- Email: [email protected]
113 Evaluation of new approach for diagnosis of fungal rhinosinusitis in patients with cystic fibrosis
Posters / Journal of Cystic Fibrosis 15 (2016) S51–S120
could reflect Aspergillus infection or colonization; GM is not useful in differentiating. Further clinical information such as radiological findings and analysis of GM performance on blood is required. 110 Pitfalls in the diagnosis of Aspergillus disease in a cohort of Brazilian CF patients T.B. Aiello1 , R.M. Mauch1 , A.A.D.C. Toro1 , M.C. Pereira1 , M.T. Nolasco da Silva1 , I.A. Paschoal1 , A.F. Ribeiro1 , J.D. Ribeiro1 , C.E. Levy1 . 1 Unicamp, Campinas, Brazil Objectives: To assess the prevalence of Aspergillus disease in CF patients from a Brazilian reference center. Methods: Data of 109 patients were gathered; 55 patients had at least 1 positive Aspergillus sputum culture (prevalence 50.5%). 38 patients had at least 2 positive cultures for Aspergillus and were included in the study. Measurement of total IgE, specific Aspergillus fumigatus IgE and IgG were made for these patients. The clinical spectrum of Aspergillus disease was defined by current literature standards. Results and Discussion: Following current criteria, no patients had invasive aspergillosis; 3 patients had elevated specific IgG levels (102 mgA/L), which configures possible Aspergillus bronchitis. No patients filled the minimum criteria for ABPA. However, 3 patients had elevated specific IgE (>0.3 kUA/L), showing possible sensitization for the fungus and need to be monitored. Of these, 1 patient showed a great potential for ABP – specific IgE = 5.23 kUA/L, clinical signs of disease and good clinical outcome after treatment – despite not filling the minimum criteria for ABPA. Conclusions: Despite the prevalence of Aspergillus disease in our center being very low, a single case drew our attention, showing high specific IgE, but not total IgE levels, even the patient having food allergy with clinical manifestations. As is known, IgE is a very little fraction of the immunoglobulins and only about 50% of allergic individuals have a high total IgE level. Thus, despite our sample being small, we suggest that the requirement of total IgE for definition of ABPA, and also the necessity of fulfilment of the classic criteria at all, should be critically addressed. 111 Fungal colonization of the respiratory tract of CF patients and its impact on the respiratory function 2 E. Romanowska1 , K. Semczuk1 , A. Wojcieszek1 , H. Dmenska ´ , 1 1 A. Smorczewska-Kiljan3 , K. Dzierzanowska-Fangrat ˙ . Children’s Memorial Health Institute, Department of Clinical Microbiology and Immunology, Warsaw, Poland; 2 Chidlren’s Memorial Health Institute, Pulmonary Outpatient’s Clinic, Warsaw, Poland; 3 Chidlren’s Memorial Health Institute, Department of Pediatrics, Warsaw, Poland
Objective: To determine the impact of the respiratory tract colonisation by Aspergillus spp., Scedosporium spp. and Candida spp. in the CF patients. Methods: A total of 20 CF patients (11 girls and 9 boys; age range 19 years), treated in the Children’s Memorial Health Institute in Warsaw were included. From January 2013 to December 2015, 62 sputum samples were collected. The clinical material was inoculated on Sabouraud dextrose agar and incubated for 14 days in 35ºC. Positive yeast cultures were identified by VITEK System. Moulds were identified by macroscopic and microscopic features. Demographic, medical data (forced expiratory volume in the first second and body mass index) and microbiological findings were analysed. Results and Conclusion: Samples were negative for fungal cultures in 30% patients. The other 70% were persistently colonised with Candida spp. Among them 29% were also affected by moulds. The mean FEV1/FVC value in the group with negative cultures (79.7%) was similar to the group colonised both with Candida spp. and moulds Aspergillus spp. and Scedosporium spp. (77.2%). The mean FEV1/FVC value in patients colonised with Candida spp. only was lower: 68.3%. BMI index was comparable in all groups. Age, underweight and other factors such as bacterial coinfection were associated with FEV1 worsening. Two patients with concomitant S. prolificans, A. fumigatus, C. lusitaniae and C. dubliniensis colonisation
