Itraconazole therapy in aspergillosis: Study in 49 patients

doi:10.1016/0190-9622(90)70263-H

Journal of the American Academy of Dermatology

Volume 23, Issue 3, Part 2, September 1990, Pages 607-614

https://doi.org/10.1016/0190-9622(90)70263-H Get rights and content

Itraconazole, 200 to 400 mg once daily, was administered to 49 patients with different types of aspergillosis: pulmonary aspergilloma (14 patients), chronic necrotizing pulmonary aspergillosis (14), and invasive aspergillosis (21). Itraconazole was prescribed alone or in combination or after treatment with amphotericin B and flucytosine. Of 14 aspergilloma patients, 2 were cured and 8 had symptomatic improvement. In chronic necrotizing pulmonary aspergillosis, 7 of 14 patients were cured and 6 improved significantly. In invasive aspergillosis treatment failed in 6 patients and 15 were cured. Itraconazole can be an alternative to amphotericin B in the treatment of invasive aspergillosis and chronic necrotizing pulmonary aspergillosis. In aspergillorna itraconazole may be useful in inoperable cases.

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The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.
CT Imaging Assessment of Response to Treatment in Chronic Pulmonary Aspergillosis
2016, Chest
Long-term antifungal therapy is usually the only treatment option for chronic pulmonary aspergillosis. However, response rates are difficult to compare because the reported clinical, mycologic, or radiologic criteria are not standardized. Objective parameters are therefore needed. To define the most relevant CT imaging variables in assessment of response to treatment, we investigated changes over time in CT imaging variables.
Changes in CT imaging variables were assessed by systematic analysis of the CT scan findings of 36 patients at diagnosis and 6 months after initiation of treatment. The relevant radiologic variables were determined by selecting those showing significant changes over time. Two experienced thoracic radiologists, blinded for clinical and serologic response, independently performed CT scan analyses. Interreader agreement and concordance between radiologic and clinical response were evaluated.
Of the 36 patients, seven experienced clinical deterioration while undergoing therapy. Significantly evolving radiologic variables included cavity and pleural wall thickening (P < .05), which were associated with clinical improvement. There was a strong association between fungus ball disappearance and cavity/pleural wall thickening reduction and clinical improvement (P = .04). There was poor agreement between size changes of cavities or nodules, and clinical evolution (Cohen’s κ, –0.13 to –0.24).
Variations in cavity and pleural wall thickness may be the most relevant CT imaging variables for assessing response to treatment. Loss of fungus ball is strongly associated with clinical and radiologic improvement, but cavity size changes are unrelated to chronic pulmonary aspergillosis evolution. All these CT imaging variables may be applied in future clinical trials to assess treatment outcome.
Recent advances in chronic pulmonary aspergillosis
2016, Respiratory Investigation
Chronic pulmonary aspergillosis (CPA) is a slowly progressing pulmonary syndrome caused by Aspergillus spp. Specific knowledge regarding the disease entity, diagnosis method, and management is needed. This review focuses on the recent advances in our understanding of CPA. A new clinical disease entity of chronic progressive pulmonary aspergillosis consisting of chronic necrotizing pulmonary aspergillosis and chronic cavitary pulmonary aspergillosis is proposed. Although newer antifungals are not available, evidence describing the treatment of CPA is accumulating. Longer administration of azoles is required for a better prognosis, but there is a risk of inducing azole resistance. Therapeutic drug monitoring and patient education are required. Establishing a drug-susceptibility test that can be performed in the general laboratory and the referral center are also important. Although the number of publications regarding CPA is growing, there are still many unanswered questions. Additional evidence and translational research regarding diagnosis, management, and drug resistance are urgently needed to improve the outcome of CPA.
Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease
2014, Revista Iberoamericana de Micologia
La aspergilosis pulmonar invasiva (API) se observa en pacientes inmunodeprimidos por una enfermedad oncohematológica o en receptores de un trasplante alogénico de progenitores hematopoyéticos, y, con menor frecuencia, en pacientes con enfermedad pulmonar obstructiva crónica (EPOC).
El deterioro de la actividad mucociliar, la disminución de la función de los macrófagos y neutrófilos por la acción de los esteroides y el uso de antibióticos de amplio espectro intervienen en el desarrollo de la API en los pacientes con EPOC. Tanto los pacientes colonizados como los que ya tienen API son de edad avanzada, se hallan en estadios evolucionados de EPOC (GOLD ≥ III) y presentan un gran número de comorbilidades. La mortalidad en estos pacientes también es alta debido a la dificultad de obtener un diagnóstico definitivo de API en la EPOC. Los principales signos clínicos y radiológicos de API son inespecíficos en la EPOC y las muestras tisulares que confirman el diagnóstico son a menudo difíciles de obtener.
