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Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2020; 19: 158-166

Рекомендации 2020 года по диагностике и терапии инвазивного аспергиллеза у детей с онкогематологическими заболеваниями

Солопова Г. Г., Масчан А. А., Новичкова Г А.

https://doi.org/10.24287/1726-1708-2020-19-1-158-166

Аннотация

Инвазивный аспергиллез (ИА) – значимая причина в структуре инфекционной заболеваемости иммунокомпрометированных пациентов детского возраста. Наиболее высок риск развития ИА у пациентов, страдающих гемобластозами, преимущественно острыми миелоидными лейкозами, рецидивами острых лейкозов, и реципиентов трансплантации гемопоэтических стволовых клеток. Несмотря на современные возможности диагностики, профилактики и лечения, смертность от ИА по-прежнему остается высокой. Известно, что факторами, оказывающими наибольшее влияние на благоприятный исход ИА, являются ранняя диагностика и незамедлительное начало противогрибковой терапии. Международными сообществами разработаны рекомендации по лечению ИА у детей, однако российские рекомендации отсутствуют. Дополнительная проблема, характерная для России, – неудовлетворительный уровень микробиологической диагностики, приводящий либо к убежденности врачей-гематологов в очень низкой заболеваемости инвазивными грибковыми инфекциями, либо к нерациональному назначению противогрибковых препаратов. В данной статье представлен алгоритм диагностики и выбора терапии ИА у иммунокомпрометированных пациентов с учетом особенностей, характерных для детей с онкогематологическими заболеваниями.
Список литературы

1. Groll A., Castagnola E., Cesaro S., Dalle J.-H., Engelhard D., Hope W., et al. Fourth Europian Conference on infections in luekaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haematopoietic stem-cell transplantation. Lancet oncol 2014; 15: 327–40. DOI: 10.1016/S1470-2045(14)70017-8

2. Warris A., Lehrnbecher T., Roilides E., Castagnola E., Brüggemann R.J.M., Groll A. ESCMID-ECMM guidlines: diagnosis and management of invasive aspergillosis in neonates and children. Clinical Microbiology and Infection 2019. DOI: 10.1016/j.cmi.2019.05.019

3. Lernbecher T., Hassler A., Groll A.H., Bochennek K. Diagnostic approaches for invasive aspergillosis – specific considerations in the pediatric population. Frontiers in Microbiology 2018; 9 (518): 1–8. DOI: 10.3389/fmicb.2018.00518

4. Apsemidou A., Petridis N., Vyzantiadis T.-A., Tragiannidis A. Invasive aspergillosis in children: update of current guidlines. Mediterr J Hematol Infect Dis 2018; 10 (1): e2018048. DOI: 10.4084/MDHID.2018.048

5. Pana Z.D., Roilides E., Warris A., Groll A., Zaoutis T. Epidemiology of invasive fungal disease in children. JPIDS 2017; 6 (Suppl 1): 3–11. DOI: 10.1093/jpids/pix046

6. Katragkou A., Fisher B., Groll A.H., Roilides E., Walsh T. Diagnostic Imaging and invasive fungal diseases in children. Journal of Pediatric Infectious Diseases Society 2017; 6 (Suppl 1): 22–31. DOI: 10.1093/jpids/pix055

7. King J., Pana Z., Lernbecher T., Steinbach W.J., Warris A. Recognition and clinical presentation of ivasive fungal disease in neonates and children. JPIDS 2017; 6 (Suppl 1): 12–21. DOI: 10.1093/jpids/pix053

8. Anantasit N., Nuntacharruksa N., Incharoen P., Preutthipan A. Clinical and pathological correlation in pediatric invasive pulmonary aspergillosis. Frontiers in Pediatrics 2018; 6 (Art 31): 1–6. DOI: 10.3389/fped.2018.00031

9. Wattier R., Ramirez-Avila L. Pediatric invasive aspergillosis. Journal of Fungi 2016; 2: 19. DOI: 10.3390/jof2020019

10. Климко Н.Н., Шадривова О.В., Хостелиди С.Н., Десятик Е.А., Борзова Ю.В., Чернопятова Р.М. и соавт. Инвазивный аспергиллез: результаты многоцентрового исследования. Онкогематология 2014; 2: 13–9.

11. Warris A. The Europian pediatric mycology network (EPMyN): towards a better understanding and management of fungal infectiouns in children. Curr Fungal Infect Rep 2016; 10: 7–9.

