jejunum and he made a complete recovery following surgery and adjuvant itraconazole. The diagnosis of a fungal aetiology in these cases requires a high index of suspicion and background knowledge of the risk factors, disease occurrence and mode of presentation. Gastrointestinal entomophthoromycosis has an impressive potential for cure if promptly diagnosed and treated.


Assuntos
Zigomicose , Adolescente , Humanos , Masculino , Dor Abdominal/etiologia , Itraconazol , Neoplasias , Zigomicose/diagnóstico
9.
BMJ Case Rep ; 17(3)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490708

RESUMO

Chromoblastomycosis is an implantation mycosis of the skin caused by certain species of melanised fungi. A man in his 50s, born in Kerala but living in England for 14 years, presented with a nodular lesion on his left buttock, which had been present for 20 years. Biopsy revealed muriform cells and fungal culture isolated Fonsecaea spp, consistent with a diagnosis of chromoblastomycosis. Treatment with oral terbinafine was initiated and changed to itraconazole based on results of antifungal susceptibility. Drug intolerance and low drug levels of itraconazole necessitated change to voriconazole and topical terbinafine. Despite long-term combined therapy, the lesions worsened, and the patient opted for surgical excision abroad. Recurrence was evident at surgical sites and combined therapy continues. Chromoblastomycosis is an insidious and burdensome neglected tropical disease. Within non-endemic countries, diagnosis remains challenging. A travel history and appropriate fungal investigations are vital.


Assuntos
Ascomicetos , Cromoblastomicose , Masculino , Humanos , Terbinafina/uso terapêutico , Itraconazol/uso terapêutico , Cromoblastomicose/diagnóstico , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/microbiologia , Nádegas/patologia , Antifúngicos/uso terapêutico
10.
Med Mycol ; 62(4)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38533658

RESUMO

Chromoblastomycosis (CBM) and pheohyphomycosis (PHM) are the most common implantation mycoses caused by dematiaceous fungi. In the past, flucytosine (5-FC) has been used to treat CBM, but development of resistance is common. Carmofur belongs to the same class as 5-FC and has in vitro inhibitory activity against the main agents of CBM and PHM. The aim of this study was to compare the action of these two pyrimidine analog drugs against CBM and PHM agents. The minimum inhibitory concentration (MIC) and the selectivity index based on cytotoxicity tests of these two drugs against some agents of these mycoses were determined, with carmofur presenting a higher selectivity index than 5-FC. Carmofur demonstrated here synergistic interactions with itraconazole and amphotericin B against Exophiala heteromorpha, Fonsecaea pedrosoi, Fonsecaea monophora, and Fonsecaea nubica strains. Additionally, carmofur plus itraconazole demonstrated here synergism against a Phialophora verrucosa strain. To evaluate the development of carmofur resistance, passages in culture medium containing subinhibitory concentrations of this pyrimidine analog were carried out, followed by in vitro susceptibility tests. Exophiala dermatitidis quickly developed resistance, whereas F. pedrosoi took seven passages in carmofur-supplemented medium to develop resistance. Moreover, resistance was permanent in E. dermatitidis but transient in F. pedrosoi. Hence, carmofur has exhibited certain advantages, albeit accompanied by limitations such as the development of resistance, which was expected as with 5-FC. This underscores its therapeutic potential in combination with other drugs, emphasizing the need for a meticulous evaluation of its application in the fight against dematiaceous fungi.


Assuntos
Cromoblastomicose , Micoses , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Flucitosina/farmacologia , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Fungos , Cromoblastomicose/microbiologia , Cromoblastomicose/veterinária , Micoses/tratamento farmacológico , Micoses/veterinária , Testes de Sensibilidade Microbiana/veterinária
11.
Arch Microbiol ; 206(4): 134, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433145

RESUMO

Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.


