Results of candidemia treatment in children with hematologic malignancies: single center experience
https://doi.org/10.17650/1818-8346-2011-6-3-24-34
Abstract
Candidemia is one of the most serious infectious complications in children with hematological malignancies and has a high morta lity rate.
Seven-year experience of candidemia diagnosis and therapy in patients with various hematologic malignancies w as analyzed. Candidemia registered in 37 patients (AML and MDS — 14, ALL — 10, solid tumors — 5, histocytic syndromes — 4, AA — 3, other non-malignancy diseases— 2). C. non-albicans (36 isolates from 32 patients) was common cause of, while C. albicans isolated in 5 patients (8 strains). Antifungal prophylactic therapy was applied to 31 patients. 22 patients at the time of candidemia have neutropenia (< 0.5 × 10 9/l). Main clinical manifestations were febrile fever (100 % cases) and pneumonia (21.6 % cases). Less frequent multiorgan failure (8.1 %), septic shoc k (5.4 %), chronic disseminated candidiasis (5.4 %) and meningitis (2.7 %) were registered. All patients received antifungal therapy (monotherapy — 17, combination therapy — 20). Central venous catheter removed in 21 patients. In 14 patients hematopoietic recovery w as registered, none of these patients died, while from group of patients without hematopoietic recovery 6 patients died (p = 0.0001). Recurrent candidemia episodes were seen in 4 patients. Overall survival was 0.37 ± 0.09.
About the Authors
I. I. KalininaRussian Federation
D. D. Baydildina
Russian Federation
E. V. Suntsova
Russian Federation
O. V. Goronkova
Russian Federation
L. A. Khachatryan
Russian Federation
U. N. Petrova
Russian Federation
G. G. Solopova
Russian Federation
V. V. Sinitsina
Russian Federation
G. A. Novichkova
Russian Federation
M. A. Maschan
Russian Federation
D. V. Litvinov
Russian Federation
N. V. Myakova
Russian Federation
G. A. Klyasova
Russian Federation
A. A. Maschan
Russian Federation
References
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.
Review
For citations:
Kalinina I.I., Baydildina D.D., Suntsova E.V., Goronkova O.V., Khachatryan L.A., Petrova U.N., Solopova G.G., Sinitsina V.V., Novichkova G.A., Maschan M.A., Litvinov D.V., Myakova N.V., Klyasova G.A., Maschan A.A. Results of candidemia treatment in children with hematologic malignancies: single center experience. Oncohematology. 2011;6(3):24-34. (In Russ.) https://doi.org/10.17650/1818-8346-2011-6-3-24-34