RESUMO
Currently, there is no available needle-free approach for diabetics to monitor glucose levels in the interstitial fluid. Here, we report a path-selective, non-invasive, transdermal glucose monitoring system based on a miniaturized pixel array platform (realized either by graphene-based thin-film technology, or screen-printing). The system samples glucose from the interstitial fluid via electroosmotic extraction through individual, privileged, follicular pathways in the skin, accessible via the pixels of the array. A proof of principle using mammalian skin ex vivo is demonstrated for specific and 'quantized' glucose extraction/detection via follicular pathways, and across the hypo- to hyper-glycaemic range in humans. Furthermore, the quantification of follicular and non-follicular glucose extraction fluxes is clearly shown. In vivo continuous monitoring of interstitial fluid-borne glucose with the pixel array was able to track blood sugar in healthy human subjects. This approach paves the way to clinically relevant glucose detection in diabetics without the need for invasive, finger-stick blood sampling.
Assuntos
Automonitorização da Glicemia/instrumentação , Líquido Extracelular/química , Glucose/análise , Grafite/química , Pele/química , Animais , Técnicas Biossensoriais/instrumentação , Eletro-Osmose , Desenho de Equipamento , Humanos , SuínosRESUMO
Ambipolar organic field-effect transistors (OFETs) based on heterojunction active films still suffer from an imbalance in the transport of electrons and holes. This problem is related to an uncontrolled phase separation between the donor and acceptor organic semiconductors in the thin films. In this work, we have developed a concept to improve the phase separation in heterojunction transistors to enhance their ambipolar performance. This concept is based on preaggregation of the donor polymer, in this case poly(3-hexylthiophene) (P3HT), before solution mixing with the small-molecular-weight acceptor, phenyl-C61-butyric acid methyl ester (PCBM). The resulting heterojunction transistor morphology consists of self-assembled P3HT fibers embedded in a PCBM matrix, ensuring balanced mobilities reaching 0.01 cm2/V s for both holes and electrons. These are the highest mobility values reported so far for ambipolar OFETs based on P3HT/PCBM blends. Preaggregation of the conjugated polymer before fabricating binary blends can be regarded as a general concept for a wider range of semiconducting systems applicable in organic electronic devices.
RESUMO
AIM: To identify the shortest components of A13-A19, B12-B17 fragments capable for fibrillation and to validate the dependability of aggregation on the presence of hydroxyl group engaged in the 'tyrosine kissing'. MATERIALS & METHODS: Fragments A13-A19 and B12-B17 of insulin and all shortened analogues were obtained by using DMT/NMM/TosO(-) as a coupling reagent. The aggregation was studied by three independent tests. RESULTS: Studies on the susceptibility to aggregation of truncated analogs of insulin amyloidogenic core show three groups of peptides. CONCLUSION: Truncation of A13-A419 fragment shows that fibrous structures are formed by all peptides bearing (13)H-LeuTyr-OH(14). Propensity to aggregation was found for (16)H-TyrLeu-OH(17) B12-B17 fragment. Tyrosine residue modification by incorporation of tert-butyl group on hydroxyl function gave analogues still predisposed to aggregation.
