Posaconazole therapy in children with cystic fibrosis and Aspergillus-related lung disease.

There is emerging evidence for the role of posaconazole in the management of Aspergillus-related cystic fibrosis (CF) lung disease. The tolerability and efficacy of posaconazole in paediatric CF is not well established. We report a prospective study over a fifty-three month period evaluating the safety, tolerability, and efficacy of posaconazole in pediatric CF. Fourteen children (seven males, median age 13 years, range 3-17 years) received a total of twenty-three courses of posaconazole (13 oral suspension and 10 tablet formulation). Of these patient episodes, nine received posaconazole for emerging or active allergic bronchopulmonary aspergillosis (ABPA) and two required a combination of posaconazole and systemic corticosteroids for difficult-to-treat ABPA. A subgroup of patients (n = 12) with persistent isolates of Aspergillus fumigatus, in the absence of serological markers of ABPA, received posaconazole monotherapy for pulmonary exacerbations not responding to conventional broad-spectrum antibiotic treatment. Posaconazole levels, full blood count, electrolytes, and liver function were monitored on day 7 of treatment and then monthly. Posaconazole was well tolerated in all but three patients. Therapeutic plasma levels >1 mg/l were achieved in all receiving the tablet formulation in comparison to 60% on the liquid preparation. There was a modest but significant improvement in FEV1 (% predicted) demonstrated for the cohort as a whole (p = 0.015) following posaconazole therapy. Posaconazole is well tolerated in children as young as six years old, improvements in lung function are observed, and therapeutic plasma levels are readily achieved in patients taking the tablet formulation and in adherent patients taking the liquid formulation.

Chronic Aspergillus fumigatus colonization of the pediatric cystic fibrosis airway is common and may be associated with a more rapid decline in lung function.

Filamentous fungi are commonly isolated from the respiratory tract of CF patients, but their clinical significance is uncertain and the reported incidence variable. We report on the degree of Aspergillus fumigatus airway colonization in a tertiary pediatric CF cohort, evaluate the sensitivity of routine clinical sampling at detecting A. fumigatus, and compare lung function of A. fumigatus-colonized and non-colonized children.We carried out an 8-year retrospective cohort analysis using local databases, examining 1024 respiratory microbiological specimens from 45 children. Nineteen (42%) had a positive A. fumigatus culture at least once during the 8-year period, with 10 (22%) children persistently colonized. Overall, 29% of 48 bronchoalveolar lavage (BAL) samples tested positive for A. fumigatus, compared with 14% of 976 sputum samples. Of 33 children for whom lung function data were available during the study period, seven were classed as having severe lung disease, of whom four (57%) were persistently colonized with A. fumigatus.We conclude that chronic A. fumigatus colonization of the CF airway is common, and may be associated with worse lung function. In our practice, BAL appears superior at detecting lower airway A. fumigatus compared to sputum samples.

The first recorded outbreak of cryptosporidiosis due to Cryptosporidium cuniculus (formerly rabbit genotype), following a water quality incident.

We report the first identified outbreak of cryptosporidiosis with Cryptosporidium cuniculus following a water quality incident in Northamptonshire, UK. A standardised, enhanced Cryptosporidium exposure questionnaire was administered to all cases of cryptosporidiosis after the incident. Stool samples, water testing, microscopy slides and rabbit gut contents positive for Cryptosporidium were typed at the Cryptosporidium Reference Unit, Singleton Hospital, Swansea. Twenty-three people were microbiologically linked to the incident although other evidence suggests an excess of 422 cases of cryptosporidiosis above baseline. Most were adult females; unusually for cryptosporidiosis there were no affected children identified under the age of 5 years. Water consumption was possibly higher than in national drinking water consumption patterns. Diarrhoea duration was negatively correlated to distance from the water treatment works where the contamination occurred. Oocyst counts were highest in water storage facilities. This outbreak is the first caused by C. cuniculus infection to have been noted and it has conclusively demonstrated that this species can be a human pathogen. Although symptomatically similar to cryptosporidiosis from C. parvum or C. hominis, this outbreak has revealed some differences, in particular no children under 5 were identified and females were over-represented. These dissimilarities are unexplained although we postulate possible explanations.

Early detection of non-tuberculous mycobacteria in children with cystic fibrosis using induced sputum at annual review.

AIM: Non-tuberculous mycobacteria (NTM) have emerged as an important pathogen in cystic fibrosis (CF). Early detection and treatment of NTM can preserve lung function and maintain good lung health. Many children with CF are not regular sputum producers and cough swabs cannot routinely be used to diagnose NTM. We aimed to test the hypothesis that performing sputum induction at routine annual review results in earlier identification of NTM in non-sputum producing children with CF. METHOD: We conducted a 5-year prospective observational cohort study involving children with CF aged 5-17 years who had sputum induction with hypertonic saline for microbiological surveillance including NTM at their annual review. RESULTS: Forty-two children (19 males, mean age 11.4 years ± 3.6, mean FEV1 % predicted 94.7 ± 20.6) participated in the study. Forty-one induced sputum samples from 29 children yielded bacterial pathogens. Six samples from six children (14% of the cohort) yielded NTM never previously isolated from the patient. We also detected three isolates of Pseudomonas aeruginosa and one isolate each of Burkholderia cepacia complex and Meticillin resistant Staphylococcus aureus (MRSA), all of which were first time isolates. CONCLUSION: We conclude that annual induced sputum for microbiological surveillance is useful for early detection of NTM and other important respiratory pathogens, particularly in non-expectorating children. This may lead to earlier identification and help inform initiation of eradication treatment in children with NTM. Children can also be cohorted earlier, before they potentially infect other children in the clinic.

What is the clinical significance of filamentous fungi positive sputum cultures in patients with cystic fibrosis?

In patients with cystic fibrosis (CF), the isolation of filamentous fungi, in particular Aspergillus spp. in the respiratory secretions is a common occurrence. Most of these patients do not fulfil the clinical criteria for a diagnosis of allergic bronchopulmonary aspergillosis (ABPA). The clinical relevance of filamentous fungi and whether antifungal therapy should be started in patients with persistent respiratory exacerbations who do not respond to two or more courses of appropriate oral or intravenous antibiotics and in whom no other organisms are isolated from respiratory secretions is a dilemma for the CF clinician. In this article, we review the epidemiology and clinical significance of filamentous fungi in the non-ABPA CF lung, with an emphasis on Aspergillus spp. colonisation (AC), the clinical relevance of Aspergillus spp. positive respiratory cultures and the outcome following antifungal therapy in these patients.