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were at the greatest risk of pulmonary exacerbations and required hospitalisation. Further studies analyzing the impact of fungal colonization on the respiratory function as well as host-pathogen response to colonisation/infection in CF patients are needed. 112 Standard versus extended fungal culture for the detection of filamentous fungi in CF sputum samples R. Ratnakumar1 , S. Oakley1 , S. Chapman1,2 , K. Jefferey1 , W.G. Flight1 . 1 Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; 2 Oxford University, Oxford, United Kingdom Background: Filamentous fungi such as Aspergillus are frequently identified in the sputum of patients with cystic fibrosis (CF). Diagnosis of fungal infection in CF is challenging, and optimal diagnostic methods unclear. We compared standard (48 hour) with extended (3 week) fungal culture of sputum from adults with CF. Methods: Paired CF sputum samples processed with both 48-hour culture on Sabouraud agar and extended culture on Sabouraud slopes from Oct 2014 to Sept 2015 were identified retrospectively and compared to assess species cultured and comparative pick-up rate of fungi. Patients with prior lung transplantation were excluded. Results: 994 sputum samples were identified from 95 patients over the study period, of which 538 had paired standard and extended fungal culture results. 174/538 (32.3%) samples were positive for a filamentous fungus. Extended culture was positive in 156 (89.7%), standard culture in 118(67.8%) and both were positive in 100 (57.5%). Standard culture had a sensitivity of 64.1% and specificity of 95.3%. 53 patients (56%) had ≥1 sample positive for a fungus. Aspergillus fumigatus was isolated from 51 patients with other species of Aspergillus found in 5 patients. Rasamsonia argillacea, Exophiala phialophora and Scedosporium apiospermum were detected in 1 patient each. Patients with ≥1 positive sample had higher Aspergillus precipitins [mean 2.5 (SD1.9) vs 0.8 (1.3) lines, p < 0.001] and were more likely to have had NTM isolated previously (49% vs 26%, p = 0.03). Conclusions: Filamentous fungi are frequently detected in CF sputum, A. fumigatus being the most common species. Extended fungal culture increases fungal detection rate. 113 Evaluation of new approach for diagnosis of fungal rhinosinusitis in patients with cystic fibrosis A. Barac1 , P. Minic2,3 , V. Tomic Spiric4,5 , E. Aleksic6 , V. Arsic Arsenijevic1 . 1 Faculty of Medicine, University of Belgrade, Institute of Microbiology and Immunology, Belgrade, Serbia; 2 Institute of Mother and Child, Belgrade, Serbia; 3 Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 4 Clinic for Allergology and Clinical Immunology, Clinical Center of Serbia, Belgrade, Serbia; 5 Faculty of Medicine University of Belgrade, Belgrade, Serbia; 6 Faculty of Stomatology, Business Academy of Novi Sad, Pancevo, Pancevo, Serbia Background: Although the pathogenesis of cystic fibrosis (CF) and fungal rhinosinusitis (FRS) have been widely studied, the relationship of the mycobiome of the sinonasal mucosa and development of FRS is not yet clear. The aim of our study was to evaluate new approach for diagnosis of FRS in patients with CF in order to prevent development of invasive respiratory fungal diseases. Methodology: A prospective study with 42 patients was conducted in the Faculty of Medicine, University of Belgrade. Patients were divided into two groups depending on the presence of CF: patients with CF (CF+) and patients without CF (CF−). After mycological analyses (using inhalation with PARI-SINUS nebulizer and sampling) patients were divided in groups: 1. patients with positive fungal finding and CF (FRS group) and 2. patients without CF and positive fungal finding (non-FRS group). Study design included: 1. rhinologic observation and 2. mycological finding of sinonasal aspirate. Results: 6.4% of patients from CF group had positive fungal finding on nasal mucosa and could be considered as FRS. Patients from FRS group
