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Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial.

ABSTRACT: Early evidence suggests the efficacy of voriconazole for chronic pulmonary aspergillosis (CPA). We conducted a prospective, open, multicenter trial to evaluate the efficacy and safety of voriconazole for proven CPA in minimally or non-immunocompromised patients. Patients had CPA confirmed by chest computed tomography (CT) and/or endoscopy, positive Aspergillus culture from a respiratory sample, and positive serologic test for Aspergillus precipitins. Patients received voriconazole (200 mg twice daily) for a period of 6-12 months and were followed for 6 months after the end of therapy (EOT). The primary endpoint was global success at 6 months, defined as complete or partial (?50 % improvement) radiological response and mycological eradication. Forty-one patients with confirmed CPA were enrolled. All patients had A. fumigatus as the etiologic agent. By EOT, five patients had died from comorbidities and seven had discontinued voriconazole due to toxicity. The global success rate at 6 months was 13/41 (32 %): 10/19 (53 %) for chronic necrotizing aspergillosis and 3/22 (14 %) for chronic cavitary aspergillosis (p?=?0.01). The respective success rates at EOT were 58 and 32 %. Clinical symptoms and quality of life also improved during treatment. Voriconazole is effective for CPA, with acceptable toxicity. The response rate is higher and obtained more rapidly in necrotizing than cavitary forms.

SUBMITTER: Cadranel J

PROVIDER: S-EPMC3479377 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial.

Cadranel J J Philippe B B Hennequin C C Bergeron A A Bergot E E Bourdin A A Cottin V V Jeanfaivre T T Godet C C Pineau M M Germaud P P

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 20120711 11

Early evidence suggests the efficacy of voriconazole for chronic pulmonary aspergillosis (CPA). We conducted a prospective, open, multicenter trial to evaluate the efficacy and safety of voriconazole for proven CPA in minimally or non-immunocompromised patients. Patients had CPA confirmed by chest computed tomography (CT) and/or endoscopy, positive Aspergillus culture from a respiratory sample, and positive serologic test for Aspergillus precipitins. Patients received voriconazole (200 mg twice ...[more]

PMID: 22782438

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Project description:BackgroundChronic pulmonary aspergillosis (CPA) is an underdiagnosed and misdiagnosed disease and now increasingly recognised. However, the diagnosis of CPA remains challenging. In this study, we aimed to investigate the diagnostic values of serum Aspergillus-specific IgG, IgA and IgM antibodies in patients with CPA.MethodsThe prospective study was performed at Chinese People's Liberation Army General Hospital in Beijing, from January 2017 to December 2017. Adult patients with lung lesions presented as cavity, nodule, mass, bronchiectasis or severe fibrotic destruction with at least two lobes in CT imaging were enrolled. One hundred healthy persons were also enrolled as additional controls. The serum levels of Aspergillus-specific IgG, IgA and IgM antibodies and galactomannan (GM) levels were measured simultaneously by plate ELISA kit.ResultsA total of 202 patients were enrolled in this study, including 42 CPA patients, 60 non-CPA patients and 100 healthy persons. The most common underlying lung diseases in CPA patients were bronchiectasis (28.6%) and COPD (19.0%). The most common symptoms in the CPA patients were cough (76.2%), sputum (71.4%), and fever (45.2%); chest pain (4.8%) was infrequent. Receiver operating characteristic (ROC) curve analysis revealed that the optimal CPA diagnostic cut-off of Aspergillus-specific IgG, IgA and IgM assays and GM test were 89.3 AU/mL, 8.2 U/mL, 73.3 AU/mL and 0.5μg/L, respectively. The serum levels of Aspergillus-specific IgG and IgA in CPA patients were higher than these in non-CPA patients or healthy persons. The sensitivities and specificities of Aspergillus-specific IgG, IgA, IgM tests and GM test were 78.6 and 94.4%, 64.3 and 89.4%, 50.0 and 53.7% and 71.4 and 58.1%, respectively.ConclusionsThe sensitivity and specificity of serum Aspergillus-specific IgG assay are satisfactory for diagnosing CPA, while the performance of Aspergillus-specific IgA assay is moderate. Aspergillus-specific IgM assay and serum GM test have limited value for CPA diagnosis.Trial registrationNCT03027089 . Registered 20 January 2017.