Assuntos
Acanthamoeba castellanii , Micelas , Humanos , Itraconazol/farmacologia , Alcinos , Polímeros
12.
Int J Pharm ; 654: 123977, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38458403

RESUMO

Bottom-up production of active pharmaceutical ingredient (API) crystal suspensions offers advantages in surface property control and operational ease over top-down methods. However, downstream separation and concentration pose challenges. This proof-of-concept study explores membrane diafiltration as a comprehensive solution for downstream processing of API crystal suspensions produced via anti-solvent crystallization. It involves switching the residual solvent (N-methyl-2-pyrrolidone, NMP) with water, adjusting the excipient (d-α-Tocopherol polyethylene glycol 1000 succinate, TPGS) quantity, and enhancing API loading (solid concentration) in itraconazole crystal suspensions. NMP concentration was decreased from 9 wt% to below 0.05 wt% (in compliance with European Medicine Agency guidelines), while the TPGS concentration was decreased from 0.475 wt% to 0.07 wt%. This reduced the TPGS-to-itraconazole ratio from 1:2 to less than 1:50 and raised the itraconazole loading from 1 wt% to 35.6 wt%. Importantly, these changes did not adversely affect the itraconazole crystal stability in suspension. This study presents membrane diafiltration as a one-step solution to address downstream challenges in bottom-up API crystal suspension production. These findings contribute to optimizing pharmaceutical manufacturing processes and hold promise for advancing the development of long-acting API crystal suspensions via bottom-up production techniques at a commercial scale.


Assuntos
Itraconazol , Água , Itraconazol/química , Solventes/química , Propriedades de Superfície , Tecnologia , Suspensões , Solubilidade , Tamanho da Partícula
13.
Sci Total Environ ; 923: 171189, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38447726

RESUMO

Antifungal resistance has emerged as a significant health concern with increasing reports of resistant variants in previously susceptible species. At present, little is known about occupational exposure to antifungal-resistant fungi. This study aimed to investigate Danish workers' occupational exposure to airborne fungi resistant to first-line treatment drugs. A retrospective study was performed on a unique collection of personal exposure samples gathered over a twenty-year period from Danish working environments, in sectors including agriculture, animal handling, waste management, and healthcare. A total of 669 samples were cultivated at 37 °C and fungal colonies were identified using MALDI-TOF MS. Subsequently, identification was confirmed by amplicon sequencing the genes of calmodulin and beta-tubulin to unveil potential cryptic species. Infectious fungi (495 isolates from 23 species) were tested for resistance against Itraconazole, Voriconazole, Posaconazole, and Amphotericin B. Working environments were highly variable in the overall fungal exposure, and showed vastly different species compositions. Resistance was found in 30 isolates of the species Aspergillus fumigatus (4 of 251 isolates), A. nidulans (2 of 13), A. niger complex (19 of 131), A. versicolor (3 of 18), and A. lentulus (2 of 2). Sequence analysis revealed several cryptic species within the A. niger complex including A. tubingensis, A. luchuensis, and A. phoenicis. Among the resistant A. fumigatus isolates, two contained the well-described TR34/L98H mutation in the cyp51A gene and promoter region, while the remainder harbored silent mutations. The results indicate that the working environment significantly contributes to exposure to resistant fungi, with particularly biofuel plant workers experiencing high exposure. Differences in the prevalence of resistance across working environments may be linked to the underlying species composition.


Assuntos
Antifúngicos , Proteínas Fúngicas , Antifúngicos/farmacologia , Estudos Retrospectivos , Proteínas Fúngicas/genética , Fungos , Itraconazol , Aspergillus fumigatus , Testes de Sensibilidade Microbiana , Azóis
14.
Am J Trop Med Hyg ; 110(5): 965-967, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38531098

RESUMO

Tinea capitis is a common fungal infection caused by dermatophytes in children, but it is rare in infants. Although oral itraconazole has been widely used to treat tinea capitis, its use in infants is limited due to its low prevalence in this age group. A previous study reported the effectiveness of itraconazole continuous therapy in treating infantile tinea capitis caused by Microsporum canis. However, this approach has not been extended to tinea capitis caused by other fungi. In this study, we present four cases of infantile tinea capitis treated with continuous itraconazole oral solution therapy (5 mg/kg/day). Two patients were infected with M. canis, one patient with Nannizzia gypsea, and another with Trichophyton tonsurans. This study assesses the efficacy and safety of itraconazole oral solution continuous therapy, expanding our understanding by demonstrating its effectiveness for infantile tinea capitis caused by T. tonsurans and N. gypsea.