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Posters / Journal of Cystic Fibrosis 15 (2016) S51–S120
(70.4%) had more severe forms of CF. Prevalence of FRS in Serbia is 2.8%. Patients with FRS had statistically more frequent asthma (p = 0.024) and chronic sinusitis more than 10 years (p = 0.000). The most common isolated species was Aspergillus niger (62%). Conclusions: This is the first study that analyzes the association of sinonasal fungal findings with their clinical and allergic status. Large amounts of fungal spores in the air of patient’s home environment would be a threat for development of FRS in patients with CF. 114 Realization and evaluation of the effectiveness of preventive actions against influenza for patients with cystic fibrosis followed in the Dunkerque Cystic Fibrosis Treatment Centre and for their healthcare workers M. Scalbert-Dujardin1 , E. Leclercq1 , A. Boldron1 , E. Leroy1 , J. Bazin1 . 1 Centre de Ressources et de Comp´etences de la Mucoviscidose, Dunkerque, France Objectives: The main aim of this work was to evaluate the effectiveness of preventive actions regarding influenza with a 1-year interval. The secondary objective was to analyze and to understand the mechanisms which bring about a behavioural change regarding the vaccination on the studied populations. Methods: The observational, descriptive and exhaustive study was written in the form of an anonymous questionnaire about the vaccination coverage and about the reasons for no vaccination. The studied populations were patients followed for cystic fibrosis (n = 62) in the Dunkerque Cystic Fibrosis Treatment Centre and for their healthcare workers (n = 107), before (April 2014) and after (April 2015) an information and awareness campaign and primary prevention actions (vaccination on the workplaces with expanded time slots) in collaboration with the occupational medicine. Results: In 2015, the vaccination coverage rate of healthcare workers was 65.63%, that is to say 2.38 times more than in 2014 (27.55%). This difference is significant (c2 (1) = 9.17, p < 0.0001). Nevertheless, no significant difference was observed among patients (children and adults) between 2014 and 2015 (c2 (1) = 0.24, NS) whose vaccination coverage was already optimal before the study (87.2%). Conclusion: Raising awareness among healthcare workers on the vaccination against influenza increases the coverage rate and decreases the virus outbreak in the care services and to people at risk. Two main levers were identified: the ease of vaccination access (vaccination on the workplace by the occupational medicine) and the conviction of the vaccination usefulness by the supervisory staff (health executives/doctors). 115 Prevalence of respiratory viruses in CF patients when clinically stable and during pulmonary exacerbation S. Pattison1 , L. Oram2 , E. Johnston1 , G. Lavelle3 , M. Murray3 , N.G. McElvaney3 , M.S. Muhlebach4 , R. Boucher4 , M. Crockard2 , M.M. Tunney1 , J.S. Elborn1 . 1 Queen’s University Belfast, Belfast, United Kingdom; 2 Randox Laboratories Ltd, Crumlin, United Kingdom; 3 Royal College of Surgeons in Ireland, Dublin, Ireland; 4 University of North Carolina at Chapel Hill, Chapel Hill, United States Objectives: To determine the prevalence of viral respiratory infection in adults with CF when clinically stable and during pulmonary exacerbation. Methods: A set of 3 sputum samples representing different states of clinical health [clinically stable, pre-treatment of a pulmonary exacerbation (PEx) and post-treatment of a PEx with IV antibiotics] were collected from each of 52 adults across 3 CF centres (Belfast, N. Ireland, n = 28; Dublin, Ireland, n = 13; Chapel Hill, North Carolina, n = 11). The prevalence of 15 respiratory viruses was assessed by Luminex xTAG® Respiratory Viral Panel. Statistical comparisons by Fisher’s Exact test. Results: Viruses were detected in 17/156 (10.1%) samples, with enterovirus/rhinovirus (EV/RV) constituting 14/17 (82.4%) positive results. No difference in total virus or EV/RV prevalence was detected between CF centres (P = 0.3 & 0.1 respectively). Comparison of virus prevalence when clinically stable and pre- and post-treatment showed