Assuntos
Amiloide/química , Insulina/química , Fragmentos de Peptídeos/química , Agregados Proteicos , Sequência de Aminoácidos , Amiloide/metabolismo , Amiloide/ultraestrutura , Humanos , Insulina/metabolismo , Leucina/química , Leucina/metabolismo , Fragmentos de Peptídeos/metabolismo , Agregação Patológica de Proteínas/metabolismo , Tirosina/química , Tirosina/metabolismoRESUMO
OBJECTIVE: Approximately 5% of women suffer from recurrent vulvovaginal candidiasis (RVVC). It has been hypothesized that genetic factors play an important role in the susceptibility to RVVC. The aim of this study was to assess the effect of genetic variants of genes encoding for pattern recognition receptors (PRRs) on susceptibility to RVVC. STUDY DESIGN: For the study, 119 RVVC patients and 263 healthy controls were recruited. Prevalence of polymorphisms in five PRRs involved in recognition of Candida were investigated in patients and controls. In silico and functional studies were performed to assess their functional effects. RESULTS: Single nucleotide polymorphisms (SNPs) in TLR1, TLR4, CLEC7A, and CARD9 did not affect the susceptibility to RVVC. In contrast, a non-synonymous polymorphism in TLR2 (rs5743704, Pro631His) increased the susceptibility to RVVC almost 3-fold. Furthermore, the TLR2 rs5743704 SNP had deleterious effects on protein function as assessed by in silico analysis, and in vitro functional assays suggested that it reduces production of IL-17 and IFNγ upon stimulation of peripheral blood mononuclear cells with Candida albicans. No effects were observed on serum mannose-binding lectin concentrations. CONDENSATION: This study demonstrates the association of susceptibility to RVVC with genetic variation in TLR2, most likely caused by decreased induction of mucosal antifungal host defense. CONCLUSION: Genetic variation in TLR2 may significantly enhance susceptibility to RVVC by modulating host defense mechanisms against Candida. Additional studies are warranted to assess systematically the role of host genetic variation for susceptibility to RVVC.
RESUMO
Lipid preparations of amphotericin B, commonly used to treat fungal infections, have been demonstrated to have reduced nephrotoxicity compared to conventional amphotericin B. However, to our knowledge, a comprehensive comparison of nephrotoxicity induced by different lipid preparations of amphotericin B has not been performed. We conducted a meta-analysis to evaluate nephrotoxicity associated with amphotericin B lipid complex (ABLC) and liposomal amphotericin B (L-AmB). We searched the PubMed MEDLINE database and abstracts presented at key scientific meetings, and identified 11 studies reported between 1995 and 2008 that compared nephrotoxicity resulting from the use of these agents. Eight of the 11 studies were included in the meta-analysis. The Cochran-Mantel-Haenszel test was used to determine odds ratio (OR) and relative risk (RR), and the Breslow-Day test was used to analyze homogeneity of ORs across different studies. Analysis of all 8 studies (n = 1160) included in the meta-analysis showed an increased probability of nephrotoxicity in patients treated with ABLC versus L-AmB (OR, 1.75; RR, 1.55), but there was a significant lack of homogeneity across these studies (p < 0.001). After excluding the study by Wingard et al, the probability of experiencing nephrotoxicity was more similar between the 2 AmB lipid preparations (OR, 1.31; RR, 1.24; n = 916), particularly when the analysis included only the salvage patient population reported by Hachem et al (OR, 1.12; RR, 1.09; n = 839); the 7 remaining studies were more homogenous by Breslow-Day test (p = 0.054). Our results suggest that nephrotoxicity is generally similar for ABLC and L-AmB in patients receiving antifungal therapy and prophylaxis.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , HumanosRESUMO
BACKGROUND: Patients with candidemia frequently have a central venous catheter (CVC) in place, and its early removal is considered the standard of care. METHODS: We performed a subgroup analysis of 2 phase III, multicenter, double-blind, randomized, controlled trials of candidemia to examine the effects of early CVC removal (within 24 or 48 h after treatment initiation) on the outcomes of 842 patients with candidemia. Inclusion criteria were candidemia, age >16 years, CVC at diagnosis, and receipt of 1 dose of the study drug. Six outcomes were evaluated: treatment success, rates of persistent and recurrent candidemia, time to mycological eradication, and survival at 28 and 42 days. Univariate and multivariate analyses were performed, controlling for potential confounders. RESULTS: In univariate analysis, early CVC removal did not improve time to mycological eradication or rates of persistent or recurrent candidemia but was associated with better treatment success and survival. These benefits were lost in multivariate analysis, which failed to show any beneficial effect of early CVC removal on all 6 outcomes and identified Acute Physiology and Chronic Health Evaluation II score, older age, and persistent neutropenia as the most significant variables. Our findings were consistent across all outcomes and time points (removal within 24 or 48 h and survival at 28 and 42 days). The median time to eradication of candidemia was similar between the 2 study groups. CONCLUSIONS: In this cohort of 842 adults with candidemia followed up prospectively, early CVC removal was not associated with any clinical benefit. These findings suggest an evidence-based re-evaluation of current treatment recommendations.
