Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 144 No. 2930 (2014)

Efficacy of anti-fungal but not anti-bacterial prophylaxis in intensive primary AML therapy: A real-world, retrospective comparative single-centre study

  • Bernhard Gerber
  • Jan Köppel
  • Michaela Paul
  • Thi Dan Linh Nguyen-Kim
  • Thomas Frauenfelder
  • Gayathri Nair
  • Urs Schanz
  • Markus G. Manz
DOI
https://doi.org/10.4414/smw.2014.13985
Cite this as:
Swiss Med Wkly. 2014;144:w13985
Published
14.07.2014

Abstract

QUESTIONS UNDER STUDY: The optimal strategy of anti-infectious prophylaxis in patients with acute leukaemia undergoing intensive chemotherapy remains a matter of debate. We assessed the impact of primary prophylaxis with posaconazole and levofloxacin on the incidence of invasive fungal infections (IFI) and bacteraemia.

METHODS: A retrospective single-centre study including two groups of adult patients with AML receiving intensive chemotherapy. Group one without anti-infective prophylaxis (September 2008 – February 2010), and group two with anti-infective prophyalaxis (March 2010 – April 2011). The primary end-point was IFI according to the EORTC/MSG 2008 definitions and bacteraemia.

RESULTS: Baseline characteristics were similar in the non-prophylaxis (n = 43 patients; 99 chemotherapy cycles) and the prophylaxis (n = 45; 104 chemotherapy cycles) group. IFI were significantly reduced in the prophylaxis group (55.3% vs. 88.9%; p = 0.0032) and there was a trend of the projected IFI-free survival at 100 days to be increased (50.1% vs. 25%; p = 0.0526). One-hundred day overall survival (84.4% and 88.4%, p = 0.35) and 2-year overall survival (64.4% and 58.1%; p = 0.64) were unaffected. No difference in the occurrence of bacteraemia was observed (32.3% vs. 34.6%; p = 0.8). A total of two (3.6%) patients in the non-prophylaxis and three (6.7%) in the prophylaxis group died due to IFI, and two (3.6%) in the non-prophylaxis and none in the prophylaxis group patients had to stop leukaemia treatment due to IFI.

CONCLUSIONS: The anti-infective prophylaxis with posaconazole and levofloxacin resulted in a significant reduction of ‘possible’ IFI with a number-needed to treat to prevent one IFI of only 3 but did not result in a reduction of the incidence of bacteraemia.

