Инвазивный кандидоз у детей
https://doi.org/10.22625/2072-6732-2021-13-2-14-26
Аннотация
Распространенность инвазивного кандидоза в педиатрических стационарах составляет от 4,3 до 15,2 на 10 000 госпитализированных, в отделениях реанимации и интенсивной терапии – от 3,5 до 7 случаев на 1000, при проведении трансплантации гемопоэтических стволовых клеток – 2,9%. Средний срок пребывания пациента в стационаре до развития инвазивного кандидоза варьирует от 21 до 56 дней, в отделениях реанимации и интенсивной терапии превышает 15 суток. Знание факторов риска (пребывание в отделениях реанимации и интенсивной терапии ≥15 дней, применение антибактериальных лекарственных средств и парентерального питания, активное злокачественное новообразование и пр.) позволяет выявить пациентов с высоким (10– 46%) риском развития инвазивного кандидоза. Сandida albicans остается ведущим возбудителем инвазивного кандидоза у детей, но увеличилось количество инфекций, вызванных не-albicans Candida spp. и отмечен рост устойчивости возбудитетей инвазивного кандидоза к азольным антимикотикам. Основной клинический вариант инвазивного кандидоза у детей – кандидемия, возможно поражение центральной нервной системы, органов брюшной полости, органов зрения, сердца, костей и суставов, почек, кожи и подкожной клетчатки, а также хронический диссеминированный (гепатолиенальный) кандидоз. Посев крови (основной метод лабораторной диагностики инвазивного кандидоза) отличается низкой чувствительностью и требует длительного времени. Методы некультуральной диагностики ИК (определение 1,3-β-d-глюкана, маннана и антиманнановых антител, Т2 Candida) у детей изучены недостаточно. Основные препараты для лечения инвазивного кандидоза у детей – эхинокандины (анидулафунгин и пр.), кроме того, необходима замена центрального венозного катетера. Общая летальность педиатрических пациентов в течение 30 дней после диагностики инвазивного кандидоза составляет от 37% до 44%.
Об авторах
Н. Н. КлимкоРоссия
заведующий кафедрой клинической микологии, аллергологии и иммунологии, д.м.н., профессор,
Санкт-Петербург
О. П. Козлова
Россия
ассистент кафедры клинический микологии, аллергологии и иммунологии,
Санкт-Петербург
Список литературы
1. Zaoutis T.E., Prasad P.A., Localio A.R., Coffin S.E., Bell L.M., Walsh T.J., Gross R. Risk factors and predictors for candidemia in pediatric intensive care unit patients: implications for prevention.Сlinical infectious disease.2010;51(5):e38-45. doi: 10.1086/655698.
2. Pfaller M.A., Diekema D.J. Epidemiology of invasive candidiasis: a persistent public health problem. Clinical Microbiology Reviews. 2007;20(1):133-163. doi:10.1128/CMR.00029-06.
3. Pana Z.D., Roilides E., Warris A., Groll A.H., Zaoutis T. Epidemiology of invasive fungal disease in children. Journal of the Pediatric Infectious Diseases Society. 2017; 6(1):S3-S11. doi: 10.1093/jpids/pix046.
4. Steinbach W.J. Pediatric invasive candidiasis: epidemiology and diagnosis in children. Journal of Fungi. 2016; 2(1):5. Published 2016 Jan 8. doi:10.3390/jof2010005.
5. Steinbach W.J., Roilides E., Berman D., Hoffman J.A., Groll A.H., Bin-Hussain I., Palazzi D.L., Castagnola E., Halasa N., Velegraki A., Dvorak C.C., Charkabarti A., Sung L., Danziger-Isakov L., Lachenauer C., Arrieta A., Knapp K., Abzug M.J., Ziebold C., Lehrnbecher T., Klingspor L., Warris A., Leckerman K., Martling T., Walsh T.J., Benjamin D.K., Zaoutis T.E. International Pediatric Fungal Network. Results from a prospective, international, epidemiologic study of invasive candidiasis in children and neonates. The Pediatric Infectious Disease Journal. 2012; 31(12): 1252-1257. doi: 10.1097/INF.0b013e3182737427. PMID: 22982980.
6. Pana Z.D., Kotzadamis D., Roilides E. Invasive Candidiasis in Pediatric Intensive Care Unit. The Pediatric Infectious Disease Journal. 2018 Dec; 37 (12):1309-1311 doi: 10.1097/INF.0000000000002186.
7. Маркова, И.В. Инвазивный кандидоз/кандидемия у детей после трансплантации гемопоэтических стволовых клеток И.В. Маркова [и др.] // Вопросы гематологии/ онкологии и иммунопатологии в педиатрии. – 2019. – № 18 (2). – С. 53‒58.
