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Amphotericin B Formulations: A Comparative Review of Efficacy and Toxicity

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Abstract

Because of the increasing prevalence and changing microbiological spectrum of invasive fungal infections, some form of amphotericin B still provides the most reliable and broad spectrum therapeutic alternative. However, the use of amphotericin B deoxycholate is accompanied by dose-limited toxicities, most importantly, infusion-related reactions and nephrotoxicity. In an attempt to improve the therapeutic index of amphotericin B, three lipid-associated formulations were developed, including amphotericin B lipid complex (ABLC), liposomal amphotericin B (L-AmB), and amphotericin B colloidal dispersion (ABCD). The lipid composition of all three of these preparations differs considerably and contributes to substantially different pharmacokinetic parameters. ABLC is the largest of the lipid preparations. Because of its size, it is taken up rapidly by macrophages and becomes sequestered in tissues of the mononuclear phagocyte system such as the liver and spleen. Consequently, compared with the conventional formulation, it has lower circulating amphotericin B serum concentrations, reflected in a marked increase in volume of distribution and clearance. Lung levels are considerably higher than those achieved with other lipid-associated preparations. The recommended therapeutic dose of ABLC is 5 mg/kg/day. Because of its small size and negative charge, L-AmB avoids substantial recognition and uptake by the mononuclear phagocyte system. Therefore, a single dose of L-AmB results in a much higher peak plasma level (Cmax) than conventional amphotericin B deoxycholate and a much larger area under the concentration–time curve. Tissue concentrations in patients receiving L-AmB tend to be highest in the liver and spleen and much lower in kidneys and lung. Recommended therapeutic dosages are 3–6 mg/kg/day. After intravenous infusion, ABCD complexes remain largely intact and are rapidly removed from the circulation by cells of the macrophage phagocyte system. On a milligram-to-milligram basis, the Cmax achieved is lower than that attained by conventional amphotericin B, although the larger doses of ABCD that are administered produce an absolute level that is similar to amphotericin B. ABCD exhibits dose-limiting, infusion-related toxicities; consequently, the administered dosages should not exceed 3–4 mg/kg/day. The few comparative clinical trials that have been completed with the lipid-associated formulations have not demonstrated important clinical differences among these agents and amphotericin B for efficacy, although there are significant safety benefits of the lipid products. Furthermore, only one published trial has ever compared one lipid product against another for any indication. The results of these trials are particularly difficult to interpret because of major heterogeneities in study design, disease definitions, drug dosages, differences in clinical and microbiological endpoints as well as specific outcomes examined. Nevertheless, it is possible to derive some general conclusions given the available data. The most commonly studied syndrome has been empiric therapy for febrile neutropenic patients, where the lipid-associated preparations did not appear to provide a survival benefit over conventional amphotericin B deoxycholate, but did offer a significant advantage for the prevention of various breakthrough invasive fungal infections. For treatment of documented invasive fungal infections that usually involved hematological malignancy patients, no individual randomized trial has demonstrated a mortality benefit due to therapy with one of the lipid formulations. Results from meta-analyses have been contradictory, with one demonstrating a mortality benefit from all-cause mortality and one that did not demonstrate a mortality benefit. In the only published study to examine HIV-infected patients with disseminated histoplasmosis, clinical success and mortality were significantly better with L-AmB compared with amphotericin B deoxycholate; there were no differences in microbiological outcomes between treatment groups. The lipid-associated preparations were not significantly better than amphotericin B deoxycholate for treatment of AIDS-associated acute cryptococcal meningitis for either clinical or microbiological outcomes that were studied. In all of the trials that specifically examined renal toxicity, the lipid-associated formulations were significantly less nephrotoxic than amphotericin B deoxycholate. Infusion-related reactions occurred less frequently with L-AmB when compared with amphotericin B deoxycholate; however, ABCD had equivalent or more frequent infusion-related reactions than conventional amphotericin B, and this resulted in the cessation of at least one clinical trial. At the present time, this particular lipid formulation is no longer commercially available. For the treatment of most invasive fungal infections, an amphotericin B lipid formulation provides a safer alternative than conventional amphotericin B, with at least equivalent efficacy. As the cost of therapy with these agents continues to decline, these drugs will likely maintain their important role in the antifungal drug armamentarium because of their efficacy and improved safety profile.

