Impact of an antifungal stewardship programme in a tertiary respiratory medicine setting: A prospective real-world study

25 There has been an increase in fungal infections in patients with chronic lung disease 26 over the past decades, which is associated with rapidly increasing costs to 27 healthcare systems. 28 An antifungal stewardship team was introduced to a tertiary cardiopulmonary 29 hospital, consisting of a medical mycologist and pharmacy support providing weekly 30 stewardship ward rounds, twice monthly multidisciplinary team meetings and a 31 dedicated weekly outpatient clinic. A database was set up to record the activity of 32 the stewardship team. 33 During the first eighteen months of implementation the antifungal stewardship team 34 had reviewed 178 patients, with 285 recommendations made to inpatients, and 287 35 outpatient visits. The commonest diagnoses treated were allergic bronchopulmonary 36 aspergillosis and chronic pulmonary aspergillosis. Cystic fibrosis was the largest 37 patient group treated followed by asthma and interstitial lung disease. There was a 38 significant, sustained reduction in monthly antifungal expenditure (p=0.005) by 39 £130,000 per month. There was also a significant reduction in antifungal use 40 measured as Defined Daily Dose/100 bed days (p=0.017). There were no significant 41 changes in expenditure on diagnostic tests. There has been a trend toward more 42 patients having therapeutic levels of voriconazole (p=0.086) and a significant 43 increase in therapeutic levels of posaconazole (p<0.0001). 44 This study shows that an effective antifungal stewardship programme can 45 significantly reduce expenditure in a specialist respiratory service. 46 47 on S etem er 6, 2018 by gest httpaac.asm . rg/ D ow nladed fom INTRODUCTION 48 Antimicrobial resistance has emerged as a major threat to modern healthcare 49 systems (1). Within this context, the major focus has been on antibacterial 50 resistance, which has had a major adverse impact on respiratory health both within 51 the context of chronic respiratory disease as well as acute respiratory infection (2). 52 There has been an incompletely understood emergence of chronic fungal infection 53 across multiple chronic respiratory diseases, in particular due to Aspergillus 54 fumigatus. This may be in part due to increased awareness and recognition, as well 55 as the introduction of prolonged fungal-specific culture and serological tests to aid in 56 diagnosis. Additionally patients with chronic respiratory disease are surviving longer 57 with impaired local immunity in the lung, allowing more fungal respiratory infections. 58 In contrast to invasive pulmonary aspergillosis, chronic pulmonary forms of 59 aspergillosis are poorly defined (though systematic approaches have begun to take 60 shape (3, 4)), and suffer from a relative lack of well-designed randomised controlled 61 trials to guide treatment. Risk factors include bronchiectasis, chronic obstructive 62 pulmonary disease (COPD), cystic fibrosis (CF), transplantation, prolonged steroid 63 use and other immunosuppressive agents such as chemotherapy (5, 6). Aspergillus 64 infections have increased in incidence over the past 40 years (7), with recent 65 estimates suggesting there may be 240,000 patients with chronic pulmonary 66 aspergillosis (CPA) (3), and over 1,000,000 patients with allergic bronchopulmonary 67 aspergillosis (ABPA) in Europe (8). A number of recent studies have highlighted the 68 emerging threat of triazole multi-drug resistance in Aspergillus fumigatus (9). We 69 and others observe emergent triazole resistance dependent both on agricultural 70 exposure to triazoles (10) and de novo emergence of resistance in individuals 71 receiving chronic triazole therapy; currently the only orally available mould-active 72 on S etem er 6, 2018 by gest httpaac.asm . rg/ D ow nladed fom antifungal drug class. There are data that increasing rates of triazole resistance 73 have been noted in patients with chronic pulmonary aspergillosis (11); that this may 74 develop during treatment, and may be associated with sub-therapeutic drug levels 75 (12). Achieving therapeutic levels of triazole using therapeutic drug monitoring 76 (TDM) are associated with treatment success in invasive fungal disease (13–15), 77 though there are no published data in chronic respiratory disease. 78 In the USA, national data suggest that 4.9% of antimicrobial expenditure in 2015 was 79 due to antifungals (approximately $2.4 billion), an 18.8% increase compared to 2014 80 (16). The principles of antifungal stewardship are to optimise antifungal prescription 81 by assessing spectrum of activity, pharmacokinetics, duration and route of 82 administration (17). This is particularly important in the context of antifungal 83 toxicities and costs. There are relatively few data on the effect of antifungal 84 stewardship programmes and largely these refer to invasive fungal disease in the 85 context of haematological disorders and on intensive care units. A UK stewardship 86 programme demonstrated crude savings of £180,000 on antifungal expenditure in a 87 year (18), whereas Spanish studies have reported reduction in antifungal 88 expenditure by 11.8% ($370,681) (19) and 13.9% ($529,163) (20). To our knowledge 89 there has not been an assessment of the effect of antifungal stewardship in chronic 90 respiratory disease patients. 91 Taken together, these observations are indicative of an urgent clinical need to limit 92 inappropriate triazole antifungal usage through judicious antifungal stewardship. We 93 report on the delivery and impact of an antifungal stewardship programme targeting 94 the use of antifungals within the respiratory directorate at our centre. 95 on S etem er 6, 2018 by gest httpaac.asm . rg/ D ow nladed fom