8. Pasqualotto A., de Moraes A., Zanini R., Severo L. Analysis of independent risk factors for death among pediatric patients with candidemia and a central venous catheter in place. Infect Control Hospital Epidemiology. 2007; 28:799-804.
9. Tragiannidis A., Fegeler W., Rellensmann G., et al. Candidaemia in a European Paediatric University Hospital: A 10-year observational study. Clinical Microbiology Infection. 2012;18:E27-E30.
10. Caggiano G., Lovero G., De Giglio O., et al. Candidemia in the Neonatal Intensive Care Unit: A Retrospective, Observational Survey and Analysis of Literature Data. Biomed Research International. 2017;2017:7901763. doi:10.1155/2017/7901763.
11. Strollo S., Lionakis M.S., Adjemian J., Steiner C.A., Prevots D.R.. Epidemiology of Hospitalizations Associated with Invasive Candidiasis, United States, 2002-2012. Emerging Infectious Diseases journal. 2016;23(1):7-13. doi:10.3201/eid2301.161198.
12. Jordan I., Balaguer M., Lopez-Castilla J.D., Belda S., Shuffelman C., Garcia-Teresa M.A., Madurga P., FloresGonzalez J.C., Anguita P., Aguilar L.; ERICAP Study Group. Per-species risk factors and predictors of invasive Candida infections in patients admitted to pediatric intensive care units: development of ERICAP scoring systems.The Pediatric Infectious Disease Journal. 2014;33(8):187-93. doi: 10.1097/INF.0000000000000274. PMID: 24717965.
13. Rodrigues L.S., Motta F.A., Picharski G.L., Vasconcelos T.M., Riccieri M.C., Dalla-Costa L.M. Invasive candidiasis: Risk factor for mortality in a pediatric tertiary care hospital in south of Brazil. Medicine (Baltimore). 2019; 98(23):e15933. doi:10.1097/MD.0000000000015933.
14. Hammoud M.S., Al-Taiar A., Fouad M., Raina A., Khan Z. Persistent candidemia in neonatal care units: risk factors and clinical significance. International Journal of Infectious Diseases. 2013;17:624-628.
15. Motta F.A., Dalla-Costa L.M., Muro M.D., Cardoso M.N., Picharski G.L., Jaeger G., et al. Risk factors for candidemia mortality in hospitalized children. Journal Pediatric (Rio J). 2017;93:165-171.
16. Blyth C.C., Chen S.C., Slavin M.A., Serena C., Nguyen Q., Marriott D., Ellis D., Meyer W., Sorrell T.C. Not just little adults: candidemia epidemiology, molecular characterization, and antifungal susceptibility in neonatal and pediatric patients. Pediatrics. 2009 May; 123(5):1360-8.
17. Tsai M.H., Hsu J.F., Chu S.M., et al. Clinical and microbiological characteristics, and impact of therapeutic strategies on the outcomes of children with candidemia. Scientific Reports. 2017;7(1):1083. Published 2017 Apr 24. doi:10.1038/s41598-017-01123-6
18. Oeser C., Lamagni T., Heath P.T., Sharland M., Ladhani S. The epidemiology of neonatal and pediatric candidemia in England and Wales, 2000–2009. The Pediatric Infectious Disease Journal. 2013; 32:23–6.
19. Warris A. European Paediatric Mycology Network (EPMyN)* The European Paediatric Mycology Network (EPMyN): towards a better understanding and management of fungal infections in children. Current Fungal Infection Reports. 2016; 10:7–9.
20. Santolaya M.E., Alvarado T., Queiroz-Telles F., et al. Active surveillance of candidemia in children from Latin America: a key requirement for improving disease outcome. The Pediatric Infectious Disease Journal. 2014; 33:40–4.
21. Hsu J.F., Lai M.Y., Lee C.W., et al. Comparison of the incidence, clinical features and outcomes of invasive candidiasis in children and neonates. BMC Infectious Diseases. 2018;18(1):194. Published 2018 Apr 24. doi:10.1186/s12879-018-3100-2.
22. Dutta A., Palazzi D.L. Candida non-albicans versus Candida albicans fungemia in the non-neonatal pediatric population. The Pediatric Infectious Disease Journal. 2011 Aug; 30(8):664-8.
23. Warris A., Pana Z.D., Oletto A., Lundin R., Castagnola E., Lehrnbecher T., Groll A.H., Roilides E.; EUROCANDY Study Group. Etiology and Outcome of Candidemia in Neonates and Children in Europe: An 11-year Multinational Retrospective Study. The Pediatric Infectious Disease Journal. 2020 Feb;39(2):114-120. doi: 10.1097/INF.0000000000002530.
