Controlled trial of natamycin in the treatment of allergic bronchopulmonary aspergillosis.

Abstract

Allergic bronchopulmonary aspergillosis often requires treatment with oral corticosteroids to control the host response to Aspergillus fumigatus. In a double blind study 25 patients with allergic bronchopulmonary aspergillosis taking maintenance oral corticosteroids were randomly allocated to receive 5 mg natamycin or placebo by nebuliser twice daily for one year. The primary aim of the study was to assess the steroid sparing potential of natamycin. Standardised reductions in corticosteroid dosage were therefore undertaken every five weeks, unless clinically contraindicated. Five patients were withdrawn in the first four months: two (1 natamycin, 1 placebo) died, two (1 natamycin, 1 placebo) had suspected drug reactions, and one (natamycin) was non-compliant. The pretreatment characteristics of the 20 patients (10 in each group) who completed the study were similar, 17 (9 natamycin, 8 placebo) having evidence of recent disease activity. At the end of the study prednisolone dose had been reduced by a similar amount in each group (median natamycin 2 25 mg, placebo 2-5 mg). Evidence of disease activity during the study year (transient shadowing on the chest radiograph, blood eosinophilia, or increases in antibodies to A fumigatus, or any combination of these)-was observed in similar numbers of patients in each group (5 natamycin, 7 placebo). There was no evidence that natamycin conferred benefit on these patients with allergic bronchopulmonary aspergillosis.Prolonged oral corticosteroid treatment is often used in patients with allergic bronchopulmonary aspergillosis in an attempt to control the host inflammatory response to Aspergillus fumigatus, but corticosteroids are associated with significant morbidity.'2 A fumigatus is found more frequently in the respiratory tract of patients with untreated allergic bronchopulmonary aspergillosis (58%) and in larger quantities than in patients with other respiratory disease."4 Antifungal agents might therefore reduce the requirement for corticosteroids.Nebulised antifungal agents, nystatin and natamycin (pimaricin), and nebulised brilliant green have been administered in an attempt to reduce the fungal load.7 The studies that have been reported were inadequately controlled and have shown equivocal evidence of benefit. In a group of eight patients with bronchopulmonary aspergillosis (initial culture positive for A fumigatus) treated with nebulised natamycin (2-5 mg thrice daily for one month and thereafter twice daily) A fumigatus disappeared from the sputum after a median of six (range 4-30) weeks.7 In a further study of four patients with allergic bronchopulmonary aspergillosis not receiving oral corticosteroids oral ketoconazole was associated with improvement in symptoms of asthma and a reduction in antibodies to A fumigatus,' but the risk of hepatotoxicity9 renders ketoconazole unsuitable as a long term alternative to corticosteroids.In a pilot study six of seven patients with allergic bronchopulmonary aspergillosis treated with nebulised natamycin (2-5 mg thrice...

The link between fungi and severe asthma: a summary of the evidence

“…The potential utility of systemic antifungal therapy for ABPA was first shown in the early 1990s [129], nebuliser therapy with nystatin having failed [130]. Two randomised placebocontrolled trials of itraconazole confirmed these results [131, 132], and a Cochrane review concluded that therapy was beneficial [133].…”

Expression of Paenibacillus polymyxa β-1,3-1,4-glucanase in Streptomyces lydicus A01 improves its biocontrol effect against Botrytis cinerea

“…Streptomyces lydicus strain A01 isolated from the soil of suburban vegetable field in Beijing, China, is capable of producing natamycin and chitinase, and has a significant inhibition effect on B. cinerea (Lu et al, 2008;Wu et al, 2013a,b). Natamycin is a tetraene macrolide antibiotic widely used as a food preservative and fungicide in food, medicine, and veterinary products, and it has the potential to control plant fungal diseases in agricultural production (Ture et al, 2011;Currie et al, 1990;Lu et al, 2008;Wu et al, 2014a). Pathogenesis-related (PR) proteins such as chitinases and glucanases can degrade fungal cell walls and play important roles in plant defence against pathogens, and are widely used as antifungal agents in plant protection (Errakhi et al, 2007;Shi et al, 2010;Park et al, 2012).…”

Treatment options in severe fungal asthma and allergic bronchopulmonary aspergillosis

“…Initial trials of the imidazole ketoconazole and the polyene natamycin (antifungal agents lacking high activity against Aspergillus spp.) in patients with ABPA were disappointing [36,37]. However, case reports and uncontrolled series over several decades have reported treatment success upon addition of the Aspergillus-active oral triazole agent itraconazole to steroids for ABPA in asthma patients [38][39][40][41].…”