YAMAZUMIT,PFALLER MA,MESSER SA,et al.Chae-acterization of heteroresistance to fluconazole among clinical isolates of Cryptococcus neoformans[J].,2003,41(1):267-272.
Strains of Cryptococcus neoformans expressing heteroresistance to fluconazole have been described previously. The present study was conducted to investigate the prevalence of heteroresistance among clinical isolates of C. neoformans and to characterize the heteroresistant phenotypes. A total of 107 clinical isolates of C. neoformans for which the MICs of fluconazole ranged from 0.25 to 32 microg/ml were selected. The isolates were chosen to represent a broad geographic distribution. Of the 107 C. neoformans isolates tested, 4 grew on medium containing fluconazole at concentrations that were four to eight times higher than the MICs for each strain. A fifth isolate, for which the fluconazole MIC was 32 microg/ml, grew on agar with 64 microg of fluconazole per ml. These five isolates (4.7% of the total number) were confirmed to exhibit heteroresistant compositions by population analysis. The degree and frequency of resistance varied among the isolates. Stepwise selection by exposure to fluconazole resulted in subclones of all five strains for which the fluconazole MIC was >64 microg/ml. Subclones of three strains demonstrated a homogeneous population of resistant cells on medium containing 64 microg of fluconazole/ml. The resistance was sensitive to incubation temperature, that is, heteroresistance was demonstrable only at 30 degrees C by agar-based tests, and was reversible through serial transfers on fluconazole-free medium over a period of 8 days. These results suggest that the fluconazole-heteroresistant phenotype of C. neoformans exists in a significant proportion of clinical isolates and that fluconazole resistance can be developed by selection from heteroresistant clones and induction by exposure to fluconazole.
SUNAKAWAK,TSUKIMOTOI,TSUNEMATSUY,et al.Evaluation of the safety and efficacy of liposomal amphotericin B (L-AMB) in children[J].,2012,18(4):456-465.
A multicenter, uncontrolled clinical study has been conducted to evaluate the safety, efficacy, and pharmacokinetics of liposomal amphotericin B (L-AMB) in children. In this article, the safety and efficacy of L-AMB are discussed. Subjects were diagnosed with invasive fungal infection (definitely diagnosed cases), possible fungal infection (clinically diagnosed cases), and febrile neutropenia with suspected fungal infection (febrile neutropenia cases). Of the 39 subjects treated with L-AMB, 18 received a definite (11) or clinical (7) diagnosis of invasive fungal infection. In these subjects, excluding one unevaluable subject, L-AMB was effective in nine out of 17 subjects (52.9%). Of 12 febrile neutropenia cases, improvement in clinical symptoms, etc., was observed for six but these were excluded from the efficacy analysis because they concomitantly used medications that may have affected efficacy. The causative fungus was identified in four out of 39 subjects and confirmed to be eliminated by treatment with L-AMB in one subject. Adverse events possibly related to L-AMB (adverse drug reactions) were reported in 36 out of 39 subjects (92.3%). The most common adverse drug reaction was decreased potassium in 20 out of 39 subjects (51.3%), but all these subjects recovered with appropriate treatment, for example potassium supplementation. In a Japanese Phase II clinical study of adult patients, the incidence of adverse drug reactions was 95.3% (82/86 subjects) and the efficacy was 63.6% (42/66). Taken together, these data indicate that the safety and efficacy of L-AMB are almost the same in pediatric and adult patients.
LANIADO-LABORíNR,CABRALES-VARGAS MN.Amphotericin B:side effects and toxicity[J].,2009,26(4):223-227.
Su principal toxicidad crónica se manifiesta a nivel renal. Los factores de riesgo para la nefrotoxicidad incluyen pertenecer al género masculino, una dosis diaria ≥3502mg/día, utilización concomitante de diuréticos o drogas nefrotóxicas, peso corporal ≥9002kg y una función renal basal anormal. El da09o renal se manifiesta como insuficiencia renal, hipocalemia, hipomagnesemia, acidosis metabólica y poliuria secundaria a diabetes insípida. Estudios en humanos han demostrado convincentemente que la administración de solución salina, ya sea por vía oral o parenteral, reduce notablemente la incidencia y severidad del da09o renal secundario a AmB.
GERBAUDE,TAMIONF,GIRAULTC,et al.Persistent acute tubular toxicity after switch from conventional amphotericin B to liposomal amphotericin B(Ambisome)[J].,2003,51(2):473-475.
Gerbaud E, Tamion F, Girault C, Clabault K, Lepretre S, Leroy J, Bonmarchand G.