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Antifungal management in cancer patients

Antifungales Management bei hämato-onkologischen Patienten

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Zusammenfassung

Invasive Pilzinfektionen sind eine Hauptursache für Morbidität und Mortalität bei Malignompatienten, die eine myelotoxische Chemotherapie erhalten. Als etablierte Risikofaktoren gelten eine vorausgegangene Pilzinfektion, länger als 10 Tage anhaltende Neutropenien, höheres Lebensalter, aktive Malignome, Kortikoidtherapie, Behandlung mit Breitspektrum-Antibiotika, allogene Stammzelltransplantation, zentralvenöse Katheter und vorbestehende Organdysfunktionen. Behandlungsstrategien invasiver Pilzinfektionen umfassen die Prophylaxe, die präemptive, empirische und erregergezielte antimykotische Therapie. Ein nachgewiesener Vorteil einer Pilzprophylaxe besteht für Fluconazol (400 mg/Tag) bei Patienten die eine allogene Transplantation erhalten, sowie für Posaconazol (600 mg/Tag) für AML/MDS-Patienten während einer Induktionschemotherapie und für Patienten, die eine GvHD entwickelten. Für eine Präemptivtherapie mit Hilfe sensitiver radiologischer, Antigen- bzw. molekularer Diagnostik ist eine weitere Validierung im Rahmen größerer randomisierter Studien nötig, eine generelle Empfehlung besteht derzeit nicht. Hingegen ist die empirische Pilztherapie etabliert und sollte entweder mit liposomalem Amphotericin B, Itraconazol, Voriconazol oder Caspofungin erfolgen. Bei Patienten mit dokumentierter invasiver Aspergillose ist die Behandlung mit Voriconazol Mittel der Wahl. Liposomales Amphotericin B stellt eine gute Alternative dar, während Caspofungin für die Salvage Therapie reserviert ist. Die invasive Candidiasis sollte entweder mit Caspofungin oder mit liposomalen Amphotericin B behandelt werden. In Anbetracht der Zunahme von non-albicans Stämmen ist der Einsatz von Fluconazol "stabilen", nicht neutropenischen Patienten vorbehalten.

Summary

Invasive fungal infections (IFI) are a major cause of morbidity and mortality in cancer patients receiving myelotoxic chemotherapy. Established risk factors are previous fungal infection, neutropenia exceeding 10 days, older age, active cancer, corticosteroid therapy, administration of broad spectrum antibiotics, allogeneic HSCT, central venous catheter and organ dysfunction. The strategies to manage IFI comprise chemoprophylaxis, preemptive, empirical and directed antifungal therapy. Benefit of antifungal prophylaxis has been proven for fluconazole (400 mg/d) in allogeneic transplant recipients, and for posaconazole (600 mg/d) in patients during AML/MDS induction chemotherapy as well as in patients with GvHD. Pre-emptive therapy based on sensitive diagnostic non-culture methods needs further validation in larger randomized studies before becoming a standard. Empirical antifungal therapy is well established and should consist of either liposomal amphotericin B, itraconazole, voriconazole, or caspofungin. In patients with documented invasive aspergillosis, therapy with voriconazole is the treatment of choice. Liposomal amphotericin B is a good alternative candidate and caspofungin is reserved for salvage treatment. Invasive candidiasis should be treated with caspofungin or one of the lipid based amphotericin B formulations. Since non-albicans species are increasingly observed, the use of fluconazole is reserved for "stable", non-neutropenic patients.

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References

  • Marr KA, Carter RA, Crippa F, Wald A, Corey L (2002) Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 34: 909–917

    Article  PubMed  Google Scholar 

  • Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39: 309–317

    Article  PubMed  Google Scholar 

  • Denning DW (1998) Invasive aspergillosis. Clin Infect Dis 26: 781–803; quiz 804–785

    PubMed  CAS  Google Scholar 

  • Marr KA, Carter RA, Boeckh M, Martin P, Corey L (2002) Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood 100: 4358–4366

    Article  PubMed  CAS  Google Scholar 

  • Lin SJ, Schranz J, Teutsch SM (2001) Aspergillosis casefatality rate: systematic review of the literature. Clin Infect Dis 32: 358–366