no significant difference when the data for all 3 CF centres were combined (P = 0.2). However, when the sites were analysed separately, differential prevalence was observed for the Belfast cohort (P = 0.044) with a relative risk of detection at PEx pre-treatment vs stable of 1.9 (95% CI 1.3–37.2, P = 0.003). This was not observed for the other sites (P = 0.8 & 1.0). Conclusion: Respiratory viruses were detected in 10% of adult CF sputum samples (previous studies report prevalence from 10–31%). Viral infection may play a role in some PEx but varies between centres. Acknowledgement: Funding: Innovate UK, Randox Laboratories Ltd and a US-Ireland Project Partnership Grant (HSC R&D, Public Health Agency, NI). 116 The use of nebulised voriconazole in CF-related fungal infections: a case series A.M. Jones1 , I. Felton1,2 , M.J. Harrison1 , E. Bowman1 , D. Bilton1,2 , N.J. Simmonds1,2 . 1 Royal Brompton Hospital, London, United Kingdom; 2 Imperial College London, National Heart and Lung Institute, London, United Kingdom Objectives: The incidence of pulmonary fungal infections in CF patients is increasing. Management of these infections is complicated with difficulties both in appropriate diagnosis and adequate treatment. Oral azole antifungals have a side-effect profile which can limit their use. Initial case reports had suggested a beneficial effect of nebulising the intravenous preparation of voriconazole. We report on our use of this in 5 CF patients with fungal infection who could not tolerate oral azoles. Methods: A retrospective case review was made of all patients receiving nebulised voriconazole. All patients received 40 mg of nebulised voriconazole twice daily (intravenous preparation, unlicensed indication). Results: Five patients received nebulised voriconazole; 2 had chronic Exophiala dermatitidis infection, 1 had chronic Rasamsonia argillacea infection, 1 had Scedosporium apiospermum and 1 had chronic Aspergillus fumigatus infection. All patients tolerated the medication with no reported side effects. No patient had a significant improvement in spirometry values and 4/5 had no change in ongoing requirements for intravenous echinocandin therapy. After review, all patients discontinued use of nebulised voriconazole due to lack of therapeutic effect. Median duration of treatment was 9.5 months (range 1–19). Conclusion: While nebulising voriconazole appeared safe with no reported side effects, there was no convincing evidence of improvement in markers of fungal infection in these 5 cases. Of note the cases represent a range on infections with differing fungal pathogens and as such making any definitive statement regarding the effect of nebulised voriconazole is not yet possible. 117 The fate of inhaled antibiotics after deposition in patients with cystic fibrosis: how to get drug to the bug? A.C. Bos1 , K.M. Passe´ 1 , J.W. Mouton2 , H.M. Janssens1 , H.A.W.M. Tiddens1 . 1 Erasmus MC-Sophia Children’s Hospital, Pediatric Pulmonology and Allergology, Rotterdam, Netherlands; 2 Erasmus Medical Center, Medical Microbiology and Infectious Diseases, Rotterdam, Netherlands Background: Chronic airway infections with, most importantly, Pseudomonas aeruginosa (Pa) are an important factor in progressive lung disease in patients with cystic fibrosis (CF). These chronic infections are most often treated with inhaled antibiotics. Clinical efficacy of this administration route is determined by aerosol, patient and device related factors which have been extensively studied. These factors determine the deposition pattern of the inhaled antibiotic within the lung. However, the journey of aerosol particles does not end after deposition within the bronchial tree; but continues through thick mucus layers and biofilm generated by the bacteria. Objectives: To establish what happens to antibiotic aerosol particles after deposition in the airways of patients with CF and how local