Project description:IntroductionCritically ill patients with chronic obstructive respiratory diseases (CORD) who require intensive care unit (ICU) admission are at particular risk for invasive bronchial-pulmonary aspergillosis (IBPA). The purpose of this study is to investigate clinical features for rapid recognition of IBPA in critically ill patients with CORD.MethodsWe included 55 consecutive CORD patients in a respiratory ICU in a prospective, single-center, cohort study. In this study, IBPA combined two entities: ATB and IPA.ResultsThirteen of 55 patients were diagnosed with IBPA. Before ICU admission, three variables were independent predictors of IBPA with statistical significance: more than three kinds of antibiotics used before the ICU admission, accumulated doses of corticosteroids (>350 mg) received before the ICU admission, and APACHE II scores >18 (OR, 1.208; P = 0.022; OR, 8.661; P = 0.038; and OR, 19.488; P = 0.008, respectively). After ICU admission, more IBPA patients had a high fever (>38.5 °C) (46.2% versus 11.9%; P = 0.021), wheeze without exertion (84.6% versus 50.0%; P = 0.027), dry rales (84.6% versus 40.4%; P = 0.005), higher white blood cell counts (21 × 109/L versus 9.4 × 109/L; P = 0.012), lower mean arterial pressures (77.9 mm Hg versus 90.5 mm Hg; P = 0.019), and serum creatinine clearances (36.2 ml/min versus 68.8 ml/min; P < 0.001), and liver-function and coagulation abnormalities. Bronchospasm, sputum ropiness, and plaque formation were more common for IBPA patients during bronchoscopy (66.7% versus 14.3%; P = 0.082; 18% versus 0; P = 0.169; and 73% versus 13%; P = 0.003, respectively). More IBPA patients had nodules and patchiness on chest radiograph on day 1 of admission, which rapidly progressed to consolidation on day 7. IBPA mortality was higher than that of non-IBPA patients (69.2% versus 16.7%; P = 0.001).ConclusionsIBPA may be suspected in critically ill CORD patients with respiratory failure and clinical and bronchoscopic manifestations of severe infection, bronchospasm, and rapid progression of radiologic lesions that are irresponsive to steroids and antibiotics. To avoid misdiagnosis and establish the microbiologic etiology, early bronchoscopy and tight radiologic follow-up should be performed.

Project description:There is a paucity of evidence surrounding the optimal antifungal therapy for use in chronic pulmonary aspergillosis (CPA) and the duration of therapy remains unclear. We retrospectively evaluated treatment outcomes, including change in quality of life scores (St George's Respiratory Questionnaire (QoL)), weight and Aspergillus IgG at 6 and 12 months following initiation of therapy in a cohort of 206 CPA patients referred to the UK National Aspergillosis Centre (NAC), Manchester between April 2013 and March 2015. One hundred and forty-two patients (69%) were azole naïve at presentation and 105 (74%) (Group A) were commenced on itraconazole, 27 (19%) on voriconazole, and 10 (7%) were not treated medically. The remainder (64 patients, 31%) had previously trialled, or remained on, azole therapy at inclusion (Group B) of whom 46 (72%) received itraconazole, 16 (25%) voriconazole, and 2 (3%) posaconazole. Initial therapy was continued for 12 months in 78 patients (48%) of those treated; the azole was changed in 62 (32%) patients and discontinued in 56 (29%) patients for adverse reactions (32, 57%), azole resistance (11, 20%), clinical failure (8, 14%) or clinical stability (5, 9%). Azole discontinuation rates were higher in Group B than in Group A (42% vs. 22%, p = 0.003). For all patients who survived, weight increased (median of 62.2Kg at baseline, to 64.8 at 12 months), mean Aspergillus IgG declined from 260 (baseline) to 154 (12 months) and QoL improved from 62.2/100 (baseline) to 57.2/100 (12 months). At 12 months, there was no difference in median survival between Groups A and B (95% vs. 91%, p = 0.173). The rate of emergence of resistance during therapy was 13% for itraconazole compared to 5% for voriconazole. Bronchial artery embolization was done in 9 (4.4%) patients and lobectomy in 7 (3.2%). The optimal duration of azole therapy in CPA is undetermined due to the absence of evidenced based endpoints allowing clinical trials to be undertaken. However we have demonstrated itraconazole and voriconazole are modestly effective for CPA, especially if given for 12 months, but fewer than 50% of patients manage this duration. This suggests extended therapy may be required for demonstrable clinical improvement.

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Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial.

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Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial.

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