    Article  PubMed  CAS  Google Scholar 

  • O'Brien SN, Blijlevens NM, Mahfouz TH, Anaissie EJ (2003) Infections in patients with hematological cancer: recent developments. Hematology Am Soc Hematol Educ Program 438–472

  • Martino R, Subira M, Rovira M et al (2002) Invasive fungal infections after allogeneic peripheral blood stem cell transplantation: incidence and risk factors in 395 patients. Br J Haematol 116: 475–482

    Article  PubMed  Google Scholar 

  • Sun QN, Fothergill AW, McCarthy DI, Rinaldi MG, Graybill JR (2002) In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes. Antimicrob Agents Chemother 46: 1581–1582

    Article  PubMed  CAS  Google Scholar 

  • Wingard JR, Leather H (2004) A new era of antifungal therapy. Biol Blood Marrow Transplant 10: 73–90

    Article  PubMed  CAS  Google Scholar 

  • Falagas ME, Apostolou KE, Pappas VD (2006) Attributable mortality of candidemia: a systematic review of matched cohort and case-control studies. Eur J Clin Microbiol Infect Dis 25: 419–425

    Article  PubMed  CAS  Google Scholar 

  • Mora-Duarte J, Betts R, Rotstein C et al (2002) Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 347: 2020–2029

    Article  PubMed  CAS  Google Scholar 

  • Maschmeyer G, Haas A, Bohme A (2005) [Update on therapy of invasive mycoses in hematology and oncology]. Dtsch Med Wochenschr 130: 1381–1384

    Article  PubMed  CAS  Google Scholar 

  • Segal BH, Almyroudis NG, Battiwalla M et al (2007) Prevention and early treatment of invasive fungal infection in patients with cancer and neutropenia and in stem cell transplant recipients in the era of newer broad-spectrum antifungal agents and diagnostic adjuncts. Clin Infect Dis 44: 402–409

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • McLintock LA, Jones BL (2004) Advances in the molecular and serological diagnosis of invasive fungal infection in haemato-oncology patients. Br J Haematol 126: 289–297

    Article  PubMed  CAS  Google Scholar 

  • Viscoli C, Paesmans M, Sanz M et al (2001) Association between antifungal prophylaxis and rate of documented bacteremia in febrile neutropenic cancer patients. Clin Infect Dis 32: 1532–1537

    Article  PubMed  CAS  Google Scholar 

  • Gotzsche PC, Johansen HK (2002) Nystatin prophylaxis and treatment in severely immunodepressed patients. Cochrane Database Syst Rev: CD002033

  • Goodman JL, Winston DJ, Greenfield RA et al (1992) A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 326: 845–851

    Article  PubMed  CAS  Google Scholar 

  • Slavin MA, Osborne B, Adams R et al (1995) Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation – a prospective, randomized, double-blind study. J Infect Dis 171: 1545–1552

    PubMed  CAS  Google Scholar 

  • Marr KA, Seidel K, Slavin MA et al (2000) 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 96: 2055–2061

    PubMed  CAS  Google Scholar 

  • Schaffner A, Schaffner M (1995) Effect of prophylactic fluconazole on the frequency of fungal infections, amphotericin B use, and health care costs in patients undergoing intensive chemotherapy for hematologic neoplasias. J Infect Dis 172: 1035–1041

    PubMed  CAS  Google Scholar 

  • Winston DJ, Chandrasekar PH, Lazarus HM et al (1993) Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial. Ann Intern Med 118: 495–503

    PubMed  CAS  Google Scholar 

  • Glasmacher A, Cornely O, Ullmann AJ et al (2006) An open-label randomized trial comparing itraconazole oral solution with fluconazole oral solution for primary prophylaxis of fungal infections in patients with haematological malignancy and profound neutropenia. J Antimicrob Chemother 57: 317–325

    Article  PubMed  CAS  Google Scholar 

  • Marr KA, Crippa F, Leisenring W et al (2004) Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Blood 103: 1527–1533

