PS1272 A SURVEY OF PRACTICE RELATING TO THE PREVENTION AND TREATMENT OF INVASIVE FUNGAL INFECTIONS IN UK HAEMATOLOGY CENTRES

Abstract

Background:Invasive fungal infections (IFIs), particularly due to Aspergillus species, are an important cause of morbidity and mortality in patients with haematological malignancies. In 2017 and 2018 the European Conference on Infections in Leukaemia (ECIL) published guidelines for both prophylaxis and treatment of IFIs in haematology patients. A previous survey of UK practice undertaken in 2010 demonstrated marked variability in practice in relation to the prevention and treatment of IFIs in this patient group, similar to what had been reported in earlier Europe‐wide surveys.Aims:The aim of the current study was to investigate whether variability in practice still exists in the UK or whether recently published guidelines have helped to standardise practice.Methods:A questionnaire was sent electronically to all members of the UKBMT pharmacists’ group. The majority of questions focused on prophylaxis and treatment of fungal infection in four clinical areas – AML induction, ALL induction, autologous stem cell transplantation (SCT) and allogeneic SCT. Further questions related to uptake of the newer azole, isavuconazole, and the use of therapeutic drug monitoring (TDM) for azoles.Results:Responses were received from 29 centres. All centres treated autologous SCT and AML/ALL patients and 25 treated allogeneic SCT patients. Seventeen centres treated adult patients only, seven were paediatric centres and five treated both adults and children. The most commonly recommended prophylactic antifungals for the four indications were:Autograft – fluconazole (59% of centres); Allograft – posaconazole (44%); AML induction – posaconazole (45%); ALL induction – lipid amphotericin (69%). There was marked variability in dosing schedules for fluconazole (50mg‐400 mg/day) and lipid amphotericin (12 different schedules ranging from 50 mg thrice weekly (TTW) to 3 mg/kg TTW) and only 69% of centres gave prophylaxis routinely to all 4 patient groups. Compared with the previous survey, itraconazole use had fallen sharply and was only used prophylactically by 38% of centres (previously 76%). Empirical therapy was recommended by 79% of centres. The criteria for starting an antifungal empirically (i.e. duration of fever unresponsive to broad spectrum antibiotics) varied from 48–120 hours. As in the previous survey, Ambisome® (at doses ranging from 1–3 mg/kg/day) was the most common empirical antifungal agent, followed by caspofungin. However, voriconazole had replaced Ambisome® as the most widely recommended first line drug for the management of invasive aspergillosis. Caspofungin, micafungin, posaconazole and IV itraconazole were only recommended in a minority of policies. Ambisome® was the most popular second line agent, being recommended in 62% of policies, followed by caspofungin (24%) and isavuconazole (17%). Twenty one centres (72%) would consider giving dual therapy. In terms of uptake of new agents, Isavuconazole was included in the antifungal policy in 34% of centres, had been used on an adhoc basis in a further 28% but had not yet been used in 38% of centres. For those centres that included the following azoles in their antifungal policies, the use of TDM was inconsistent – 76% of centres undertook TDM for voriconazole, 71% for itraconazole and 55% for posaconazole.Summary/Conclusion:Similar to the previous 2010 survey, this study showed significant variations in practice between UK haematology centres with respect to both preventing and treating invasive fungal infections. Recent guidelines in this area do not appear to have resulted in a noticeable standardisation of practice.