could reflect Aspergillus infection or colonization; GM is not useful in differentiating. Further clinical information such as radiological findings and analysis of GM performance on blood is required. 110 Pitfalls in the diagnosis of Aspergillus disease in a cohort of Brazilian CF patients T.B. Aiello1 , R.M. Mauch1 , A.A.D.C. Toro1 , M.C. Pereira1 , M.T. Nolasco da Silva1 , I.A. Paschoal1 , A.F. Ribeiro1 , J.D. Ribeiro1 , C.E. Levy1 . 1 Unicamp, Campinas, Brazil Objectives: To assess the prevalence of Aspergillus disease in CF patients from a Brazilian reference center. Methods: Data of 109 patients were gathered; 55 patients had at least 1 positive Aspergillus sputum culture (prevalence 50.5%). 38 patients had at least 2 positive cultures for Aspergillus and were included in the study. Measurement of total IgE, specific Aspergillus fumigatus IgE and IgG were made for these patients. The clinical spectrum of Aspergillus disease was defined by current literature standards. Results and Discussion: Following current criteria, no patients had invasive aspergillosis; 3 patients had elevated specific IgG levels (102 mgA/L), which configures possible Aspergillus bronchitis. No patients filled the minimum criteria for ABPA. However, 3 patients had elevated specific IgE (>0.3 kUA/L), showing possible sensitization for the fungus and need to be monitored. Of these, 1 patient showed a great potential for ABP – specific IgE = 5.23 kUA/L, clinical signs of disease and good clinical outcome after treatment – despite not filling the minimum criteria for ABPA. Conclusions: Despite the prevalence of Aspergillus disease in our center being very low, a single case drew our attention, showing high specific IgE, but not total IgE levels, even the patient having food allergy with clinical manifestations. As is known, IgE is a very little fraction of the immunoglobulins and only about 50% of allergic individuals have a high total IgE level. Thus, despite our sample being small, we suggest that the requirement of total IgE for definition of ABPA, and also the necessity of fulfilment of the classic criteria at all, should be critically addressed. 111 Fungal colonization of the respiratory tract of CF patients and its impact on the respiratory function 2 E. Romanowska1 , K. Semczuk1 , A. Wojcieszek1 , H. Dmenska ´ , 1 1 A. Smorczewska-Kiljan3 , K. Dzierzanowska-Fangrat ˙ . Children’s Memorial Health Institute, Department of Clinical Microbiology and Immunology, Warsaw, Poland; 2 Chidlren’s Memorial Health Institute, Pulmonary Outpatient’s Clinic, Warsaw, Poland; 3 Chidlren’s Memorial Health Institute, Department of Pediatrics, Warsaw, Poland
Objective: To determine the impact of the respiratory tract colonisation by Aspergillus spp., Scedosporium spp. and Candida spp. in the CF patients. Methods: A total of 20 CF patients (11 girls and 9 boys; age range 19 years), treated in the Children’s Memorial Health Institute in Warsaw were included. From January 2013 to December 2015, 62 sputum samples were collected. The clinical material was inoculated on Sabouraud dextrose agar and incubated for 14 days in 35ºC. Positive yeast cultures were identified by VITEK System. Moulds were identified by macroscopic and microscopic features. Demographic, medical data (forced expiratory volume in the first second and body mass index) and microbiological findings were analysed. Results and Conclusion: Samples were negative for fungal cultures in 30% patients. The other 70% were persistently colonised with Candida spp. Among them 29% were also affected by moulds. The mean FEV1/FVC value in the group with negative cultures (79.7%) was similar to the group colonised both with Candida spp. and moulds Aspergillus spp. and Scedosporium spp. (77.2%). The mean FEV1/FVC value in patients colonised with Candida spp. only was lower: 68.3%. BMI index was comparable in all groups. Age, underweight and other factors such as bacterial coinfection were associated with FEV1 worsening. Two patients with concomitant S. prolificans, A. fumigatus, C. lusitaniae and C. dubliniensis colonisation
