Az amfotericin B az egyik legrégebben használt, leghatékonyabb és legszélesebb spektrumú, polién antifungális vegyület, mely alkalmas hematológiai betegekben kialakuló invazív gombainfekciók megelőzésére és kezelésére. Hagyományos kiszerelése az amfotericin B-deoxikolát, melynek biztonságos alkalmazását számos akut és szubakut mellékhatás korlátozza. Ezek mérséklésére fejlesztették ki a vegyület lipid formulációit, melyek közül jelenleg az amfotericin B lipid komplex és a liposzómás amfotericin B van forgalomban. A terápiás fegyvertár egyidejűleg más hatástani csoportba tartozó, új gombaellenes szerekkel is bővült, így sokan az amfotericin B éra végét jósolták. Alkalmazása azonban napjaink klinikai gyakorlatában sem mellőzhető. Szélesebb spektrumot igénylő empirikus terápiában és profilaxisban, rezisztens speciesek felbukkanása esetén, áttöréses gombafertőzésekben és amikor gyógyszerkölcsönhatások vagy toxicitás miatt egyéb vegyületek nem használhatóak, az amfotericin B szerepe változatlan. Mivel a kedvezőtlen tolerancia a hatékonyságot is befolyásolja, a szer lipid formulációinak alkalmazását kell előtérbe helyezni.
Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in U.S. hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004; 39: 309–317.
Pagano L, Caira M, Candoni A, et al. Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study. Haematologica 2010; 95: 644–650.
Kontoyiannis DP, Marr KA, Park BJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis. 2010; 50: 1091–1100.
Pizzo PA, Robichaud KJ, Gill FA, et al. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med. 1982; 72: 101–111.
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.
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.
Cordonnier C, Pautas C, Maury S, et al. Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: a randomized, controlled trial. Clin Infect Dis. 2009; 48: 1042–1051.
Agrawal S, Hope W, Sinkó J, et al. Optimizing management of invasive mould diseases. J Antimicrob Chemother. 2011; 66(Suppl 1): i45–53.
Lemke A, Kiderlen AF, Kayser O. Amphotericin B. Appl Microbiol Biotechnol 2005; 68: 151–162.
Mesa-Arango AC, Scorzoni L, Zaragoza O. It only takes one to do many jobs: Amphotericin B as antifungal and immunomodulatory drug. Front Microbiol. 2012; 3: 286. eCollection 2012.
Deray G. Amphotericin B nephrotoxicity. J Antimicrob Chemother. 2002; 49(Suppl 1): 37–41.
Wingard, JR, Kubilis P, Lee L, et al. Clinical significance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis. Clin Infect Dis. 1999; 29, 1402–1407.
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.
Viscoli C, Castagnola E, Van Lint MT, et al. Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial. Eur J Cancer 1996; 32A: 814–820.
Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001; 32: 358–366.
Guo LSS. Amphotericin B colloidal dispersion: an improved antifungal therapy. Adv Drug Deliv Rev. 2001; 47: 149–163.
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. 2002; 35: 359–366.
Bassetti M, Aversa F, Ballerini F, et al. Amphotericin B lipid complex in the management of invasive fungal infections in immunocompromised patients. Clin Drug Investig. 2011; 31: 745–758.
Ito JI, Hooshmand-Rad R. Treatment of Candida infections with amphotericin B lipid complex. Clin Infect Dis. 2005; 40(Suppl. 6): S384–391.
Chandrasekar PH, Ito JI. Amphotericin B lipid complex in the management of invasive aspergillosis in immunocompromised patients. Clin Infect Dis. 2005; 40(Suppl. 6): S392–400.
Perfect JR. Treatment of non-Aspergillus moulds in immunocompromised patients, with amphotericin B lipid complex. Clin Infect Dis. 2005; 40(Suppl. 6): S401–408.
Clark AD, McKendrick S, Tansey PJ, et al. A comparative analysis of lipid-complexed and liposomal amphotericin B preparations in hematological oncology. Br J Haematol. 1998; 103: 198–204.