Assuntos
Antifúngicos , Itraconazol , Tinha do Couro Cabeludo , Humanos , Itraconazol/uso terapêutico , Itraconazol/administração & dosagem , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha do Couro Cabeludo/microbiologia , Antifúngicos/uso terapêutico , Antifúngicos/administração & dosagem , Lactente , Masculino , Feminino , Administração Oral , Microsporum/efeitos dos fármacos , Resultado do Tratamento
15.
Drug Metab Pharmacokinet ; 55: 101000, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458122

RESUMO

In this study, a physiologically based pharmacokinetic (PBPK) model of the cytochrome P450 3A (CYP3A) substrate azelnidipine was developed using in vitro and clinical data to predict the effects of azole antifungals on azelnidipine pharmacokinetics. Modeling and simulations were conducted using the Simcyp™ PBPK simulator. The azelnidipine model consisted of a full PBPK model and a first-order absorption model. CYP3A was assumed as the only azelnidipine elimination route, and CYP3A clearance was optimized using the pharmacokinetic profile of single-dose 5-mg azelnidipine in healthy participants. The model reproduced the results of a clinical drug-drug interaction study and met validation criteria. PBPK model simulations using azole antifungals (itraconazole, voriconazole, posaconazole, fluconazole, fosfluconazole) and azelnidipine or midazolam (CYP3A index substrate) were performed. Increases in the simulated area under the plasma concentration-time curve from time zero extrapolated to infinity with inhibitors were comparable between azelnidipine (range, 2.11-6.47) and midazolam (range, 2.26-9.22), demonstrating that azelnidipine is a sensitive CYP3A substrate. Increased azelnidipine plasma concentrations are expected when co-administered with azole antifungals, potentially affecting azelnidipine safety. These findings support the avoidance of azole antifungals in patients taking azelnidipine and demonstrate the utility of PBPK modeling to inform appropriate drug use.


Assuntos
Antifúngicos , Ácido Azetidinocarboxílico/análogos & derivados , Di-Hidropiridinas , Midazolam , Humanos , Midazolam/farmacocinética , Inibidores do Citocromo P-450 CYP3A/farmacologia , Citocromo P-450 CYP3A , Interações Medicamentosas , Itraconazol , Modelos Biológicos
16.
Emerg Infect Dis ; 30(4): 807-809, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437706

RESUMO

We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.


Assuntos
Antifúngicos , Trichophyton , Feminino , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Farmacorresistência Fúngica , Itraconazol/uso terapêutico , Testes de Sensibilidade Microbiana , Terbinafina/farmacologia , Terbinafina/uso terapêutico
17.
J Med Microbiol ; 73(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38530134

RESUMO

Introduction. Cryptococcal biofilms have been associated with persistent infections and antifungal resistance. Therefore, strategies, such as the association of natural compounds and antifungal drugs, have been applied for the prevention of biofilm growth. Moreover, the Caenorhabditis elegans pathogenicity model has been used to investigate the capacity to inhibit the pathogenicity of Cryptococcus neoformans sensu stricto.Hypothesis. Anthraquinones and antifungals are associated with preventing C. neoformans sensu stricto biofilm formation and disrupting these communities. Antraquinones reduced the C. neoformans sensu stricto pathogenicity in the C. elegans model.Aim. This study aimed to evaluate the in vitro interaction between aloe emodin, barbaloin or chrysophanol and itraconazole or amphotericin B against growing and mature biofilms of C. neoformans sensu stricto.Methodology. Compounds and antifungal drugs were added during biofilm formation or after 72 h of growth. Then, the metabolic activity was evaluated by the MTT reduction assay, the biomass by crystal-violet staining and the biofilm morphology by confocal laser scanning microscopy. C. neoformans sensu stricto's pathogenicity was investigated using the nematode C. elegans. Finally, pathogenicity inhibition by aloe emodin, barbarloin and chrysophanol was investigated using this model.Results. Anthraquinone-antifungal combinations affected the development of biofilms with a reduction of over 60 % in metabolic activity and above 50 % in biomass. Aloe emodin and barbaloin increased the anti-biofilm activity of antifungal drugs. Chrysophanol potentiated the effect of itraconazole against C. neoformans sensu stricto biofilms. The C. elegans mortality rate reached 76.7 % after the worms were exposed to C. neoformans sensu stricto for 96 h. Aloe emodin, barbaloin and chrysophanol reduced the C. elegans pathogenicity with mortality rates of 61.12 %, 65 % and 53.34 %, respectively, after the worms were exposed for 96 h to C. neoformans sensu stricto and these compounds at same time.Conclusion. These results highlight the potential activity of anthraquinones to increase the effectiveness of antifungal drugs against cryptococcal biofilms.


