Treatment of invasive Candida infections. Clinical decision-making

Contains fulltext : 110050.pdf (Publisher’s version ) (Open Access)Radboud Universiteit Nijmegen, 03 juli 2012Promotor : Kullberg, B.J

[Amphotericin B: the end of an era]

For 45 years, amphotericin B has been the drug of choice for the treatment of invasive mycoses. Because of its severe toxicity, lipid-associated formulations of amphotericin B have been developed. Although comparative trials are scarce, there appears to be no convincing advantage of these new formulations in terms of efficacy. The lipid-associated amphotericins are significantly less nephrotoxic than conventional amphotericin B, although there are major differences in the infusion-related toxicity of the various lipid-associated preparations. The current armamentarium of azoles and echinocandins for the treatment of invasive mycoses has only left a very minor role for both conventional and lipid-associated amphotericin B in the treatment of a few specific, rare mycoses

Epidemiology of opportunistic invasive mycoses.

Invasive aspergillosis and disseminated candidiasis are the two major manifestations of opportunistic invasive mycoses. Their incidence has risen considerably during the past decades, due to more intensive anticancer chemotherapy, organ transplantations, intensive care, and aggressive surgical interventions. Especially bone marrow transplant recipients are at risk for developing invasive aspergillosis. Whether the infection is acquired through contaminated water or through airborne spores is a matter of much debate. Candidemia and disseminated candidiasis commonly originate from the gastrointestinal tract. Abdominal surgery and mucosal damage due to anticancer chemotherapy are the majors factor through which gut colonization may lead to invasive disease. A shift in the epidemiology of disseminated candidiasis has been noted, with an increasing incidence of Candida glabrata, C. tropicalis and C. krusei strains

Epidemiology of opportunistic invasive mycoses.

Item does not contain fulltextInvasive aspergillosis and disseminated candidiasis are the two major manifestations of opportunistic invasive mycoses. Their incidence has risen considerably during the past decades, due to more intensive anticancer chemotherapy, organ transplantations, intensive care, and aggressive surgical interventions. Especially bone marrow transplant recipients are at risk for developing invasive aspergillosis. Whether the infection is acquired through contaminated water or through airborne spores is a matter of much debate. Candidemia and disseminated candidiasis commonly originate from the gastrointestinal tract. Abdominal surgery and mucosal damage due to anticancer chemotherapy are the majors factor through which gut colonization may lead to invasive disease. A shift in the epidemiology of disseminated candidiasis has been noted, with an increasing incidence of Candida glabrata, C. tropicalis and C. krusei strains

[Amphotericin B: the end of an era]

Contains fulltext : 59027.pdf (publisher's version ) (Closed access)For 45 years, amphotericin B has been the drug of choice for the treatment of invasive mycoses. Because of its severe toxicity, lipid-associated formulations of amphotericin B have been developed. Although comparative trials are scarce, there appears to be no convincing advantage of these new formulations in terms of efficacy. The lipid-associated amphotericins are significantly less nephrotoxic than conventional amphotericin B, although there are major differences in the infusion-related toxicity of the various lipid-associated preparations. The current armamentarium of azoles and echinocandins for the treatment of invasive mycoses has only left a very minor role for both conventional and lipid-associated amphotericin B in the treatment of a few specific, rare mycoses

Voriconazole salvage treatment of invasive candidiasis.

Item does not contain fulltextData on the salvage treatment of invasive candidiasis with voriconazole in 52 patients intolerant of other antifungal agents or with infection refractory to other antifungal agents were analyzed. Patients had received a mean of two previous antifungal agents (range, 1-4 agents), and 83% had received an azole. Manifestations of invasive candidiasis included candidemia (37%), disseminated disease (25%), and infection of other sites (38%). The median duration of voriconazole therapy was 60 days (range, 1-314 days). The overall rate of response was 56% (95%CI, 41-70), with the following response rates observed for individual Candida species: Candida albicans, 44% (20-70); Candida glabrata, 38% (14-68); Candida krusei, 70% (35-93); Candida tropicalis, 67% (30-93); and other Candida spp., 100% (40-100). The response rate in patients who had failed previous azole therapy was 58% (42-73). Common adverse events (~20%) included nausea and emesis, abnormal liver enzymes, and visual disturbances. Serious adverse events occurred in four patients, and nine patients died. Voriconazole has promise as a salvage agent for the treatment of invasive candidiasis, even in the settings of previous azole therapy and infection due to Candida krusei

Colitis in an alcohol-dependent woman.

Contains fulltext : 51940.pdf (publisher's version ) (Closed access

Cutane nodulus als uiting van systemische cryptococcose bij een levertransplantatie patient.

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Safety and tolerability of voriconazole in patients with baseline renal insufficiency and candidemia.

Item does not contain fulltextAcutely ill patients with candidemia frequently suffer from renal insufficiency. Voriconazole's intravenous formulation with sulfobutylether beta-cyclodextrin (SBECD) is restricted in patients with renal insufficiency. We evaluated the use of intravenous voriconazole formulated with SBECD in candidemic patients with renal insufficiency and compared treatment outcome and safety to those who received a short course of amphotericin B deoxycholate followed by fluconazole. We reviewed data on treatment outcome, survival, safety, and tolerability from the subset of patients with moderate (creatinine clearance [CrCl], 30 to 50 ml/min) or severe (CrCl, <30 ml/min) renal insufficiency enrolled in a trial of voriconazole compared to amphotericin B deoxycholate followed by fluconazole for treatment of candidemia in 370 patients. Fifty-eight patients with renal impairment were identified: 41 patients on voriconazole and 17 on amphotericin B/fluconazole. The median duration of treatment was 14 days for voriconazole (median, 7 days intravenous) and 11 days for amphotericin B/fluconazole, 3 days of which were for amphotericin B. Despite the short duration of exposure, worsening of renal function or newly emerged renal adverse events were reported in 53% of amphotericin B-treated patients compared to 39% of voriconazole-treated patients. During treatment, median serum creatinine decreased in the voriconazole arm, whereas creatinine increased in the amphotericin B/fluconazole arm, before return to baseline at week 3. All-cause mortality at 14 weeks was 49% in the voriconazole arm compared to 65% in the amphotericin B/fluconazole arm. Intravenous voriconazole formulated with SBECD was effective in patients with moderate or severe renal insufficiency and candidemia and was associated with less acute renal toxicity than amphotericin B/fluconazole.1 juni 201