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References

  1. Kontoyiannis DP, Marr KA, Park BJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 1002–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) database. Clin Infect Dis. 2010;50(8):1091–100.

    Article  PubMed  Google Scholar 

  2. Park BJ, Pappas PG, Wannemuehler KA, et al. Invasive non-aspergillus mold infections in transplant recipients, United States, 2001–2006. Emerg Infect Dis. 2011;17(10):1855–64.

    Article  PubMed  Google Scholar 

  3. Azie N, Neofytos D, Pfaller M, et al. The PATH (Prospective Antifungal Therapy) Alliance® registry and invasive fungal infections: update 2012. Diagn Microbiol Infect Dis. 2012;73(4):293–300.

    Article  PubMed  Google Scholar 

  4. Gallis HA, Drew RH, Pickard WW. Amphotericin B: 30 years of clinical experience. Rev Infect Dis. 1990;12(2):308–29.

    Article  PubMed  CAS  Google Scholar 

  5. Wasan KM, Lopez-Berestein G. Diversity of lipid-based polyene formulations and their behavior in biological systems. Eur J Clin Microbiol Infect Dis. 1997;16(1):81–92.

    Article  PubMed  CAS  Google Scholar 

  6. Wong-Beringer A, Jacobs RA, Guglielmo BJ. Lipid formulations of amphotericin B: clinical efficacy and toxicities. Clin Infect Dis. 1998;27(3):603–18.

    Article  PubMed  CAS  Google Scholar 

  7. Vogelsinger H, Weiler S, Djanani A, et al. Amphotericin B tissue distribution in autopsy material after treatment with liposomal amphotericin B and amphotericin B colloidal dispersion. J Antimicrob Chemother. 2006;57(6):1153–60.

    Article  PubMed  CAS  Google Scholar 

  8. Bekersky I, Fielding RM, Dressler DE, et al. Plasma protein binding of amphotericin B and pharmacokinetics of bound versus unbound amphotericin B after administration of intravenous liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate. Antimicrob Agents Chemother. 2002;46(3):834–40.

    Article  PubMed  CAS  Google Scholar 

  9. Hammond SM. Biological activity of polyene antibiotics. Prog Med Chem. 1977;14:105–79.

    Article  PubMed  CAS  Google Scholar 

  10. Sutton DA, Sanche SE, Revankar SG, et al. In vitro amphotericin B resistance in clinical isolates of Aspergillus terreus, with a head-to-head comparison to voriconazole. J Clin Microbiol. 1999;37(7):2343–5.

    PubMed  CAS  Google Scholar 

  11. Pujol I, Gurarro J, Gené J, et al. In-vitro antifungal susceptibility of clinical and environmental Fusarium spp. strains. J Antimicrob Chemother. 1997;39(2):163–7.

    Article  PubMed  CAS  Google Scholar 

  12. Lackner M, de Hoog GS, Verweij PE, et al. Species-specific antifungal susceptibility patterns of Scedosporium and Pseudallescheria species. Antimicrob Agents Chemother. 2012;56(5):2635–42.

    Article  PubMed  CAS  Google Scholar 

  13. Walsh TJ, Melcher GP, Rinaldi MG, et al. Trichosporon beigelii, an emerging pathogen resistant to amphotericin B. J Clin Microbiol. 1990;28(7):1616–22.

    PubMed  CAS  Google Scholar 

  14. Chagas-Neto TC, Chaves GM, Colombo AL. Update on the genus Trichosporon. Mycopathologia. 2008;166(3):121–32.

    Article  PubMed  Google Scholar 

  15. Chagas-Neto TC, Chaves GM, Melo ASA, et al. Bloodstream infections due to Trichosporon spp.: species distribution, Trichosoporon ashahii genotypes determined on the basis of ribosomal DNA intergenic spacer 1 sequencing, and antifungal susceptibility testing. J Clin Microbiol. 2009;47(4):1074–81.

    Article  PubMed  CAS  Google Scholar 

  16. Yoon SA, Vazquez JA, Steffan PE, et al. High-frequency, in vitro reversible switching of Candida lusitaniae clinical isolates from amphotericin B susceptibility to resistance. Antimicrob Agents Chemother. 1999;43(4):836–45.

    PubMed  CAS  Google Scholar 

  17. Klepser ME, Wolfe EJ, Jones RN, et al. Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B tested against Candida albicans. Antimicrob Agents Chemother. 1997;41(6):1392–5.