24. Prasad P.A., Fisher B.T., Coffin S.E., Walsh T.J., McGowan K.L., Gross R., Zaoutis T.E. Pediatric Risk Factors for Candidemia Secondary to Candida glabrata and Candida krusei Species. Journal of the Pediatric Infectious Diseases Society. 2013 Sep;2(3):263-6. doi: 10.1093/jpids/pis093. Epub 2012 Oct 30. PMID: 24009984; PMCID: PMC3761321.
25. Bakir M., Cerikcioglu N., Barton R., Yagci A. Epidemiology of candidemia in a Turkish tertiary care hospital. // APMIS. 2006 Sep; 114(9):601-10.
26. Sutçг M., Acar M., Genç G. E., Kokçu İ., Akturk H., Atay G., Torun S. H., Salman, N., Erturan, Z., Somer A. Evaluation of Candida species and antifungal susceptibilities among children with invasive candidiasis. Turk pediatri arsivi, 2017; 52(3): 145–153.
27. Hope W.W., Castagnola E., Groll A.H., Roilides E., Akova M., Arendrup M.C., et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp. Clinical Microbiology and Infection. 2012; 18(Suppl 7):38–52.
28. Tissot F., Agrawal S., Pagano L., Petrikkos G., Groll A.H., Skiada A., et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017; 102(3):433–44.
29. King J., Pana Z.D., Lehrnbecher T., Steinbach W.J., Warris A. Recognition and Clinical Presentation of Invasive Fungal Disease in Neonates and Children. Journal of the Pediatric Infectious Diseases Society. 2017;6(suppl_1):S12-S21. doi:10.1093/jpids/pix053.
30. McCullers J.A., Vargas S.L., Flynn P.M., et al. Candidal meningitis in children with cancer. Clinical Infectious Diseases. 2000; 31:451–7.
31. Fierro J.L., Prasad P., Fisher B., Gerber J., Coffin S.E., Walsh T.J., Zaoutis T.E. Ocular manifestations of candidemia in a pediatric population. The Pediatric Infectious Disease Journal. 2013;32:84–86. doi: 10.1097/INF.0b013e31826f547c.
32. Baley J.E., Ellis F.J. Neonatal candidiasis: ophthalmologic infection. Seminars in Perinatology. 2003; 27:401–5.
33. Pappas P.G., Kauffman C.A., Andes D.R., et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2016; 62:e1–50.
34. Gamaletsou M.N., Kontoyiannis D.P., Sipsas N.V., et al. Candida osteomyelitis: analysis of 207 pediatric and adult cases (1970–2011). Clinical Infectious Diseases. 2012; 55:1338–51.
35. Gamaletsou M.N., Rammaert B., Bueno M.A., et al. Candida arthritis: analysis of 112 pediatric and adult cases. Open Forum Infectious Diseases. 2016; 3:ofv207.
36. Garcia-Agudo R., Garcia-Martos P. Clinical and microbiological aspects of fungal peritonitis in peritoneal dialysis. Nefrologia. 2009;29(6):506-17. Spanish. doi: 10.3265/Nefrologia.2009.29.6.5650.en.full.
37. Raaijmakers R., Schroder C., Monnens L., Cornelissen E., Warris A. Fungal peritonitis in children on peritoneal dialysis. Pediatric Nephrology. 2007 Feb;22(2):288-93. doi: 10.1007/s00467-006-0289-x. Epub 2006 Nov 17. PMID: 17111161.
38. Lin Y.T., Hsieh K.S., Chen Y.S., et al. Infective endocarditis in children without underlying heart disease. Journal of Microbiology, Immunology. 2013; 46:121–8.
39. Kara A., Devrim İ., Meşe T., Bayram N., Yılmazer M., G lfidan G. The Frequency of Infective Endocarditis in Candida Bloodstream Infections: a Retrospective Study in a Child Hospital. Brazilian Journal of Cardiovascular Surgery. 2018; 33(1):54- 58. doi:10.21470/1678-9741-2017-0049
40. Ruhnke M., Schwartz S. Recent developments in the management of invasive fungal infections in patients with oncohematological diseases. Therapeutic Advances in Hematology. 2016; 7(6):345-359. doi:10.1177/2040620716656381.
41. Castagnola E., Faraci M., Moroni C., et al. Invasive mycoses in children receiving hemopoietic SCT. Bone Marrow Transplant. 2008; 41(Suppl 2):S107–11.
42. Donker A.E., Mavinkurve-Groothuis A.M., van Die L.E., et al. Favorable outcome of chronic disseminated candidiasis in four pediatric patients with hematological malignancies. Medical Mycology. 2012; 50:315–9.