References

  1. Hahn-Ast C, Glasmacher A, Muckter S, Schmitz A, Kraemer A, Marklein G, et al. Overall survival and fungal infection-related mortality in patients with invasive fungal infection and neutropenia after myelosuppressive chemotherapy in a tertiary care centre from 1995 to 2006. J Antimicrob Chemother. 2010;65(4):761–8.
  2. Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, et al. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med. 2005;353(10):977–87.
  3. Slobbe L, Polinder S, Doorduijn JK, Lugtenburg PJ, el Barzouhi A, Steyerberg EW, et al. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: an observational study. Clin Infect Dis. 2008;47(12):1507–12.
  4. Kjellander C, Bjorkholm M, Cherif H, Kalin M, Giske CG. Hematological: Low all-cause mortality and low occurrence of antimicrobial resistance in hematological patients with bacteremia receiving no antibacterial prophylaxis: a single-center study. Eur J Haematol. 2012 Feb 15.
  5. Syrjala H, Ohtonen P, Kinnunen U, Raty R, Elonen E, Nousiainen T, et al. Blood stream infections during chemotherapy-induced neutropenia in adult patients with acute myeloid leukemia: treatment cycle matters. Eur J Clin Microbiol Infect Dis. 2010;29(10):1211–8.
  6. Girmenia C, Frustaci AM, Gentile G, Minotti C, Cartoni C, Capria S, et al. Posaconazole prophylaxis during front-line chemotherapy of acute myeloid leukemia: a single-center, real-life experience. Haematologica. 2012;97(4):560–7.
  7. Neofytos D, Lu K, Hatfield-Seung A, Blackford A, Marr KA, Treadway S, et al. Epidemiology, outcomes, and risk factors of invasive fungal infections in adult patients with acute myelogenous leukemia after induction chemotherapy. Diagn Microbiol Infect Dis. 2013;75(2):144–9.
  8. Denning DW. Invasive aspergillosis. Clin Infect Dis. 1998;26(4):781–803; quiz 4–5.
  9. Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(3):327–60.
  10. Cordonnier C, Pautas C, Maury S, Vekhoff A, Farhat H, Suarez F, et al. Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: a randomized, controlled trial. Clin Infect Dis. 2009;48(8):1042–51.
  11. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356(4):348–59.
  12. Maertens J, Theunissen K, Verhoef G, Verschakelen J, Lagrou K, Verbeken E, 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(9):1242–50.
  13. Hebart H, Klingspor L, Klingebiel T, Loeffler J, Tollemar J, Ljungman P, et al. A prospective randomized controlled trial comparing PCR-based and empirical treatment with liposomal amphotericin B in patients after allo-SCT. Bone Marrow Transplant. 2009;43(7):553–61.
  14. Pagano L, Caira M, Nosari A, Cattaneo C, Fanci R, Bonini A, et al. The use and efficacy of empirical versus pre-emptive therapy in the management of fungal infections: the HEMA e-Chart Project. Haematologica. 2011;96(9):1366–70.
  15. Gafter-Gvili A, Fraser A, Paul M, van de Wetering M, Kremer L, Leibovici L. Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy. Cochrane Database Syst Rev. 2005(4):CD004386.
  16. Gafter-Gvili A, Fraser A, Paul M, Vidal L, Lawrie TA, van de Wetering MD, et al. Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy. Cochrane Database Syst Rev. 2012;1:CD004386.
  17. Lowenberg B, van Putten W, Theobald M, Gmur J, Verdonck L, Sonneveld P, et al. Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. N Engl J Med. 2003;349(8):743–52.
  18. Eriksson U, Seifert B, Schaffner A. Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled trial. BMJ. 2001;322(7286):579–82.
  19. Swerdlow SH CE, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC, 2008.
  20. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46(12):1813–21.
  21. Team RDC. R: A language and environment for statistical computing. In: Computing RFfS, ed. Vienna, Austria., 2012.
  22. Pagano L, Caira M, Candoni A, Offidani M, Martino B, Specchia G, et al. Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study. Haematologica. 2010;95(4):644–50.
  23. Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001;32(3):358–66.
  24. Even C, Bastuji-Garin S, Hicheri Y, Pautas C, Botterel F, Maury S, et al. Impact of invasive fungal disease on the chemotherapy schedule and event-free survival in acute leukemia patients who survived fungal disease: a case-control study. Haematologica. 2011;96(2):337–41.
  25. Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079–89.
  26. Benet T, Nicolle MC, Thiebaut A, Piens MA, Nicolini FE, Thomas X, et al. Reduction of invasive aspergillosis incidence among immunocompromised patients after control of environmental exposure. Clin Infect Dis. 2007;45(6):682–6.
  27. Panackal AA, Li H, Kontoyiannis DP, Mori M, Perego CA, Boeckh M, et al. Geoclimatic influences on invasive aspergillosis after hematopoietic stem cell transplantation. Clin Infect Dis. 2010;50(12):1588–97.
  28. Sautour M, Sixt N, Dalle F, L’Ollivier C, Fourquenet V, Calinon C, et al. Profiles and seasonal distribution of airborne fungi in indoor and outdoor environments at a French hospital. Sci Total Environ. 2009;407(12):3766–71.
  29. Hospenthal DR, Kwon-Chung KJ, Bennett JE. Concentrations of airborne Aspergillus compared to the incidence of invasive aspergillosis: lack of correlation. Med Mycol. 1998;36(3):165–8.
  30. Anaissie EJ, Stratton SL, Dignani MC, Lee CK, Summerbell RC, Rex JH, et al. Pathogenic molds (including Aspergillus species) in hospital water distribution systems: a 3–year prospective study and clinical implications for patients with hematologic malignancies. Blood. 2003;101(7):2542–6.
  31. Gerber B, Guggenberger R, Fasler D, Nair G, Manz MG, Stussi G, et al. Reversible skeletal disease and high fluoride serum levels in hematologic patients receiving voriconazole. Blood. 2012;120(12):2390–4.
  32. Cowen EW, Nguyen JC, Miller DD, McShane D, Arron ST, Prose NS, et al. Chronic phototoxicity and aggressive squamous cell carcinoma of the skin in children and adults during treatment with voriconazole. J Am Acad Dermatol. 2010;62(1):31–7.
  33. Cronin S, Chandrasekar PH. Safety of triazole antifungal drugs in patients with cancer. J Antimicrob Chemother. 2010;65(3):410–6.
  34. Jang SH, Colangelo PM, Gobburu JV. Exposure-response of posaconazole used for prophylaxis against invasive fungal infections: evaluating the need to adjust doses based on drug concentrations in plasma. Clin Pharmacol Ther. 2010;88(1):115–9.
  35. Bohme A, Atta J, Mousset S, Ehlken B, Shlaen M, Bug G, et al. Antifungal management and resource use in patients with acute myeloid leukaemia after chemotherapy – retrospective analysis of changes over 3 yr in a German hospital. Eur J Haematol. 2012;88(1):68–77.

Most read articles by the same author(s)