    PubMed  CAS  Google Scholar 

  18. Sau K, Mambula SS, Latz E, et al. The antifungal drug amphotericin B promotes inflammatory cytokine release by a Toll-like receptor- and CD14-dependent mechanism. J Biol Chem. 2003;278(39):37561–8.

    Article  PubMed  CAS  Google Scholar 

  19. Ben-Ami R, Lewis RE, Kontoyiannis DP. Immunopharmacology of modern antifungals. Clin Infect Dis. 2008;47(2):226–35.

    Article  PubMed  CAS  Google Scholar 

  20. Arning M, Kliche KO, Heer-Sonderhoff AH, et al. Infusion-related toxicity of three different amphotericin B formulations and its relation to cytokine plasma levels. Mycoses. 1995;38(11–12):459–65.

    Article  PubMed  CAS  Google Scholar 

  21. Rogers PD, Jenkins JK, Chapman SW, et al. Amphotericin B activation of human genes encoding for cytokines. J Infect Dis. 1998;178(6):1726–33.

    Article  PubMed  CAS  Google Scholar 

  22. Cleary JD, Rogers PD, Chapman SW. Variability in polyene content and cellular toxicity among deoxycholate amphotericin B formulations. Pharmacotherapy. 2003;23(5):572–8.

    Article  PubMed  CAS  Google Scholar 

  23. Goodwin SD, Cleary JD, Walawander CA, et al. Pretreatment regiments for adverse events related to infusion of amphotericin B. Clin Infect Dis. 1995;20(4):755–61.

    Article  PubMed  CAS  Google Scholar 

  24. Sawaya BP, Briggs JP, Schnermann J. Amphotericin B nephrotoxicity: the adverse consequences of altered membrane properties. J Am Soc Nephrol. 1995;6(2):154–64.

    PubMed  CAS  Google Scholar 

  25. Readio JD, Bittman R. Equilibrium binding of amphotericin B and its methyl ester and borate complex to sterols. Biochim Biophys Acta. 1982;685(2):219–34.

    Article  PubMed  CAS  Google Scholar 

  26. Wasan KM, Lopez-Berestein G. Characteristics of lipid-based formulations that influence their biological behavior in the plasma of patients. Clin Infect Dis. 1996;23(5):1126–38.

    Article  PubMed  CAS  Google Scholar 

  27. Wasan KM, Rosenblum MG, Cheung L, et al. Influence of lipoproteins on renal cytotoxicity and antifungal activity of amphotericin B. Antimicrob Agents Chemother. 1994;38(2):223–7.

    Article  PubMed  CAS  Google Scholar 

  28. Krieger M. The use of amphotericin B to detect inhibitors of cellular cholesterol biosynthesis. Anal Biochem. 1983;135(2):383–91.

    Article  PubMed  CAS  Google Scholar 

  29. 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(12):1402–7.

    Article  PubMed  CAS  Google Scholar 

  30. Bates DW, Su L, Yu DT, et al. Mortality and costs of acute renal failure associated with amphotericin B therapy. Clin Infect Dis. 2001;32(3):686–93.

    Article  PubMed  CAS  Google Scholar 

  31. Harbarth S, Burke JP, Lloyd JF, et al. Clinical and economic outcomes of conventional amphotericin B-associated nephrotoxicity. Clin Infect Dis. 2002;15(35):e120–7.

    Article  Google Scholar 

  32. Janknegt R, de Marie S, Bakker-Woudenberg IA, et al. Liposomal and lipid formulations of amphotericin B. Clinical pharmacokinetics. Clin Pharmacokinet. 1992;23(4):279–91.

    Article  PubMed  CAS  Google Scholar 

  33. Hiemenz JW, Walsh TJ. Lipid formulations of amphotericin B: recent progress and future directions. Clin Infect Dis. 1996;22(Suppl 2):S133–44.

    Article  PubMed  CAS  Google Scholar 

  34. Mehta J. Do variations in molecular structure affect the clinical efficacy and safety of lipid-based amphotericin B preparations? Leukemia Res. 1997;23(5):183–8.

    Article  Google Scholar 

  35. Hillery AM. Supramolecular lipidic drug delivery systems: from laboratory to clinic. A review of the recently introduced commercial liposomal and lipid-based formulations of amphotericin B. Adv Drug Del Rev. 1997;24(2–3):345–63.

