Результаты терапии кандидемии у детей с различными гематологическими и онкологическими заболеваниями в условиях одного центра

Кандидемия является одним из самых тяжелых инфекционных осложнений у детей с гематологическими и онкологическими заболеваниями и характеризуется высокой летальностью. В статье проанализирован 7-летний опыт диагностики и терапии кандидемии у 37 детей, больных различными гематологическими и онкологическими заболеваниями: миелодиспластическим синдромом и острыми миело- и лимфолейкозами 24 случая, солидные опухоли — 5, гистиоцитарные синдромы — 4, апластическая анемия — 3, другие незлокачественные заболевания — 2. Возбудителями кандидемии у 32 больных были C. non-albicans (36 штаммов), у 5 — C. albicans (8 штаммов). Противогрибковую профилактику получал 31 пациент. На момент развития кандидемии нейтропения (< 0,5 × 10 9/л) была у 22 пациентов. Основными клиническими проявлениями у всех больных была лихорадка, в 6 случаях — пневмония. Более редкими проявлениями были: полиорганная недостаточность — 8,1 %; септический шок и хронический диссеминированный кандидиаз —по 5,4 %; менингит — 2,7 %. Всем больным был установлен центральный венозный катетер (ЦВК). Все пациенты получали антимикотическую терапию (одним препаратом — 17 больных, комбинированную терапию — 20). ЦВК был удален у 21 пациента. Восстановление гемопоэза было у 14 пациентов, никто из них не умер от кандидемии. Из 8 больных без восстановления гемопоэза умерли 6. Повторные эпизоды кандидемии развились у 4 пациентов. Общая выживаемость составила 0,37 ± 0,09.

1. Pagano L., Girmenia C., Mele L., Ricci P., Tosti M.E., Nosari A. et al. Infections caused by filamentous fungi in patients with hematologic malignancies. A report of 391 cases by GIMEMA Infection Program.

2. GIMEMA Infection Program; Gruppo Italiano Malattie Ematologiche dell’Adulto. Haematologica 2001;86:862–70.

3. Nucci M., Spector N., Bueno A.P., Solza C. et al. Risk factors and attributable mortality associated with superinfections in neutropenic patients with cancer. Clin Infect Dis 1997;24:575–9.

4. Marr K.A., Seidel K., White T.C., Bowden R.A. Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole. J Infect Dis 2000;181:309–16.

5. Marr K.A., Carter R.A., Crippa F., Wald A., Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002; 34:909–17.

6. Groll A.H., Walsh T.J. Fungal infections in the pediatric patient. In: Anaissie E.J., McGinnis M.R., Pfaller M.A., eds. Clinical mycology. 1st ed. New York: Churchill Livingstone 2003; pp. 417–42.

7. Pagano L. et al. Chronic disseminated candidiasis in patients with hematologic malignancies. Clinical features and outcome of 29 episodes. Haematologica 2002;87:535–41. 7. Bodey G., Bueltmann B., Duguid W., Gibbs D. et al. Fungal infections in cancer patients: an international autopsy survey. Eur J Clin Microbiol Infect Dis 1992;11:99–109.

8. Ascioglu S., Rex J.H., de Pauw B. et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 2002;34:7–14.

9. Viscoli C., Girmenia C., Marinus A., Collette L. et al. Candidemia in cancer patients: a prospective, multicenter urveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC). Clin Infect Dis 1999;28:1071–9.

10. Pagano L., Antinori A., Ammassari A. et al. Retrospective study of candidemia in patients with hematological malignancies. Clinical features, risk factors and outcome of 76 episodes. Eur J Haematol 1999;63:77–85.

11. Marodi L., Johnston R.B. Jr. Invasive Candida species disease in infants and children: occurrence, risk factors, management and innate host defense mechanisms. Curr Opin Pediatr 2007;19:693–7.

12. Kao A.S., Brandt M.E., Pruitt W.R. et al. The Epidemiology of candidemia in two United States cities: results of a populationbased active surveillance. Clin Infec Dis 1999;29:1164–70.

13. Pfaller M.A., Jones R.N., Doern G.V. et al. International surveillance of blood stream infections due to Candida species in the European SENTRY program: species distribution and antifungal susceptibility including the investigational triazole and echinocandin agents. Diagn Microbiol Infect Dis 1999;35:19–25.