43. Walsh T.J., Katragkou A., Chen T., Salvatore C.M., Roilides E. Invasive Candidiasis in Infants and Children: Recent Advances in Epidemiology, Diagnosis, and Treatment. Journal of Fungi. 2019; 5(1):11. Published 2019 Jan 24. doi:10.3390/jof5010011.
44. Roilides E. Invasive candidiasis in neonates and children. Early Human Development. 2011;87:S75–S76. doi: 10.1016/j.earlhumdev.2011.01.017.
45. Clancy C.J., Nguyen M.H. Finding the “missing 50%” of invasive candidiasis: How nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clinical Infectious Diseases. 2013;56:1284–1292. doi: 10.1093/cid/cit006.
46. Cuenca-Estrella M., Verweij P.E., Arendrup M.C., Arikan-Akdagli S., Bille J., Donnelly J.P., Jensen H.E., Lass-Florl C., Richardson M.D., Akova M., et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: Diagnostic procedures. Clinical Microbiology and Infection. 2012;18:9– 18. doi: 10.1111/1469-0691.12038.
47. Beyda N.D., Alam M.J., Garey K.W. Comparison of the T2Dx instrument with T2Candida assay and automated blood culture in the detection of Candida species using seeded blood samples. Diagnostic Microbiology and Infectious Disease. 2013;77(4):324-6. https://doi.org/10.1016/j.diagmicrobio.2013.07.007
48. Lamoth F., Cruciani M., Mengoli C., Castagnola E., Lortholary O., Richardson M., Marchetti O. -Glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: A systematic review and meta-analysis of cohort studies from the Third European Conference on Infections in Leukemia (ECIL-3) Clin. Infect. Dis. 2012;54:633–643. doi: 10.1093/cid/cir897.
49. Goudjil S., Kongolo G., Dusol L., Imestouren F., Cornu M., Leke A., Chouaki T. (1–3)-β-d-glucan levels in candidiasis infections in the critically ill neonate. The journal of maternalfetal and neonatal medicine. 2013; 26:44–48. doi:10.3109/14767058.2012.722716.
50. Smith P.B., Benjamin D.K.J., Alexander B.D., Johnson M.D., Finkelman M.A., Steinbach W.J. Quantification of 1,3-β-d-glucan levels in children: Preliminary data for diagnostic use of the β-glucan assay in a pediatric setting. Clinical and Vaccine Immunology. 2007;14:924–925. doi: 10.1128/CVI.00025-07.
51. Cornu M., Goudjil S., Kongolo G., Leke A., Poulain D., Chouaki T., Sendid B. Evaluation of the (1,3)-β-D-glucan assay for the diagnosis of neonatal invasive yeast infections. Medical Mycology. 2018 Jan 1;56(1):78-87. doi: 10.1093/mmy/myx021.
52. Диагностика и лечение микозов в отделениях реанимации и интенсивной терапии: Российские рекомендации / отв. ред. Н.Н. Климко . – 2-е изд. доп. и перераб. – М.: Фармтек, 2015.– 96 с.
53. Marchetti O., Lamoth F., Mikulska M., Viscoli C., Verweij P., Bretagne S. ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients.Bone Marrow Transplant. 2012;47:846–854. doi: 10.1038/bmt.2011.178.
54. Tang D.L., Chen X., Zhu C.G., Li Z.W., Xia Y., Guo X.G.. Pooled analysis of T2 Candida for rapid diagnosis of candidiasis. BMC Infection Disease. 2019 Sep 11;19(1):798. doi: 10.1186/s12879-019-4419-z.
55. Климко, Н.Н. Результаты проспективного многоцентрового исследования применения анидулафунгина – ЭРА / Н.Н. Климко [и др.] // Проблемы медицинской микологии. – 2018. – T. 20, № 3. – С. 21–25.
56. Bow EJ, Evans G, Fuller J, Laverdière M, Rotstein C, Rennie R, et al. Canadian clinical practice guidelines for invasive candidiasis in adults. Can J Infect Dis Med Microbiol. 2010;21(4):122–50.
57. Ruhnke M., Rickerts V., Cornely O.A., Buchheidt D., Glöckner A., Heinz W., et al. Diagnosis and therapy of Candida infections: joint recommendations of the German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy. Mycoses. 2011; 54(4): 279–310.
Рецензия
Для цитирования:
Климко Н.Н., Козлова О.П. Инвазивный кандидоз у детей. Журнал инфектологии. 2021;13(2):14-26. https://doi.org/10.22625/2072-6732-2021-13-2-14-26
For citation:
Klimko N.N., Kozlova O.P. Invasive candidiasis in children. Journal Infectology. 2021;13(2):14-26. (In Russ.) https://doi.org/10.22625/2072-6732-2021-13-2-14-26