    Article  CAS  Google Scholar 

  36. Slain D. Lipid-based amphotericin B for the treatment of fungal infections. Pharmacotherapy. 1999;19(3):306–23.

    Article  PubMed  CAS  Google Scholar 

  37. Hann IM, Prentice HG. Lipid-based amphotericin B: a review of the last 10 years of use. Int J Antimicrob Agents. 2001;17(3):161–9.

    Article  PubMed  CAS  Google Scholar 

  38. Dupont B. Overview of the lipid formulations of amphotericin B. J Antimicrob Chemother. 2002;49(suppl S1):31–6.

    Article  PubMed  CAS  Google Scholar 

  39. Herbrecht R, Natarajan-Amé S, Nivoix Y, et al. The lipid formulations of amphotericin B. Expert Opin Pharmacother. 2003;4(8):1277–87.

    Article  PubMed  CAS  Google Scholar 

  40. Adler-Moore JP, Proffitt RT. Amphotericin B lipid preparations: what are the differences? Clin Microbiol Infect. 2008;14(Suppl 4):25–36.

    Article  PubMed  CAS  Google Scholar 

  41. Kennedy AL, Wasan KM. Preferential distribution of amphotericin B lipid complex into human HDL3 is a consequence of high density lipoprotein coat lipid content. J Pharm Sci. 1999;88(11):1149–55.

    Article  PubMed  CAS  Google Scholar 

  42. Lee JW. Pharmacokinetics and safety of a unilamellar liposomal formulation of amphotericin B (AmBisome) in rabbits. Antimicrob Agents Chemother. 1994;38(4):713–8.

    Article  PubMed  CAS  Google Scholar 

  43. Juliano RL, Lopez-Berestein G, Hopfer R, et al. Selective toxicity and enhanced therapeutic index of liposomal polyene antibiotics in systemic fungal infections. Ann N Y Acad Sci. 1985;446(1):390–402.

    Article  PubMed  CAS  Google Scholar 

  44. Hope WW, Goodwin J, Felton TW, et al. Population pharmacokinetics of conventional and intermittent dosing of liposomal amphotericin B in adults: a first critical step for rational dosing of innovative regimens. Antimicrob Agents Chemother. 2013;56(10):5303–8.

    Article  Google Scholar 

  45. Louie A, Baltch AL, Fanke MA, et al. Comparative capacity of four antifungal agents to stimulate murine macrophages to produce tumour necrosis factor alpha: an effect that is attenuated by pentoxifylline, liposomal vesicles, and dexamethasone. J Antimicrob Chemother. 1994;24(6):975–87.

    Article  Google Scholar 

  46. Bellocchio S, Gaziano R, Bozza S, et al. Liposomal amphotericin B activates antifungal resistance with reduced toxicity by diverting Toll-like receptor signaling from TLR-2 to TLR-4. J Antimicrob Chemother. 2005;55(2):214–22.

    Article  PubMed  CAS  Google Scholar 

  47. Simitsopoulou M, Roilides E, Dotis J, et al. Differential expression of cytokines and chemokines in human monocytes induced by lipid formulations of amphotericin B. Antimicrob Agents Chemother. 2005;49(4):1397–403.

    Article  PubMed  CAS  Google Scholar 

  48. Martino R. Efficacy, safety and cost-effectiveness of amphotericin B lipid complex (ABLC): a review of the literature. Curr Med Res Opin. 2004;20(4):485–504.

    Article  PubMed  CAS  Google Scholar 

  49. Adedoyin A, Bernardo JF, Swenson CE, et al. Pharmacokinetic profile of ABELCET (amphotericin B lipid complex injection): combined experience from phase I and phase II studies. Antimicrob Agents Chemother. 1997;41(10):2201–8.

    PubMed  CAS  Google Scholar 

  50. Swenson CE, Perkins WR, Roberts P, et al. In vitro and in vivo antifungal activity of amphotericin B lipid complex: are phospholipases important? Antimicrob Agents Chemother. 1998;32(4):767–71.

    Google Scholar 

  51. Gottfredsson M, Jessup CJ, Cox GM, et al. Fungal phospholipase activity and susceptibility to lipid preparations of amphotericin B. Antimicrob Agents Chemother. 2001;45(11):3231–3.