Assuntos
Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/terapia , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/terapia , Fungemia/tratamento farmacológico , Fungemia/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Sangue/microbiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoAssuntos
Coccidioides/isolamento & purificação , Coccidioidomicose/microbiologia , Transplante de Pulmão/efeitos adversos , Doadores de Tecidos , Viagem , Anticorpos Antifúngicos/sangue , Antifúngicos/uso terapêutico , Arizona , Coccidioides/imunologia , Coccidioidomicose/diagnóstico , Coccidioidomicose/tratamento farmacológico , Coccidioidomicose/transmissão , França , Humanos , Fibrose Pulmonar Idiopática/cirurgia , Imunossupressores/uso terapêutico , Itraconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
INTRODUCTION: Invasive candidiasis and candidemia are life-threatening nosocomial infections in intensive care patients. METHODS: A post hoc analysis of a phase 3 trial assessing micafungin (100 mg/day for subjects > 40 kg; 2 mg/kg/day for subjects Assuntos
Anfotericina B/farmacologia
, Antifúngicos/farmacologia
, Candidíase/tratamento farmacológico
, Equinocandinas/farmacologia
, Unidades de Terapia Intensiva
, Lipopeptídeos/farmacologia
, Adulto
, Idoso
, Anfotericina B/administração & dosagem
, Anfotericina B/uso terapêutico
, Antifúngicos/administração & dosagem
, Antifúngicos/uso terapêutico
, Infecção Hospitalar/tratamento farmacológico
, Equinocandinas/administração & dosagem
, Equinocandinas/uso terapêutico
, Feminino
, Humanos
, Lipopeptídeos/administração & dosagem
, Lipopeptídeos/uso terapêutico
, Masculino
, Micafungina
, Pessoa de Meia-Idade
, Análise Multivariada
RESUMO
Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.
Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Pesquisa Biomédica/normas , Candidíase/tratamento farmacológico , Coccidioidomicose/tratamento farmacológico , Criptococose/tratamento farmacológico , Histoplasmose/tratamento farmacológico , Humanos , Resultado do TratamentoRESUMO
INTRODUCTION: Coccidioidomycosis is a deep mycosis rare in France. CASE: We report the case of a patient with disseminated coccidioidomycosis and meningitis after travel to California. It initially suggested tuberculosis. The ensuing hydrocephalus required a ventricular peritoneal shunt, replaced by a ventricular cardiac shunt after an obstruction occurred. Diagnosis was made 18 months later when the patient developed specific plantar ulcerations. Dramatic improvement was observed under fluconazole and maintained after prolonged follow-up. COMMENTS: Coccidioidomycosis should be considered in any patient who presents with meningitis suggestive of tuberculosis who has traveled to endemic zones. Cutaneous dissemination secondary to a ventricular cardiac shunt is rare.
Assuntos
Ventrículos Cerebrais/cirurgia , Coccidioidomicose/diagnóstico , Úlcera do Pé/microbiologia , Meningite Fúngica/microbiologia , Meningite Fúngica/cirurgia , Idoso , Anastomose Cirúrgica , Animais , Procedimentos Cirúrgicos Cardíacos , Doença Crônica , Coccidioidomicose/complicações , Humanos , Meningite Fúngica/complicações , Meningite Fúngica/diagnósticoRESUMO
A systematic review was performed to examine renal function in patients with invasive fungal infections, comparing the nephrotoxicity caused by conventional amphotericin B deoxycholate (c-AmB) with that induced by the use of lipid-based amphotericin B formulations. The analysis considered all comparative studies published in the literature between January 1996 and May 2007. The outcome data reviewed herein focused on renal toxicity as measured by serum creatinine (S-Cr) and the doubling or the mean difference in S-Cr levels from baseline to the end of therapy or the need for dialysis. We found that AmB lipid complex (ABLC), liposomal AmB (L-AmB) and AmB colloidal dispersion (ABCD) were significantly less nephrotoxic than c-AmB in all reported studies. ABLC and L-AmB caused low and comparable nephrotoxicity in nine studies. In one randomized study, L-AmB was significantly less nephrotoxic than ABLC. No studies compared ABCD nephrotoxicity to the other lipid formulations. Based on our review we conclude that lipid formulations of amphotericin B are an important strategy to preserve renal function and improve survival in critically ill patients who require treatment for systemic fungal infections.