14. Pfaller M.A., Jones R.N., Doern G.V. et al. International surveillance of blood stream infections due to Candida species: frequency of occurrence and antifungal susceptibilities of isolates collected in 1997 in the United States, Canada and South America for the SENTRY program. J Clin Microbiol 1998;36:1886–9.

15. Pfaller M.A., Jones R.N., Messer S.A. et al. SCOPE Participant Group: national surveillance of nosocomial blood stream infection due to species of Candida other than Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE program. Diagn Microbiol Inf Dis 1998;30:121–9.

16. Pfaller M.A., Messer S.A., Houston A. et al. National epidemiology of mycoses survey: multicenter study of strain variation and antifungal susceptibility among isolates of Candida species. Diagn Microbiol Inf Dis 1998;31:289–96.

17. Rennert G., Rennert H.S., Pitlik S. et al. Epidemiology of candidemia: a nationwide survey in Israel. Infection 2000;28:26–9.

18. Wenzel R.P. Nosocomial candidemia: risk factors and attributable mortality. Clin Infect Dis 1995;20:1531–4.

19. Zaoutis T.E., Argon J., Chu J., Berlin J.A., Walsh T.J., Feudtner C. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis 2005;41:1232–9.

20. Van Burik J.A., Ratanatharathorn V., Stepan D.E. et al. Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell

21. transplantation. Clin Infect Dis 2004;39:1407–16.

22. Trick W.E., Fridkin S.K., Edwards J.R. et al. Secular trend of hospital acquired candidemia among intensive care unit patients in the USA during 1989–1999. Clin Infect Dis 2002;35:627–30.

23. Blumberg H. et al. Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. Clin Infect Dis 2001;33:177–86.

24. Ellepola A.N.B., C.J. Morrison. Laboratory diagnosis of invasive candidiasis. J Microbiol 2005;43:65–84.

25. Fasahat F.A., Mustafa A.S., Khan Z.U. Comparative evaluation of (1, 3)-β-Dglucan, mannan and anti-mannan antibodies and Candida species-specific snPCR in patients with candidemia. BMC Infectious

26. Diseases 2007:7:103–11.

27. Morace G., Pagano L. et al. PCRRestriction enzyme analysis for detection of Candida DNA in blood from febrile patients with hematological malignancies. J Clin Microbiol 1999;37:1871–5.

28. Horstkotte D. et al. Guidelines on prevention, diagnosis and treatment of infective endocarditis executive summary; the task force on infective endocarditis of the European society of cardiology Eur Heart J 2004;25:267–76.

29. Lecciones J.A., Lee J.A., Navarro E.E. et al. Vascular catheter-associated fungemia in patients with cancer: analysis of 155 episodes. Clin Infect Dis 1992; 14:875–83.

30. Bow E.J., Laverdiere M. et al. Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta-analysis of randomized-controlled clinical trials. Cancer 2002;94:3230–46.

31. Marr K., Seidel K., Slavin M.A. et al. Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long term follow-up of a randomized placebo-controlled trial. Blood 2000;96:2055–61.

32. Kamaluddin M., McNally P., Breathach F. et al. Potentiation of vincristine toxicity by itraconazole in children with lymphoid malignancies. Acta Paediatr 2001 Oct; 90(10):1204–7.

33. Raad J., Tarrand J., Hanna H. et al. Epidemiology, molecular mycology and environmental sources of Fusarium infection in patients with cancer. Infect Control Hosp Epidemiol 2002; 23:532–7.

34. ECIL-2, 2007, antifungal therapy guidelines. http://www.eortc.be/services/unit/idg/documents/06.Antifungaltherapy.pdf.

35. Price T., Bowden R., Boeckh M. et al. Phase I/II trial of neutrophil transfusions from donors stimulated with G-CSF and dexamethasone for treatment of patients with infections in hematopoietic stem cell transplantation. Blood 2000;95:3302–9.

36. Sychev D., Maya I., Allon M. Clinical outcomes of dialysis catheter – related candidemia in hemodialysis patients. Clin J Am Soc Nephrol 2009;4:1102–5.

37. Morgan J., Meltzer M.I., Plikaytis B.D. et al. Excess mortality, hospital stay and cost due to candidemia: a case-control study using data from population-basedcandidemia surveillance. Infect Control Hosp Epidemiol 2005;26:540–7.