    Article  PubMed  CAS  Google Scholar 

  52. Boswell GW, Buell D, Bekersky I. AmBisome (liposomal amphotericin B): a comparative review. J Clin Pharmacol. 1998;38(7):583–92.

    Article  PubMed  CAS  Google Scholar 

  53. Moen MD, Lyseng-Williamson KA, Scott LJ. Liposomal amphotericin B. A review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections. Drugs. 2009;69(3):361–92.

    Article  PubMed  CAS  Google Scholar 

  54. Adler-Moore JP, Fujii G, Lee MA. In vitro and in vivo interactions of AmBisome with pathogenic fungi. J Liposome Res. 1993;3(3):151–6.

    Article  Google Scholar 

  55. Adler-Moore JP, Proffitt T. Development, characterization, efficacy and mode of action of AmBisome, a unilamellar liposomal formulation of amphotericin B. J Liposome Res. 1993;3(3):429–50.

    Article  CAS  Google Scholar 

  56. Walsh TJ, Goodman JL, Pappas P, et al. Safety, tolerance, and pharmacokinetics of high-dose liposomal amphotericin B (AmBisome) in patients infected with Aspergillus species and other filamentous fungi: maximum tolerated dose study. Antimicrob Agents Chemother. 2001;45(12):3487–96.

    Article  PubMed  CAS  Google Scholar 

  57. Groll AH, Giri N, Petraitis V, et al. Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system. J Infect Dis. 2000;182(1):274–82.

    Article  PubMed  CAS  Google Scholar 

  58. Guo LS, Fielding RM, Lasic DD, et al. Novel antifungal drug delivery: stable amphotericin B-cholesteryl sulfate discs. Int J Pharm. 1991;75(1):45–54.

    Article  CAS  Google Scholar 

  59. Working PK, Amphotericin B. Colloidal dispersion. A pre-clinical review. Chemotherapy. 1999;45(Suppl 1):15–26.

    Article  PubMed  CAS  Google Scholar 

  60. Bowden RA, Cays M, Gooley T, et al. Phase 1 study of amphotericin B colloidal dispersion for the treatment of invasive fungal infections after marrow transplantation. J Infect Dis. 1996;173(5):1208–15.

    Article  PubMed  CAS  Google Scholar 

  61. Herbrecht R, Letscher V, Andres E, et al. Safety and efficacy of amphotericin B colloidal dispersion. Chemotherapy. 1999;45(Suppl 1):67–76.

    Article  PubMed  CAS  Google Scholar 

  62. Timmers GJ, Zweegman S, Simoons-Smit AM, et al. Amphotericin B colloidal dispersion (Amphocil) versus fluconazole for the prevention of fungal infection in neutropenic patients: data of a prematurely stopped clinical trial. Bone Marrow Transplant. 2000;25(8):879–84.

    Article  PubMed  CAS  Google Scholar 

  63. Subirà M, Martino R, Gómez L, et al. Low-dose amphotericin B lipid complex vs. conventional amphotericin B for empirical antifungal therapy of neutropenic fever in patients with hematologic malignancies—a randomized, controlled trial. Eur J Haematol. 2004;72(5):342–7.

    Article  PubMed  Google Scholar 

  64. Prentice HG, Hann IM, Herbrecht R, 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(3):711–8.

    Article  PubMed  CAS  Google Scholar 

  65. Walsh TJ, Finberg RW, Arndt C, et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. N Engl J Med. 1999;340(10):764–71.

    Article  PubMed  CAS  Google Scholar 

  66. Wingard JR, White MH, Anaissie E, L Amph/ABLC Collaborative Study Group, et al. A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. Clin Infect Dis. 2000;31(5):1155–63.

    Article  PubMed  CAS  Google Scholar 

  67. White MH, Bowden RA, Sandler ES, et al. Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia. Clin Infect Dis. 1998;27(2):296–302.

    Article  PubMed  CAS  Google Scholar 

  68. Bowden R, Chandresekar P, White MH, et al. 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(2):359–66.

    Article  PubMed  CAS  Google Scholar 

  69. White MH, Anaissie EJ, Kusne S, et al. Amphotericin B colloidal dispersion vs. amphotericin B as therapy for invasive aspergillosis. Clin Infect Dis. 1997;24(4):635–42.

    PubMed  CAS  Google Scholar 

  70. Cornely OA, Maertens J, Bresnik M, for the AmBiLoad Trial Study Group, 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(10):1289–306.