Assuntos
Anfotericina B/toxicidade , Antifúngicos/toxicidade , Micoses/tratamento farmacológico , Insuficiência Renal/induzido quimicamente , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Humanos , Diálise Renal , Resultado do TratamentoRESUMO
BACKGROUND: Chronic disseminated candidiasis (CDC) is typically observed during neutrophil recovery in patients with acute leukemia and requires protracted antifungal therapy. OBJECTIVE: Our objective was to document the efficacy and tolerance of corticosteroid therapy (CST) in patients with symptomatic CDC, including those who experienced fever and abdominal pain despite ongoing antifungal therapy. METHODS: We performed a retrospective, multicenter study involving 10 pediatric and adult patients who experienced ongoing symptomatic CDC despite receipt of appropriate antifungal therapy for whom adjuvant oral CST was initiated. RESULTS: All cases of CDC were proven or probable, as determined on the basis of the European Organization for Research and Treatment of Cancer-Mycosis Study Group definition criteria, and occurred in patients with leukemia. CDC-attributable clinical symptoms resolved with CST, which was started a mean of 33.8 days after antifungal therapy had been initiated. Fever and abdominal pain disappeared a median of 4-5 days, and serum fibrinogen and C-reactive protein levels returned to normal values within 14-30 days. The median duration of hospitalization after CST initiation was 8.8 days. Hepatosplenic microabscesses decreased or disappeared within a mean period of 107 days (range, 30-210 days). No relapses of CDC were observed during a median duration of follow-up of 6.5 years (range, 4-9 years). CONCLUSIONS: In children and adults who experience persistently symptomatic CDC despite ongoing receipt of antifungal therapy, CST involving a prednisone equivalent at a dosage of > or =0.5 mg/kg per day for at least 3 weeks is associated with a prompt resolution of symptoms and of inflammatory response. These findings support the pathophysiological hypothesis that CDC belongs to the spectrum of fungus-related immune reconstitution inflammatory syndrome.
Assuntos
Corticosteroides/uso terapêutico , Candidíase/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Dor Abdominal/microbiologia , Adolescente , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Idoso , Antifúngicos/uso terapêutico , Proteína C-Reativa/análise , Candidíase/fisiopatologia , Criança , Pré-Escolar , Feminino , Febre/microbiologia , Fibrinogênio/análise , Humanos , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/microbiologia , Síndrome Inflamatória da Reconstituição Imune/patologia , Síndrome Inflamatória da Reconstituição Imune/fisiopatologia , Tempo de Internação , Leucemia/complicações , Abscesso Hepático/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Baço/patologia , Fatores de TempoRESUMO
BACKGROUND: Invasive candidiasis is an important cause of morbidity and mortality among patients with health care-associated infection. The echinocandins have potent fungicidal activity against most Candida species, but there are few data comparing the safety and efficacy of echinocandins in the treatment of invasive candidiasis. METHODS: This was an international, randomized, double-blind trial comparing micafungin (100 mg daily) and micafungin (150 mg daily) with a standard dosage of caspofungin (70 mg followed by 50 mg daily) in adults with candidemia and other forms of invasive candidiasis. The primary end point was treatment success, defined as clinical and mycological success at the end of blinded intravenous therapy. RESULTS: A total of 595 patients were randomized to one the treatment groups and received at least 1 dose of study drug. In the modified intent-to-treat population, 191 patients were assigned to the micafungin 100 mg group, 199 to the micafungin 150 mg group, and 188 to the caspofungin group. Demographic characteristics and underlying disorders were comparable across the groups. Approximately 85% of patients had candidemia; the remainder had noncandidemic invasive candidiasis. At the end of blinded intravenous therapy, treatment was considered successful for 76.4% of patients in the micafungin 100 mg group, 71.4% in the micafungin 150 mg group, and 72.3% in the caspofungin group. The median time to culture negativity was 2 days in the micafungin 100 mg group and the caspofungin group, compared with 3 days in the micafungin 150 mg groups. There were no significant differences in mortality, relapsing and emergent infections, or adverse events between the study arms. CONCLUSIONS: Dosages of micafungin 100 mg daily and 150 mg daily were noninferior to a standard dosage of caspofungin for the treatment of candidemia and other forms of invasive candidiasis.
