ABSTRACT
As invasive mucormycosis (IM) numbers rise, clinicians suspect prior voriconazole worsens IM incidence and severity, and believe combination anti-fungal therapy improves IM survival. To compare the cumulative incidence (CI), severity and mortality of IM in eras immediately before and after the commercial availability of voriconazole all IM cases from 1995 to 2011 were analysed across four risk-groups (hematologic/oncologic malignancy (H/O), stem cell transplantation (SCT), solid organ transplantation (SOT) and other), and two eras, E1 (1995-2003) and E2, (2004-2011). Of 101 IM cases, (79 proven, 22 probable): 30 were in E1 (3.3/year) and 71 in E2 (8.9/year). Between eras, the proportion with H/O or SCT rose from 47% to 73%, while 'other' dropped from 33% to 11% (P = 0.036). Between eras, the CI of IM did not significantly increase in SCT (P = 0.27) or SOT (P = 0.30), and patterns of anatomic location (P = 0.122) and surgical debridement (P = 0.200) were similar. Significantly more patients received amphotericin-echinocandin combination therapy in E2 (31% vs. 5%, P = 0.01); however, 90-day survival did not improve (54% vs. 59%, P = 0.67). Since 2003, the rise of IM reflects increasing numbers at risk, not prior use of voriconazole. Frequent combination of anti-fungal therapy has not improved survival.
Subject(s)
Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Echinocandins/therapeutic use , Mucormycosis/drug therapy , Voriconazole/therapeutic use , Adult , Aged , Amphotericin B/history , Antifungal Agents/history , Drug Therapy, Combination/history , Echinocandins/history , Female , Fungi/classification , Fungi/genetics , Fungi/isolation & purification , History, 21st Century , Humans , Male , Middle Aged , Mucormycosis/epidemiology , Mucormycosis/microbiology , Mucormycosis/mortality , United States/epidemiology , Voriconazole/history , Young AdultABSTRACT
La anfotericina B es un antifúngico ampliamente usado en infecciones sistémicas por hongos levaduriformes y filamentosos, entre ellas las meningitis por Cryptococcus neoformans. Sus reacciones adversas pueden ser inmediatas o dosis y tiempo dependiente. En nuestro trabajo en el hospital C. van Buren de Valparaíso, se revisaron 27 fichas de pacientes que cumplieron con los criterios de inclusión (24 hombres y 3 mujeres). El principal síntoma de la meningitis por Crytococcus fue la cefalea (96,3 por ciento). En 25 casos hubo confirmación con tinta china y/o cultivo. Durante el tratamiento con anfotericina B la hipokalemia fue la reacción adversa que se presento con mayor frecuencia (83 por ciento) y la nefrotoxicidad en un 59,1 por ciento. La dosis acumulada administrada fue en promedio 525 mg, suspendiendo generalmente su administración cuando se lograba una mejoría clínica junto a esterilidad del LCR (tinta china y/o cultivo negativo). Un 33,3 por ciento de los pacientes con diagnostico de meningitis por C. neoformans falleció por distintas complicaciones.
Amphotericin B is a antifungal drug widely used in systemic infections by filamentous and levaduriform fungi, as in meningitis by Cryptococcus neoformans. Its adverse reactions can be immediate or dose and time dependent. In our paper, 27 patient files were reviewed in C. van Buren hospital of Valparaíso and all of them met the criteria for inclusion (24 men and 3 women). In 96.3 percent of cases, headaches were the main symptom of meningitis caused by Cryptococcus. Twenty five cases were confirmed by the use of chinese ink and/or by culture. During the treatment with amphotericin B, the most frequent changes were hypokalemia (83 percent) and nefrotoxicity in 59.1 percent. The average of cumulative dose administered was 525 mg and was suspended when a clinical recovery was achieved next to a sterile cefalorraquid liquid (negative to chinese ink and/or culture). 33.3 percent of the patients diagnosed with meningitis by C. neoformans died due to different complications.
Subject(s)
Humans , Male , Female , Amphotericin B/administration & dosage , Amphotericin B/adverse effects , Amphotericin B/history , Amphotericin B/toxicity , Amphotericin B/therapeutic use , HIV Infections , Meningitis, Cryptococcal/complications , Meningitis, Cryptococcal/diagnosis , Meningitis, Cryptococcal/history , Meningitis, Cryptococcal/therapy , ChileABSTRACT
PURPOSE: The purpose of this review article is to review the development of a number of liposomal polyene antibiotics. BACKGROUND: In the past thirty years, the increase in life-threatening pre-systemic and systemic fungal infections within cancer, diabetic and AIDS patients have reached alarming proportions. A number of antifungal agents have been developed to combat this problem. In particular, polyene antibiotics such as Amphotericin B (AmB) and Nystatin (Nys) have remained the most effective and widely used agents in the treatment of these infections. However, their administration is limited by dose-dependent toxicities. One such dose-limiting toxicity is renal toxicity. Polyene antibiotic-induced renal toxicity is believed to be mediated by the drug anchoring to cholesterol within the mammalian cell membrane, resulting in pore formation, abnormal electrolyte flux, decrease in adenosine triphosphate (ATP), and eventually a loss of cell viability. CONCLUSION: In the 1980s and 90s a number of promising lipid-based AmB and Nys formulations were developed to overcome these toxicities. This article will review the development of these liposomal polyene antibiotics.