    Article  PubMed  CAS  Google Scholar 

  71. Leenders AC, Daenen S, Jansen RLH, et al. Liposomal amphotericin B compared with amphotericin B deoxycholate in the treatment of documented and suspected neutropenia-associated invasive fungal infections. Br J Haematol. 1998;103(3):205–12.

    Article  PubMed  CAS  Google Scholar 

  72. 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. Leukemia Lymphoma. 2001;40(5–6):511–20.

    Article  PubMed  CAS  Google Scholar 

  73. Martín MT, Gavaldà J, López P, et al. Efficacy of high doses of liposomal amphotericin B in the treatment of experimental aspergillosis. J Antimicrob Chemother. 2003;52(6):1032–4.

    Article  PubMed  Google Scholar 

  74. Gavaldà J, Martín T, López P, et al. Efficacy of high loading doses of liposomal amphotericin B in the treatment of experimental invasive pulmonary aspergillosis. Clin Microbiol Infect. 2005;11(12):999–1004.

    Article  PubMed  Google Scholar 

  75. Johnson PC, Wheat LJ, Cloud GA, for the U.S. National Institute of Allergy and Infectious Diseases Mycoses Study Group, et al. Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS. Ann Intern Med. 2002;137(2):105–9.

    Article  PubMed  CAS  Google Scholar 

  76. Sharkey PK, Graybill JR, Johnson ES, et al. Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1996;22(2):315–21.

    Article  PubMed  CAS  Google Scholar 

  77. Leenders AC, Reiss P, Portegies P, et al. Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis. AIDS. 1997;11(12):1463–71.

    Article  PubMed  CAS  Google Scholar 

  78. Hamill RJ, Sobel JD, El-Sadr W, the AmBisome Cryptococcal Meningitis Study Group, et al. Comparison of 2 doses of liposomal amphotericin B and conventional amphotericin B deoxycholate for treatment of AIDS-associated acute cryptococcal meningitis: a randomized, double-blind clinical trial of efficacy and safety. Clin Infect Dis. 2010;51(2):225–32.

    Article  PubMed  CAS  Google Scholar 

  79. den Boer M, Argaw D, Jannin J, et al. Leishmaniasis impact and treatment access. Clin Microbiol Infect. 2011;17(10):1471–7.

    Article  Google Scholar 

  80. Bern C, Adler-Moore J, Berenguer J, et al. Liposomal amphotericin B for the treatment of visceral leishmaniasis. Clin Infect Dis. 2006;43(7):917–24.

    Article  PubMed  CAS  Google Scholar 

  81. Meyerhoff AUS. Food and Drug Administration approval of AmBisome (liposomal amphotericin B) for treatment of visceral leishmaniasis. Clin Infect Dis. 1999;28(1):42–8.

    Article  PubMed  CAS  Google Scholar 

  82. Sundar S, Chakravarty J, Agarwal D, et al. Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med. 2010;362(6):504–12.

    Article  PubMed  CAS  Google Scholar 

  83. Barrett JP, Vardulaki KA, Conlon C, The Amphotericin B Systematic Review Study Group, et al. A systematic review of the antifungal effectiveness and tolerability of amphotericin B formulations. Clin Ther. 2003;25(5):1295–320.

    Article  PubMed  CAS  Google Scholar 

  84. Johansen HK, Gøtzsche PC. Amphotericin B lipid soluble formulations versus amphotericin B in cancer patients with neutropenia. Cochrane Database Syst Rev. 2000;(3):CD000969. doi:10.1002/14651858.CD000969.

  85. Girois SB, Chapuis F, Decullier E, et al. Adverse effects of antifungal therapies in invasive fungal infections: review and meta-analysis. Eur J Clin Microbiol Infect Dis. 2006;25(2):138–49.

    Article  PubMed  CAS  Google Scholar 

  86. Safdar A, Ma J, Saliba F, et al. Drug-induced nephrotoxicity caused by amphotericin B lipid complex and liposomal amphotericin B: a review and meta-analysis. Medicine. 2010;89(4):236–44.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This project was supported in part by the facilities and resources of the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine. The author would like to acknowledge Peguy Saad, MD, for assistance with the literature review.

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Hamill, R.J. Amphotericin B Formulations: A Comparative Review of Efficacy and Toxicity. Drugs 73, 919–934 (2013). https://doi.org/10.1007/s40265-013-0069-4

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