El mal pronóstico de la API en pacientes con EPOC mejoraría con un diagnóstico más precoz que permitiera la pronta instauración del tratamiento apropiado. Algunas herramientas, como escalas y algoritmos basados en factores de riesgo de API, podrían ayudar al reconocimiento temprano de esta complicación en la EPOC.
Invasive pulmonary aspergillosis (IPA) is a common infection in immunocompromised patients with hematological malignancies or allogenic stem cell transplantation, and is less frequent in the context of chronic obstructive pulmonary disease (COPD).
Mucociliary activity impairment, immunosuppression due to the inhibition of alveolar macrophages and neutrophils by steroids, and receiving broad-spectrum antibiotics, play a role in the development of IPA in COPD patients. Colonized patients or those with IPA are older, with severe CODP stage (GOLD ≥ III), and have a higher number of comorbidities. The mortality rate is high due to the fact that having a definitive diagnosis of IPA in COPD patients is often difficult. The main clinical and radiological signs of IPA in these types of patients are non-specific, and tissue samples for definitive diagnosis are often difficult to obtain.
The poor prognosis of IPA in COPD patients could perhaps be improved by faster diagnosis and prompt initiation of antifungal treatment. Some tools, such as scales and algorithms based on risk factors of IPA, may be useful for its early diagnosis in these patients.
Recurrence of chronic pulmonary aspergillosis after discontinuation of maintenance treatment by antifungal triazoles
2014, Journal of Infection and Chemotherapy
Citation Excerpt :
However, multivariate analysis indicated only expansion of the CPA-affected area to more than one lung lobe as a risk factor for recurrence. CPA is a persistent infectious disease that needs long treatment duration, and some of the patients need antifungal oral triazoles, e.g. itraconazole and voriconazole, as maintenance therapy for life long [3,8]. Although we need to clarify criteria for the possible completion of the triazole therapy and risks of CPA recurrence after the treatment completion, the data has been very scarce.
To assess the prevalence and risk factors of recurrence of chronic pulmonary aspergillosis (CPA) after discontinuation of antifungal triazoles.
We reviewed the medical records of CPA patients who achieved resolution of clinical and radiographic manifestations and stopped taking antifungal triazoles between June 2006 and June 2012 at Tokyo National Hospital. We evaluated whether there was CPA recurrence within 1 year after treatment cessation and investigated risk factors for relapse. The association of anti-Aspergillus antibody conversion with CPA recurrence was also reviewed.
A total of 39 patients were included in this study and there was CPA recurrence in 14 patients. Compared with the Non-recurrence group, the Recurrence group exhibited 1) younger age (p = 0.017), 2) more than one lung lobe affected by CPA more frequently (p = 0.008), 3) longer duration needed to remit manifestations of chest radiograph (p = 0.031), 4) longer antifungal treatment duration (p = 0.042). The present study did not reveal an association between negative conversion of serum anti-Aspergillus antibody and recurrence risk. Multivariate logistic regression analysis revealed that patients with CPA with affected area of more than one lung lobe had increased risk (odds ratio, 10.20; 95% confidence interval, 1.49–69.77; p = 0.018).
CPA recurrence can be seen in about one-third of cases after discontinuing azole treatment. We should make decisions about treatment duration and follow up depending on the severity of each case, particularly on the expansion of CPA-affected area.
Clinical practice guidelines for the treatment of invasive Aspergillus infections in adults in the Middle East region: Expert panel recommendations
2014, Journal of Infection and Public Health
The incidence of invasive Aspergillus infections in the Middle East continues to rise with the increase in the number of immunocompromised patients, and carries significant morbidity and mortality. A panel of experts analysed the evidence from the most recent international guidelines and relevant published literature to reach consensus and develop clear clinical practice guidelines to aid diagnosis and treatment of invasive Aspergillus infections in the Middle East. Disease-specific recommendations were provided for the management of invasive aspergillosis. The expert panel acknowledged that these guidelines should be followed as closely as possible but used alongside clinical judgement.

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Itraconazole therapy in aspergillosis: Study in 49 patients

Am J Med

J Infect

Am J Med

Itraconazole: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in superficial and systemic mycoses

Drugs

In vitro and in vivo models to study the activity of antifungals against Aspergillus