12. Segal B., Herbrecht R., Stevens D., Ostrosky-Zeichner L., Sobel J., Viscoli C., et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and Europian Organization for Research and Treatment of Cancer Consensus Criteria. Clin Infect Dis 2008 Sep 1; 47 (5): 674–83. DOI: 10.1086/590566

13. Donnelly P., Chen S., Kauffman C., Steinbach W., Baddley J., Verweij P., et al. Revision and update of the consensus definitions of the invasive fungal disease from the European organization for research and treatment of cancer and the mycoses study group education and research consortium. Clinical Infectious Diseases 2019. DOI: 10.1093/cid/ciz 1008

14. Huppler A.R., Fisher B.T., Lernbecher T., Walsh T., Steinbach W.J. Role of molecular biomarkers in the diagnosis of invasive fungal diseases in children. JPIDS 2016; 6 (Suppl 1): 32–44. DOI: 10.1093/jpids/pix054

15. Morgan J., Hassan H., Cockle J., Lethaby Ch., James B., Phillips R. Critial review of current clinical practice guidelines for antifungal therapy in paediatric haematology and oncology. Support Care Cancer 2017. ISSN 1433–7339. DOI: 10.1007/s00520-016-3412-y

16. Wattier R., Dvorak C., Hoffman J., Brozovich A.A., Bin-Hussain I., Groll A., et al. A prospective, international cohort study of invasive mold infections in children. JPIDS 2015; 4 (4): 313–22. DOI: 10.1093/jpids/piu074

17. Huurneman L., Neely M., Veringa A., Perez F.D., Ramos-Martin V., Tissing W.J., et al. Pharmacodynamics of voriconazole in children: further step along the path to true individualized therapy. Antimicrob Agents Chemother 2016; 60: 2336–42.

18. Soler-Palacin P., Frick M.A., MartinNalda A., Lanaspa M., Pou L., Rosello E., et al. Voriconazole drug monitoring in the management of invasive fungal infection in immunocompromised children: a prospective study. J Antimicrob Chemother 2012; 67: 700–6. DOI: 10.1093/jac/dkr517

19. Lilienfeld-Toal M., Wagener J., Einsele H., Cornely O.A., Kurzai O. Invasive fungal infection. Dtsch Aratebl Int 2019; 116: 271–8. DOI: 10.3238/arztebl. 2019.0271

20. Масчан А.А., Клясова Г.А., Веселов А.В. Обзор рекомендаций американского общества по инфекционным болезням по лечению аспергиллеза. Клин микробиол антимикроб химиотер 2008; 10 (2): 133–70.

21. Qiu K., Liao X., Fang J., Xu H., Li Y., Huang K., Zhou D. Combination antifungal treatment for invasive fungal disease after hematopoietic stem cell transplantation in children with hematological disorders. Transpl Infect Dis. 2019; 21:e13066. DOI: 10.1111/tid.13066

22. Солопова Г.Г., Новичкова Г.А. Опыт внедрения алгоритма эмпирической антибактериальной терапии при развитии фебрильной нейтропении в Центре детской гематологии/онкологии». Вопросы гематологии/онкологии и иммунопатологии в педиатрии 2017; 16 (3): 35–47.

23. Hamdy R., Zaoutis T., Seo S. Antifungal stewardship considerations for adults and pediatrics. Virulence 2017; 8 (6): 658–72.

Pediatric Hematology/Oncology and Immunopathology. 2020; 19: 158-166

Updated 2020 guidelines for diagnosis and treatment of invasive aspergillosis in children with hematologic malignancy

Solopova G. G., Maschan A. A., Novichkova G. A.

https://doi.org/10.24287/1726-1708-2020-19-1-158-166

Abstract

Invasive aspergillosis (IA) is a major cause of morbidity in immunocompromised children. Patients with acute myeloid leukemia, relapsed acute luekemia and stem cells recipients are at high-risk for IA. Despite improving of diagnosis, prevention and treatment of IA mortality remains high. The main factors for favorable outcome of IA are early diagnosis and prompt appropriate treatment. Currently, few different international guidelines for IA have been developed but there are no Russian recommendations. An additional problem typical for Russia is poor level of microbiological diagnostic leading to underestimated frequency of IA or non-appropriate usage of antifungal drugs. This article presents an algorithm for diagnosis and treatment of IA in immunocompromised patient taking into account the characteristics of children with hematologic malignancy.
References

1. Groll A., Castagnola E., Cesaro S., Dalle J.-H., Engelhard D., Hope W., et al. Fourth Europian Conference on infections in luekaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haematopoietic stem-cell transplantation. Lancet oncol 2014; 15: 327–40. DOI: 10.1016/S1470-2045(14)70017-8

2. Warris A., Lehrnbecher T., Roilides E., Castagnola E., Brüggemann R.J.M., Groll A. ESCMID-ECMM guidlines: diagnosis and management of invasive aspergillosis in neonates and children. Clinical Microbiology and Infection 2019. DOI: 10.1016/j.cmi.2019.05.019

3. Lernbecher T., Hassler A., Groll A.H., Bochennek K. Diagnostic approaches for invasive aspergillosis – specific considerations in the pediatric population. Frontiers in Microbiology 2018; 9 (518): 1–8. DOI: 10.3389/fmicb.2018.00518

4. Apsemidou A., Petridis N., Vyzantiadis T.-A., Tragiannidis A. Invasive aspergillosis in children: update of current guidlines. Mediterr J Hematol Infect Dis 2018; 10 (1): e2018048. DOI: 10.4084/MDHID.2018.048