S79
were at the greatest risk of pulmonary exacerbations and required hospitalisation. Further studies analyzing the impact of fungal colonization on the respiratory function as well as host-pathogen response to colonisation/infection in CF patients are needed. 112 Standard versus extended fungal culture for the detection of filamentous fungi in CF sputum samples R. Ratnakumar1 , S. Oakley1 , S. Chapman1,2 , K. Jefferey1 , W.G. Flight1 . 1 Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; 2 Oxford University, Oxford, United Kingdom Background: Filamentous fungi such as Aspergillus are frequently identified in the sputum of patients with cystic fibrosis (CF). Diagnosis of fungal infection in CF is challenging, and optimal diagnostic methods unclear. We compared standard (48 hour) with extended (3 week) fungal culture of sputum from adults with CF. Methods: Paired CF sputum samples processed with both 48-hour culture on Sabouraud agar and extended culture on Sabouraud slopes from Oct 2014 to Sept 2015 were identified retrospectively and compared to assess species cultured and comparative pick-up rate of fungi. Patients with prior lung transplantation were excluded. Results: 994 sputum samples were identified from 95 patients over the study period, of which 538 had paired standard and extended fungal culture results. 174/538 (32.3%) samples were positive for a filamentous fungus. Extended culture was positive in 156 (89.7%), standard culture in 118(67.8%) and both were positive in 100 (57.5%). Standard culture had a sensitivity of 64.1% and specificity of 95.3%. 53 patients (56%) had ≥1 sample positive for a fungus. Aspergillus fumigatus was isolated from 51 patients with other species of Aspergillus found in 5 patients. Rasamsonia argillacea, Exophiala phialophora and Scedosporium apiospermum were detected in 1 patient each. Patients with ≥1 positive sample had higher Aspergillus precipitins [mean 2.5 (SD1.9) vs 0.8 (1.3) lines, p < 0.001] and were more likely to have had NTM isolated previously (49% vs 26%, p = 0.03). Conclusions: Filamentous fungi are frequently detected in CF sputum, A. fumigatus being the most common species. Extended fungal culture increases fungal detection rate. 113 Evaluation of new approach for diagnosis of fungal rhinosinusitis in patients with cystic fibrosis A. Barac1 , P. Minic2,3 , V. Tomic Spiric4,5 , E. Aleksic6 , V. Arsic Arsenijevic1 . 1 Faculty of Medicine, University of Belgrade, Institute of Microbiology and Immunology, Belgrade, Serbia; 2 Institute of Mother and Child, Belgrade, Serbia; 3 Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 4 Clinic for Allergology and Clinical Immunology, Clinical Center of Serbia, Belgrade, Serbia; 5 Faculty of Medicine University of Belgrade, Belgrade, Serbia; 6 Faculty of Stomatology, Business Academy of Novi Sad, Pancevo, Pancevo, Serbia Background: Although the pathogenesis of cystic fibrosis (CF) and fungal rhinosinusitis (FRS) have been widely studied, the relationship of the mycobiome of the sinonasal mucosa and development of FRS is not yet clear. The aim of our study was to evaluate new approach for diagnosis of FRS in patients with CF in order to prevent development of invasive respiratory fungal diseases. Methodology: A prospective study with 42 patients was conducted in the Faculty of Medicine, University of Belgrade. Patients were divided into two groups depending on the presence of CF: patients with CF (CF+) and patients without CF (CF−). After mycological analyses (using inhalation with PARI-SINUS nebulizer and sampling) patients were divided in groups: 1. patients with positive fungal finding and CF (FRS group) and 2. patients without CF and positive fungal finding (non-FRS group). Study design included: 1. rhinologic observation and 2. mycological finding of sinonasal aspirate. Results: 6.4% of patients from CF group had positive fungal finding on nasal mucosa and could be considered as FRS. Patients from FRS group
