title: Voriconazole, combined with amphotericin B, in the treatment for pulmonary cryptococcosis caused by C. neoformans (serotype A) in mice with severe combined immunodeficiency (SCID).
abstract: Cryptococcosis is a subacute or chronic systemic mycosis with a cosmopolitan nature, caused by yeast of the genus Cryptococcus neoformans. The model of systemic cryptococcosis in mice with severe combined immunodeficiency (SCID) is useful for immunological and therapeutic study of the disease in immunodeficient hosts. Amphotericin B, fluconazole and flucytosine are the drugs most commonly used to treat cryptococcosis. Voriconazole is a triazole with high bioavailability, large distribution volume, and excellent penetration of the central nervous system. The objective of this study was to evaluate treatment with amphotericin B (AMB), voriconazole (VRC), and AMB, used in combination with VRC, of experimental pulmonary cryptococcosis in a murine model (SCID). The animals were inoculated intravenously (iv) with a solution containing 3.0 × 10(5) viable cells of C. neoformans ATCC 90112, (serotype A). Treatments were performed with amphotericin B (1.5 mg/kg/day), voriconazole (40.0 mg/kg/day) and AMB (1.5 mg/kg/day) combined with VRC (40.0 mg/kg/day); began 1 day after the initial infection; were daily; and lasted 15 days. Evaluations were performed using analysis of the survival curve and isolation of yeast in the lung tissue. There was a significant increase in survival in groups treated with AMB combined with VRC, compared with the untreated group and groups receiving other treatments (P < 0.05). In the group treated only with VRC and AMB combined with VRC, there was a significant reduction (P < 0.05) in the isolation of C. neoformans in lung tissue. Amphotericin B combined with voriconazole may be an effective alternative to increasing survival and may reduce yeast in the lung tissue of mice with pulmonary cryptococcosis and SCID.
authors.affiliation: Department of Microbiology, University of São Paulo, São Paulo, Brazil. eriques@usp.br
authors.forename: Eriques Gonçalves
authors.initials: EG
authors.lastname: Silva
authors.forename: Claudete Rodrigues
authors.initials: CR
authors.lastname: Paula
authors.forename: Francisco
authors.initials: F
authors.lastname: de Assis Baroni
authors.forename: Walderez
authors.initials: W
authors.lastname: Gambale
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D003453:Cryptococcosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000302:isolation & purification*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008168:Lung / Q000382:microbiology; D008172:Lung Diseases, Fungal / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D016513:Mice, SCID; D011743:Pyrimidines / Q000008:administration & dosage*; D016511:Severe Combined Immunodeficiency / Q000150:complications*; D016019:Survival Analysis; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D065819:Voriconazole
references.citation: Rev Inst Med Trop Sao Paulo. 2006 Mar-Apr;48(2):71-5
references.pmid: 16699626
references.citation: Curr Infect Dis Rep. 2000 Aug;2(4):352-357
references.pmid: 11095877
references.citation: Clin Infect Dis. 2000 Apr;30(4):710-8
references.pmid: 10770733
references.citation: J Antimicrob Chemother. 2007 Jul;60(1):162-5
references.pmid: 17483143
references.citation: Nephrologie. 2002;23(3):119-22
references.pmid: 12087808
references.citation: Antimicrob Agents Chemother. 2006 Jan;50(1):113-20
references.pmid: 16377675
references.citation: Antimicrob Agents Chemother. 2006 Jun;50(6):2009-15
references.pmid: 16723559
references.citation: Mycopathologia. 2011 Apr;171(4):261-6
references.pmid: 20972836
references.citation: Saudi J Kidney Dis Transpl. 2002 October-December;13(4):481-91
references.pmid: 17660672
references.citation: Med Mycol. 2006 Nov;44(7):601-10
references.pmid: 17071553
references.citation: J Antimicrob Chemother. 2004 Aug;54(2):563-5
references.pmid: 15254027
references.citation: Lancet. 2004 May 29;363(9423):1764-7
references.pmid: 15172774
references.citation: Antimicrob Agents Chemother. 2000 Sep;44(9):2435-41
references.pmid: 10952592
references.citation: J Antimicrob Chemother. 2005 Jun;55(6):1020-3
references.pmid: 15845779
references.citation: Antimicrob Agents Chemother. 2001 Nov;45(11):3065-9
references.pmid: 11600357
references.citation: J Med Vet Mycol. 1996 Sep-Oct;34(5):331-5
references.pmid: 8912166
references.citation: Ther Clin Risk Manag. 2006 Jun;2(2):129-58
references.pmid: 18360588
references.citation: J Med Microbiol. 2006 Feb;55(Pt 2):139-142
references.pmid: 16434704
references.citation: Mycopathologia. 2006 Aug;162(2):111-4
references.pmid: 16897589