Fluconazole versus nystatin in the prevention of candida infections in children and adolescents undergoing remission induction or consolidation chemotherapy for cancer

Abstract

An open, prospective, randomized pilot study was performed to assess the efficacy and safety of oral fluconazole 3 mg/kg once daily compared with oral nystatin 50,000 units/kg/day in four divided doses in preventing candida infections in 50 children undergoing remission induction or consolidation therapy for cancer. In 21 of 25 fluconazole-treated and 20 of 25 nystatin-treated patients the overall outcome of prophylaxis was clearly successful. Mild and transient oropharyngeal candidosis was observed in two and three patients in the fluconazole and nystatin groups respectively. One patient randomized to fluconazole and two patients randomized to nystatin required empirical treatment with amphotericin B and one patient assigned to fluconazole developed tissue-proven candida colitis. Initially non-colonized patients remained yeast-free throughout treatment with no differences between the two study arms. Initially colonized patients stayed colonized throughout treatment although at the end of the study, more patients randomized to nystatin were still harbouring yeasts (P = 0.05). Almost exclusively, Candida albicans (95%) was isolated. A change in species was observed in one patient in each arm of the study. Candida krusei or Candida glabrata were not encountered. Transient elevations of hepatic transaminases were more common in the fluconazole group, although not statistically significant (28% vs 12%, P = 0.15). Reversible grade I gastrointestinal and skin symptoms were observed in four patients randomized to fluconazole (16 vs 0%, P < 0.05). Fluconazole was as safe and effective as nystatin in controlling yeast colonization and in preventing superficial and invasive candida infections and the empirical use of amphotericin B in children and adolescents undergoing intensive chemotherapy for cancer.

Safety of fluconazole in paediatrics: a systematic review

“…One study compared different routes of administration [17]. Seven of the 14 RCTs were exclusively conducted in neonates (term and preterm) [17–23], while the remainder involved children across the paediatric age spectrum (birth–17 years) [24–31]. Fluconazole was used as prophylaxis in six of the eight neonatal RCTs.…”

Invasive Aspergillosis in Paediatric Patients

“…General measures for prevention of IA have been discussed in other chapters of this textbook and elsewhere [107]. Since there are no principal differences in this area between paediatric and adult patients, we will limit the discussion in this section to the current approaches to chemoprophylaxis in paediatric patients.…”

“…A variety of different approaches have been explored in the past -mostly in adult patients with haematologic malignancies and/or allogeneic HSCT -without providing convincing preventative evidence for efficacy against IA [107][108][109]. Two recent large randomized clinical trials, however, have demonstrated that prophylactic posaconazole is effective in preventing IA in patients with acute myeloblastic leukaemia or myelodysplastic syndrome [110] and those with GVHD receiving augmented immunosuppressive therapy [111]; the first study also demonstrated a survival advantage in the posaconazole cohort.…”

“…Whilst the role of surgical resection of residual lesions, if feasible, is unclear, patients should have had at least a partial response before continuation of anticancer treatment and continue to receive effective antifungal therapy [94,107]. In a recently published paediatric case series, patients with leukaemia and a history of invasive pulmonary aspergillosis undergoing allogeneic HSCT received L-AMB (1 mg/kg/d) from conditioning until engraftment, followed by oral voriconazole (200 mg 12 hourly) until the end of the at-risk period.…”

Prävention von Pilzinfektionen bei Kindern und Jugendlichen mit neoplastischen Erkrankungen

“…In kleinen vergleichenden Studien zeigte Nystatin geringere Effekte auf die orointestinalen Hefekolonisation als systemisch verabreichte Azole und war ineffektiv in der Prävention oberflächlicher bzw. invasiver Pilzinfektionen [52,60,159,170].…”