Fleming RV, Kantarjian HM, Husni R, et al. Comparison of amphotericin B lipid complex (ABLC) vs. ambisome in the treatment of suspected or documented fungal infections in patients with leukemia. Leuk Lymphoma 2001; 40: 511–520.
Cannon JP, Garey KW, Danziger LH. A prospective and retrospective analysis of the nephrotoxicity and efficacy of lipid-based amphotericin B formulations. Pharmacotherapy 2001; 21: 1107–1114.
Mattiuzzi GN, Kantarjian H, Faderl S, et al. Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and yelodysplastic syndrome undergoing induction chemotherapy. Cancer 2004; 100: 581–589.
Walsh TJ, Yeldandi V, McEvoy M, et al. Safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) in neutropenic patients. Antimicrob Agents Chemother. 1998; 42: 2391–2398.
Wade RL, Chaudhari P, Natoli JL, et al. Nephrotoxicity and other adverse events among inpatients receiving liposomal amphotericin B or amphotericin B lipid complex. Diagn Microbiol Infect Dis. 2013; 76: 361–367.
Kolve H, Ahlke E, Fegeler W, et al. Safety, tolerance and outcome of treatment with liposomal amphotericin B in paediatric patients with cancer or undergoing haematopoietic stem cell transplantation. J Antimicrob Chemother. 2009; 64: 383–387.
Penack O, Schwartz S, Martus P, et al. 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. 2006; 17: 1306–1312.
Cornely OA, Leguay T, Maertens J, et al. Randomized comparison of liposomal amphotericin B versus placebo to prevent invasive mycoses in acute lymphoblastic leukaemia. J Antimicrob Chemother. 2017; 72: 2359–2367.
Biehl LM, Vehreschild JJ, Liss B, et al. A cohort study on breakthrough invasive fungal infections in high-risk patients receiving antifungal prophylaxis. J Antimicrob Chemother. 2016; 71: 2634–2641.
Prentice HG, Hann IM, Herbrecht R, Aoun M, et al. A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients. Br J Haematol. 1997; 98: 711–718.
Walsh TJ, Finberg RW, Arndt C, et al. 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. 1999; 340: 764–771.
Walsh TJ, Pappas P, Winston DJ, et al. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med. 2002; 346: 225–234.
Walsh TJ, Teppler H, Donowitz GR, et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004; 351: 1391–1402.
Kuse ER, Chetchotisakd P, da Cunha CA, et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet. 2007; 369: 1519–27.
Ellis M, Spence D, de Pauw B, et al. An EORTC international multicenter randomized trial (EORTC number 19923) comparing two dosages of liposomal amphotericin B for treatment of invasive aspergillosis. Clin Infect Dis. 1998; 27: 1406–1412.
Cornely OA, Maertens J, Bresnik M, et al. Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). Clin Infect Dis. 2007; 44: 1289–1297.
Verweij PE, Ananda-Rajah M, Andes D, et al. International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus. Drug Resist Updat. 2015; 21–22: 30–40.
Lanternier F, Lortholary O. [AMBIZYGO: phase II study of high dose liposomal amphotericin B (AmBisome) [10 mg/kg/j] efficacy against zygomycosis]. Med Mal Infect. 2008; 38(Suppl 2): S90–91. [French]
Spellberg B, Ibrahim AS, Chin-Hong PV, et al. The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) study: a randomized, double-blinded, placebo-controlled trial. J Antimicrob Chemother. 2012; 67: 715–722.
Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010; 50: 291–322.
Maertens J, Marchetti O, Herbrecht R, et al. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3--2009 update. Bone Marrow Transplant. 2011; 46: 709–718.
Ullmann AJ, Akova M, Herbrecht R, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: Adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect. 2012; 18(Suppl 7): 53–67.
Tissot F, Agrawal S, Pagano L, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 2017; 102: 433–444.
Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018; 24(Suppl 1): e1–e38.
Cornely OA, Arikan-Akdagli S, Dannaoui E, et al. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin Microbiol Infect. 2014; 20(Suppl 3): 5–26.