    Article  PubMed  CAS  Google Scholar 

  • Marr KA, Leisenring W, Crippa F et al (2004) Cyclophosphamide metabolism is affected by azole antifungals. Blood 103: 1557–1559

    Article  PubMed  CAS  Google Scholar 

  • Philpott-Howard JN, Wade JJ, Mufti GJ, Brammer KW, Ehninger G (1993) Randomized comparison of oral fluconazole versus oral polyenes for the prevention of fungal infection in patients at risk of neutropenia. Multicentre Study Group. J Antimicrob Chemother 31: 973–984

    Article  PubMed  CAS  Google Scholar 

  • Rozenberg-Arska M, Dekker AW, Branger J, Verhoef J (1991) A randomized study to compare oral fluconazole to amphotericin B in the prevention of fungal infections in patients with acute leukaemia. J Antimicrob Chemother 27: 369–376

    Article  PubMed  CAS  Google Scholar 

  • Penack O, Schwartz S, Martus P et al (2006) Low-dose liposomal amphotericin B in the prevention of invasive fungal infections in patients with prolonged neutropenia: results from a randomized, single-center trial. Ann Oncol 17: 1306–1312

    Article  PubMed  CAS  Google Scholar 

  • Kelsey SM, Goldman JM, McCann S et al (1999) Liposomal amphotericin (AmBisome) in the prophylaxis of fungal infections in neutropenic patients: a randomised, double-blind, placebo-controlled study. Bone Marrow Transplant 23: 163–168

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Mattiuzzi GN, Alvarado G, Giles FJ et al (2006) Open-label, randomized comparison of itraconazole versus caspofungin for prophylaxis in patients with hematologic malignancies. Antimicrob Agents Chemother 50: 143–147

    Article  PubMed  CAS  Google Scholar 

  • van Burik J-AH, Ratanatharathorn V, Stepan DE et al (2004) Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis 39: 1407–1416

    Article  PubMed  CAS  Google Scholar 

  • de Pauw BE (2005) Between over- and undertreatment of invasive fungal disease. Clin Infect Dis 41: 1251–1253

    Article  PubMed  Google Scholar 

  • Maertens J, Theunissen K, Verhoef G et al (2005) 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 41: 1242–1250

    Article  PubMed  CAS  Google Scholar 

  • Hebart HKL, Klingebiehl T et al (2004) PCR-based liposomal amphotericin B treatment following allogeneic stem cell transplantation is a safe treatment strategy: preliminary results of a prospective study. ASH Annual Meeting Abstracts 104: 192

    Google Scholar 

  • No authors listed (1989) Empiric antifungal therapy in febrile granulocytopenic patients. EORTC International Antimicrobial Therapy Cooperative Group. Am J Med 86: 668–672

    Google Scholar 

  • Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG (1982) Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med 72: 101–111

    Article  PubMed  CAS  Google Scholar 

  • Wingard JR (2004) Empirical antifungal therapy in treating febrile neutropenic patients. Clin Infect Dis 39 (Suppl 1): S38–S43

    Article  PubMed  CAS  Google Scholar 

  • Walsh TJ, Finberg RW, Arndt C et al (1999) Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med 340: 764–771

    Article  PubMed  CAS  Google Scholar 

  • Boogaerts M, Winston DJ, Bow EJ et al (2001) Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. A randomized, controlled trial. Ann Intern Med 135: 412–422

    PubMed  CAS  Google Scholar 

  • Walsh TJ, Pappas P, Winston DJ et al (2002) Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 346: 225–234

    Article  PubMed  CAS  Google Scholar 

  • Jorgensen KJ, Gotzsche PC, Johansen HK (2006) Voriconazole versus amphotericin B in cancer patients with neutropenia. Cochrane Database Syst Rev: CD004707

  • Jorgensen KJ, Johansen HK, Gotzsche PC (2006) Flaws in design, analysis and interpretation of Pfizer's antifungal trials of voriconazole and uncritical subsequent quotations. Trials 7: 3

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Bowden R, Chandrasekar P, White MH et al (2002) A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients. Clin Infect Dis 35: 359–366