5. Pana Z.D., Roilides E., Warris A., Groll A., Zaoutis T. Epidemiology of invasive fungal disease in children. JPIDS 2017; 6 (Suppl 1): 3–11. DOI: 10.1093/jpids/pix046

6. Katragkou A., Fisher B., Groll A.H., Roilides E., Walsh T. Diagnostic Imaging and invasive fungal diseases in children. Journal of Pediatric Infectious Diseases Society 2017; 6 (Suppl 1): 22–31. DOI: 10.1093/jpids/pix055

7. King J., Pana Z., Lernbecher T., Steinbach W.J., Warris A. Recognition and clinical presentation of ivasive fungal disease in neonates and children. JPIDS 2017; 6 (Suppl 1): 12–21. DOI: 10.1093/jpids/pix053

8. Anantasit N., Nuntacharruksa N., Incharoen P., Preutthipan A. Clinical and pathological correlation in pediatric invasive pulmonary aspergillosis. Frontiers in Pediatrics 2018; 6 (Art 31): 1–6. DOI: 10.3389/fped.2018.00031

9. Wattier R., Ramirez-Avila L. Pediatric invasive aspergillosis. Journal of Fungi 2016; 2: 19. DOI: 10.3390/jof2020019

10. Klimko N.N., Shadrivova O.V., Khostelidi S.N., Desyatik E.A., Borzova Yu.V., Chernopyatova R.M. i soavt. Invazivnyi aspergillez: rezul'taty mnogotsentrovogo issledovaniya. Onkogematologiya 2014; 2: 13–9.

11. Warris A. The Europian pediatric mycology network (EPMyN): towards a better understanding and management of fungal infectiouns in children. Curr Fungal Infect Rep 2016; 10: 7–9.

12. Segal B., Herbrecht R., Stevens D., Ostrosky-Zeichner L., Sobel J., Viscoli C., et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and Europian Organization for Research and Treatment of Cancer Consensus Criteria. Clin Infect Dis 2008 Sep 1; 47 (5): 674–83. DOI: 10.1086/590566

13. Donnelly P., Chen S., Kauffman C., Steinbach W., Baddley J., Verweij P., et al. Revision and update of the consensus definitions of the invasive fungal disease from the European organization for research and treatment of cancer and the mycoses study group education and research consortium. Clinical Infectious Diseases 2019. DOI: 10.1093/cid/ciz 1008

14. Huppler A.R., Fisher B.T., Lernbecher T., Walsh T., Steinbach W.J. Role of molecular biomarkers in the diagnosis of invasive fungal diseases in children. JPIDS 2016; 6 (Suppl 1): 32–44. DOI: 10.1093/jpids/pix054

15. Morgan J., Hassan H., Cockle J., Lethaby Ch., James B., Phillips R. Critial review of current clinical practice guidelines for antifungal therapy in paediatric haematology and oncology. Support Care Cancer 2017. ISSN 1433–7339. DOI: 10.1007/s00520-016-3412-y

16. Wattier R., Dvorak C., Hoffman J., Brozovich A.A., Bin-Hussain I., Groll A., et al. A prospective, international cohort study of invasive mold infections in children. JPIDS 2015; 4 (4): 313–22. DOI: 10.1093/jpids/piu074

17. Huurneman L., Neely M., Veringa A., Perez F.D., Ramos-Martin V., Tissing W.J., et al. Pharmacodynamics of voriconazole in children: further step along the path to true individualized therapy. Antimicrob Agents Chemother 2016; 60: 2336–42.

18. Soler-Palacin P., Frick M.A., MartinNalda A., Lanaspa M., Pou L., Rosello E., et al. Voriconazole drug monitoring in the management of invasive fungal infection in immunocompromised children: a prospective study. J Antimicrob Chemother 2012; 67: 700–6. DOI: 10.1093/jac/dkr517

19. Lilienfeld-Toal M., Wagener J., Einsele H., Cornely O.A., Kurzai O. Invasive fungal infection. Dtsch Aratebl Int 2019; 116: 271–8. DOI: 10.3238/arztebl. 2019.0271

20. Maschan A.A., Klyasova G.A., Veselov A.V. Obzor rekomendatsii amerikanskogo obshchestva po infektsionnym boleznyam po lecheniyu aspergilleza. Klin mikrobiol antimikrob khimioter 2008; 10 (2): 133–70.

21. Qiu K., Liao X., Fang J., Xu H., Li Y., Huang K., Zhou D. Combination antifungal treatment for invasive fungal disease after hematopoietic stem cell transplantation in children with hematological disorders. Transpl Infect Dis. 2019; 21:e13066. DOI: 10.1111/tid.13066

22. Solopova G.G., Novichkova G.A. Opyt vnedreniya algoritma empiricheskoi antibakterial'noi terapii pri razvitii febril'noi neitropenii v Tsentre detskoi gematologii/onkologii». Voprosy gematologii/onkologii i immunopatologii v pediatrii 2017; 16 (3): 35–47.

23. Hamdy R., Zaoutis T., Seo S. Antifungal stewardship considerations for adults and pediatrics. Virulence 2017; 8 (6): 658–72.