Assuntos
Antifúngicos/administração & dosagem , Candidíase/tratamento farmacológico , Fungemia/tratamento farmacológico , Lipoproteínas/administração & dosagem , Peptídeos Cíclicos/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Caspofungina , Relação Dose-Resposta a Droga , Método Duplo-Cego , Equinocandinas , Feminino , Humanos , Lipopeptídeos , Masculino , Micafungina , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
African histoplasmosis caused by Histoplasma capsulatum var. duboisii is an invasive fungal infection endemic in central and west Africa. Most of its ecology and pathogenesis remain unknown. H. capsulatum var. capsulatum is an AIDS-defining opportunistic infection in HIV-infected patients who are living in or have traveled to histoplasmosis-endemic areas. In contrast, reports concerning African histoplasmosis during HIV infection are rare, although both pathogens coexist in those regions. We report 3 cases of imported African histoplasmosis diagnosed in France in HIV-infected patients and a literature review on similar cases.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções por HIV/microbiologia , HIV-1/imunologia , Histoplasma/isolamento & purificação , Histoplasmose/virologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Pré-Escolar , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Histoplasmose/tratamento farmacológico , Histoplasmose/epidemiologia , Histoplasmose/microbiologia , Humanos , MasculinoRESUMO
BACKGROUND: Fungal aneurysms of the carotid artery are rare. We report here a case of Aspergillus fumigatus invasive sphenoidal sinusitis complicated by carotid artery aneurysms in a severely neutropenic patient who was successfully treated with a combination of antifungal therapy and embolization of all aneurysms. METHODS AND RESULTS: Carotid aneurysms were suspected when severe epistaxis occurred during follow-up for sinusitis. MRI angiograph and cerebral angiograph revealed 5 aneurysms involving the right intracavernous carotid artery. Coil endovascular embolization was successfully used for the first time in this context, and the patient is alive 2 years later. We also reviewed the literature and identified 10 cases of fungal carotid artery aneurysms. Aspergillus species was the most common fungal organism. All patients were immunocompromised and had to be treated surgically. CONCLUSIONS: Internal carotid arterial involvement is a rare but life-threatening complication of invasive fungal sinusitis. Fungal aneurysms should be diagnosed early, so that the embolization procedure can be performed before the occurrence of severe bleeding.
Assuntos
Aneurisma Infectado/diagnóstico , Aspergilose/diagnóstico , Aspergillus fumigatus , Doenças das Artérias Carótidas/diagnóstico , Adolescente , Adulto , Idoso , Aneurisma Infectado/epidemiologia , Aneurisma Infectado/microbiologia , Aneurisma Infectado/terapia , Aspergilose/epidemiologia , Aspergilose/microbiologia , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/microbiologia , Artéria Carótida Interna/microbiologia , Criança , Pré-Escolar , Embolização Terapêutica , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
Fungal mycetoma (or eumycetoma) are endemic diseases in tropical areas that have economic effects because of their chronic and disabling evolution. Classic treatments include surgery and antifungal drugs, but these have multiple side effects. We report a case of black-grain fungal mycetoma successfully treated with voriconazole without side effects. The duration of the treatment remains unclear, but must be prolonged because of the frequency of relapses.
