Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline

Abstract

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.

Invasive Aspergillosis and Mucormycosis in Oncohematological Patients

“…Внашемисследованииубольныхмукормикозомхи-рургическое лечение применяли достоверно чаще (37%против3%,p=0,0001).Такжепримукормико-зедостоверночащеиспользоваликомбинированную антимикотическуютерапию(42%против8%,p=0,01). Всоответствиисмеждународнымирекомендациям ECIL-6иESCMID-ECMM-ERSпрепаратамивыбора длялеченияИАявляютсявориконазолиизавукона зол [2,3,27].Нашипациентыполучалипреимущественно вориконазол(74%).…”

“…Дляинвазивногоаспергиллеза(ИА)имукормико-захарактернысходныефакторыриска,клинические ирентгенологическиепризнаки.Вместестеммукор-микоз и ИА различаются по методам диагностики, профилактикиилечения,аосновнымиметодамидиф-ференциальнойдиагностикиэтихИМостаютсяпря-мая микроскопия биосубстратов и гистологическое исследование [1][2][3].…”

Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives

“…Given the high intra-and interpatient variability of voriconazole and itraconazole plasma concentrations, TDM has been strongly recommended by the European Conference on Infections in Leukemia-6 (ECIL-6) and the ESCMID/ECMM/ERS 2017 guidelines for both triazoles, to ensure efficacy and avoid toxicity (Table 2) [28,29]. For voriconazole, the first trough level should be obtained between days 2 and 5 and, given the high intrapatient variability, optimally repeated once per week, to ensure plasma concentrations remain within the small therapeutic window of > 1 mg/L and < 6 mg/L [30,31].…”

Isavuconazole: Case Report and Pharmacokinetic Considerations

“…It is worth to note that the enzymatic activity of CYPs could vary from one patient to another depending on endogenous factors (e.g., genetic polymorphisms) and/or exogenous factors (e.g., concomitant pharmacologic inducers, substrates, or inhibitors) [4]; therefore, intra- and interindividual pharmacokinetic variability may influence the metabolism and clinical outcome of VCZ and PCZ even when administered in standard doses [2-4]. Therefore, international guidelines recommend therapeutic drug monitoring (TDM) for monitoring and optimizing therapy with VCZ or PCZ [7-9]. …”

“…These patients usually present with a burden of comorbidities and pharmacologic treatments that might well change the pharmacokinetics (PK) and hence, the efficacy or toxicity of IVZ. Due to the lack of conclusive data and formally approved guidelines, one cannot exclude that TDM might actually prove useful for real-life patients [7]. …”