S80
Posters / Journal of Cystic Fibrosis 15 (2016) S51–S120
(70.4%) had more severe forms of CF. Prevalence of FRS in Serbia is 2.8%. Patients with FRS had statistically more frequent asthma (p = 0.024) and chronic sinusitis more than 10 years (p = 0.000). The most common isolated species was Aspergillus niger (62%). Conclusions: This is the first study that analyzes the association of sinonasal fungal findings with their clinical and allergic status. Large amounts of fungal spores in the air of patient’s home environment would be a threat for development of FRS in patients with CF. 114 Realization and evaluation of the effectiveness of preventive actions against influenza for patients with cystic fibrosis followed in the Dunkerque Cystic Fibrosis Treatment Centre and for their healthcare workers M. Scalbert-Dujardin1 , E. Leclercq1 , A. Boldron1 , E. Leroy1 , J. Bazin1 . 1 Centre de Ressources et de Comp´etences de la Mucoviscidose, Dunkerque, France Objectives: The main aim of this work was to evaluate the effectiveness of preventive actions regarding influenza with a 1-year interval. The secondary objective was to analyze and to understand the mechanisms which bring about a behavioural change regarding the vaccination on the studied populations. Methods: The observational, descriptive and exhaustive study was written in the form of an anonymous questionnaire about the vaccination coverage and about the reasons for no vaccination. The studied populations were patients followed for cystic fibrosis (n = 62) in the Dunkerque Cystic Fibrosis Treatment Centre and for their healthcare workers (n = 107), before (April 2014) and after (April 2015) an information and awareness campaign and primary prevention actions (vaccination on the workplaces with expanded time slots) in collaboration with the occupational medicine. Results: In 2015, the vaccination coverage rate of healthcare workers was 65.63%, that is to say 2.38 times more than in 2014 (27.55%). This difference is significant (c2 (1) = 9.17, p < 0.0001). Nevertheless, no significant difference was observed among patients (children and adults) between 2014 and 2015 (c2 (1) = 0.24, NS) whose vaccination coverage was already optimal before the study (87.2%). Conclusion: Raising awareness among healthcare workers on the vaccination against influenza increases the coverage rate and decreases the virus outbreak in the care services and to people at risk. Two main levers were identified: the ease of vaccination access (vaccination on the workplace by the occupational medicine) and the conviction of the vaccination usefulness by the supervisory staff (health executives/doctors). 115 Prevalence of respiratory viruses in CF patients when clinically stable and during pulmonary exacerbation S. Pattison1 , L. Oram2 , E. Johnston1 , G. Lavelle3 , M. Murray3 , N.G. McElvaney3 , M.S. Muhlebach4 , R. Boucher4 , M. Crockard2 , M.M. Tunney1 , J.S. Elborn1 . 1 Queen’s University Belfast, Belfast, United Kingdom; 2 Randox Laboratories Ltd, Crumlin, United Kingdom; 3 Royal College of Surgeons in Ireland, Dublin, Ireland; 4 University of North Carolina at Chapel Hill, Chapel Hill, United States Objectives: To determine the prevalence of viral respiratory infection in adults with CF when clinically stable and during pulmonary exacerbation. Methods: A set of 3 sputum samples representing different states of clinical health [clinically stable, pre-treatment of a pulmonary exacerbation (PEx) and post-treatment of a PEx with IV antibiotics] were collected from each of 52 adults across 3 CF centres (Belfast, N. Ireland, n = 28; Dublin, Ireland, n = 13; Chapel Hill, North Carolina, n = 11). The prevalence of 15 respiratory viruses was assessed by Luminex xTAG® Respiratory Viral Panel. Statistical comparisons by Fisher’s Exact test. Results: Viruses were detected in 17/156 (10.1%) samples, with enterovirus/rhinovirus (EV/RV) constituting 14/17 (82.4%) positive results. No difference in total virus or EV/RV prevalence was detected between CF centres (P = 0.3 & 0.1 respectively). Comparison of virus prevalence when clinically stable and pre- and post-treatment showed