    Article  PubMed  CAS  Google Scholar 

  • Stevens DA, Kan VL, Judson MA et al (2000) Practice guidelines for diseases caused by Aspergillus. Infectious Diseases Society of America. Clin Infect Dis 30: 696–709

    Article  PubMed  CAS  Google Scholar 

  • Herbrecht R, Nivoix Y, Fohrer C, Natarajan-Ame S, Letscher-Bru V (2005) Management of systemic fungal infections: alternatives to itraconazole. J Antimicrob Chemother 56 (Suppl 1): i39–i48

    Article  PubMed  CAS  Google Scholar 

  • Maertens J, Raad I, Petrikkos G et al (2004) Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis 39: 1563–1571

    Article  PubMed  CAS  Google Scholar 

  • Caillot D, Couaillier JF, Bernard A et al (2001) Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J Clin Oncol 19: 253–259

    PubMed  CAS  Google Scholar 

  • Masood A, Sallah S (2005) Chronic disseminated candidiasis in patients with acute leukemia: emphasis on diagnostic definition and treatment. Leuk Res 29: 493–501

    Article  PubMed  Google Scholar 

  • Bow EJ (2006) Of Yeasts and Hyphae: A Hematologist's approach to antifungal therapy. Hematology Am Soc Hematol Educ Program 51: 361–367

    Google Scholar 

  • Kontoyiannis DP, Bodey GP, Mantzoros CS (2001) Fluconazole vs. amphotericin B for the management of candidaemia in adults: a meta-analysis. Mycoses 44: 125–135

    Article  PubMed  CAS  Google Scholar 

  • Kullberg BJ, Sobel JD, Ruhnke M et al (2005) Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet 366: 1435–1442

    Article  PubMed  CAS  Google Scholar 

  • Pappas PG, Rex JH, Sobel JD et al (2004) Guidelines for treatment of candidiasis. Clin Infect Dis 38: 161–189

    Article  PubMed  Google Scholar 

  • Wingard JR, Nichols WG, McDonald GB (2004) Supportive care. Hematology Am Soc Hematol Educ Program 55: 372–389

    Google Scholar 

  • Zaoutis TE, Heydon K, Chu JH, Walsh TJ, Steinbach WJ (2006) Epidemiology, outcomes, and costs of invasive aspergillosis in immunocompromised children in the United States, 2000. Clin Infect Dis 117: 711–716

    Google Scholar 

  • Walmsley S, Devi S, King S et al (1993) Invasive Aspergillus infections in a pediatric hospital: a ten year review. Pediatr Infect Dis J 12: 673–682

    Article  PubMed  CAS  Google Scholar 

  • Thomas KE, Owens CM, Veys PA, Novelli V, Costoli V (2003) The radiological spectrum of invasive aspergillosis in children: a 10-year review. Pediatr Radiol 33: 453–460

    Article  PubMed  Google Scholar 

  • Mennink-Kersten MASH, Verwej PE (2006) Non-culture-based diagnostics for opportunistic fungi. Infect Dis Clin N Am 20: 711–727

    Article  Google Scholar 

  • Groll AH, Ritter J (2005) Diagnose und Therapie von Pilzinfektionen und der Pneumocystis-Pneumonie bei Kindern und Jugendlichen mit neoplastischen Erkrankungen. Klin Padiatr 217(Suppl 1): S37–S66

    Article  PubMed  Google Scholar 

  • Blyth CC, Palasanthiran P, O'Brien TA (2007) Antifungal therapy in children with invasive fungal infections: a systematic review. Pediatrics 119: 772–784

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

    Philipp Staber, Stefan Langner & Peter Neumeister

  2. Department of Paediatrics, Medical University Graz, Graz, Austria

    Hans Jürgen Dornbusch

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  1. Philipp Staber
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  2. Stefan Langner
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  3. Hans Jürgen Dornbusch
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  4. Peter Neumeister
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Correspondence to Peter Neumeister.

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Staber, P., Langner, S., Dornbusch, H. et al. Antifungal management in cancer patients. Wien Med Wochenschr 157, 503–510 (2007). https://doi.org/10.1007/s10354-007-0466-y

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