Failure of voriconazole to cure disseminated zygomycosis in an immunocompromised child.

UNLABELLED: Voriconazole is increasingly used as a first-line agent for empirical antifungal therapy of prolonged febrile neutropenia in paediatric cancer patients. We describe the case of a 9-year-old patient with stage IV Burkitt lymphoma, who developed pulmonary and splenic zygomycosis while receiving voriconazole for persistent febrile neutropenia. The causative agent, Absidia corymbifera, was identified by broad-range fungal PCR in a lung biopsy sample. The patient was successfully treated with a combination of partial resection of the left upper lobe and antifungal therapy with high-dose liposomal amphotericin B followed by oral itraconazole as demonstrated by resolving pulmonary infiltrates on serial high resolution CT scans. CONCLUSION: This case emphasises that the lack of in vitro activity of voriconazole against zygomycetes is clinically relevant. Failure of voriconazole in suspected fungal infection should be investigated for the possibility of zygomycosis. Broad-range polymerase chain reaction may be able to identify the causative organism when cultures remain sterile.

Growth in prepubertal children with cystic fibrosis, homozygous for the Delta F508 mutation.

BACKGROUND AND METHODS: In cystic fibrosis, growth and lung function have been identified as prognostic markers of both severity of pulmonary disease and survival. Cross-sectional studies in patients with cystic fibrosis (CF) including all genotypes have shown that in prepubertal patients with lifetime continuous care within a specialised CF centre, growth can normalise. No corresponding improvement in lung function has been found. We used a longitudinal design to determine whether normalisation of growth could be found in the genetic subgroup of prepubertal children with CF with the homozygous Delta F508 mutation, which is one of the known severe mutations. METHODS: Data of all children born after 1980 with the homozygous Delta F508 mutation, diagnosed in early childhood at the specialised centre of the Children's Hospital of Berne were systematically assessed up to the age of 11 years and retrospectively analysed. Follow-up data of height, weight and BMI were compared to the Swiss reference population using z-scores. The correlations between lung function parameters (FEV1, MEF50, VC) and age, as well as lung function parameters and growth indices, were calculated. Additionally, the same correlations were examined in a cohort with the same mutation born 10 years earlier. RESULTS: In the study, cohort growth (height, weight and BMI) was significantly below that of the normal Swiss population. A significant decline of lung function with age was also found, however, no association between lung function and growth could be seen. Compared to an earlier cohort, an improved growth over the last decade could be shown but no improvement on lung function could be detected. Lung function varied widely in both groups. CONCLUSION: In contrast to sequential cross-sectional studies of children with CF, the present longitudinal study of children with homozygous for the Delta F508 mutation failed to confirm normalisation of growth over time. However, compared to the data of children born in the previous decade, improved growth was observed.