no significant difference when the data for all 3 CF centres were combined (P = 0.2). However, when the sites were analysed separately, differential prevalence was observed for the Belfast cohort (P = 0.044) with a relative risk of detection at PEx pre-treatment vs stable of 1.9 (95% CI 1.3–37.2, P = 0.003). This was not observed for the other sites (P = 0.8 & 1.0). Conclusion: Respiratory viruses were detected in 10% of adult CF sputum samples (previous studies report prevalence from 10–31%). Viral infection may play a role in some PEx but varies between centres. Acknowledgement: Funding: Innovate UK, Randox Laboratories Ltd and a US-Ireland Project Partnership Grant (HSC R&D, Public Health Agency, NI). 116 The use of nebulised voriconazole in CF-related fungal infections: a case series A.M. Jones1 , I. Felton1,2 , M.J. Harrison1 , E. Bowman1 , D. Bilton1,2 , N.J. Simmonds1,2 . 1 Royal Brompton Hospital, London, United Kingdom; 2 Imperial College London, National Heart and Lung Institute, London, United Kingdom Objectives: The incidence of pulmonary fungal infections in CF patients is increasing. Management of these infections is complicated with difficulties both in appropriate diagnosis and adequate treatment. Oral azole antifungals have a side-effect profile which can limit their use. Initial case reports had suggested a beneficial effect of nebulising the intravenous preparation of voriconazole. We report on our use of this in 5 CF patients with fungal infection who could not tolerate oral azoles. Methods: A retrospective case review was made of all patients receiving nebulised voriconazole. All patients received 40 mg of nebulised voriconazole twice daily (intravenous preparation, unlicensed indication). Results: Five patients received nebulised voriconazole; 2 had chronic Exophiala dermatitidis infection, 1 had chronic Rasamsonia argillacea infection, 1 had Scedosporium apiospermum and 1 had chronic Aspergillus fumigatus infection. All patients tolerated the medication with no reported side effects. No patient had a significant improvement in spirometry values and 4/5 had no change in ongoing requirements for intravenous echinocandin therapy. After review, all patients discontinued use of nebulised voriconazole due to lack of therapeutic effect. Median duration of treatment was 9.5 months (range 1–19). Conclusion: While nebulising voriconazole appeared safe with no reported side effects, there was no convincing evidence of improvement in markers of fungal infection in these 5 cases. Of note the cases represent a range on infections with differing fungal pathogens and as such making any definitive statement regarding the effect of nebulised voriconazole is not yet possible. 117 The fate of inhaled antibiotics after deposition in patients with cystic fibrosis: how to get drug to the bug? A.C. Bos1 , K.M. Passe´ 1 , J.W. Mouton2 , H.M. Janssens1 , H.A.W.M. Tiddens1 . 1 Erasmus MC-Sophia Children’s Hospital, Pediatric Pulmonology and Allergology, Rotterdam, Netherlands; 2 Erasmus Medical Center, Medical Microbiology and Infectious Diseases, Rotterdam, Netherlands Background: Chronic airway infections with, most importantly, Pseudomonas aeruginosa (Pa) are an important factor in progressive lung disease in patients with cystic fibrosis (CF). These chronic infections are most often treated with inhaled antibiotics. Clinical efficacy of this administration route is determined by aerosol, patient and device related factors which have been extensively studied. These factors determine the deposition pattern of the inhaled antibiotic within the lung. However, the journey of aerosol particles does not end after deposition within the bronchial tree; but continues through thick mucus layers and biofilm generated by the bacteria. Objectives: To establish what happens to antibiotic aerosol particles after deposition in the airways of patients with CF and how local