Assuntos
Antifúngicos/uso terapêutico , Micetoma/tratamento farmacológico , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , Humanos , Madurella/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Recidiva , VoriconazolAssuntos
Ética em Pesquisa , Jornais como Assunto/ética , Má Conduta Profissional/ética , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Caspofungina , Aprovação de Drogas/métodos , Equinocandinas , Comitês de Ética em Pesquisa/ética , Humanos , Lipopeptídeos , Los Angeles , Estudos Multicêntricos como Assunto/ética , Estudos Multicêntricos como Assunto/métodos , Seleção de Pacientes , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/efeitos adversos , Pesquisa/normas , Estados UnidosRESUMO
Topical antifungal agents are not absorbed when given orally. They act by direct contact on the fungus, this type of action requires the simultaneous presence of antifungal and fungus for a minimum of time. There are a large number of compounds belonging to different families of antifungals: polyens, azoles, allylamine and morpholine and antiseptic substances. The treatment of oropharyngeal candidiasis is based on topical antifungal agents: amphotericin B or nystatin, imidazoles such as clotrimazole or miconazole. Systemic antifungal agents are indicated in case or poor compliance to topical agents, in prophylaxis of highly relapsing disease, in oesophageal candidiasis and in Candida onychomycosis. A topical antifungal agent is the first choice to treat Candida intertrigo. In any case predisposing factors should be eradicated or amended. Infection to Malassezia spp. are treated topically with azoles or selenium sulphur. Oral ketoconazole is an alternative in severe cases. Dermatophytosis requires a systemic antifungal treatment such as terbinafine in chronic, dry, moccassin type palmoplantar infection and for onychomycosis. Intertrigo and tinea corporis are treated with topical agents such as azoles, terbinafine or tolnaftate. Tinea capitis responds to oral griseofulvine, however a topical antifungal must be added to eradicate contagious conidia. Whatever the localisation is, an other superficial site of infection must be looked for and a source of infection should be investigated and eradicated.
Assuntos
Anti-Infecciosos Locais/uso terapêutico , Antifúngicos/uso terapêutico , Micoses/tratamento farmacológico , Animais , Candidíase Cutânea/tratamento farmacológico , Dermatomicoses/tratamento farmacológico , Dermatomicoses/microbiologia , Humanos , Micoses/microbiologiaRESUMO
BACKGROUND: Voriconazole is a novel triazole antifungal with a broad spectrum including Aspergillus species. We conducted an open, noncomparative multicenter study to evaluate the efficacy and safety of voriconazole in subacute invasive and chronic pulmonary aspergillosis (CPA). METHODS: Patients without profound neutropenia and a proven or probable diagnosis of subacute invasive aspergillosis (IA) or CPA received voriconazole 200 mg twice daily for a period of 4-24 weeks as primary or salvage therapy. Dose escalation was allowed if efficacy was suboptimal, and toleration and safety were satisfactory. Response was assessed by clinical, radiological and mycological changes. A complete or partial response in subacute IA and improved or stable in CPA were assessed as favorable responses. RESULTS: Of 39 patients treated, 36 were assessable. The majority of patients had subacute IA (n = 21), proven in all 11 extra-pulmonary and in 23/25 (92%) of the pulmonary cases. Voriconazole was given as primary therapy in 22 (61%). All patients receiving salvage therapy (n = 14) had refractory IA, having failed itraconazole or amphotericin B (AmB) or both. Overall, a complete or partial response was seen in 9/21(43%) of subacute IA and improved or stable in 12/15 (80%) of those with CPA. Adverse events, mainly liver function test abnormalities, skin reactions, and visual disturbances were mild and transient, leading to early discontinuation of treatment in 5 cases. CONCLUSIONS: In patients with subacute IA and CPA, voriconazole was efficacious as salvage or primary therapy.