#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Invasive aspergillosis in hematooncological patients: advantages and disadvantages of various diagnostic methods, treatment options and financial costs of therapy


Authors: Z. Ráčil 1;  J. Mayer 1;  I. Kocmanová 2;  B. Wagnerová 1;  J. Winterová 1;  F. Folber 1;  M. Lengerová 1;  M. Moulis 3;  D. Žáčková 1;  L. Šmardová 1;  A. Janíková 1;  M. Navrátil 1;  D. Dvořáková 1;  J. Vorlíček 1
Authors‘ workplace: Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Vorlíček, CSc. 1;  Oddělení klinické mikrobiologie FN Brno, pracoviště Bohunice, přednostka prim. MUDr. Alena Ševčíková 2;  Ústav patologie Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jirka Mačák, CSc. 3
Published in: Vnitř Lék 2008; 54(2): 157-168
Category: Original Contributions

Overview

Background:
Invasive aspergillosis (IA) is a leading invasive fungal infection in hematooncological patients. The aim of this study was to analyse the incidence, diagnostic procedures and treatment of IA in hematooncological department in large hospital in the Czech Republic.

Patients and methods:
A retrospective analysis of medical and laboratory records from patients hospitalised in our department with proven/probable IA between January 2000 and December 2006 was performed.

Results:
52 cases of IA in 51 patients were identified (17.3 % proven IA/82.7 % probable IA). Number of IA cases notably increased during study period (1 case of IA in 2000 vs 21 cases of IA in 2006) and majority of them was of nosocomial origin (61.5 %). Pulmonary aspergillosis was diagnosed in 46 cases (88.5 %). Patients treated for acute leukemia or undergoing allogeneic stem cell transplantation represent the group at the highest risk of IA (in total 52 % of cases). Fever and signs of pulmonary involvement were the most common clinical signs of infection (presented in 92.3 % and 69.2 cases respectively). Conventional diagnostic methods including autopsy were able to diagnose only 15 cases of IA (28.8 %). In all other cases (71.2 %) the diagnosis was done by detection of galactomannan (GM) in serum. Introduction of GM monitoring enabled erlier initiation of antifungal treatment by 4 days. Initial therapy of IA led to the treatment response (partial and complete) in 18 (34.6 %) of infections - the highest percentage of response has been seen in voriconazole monotherapy group (42 %) and when combination of voriconazole and caspofungin has been used (83 %). Salvage therapy was initiated due to the failure of initial treatment in 21 (40.3 %) of cases. Patients were treated mostly with combination of voriconazole and caspofungin and/or monotherapy with voriconazole has been used with treatment response 55 % and 50 % respectively. Introduction of new antifungal drugs together with increased number of patients with IA led to the marked increase of total costs spent on treatment of IA per year - from 11,5 thousands CZK in 2000 to 6,2 millions CZK in 2006.

Conclusions:
IA is the most frequent cause of infection-related mortality in patients with haematological malignancies. Routine use of non-culture base methods in diagnosis of IA together with treatment using new, effective antifungals can improve prognosis of patients with this life threatening infection.

Key words:
invasive fungal infection - Aspergillus - invasive aspergillosis - galactomannan - early diagnosis - antifungal therapy - hematological malignancies


Sources

1. O'Brien SN, Blijlevens NMA, Mahfouz TH et al. Infections in Patients with Hematological Cancer: Recent Developments. Hematology 2003; 2003: 438-472.

2. Lin SJ, Schranz J, Teutsch SM Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis 2001; 32: 358-366.

3. Singh N, Paterson DL Aspergillus infections in transplant recipients. Clin Microbiol Rev 2005; 18: 44-69.

4. Caillot D, Casasnovas O, Bernard A et al. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol 1997; 15: 139-147.

5. Maertens J, Theunissen K, Verhoef G et al. Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study. Clin Infect Dis 2005; 41: 1242-1250.

6. Patterson TF Treatment of invasive aspergillosis: Polyenes, echinocandins, or azoles? Medical Mycology 2006; 44: 357-362.

7. Pagano L, Caira M, Picardi M et al. Invasive Aspergillosis in patients with acute leukemia: update on morbidity and mortality-SEIFEM-C Report. Clin Infect Dis 2007; 44: 1524-1525.

8. Upton A, Kirby KA, Carpenter P et al. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis 2007; 44: 531-540.

9. Ascioglu S, Rex JH, 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.

10. Cornillet A, Camus C, Nimubona S et al. Comparison of epidemiological, clinical, and biological features of invasive aspergillosis in neutropenic and nonneutropenic patients: a 6-year survey. Clin Infect Dis 2006; 43: 577-584.

11. Pagano L, Caira M, Candoni A et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 2006; 91: 1068-1075.

12. Benet T, Nicolle MC, Thiebaut A et al. Reduction of invasive aspergillosis incidence among immunocompromised patients after control of environmental exposure. Clin Infect Dis 2007; 45: 682-686.

13. Chamilos G, Luna M, Lewis RE et al. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989-2003). Haematologica 2006; 91: 986-989.

14. Gerson SL, Talbot GH, Hurwitz S et al. Prolonged granulocytopenia: the major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia. Ann Intern Med 1984; 100: 345-351.

15. Marr KA, Carter RA, Boeckh M et al. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood 2002; 100: 4358-4366.

16. Hope WW, Walsh TJ, Denning DW Laboratory diagnosis of invasive aspergillosis. Lancet Infect Dis 2005; 5: 609-622.

17. Aquino VR, Goldani LZ, Pasqualotto AC Update on the contribution of galactomannan for the diagnosis of invasive aspergillosis. Mycopathologia 2007; 163: 191-202.

18. Maertens JA, Klont R, Masson C et al. Optimization of the cutoff value for the Aspergillus double-sandwich enzyme immunoassay. Clin Infect Dis 2007; 44: 1329-1336.

19. Marr KA, Balajee SA, McLaughlin L et al. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: variables that affect performance. J Infect Dis 2004; 190: 641-649.

20. Herbrecht R, Denning DW, Patterson TF et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002; 347: 408-415.

21. Cornely OA, Maertens J, Winston DJ et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007; 356: 348-359.

22. Ullmann AJ, Lipton JH, Vesole DH et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 2007; 356: 335-347.

Labels
Diabetology Endocrinology Internal medicine

Article was published in

Internal Medicine

Issue 2

2008 Issue 2

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#