Assuntos
Antracenos , Criptococose , Cryptococcus neoformans , Animais , Antifúngicos/farmacologia , Caenorhabditis elegans , Itraconazol , Virulência , Antraquinonas/farmacologia , Biofilmes
18.
Antimicrob Agents Chemother ; 68(4): e0162023, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38385701

RESUMO

Sporothrix brasiliensis is an emerging zoonotic fungal pathogen that can be difficult to treat. Antifungal susceptibility testing was performed on the mold phase of a convenience sample of 61 Sporothrix spp. isolates from human and cat sporotrichosis cases in Brazil using the Clinical and Laboratory Standards Institute standard M38. A bimodal distribution of azole susceptibility was observed with 50% (28/56) of S. brasiliensis isolates showing elevated itraconazole minimum inhibitory concentrations ≥16 µg/mL. Phylogenetic analysis found the in vitro resistant isolates were not clonal and were distributed across three different S. brasiliensis clades. Single nucleotide polymorphism (SNP) analysis was performed to identify potential mechanisms of in vitro resistance. Two of the 28 resistant isolates (MIC ≥16 mg/L) had a polymorphism in the cytochrome P450 gene, cyp51, corresponding to the well-known G448S substitution inducing azole resistance in Aspergillus fumigatus. SNPs corresponding to other known mechanisms of azole resistance were not identified in the remaining 26 in vitro resistant isolates.


Assuntos
Sporothrix , Esporotricose , Humanos , Antifúngicos/farmacologia , Azóis/farmacologia , Brasil , Filogenia , Itraconazol/farmacologia , Esporotricose/tratamento farmacológico , Testes de Sensibilidade Microbiana , Farmacorresistência Fúngica/genética
19.
Eur Respir J ; 63(4)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423624

RESUMO

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.


Assuntos
Aspergilose Broncopulmonar Alérgica , Aspergilose Pulmonar Invasiva , Adulto , Criança , Animais , Humanos , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Itraconazol/uso terapêutico , Micologia , Prednisolona , Imunoglobulina E
20.
Int J Pharm ; 654: 123952, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38417729

RESUMO

Spray drying is a well-established method for screening spray dried dispersions (SDDs) but is material consuming, and the amorphous solid dispersions (ASDs) formed have low bulk density. Vacuum Compression Molding (VCM) is a potential method to avoid these limitations. This study focuses on VCM to screen ASDs containing itraconazole and L, M, or H polymer grades of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and compares their morphology, amorphous stability, and dissolution performance with spray drying. Results indicate that VCM ASDs were comparable to SDDs. Both VCM ASDs and spray drying SDDs with HPMCAS-L and HPMCAS-M had improved dissolution profiles, while HPMCAS-H did not. Dynamic light scattering findings agreed with dissolution profiles, indicating that L and M grades produced monodisperse, smaller colloids, whereas H grade formed larger, polydisperse colloids. Capsules containing ASDs from VCM disintegrated and dissolved in the media; however, SDD capsules formed agglomerates and failed to disintegrate completely. Findings indicate that the VCM ASDs are comparable to SDDs in terms of dissolution performance and amorphous stability. VCM may be utilized in early ASD formulation development to select drug-polymer pairs for subsequent development.


Assuntos
Dapsona/análogos & derivados , Itraconazol , Secagem por Atomização , Vácuo , Solubilidade , Polímeros , Coloides , Metilcelulose , Composição de Medicamentos
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