PJ Newton, C Harris, J Morris, DW Denning


Intravenous amphotericin B therapy is a recognised therapy for patients with chronic pulmonary aspergillosis (CPA). Limited data is available on the clinical benefit associated with liposomal amphotericin (LAmB) therapy in CPA patients and whether repeated treatment courses are associated with a deterioration in renal function.
We retrospectively audited the clinical response and renal function observed in CPA patients who received one or more short-courses (< 6 weeks duration) of LAmB therapy (Gilead Sciences) at the National Aspergillosis Centre in Manchester before July 2013. A patient case-note review was undertaken using a standardised proforma. Data collected included patient demographics, indication for LAmB treatment, renal function (estimated glomerular filtration rate {eGFR} at baseline, during treatment and up to 6 to 8 months post treatment) and whether they developed an increased risk of or an acute kidney injury (AKI; RIFLE criteria) with treatment, the dose and duration of LAmB therapy and the clinical response to treatment. Patients who received <3 doses of LAmB or started intermittent long-term LAmB treatment within one month of completing a short-course of therapy were not evaluated for a clinical response (N=6). Changes in renal function were not assessed in patients who received < 1 full dose of LAmB (N=2) or in one patient who received intermittent long-term LAmB therapy between his short-courses of LAmB therapy.
71 CPA patients (41 male) were identified aged 28 – 86 years (median 64) when treated. Median duration of prior azole therapy was 12 months (range 0 - 112). Primary indications for LAmB therapy were respiratory symptoms (N=33; 50.7%), constitutional symptoms (N=2; 2.8%) or both (N=36; 50.7%). LAmB doses ranged between 2.5 – 5 mg/Kg/day. The duration of therapy ranged between 4 to 36 days (median 20.5 days). 48 patients (73.8%) had a clinical response (respiratory and / or constitutional symptoms) to their first LAmB course and quality of life (QOL) improvements were noted in 37 (92.5%) of 40 patients with pre- and post- treatment QOL data available.
20 patients received at least two short-courses of LAmB therapy. Clinical response rates for repeated short-courses of LAmB were 76.6% and QOL improvements were seen in 91.7% of treatment courses.
34 (50%) and 17 (25%) patients respectively developed an increased risk of AKI or AKI with their first LAmB course. 24 (35.3%) patients had at least one other contributing factor to their deteriorating renal function; 17 (25%) had a contrast scan and 9 (13.2%) patients received concomitant medications with associated nephrotoxicity risks. The adjusted geometric mean eGFR significantly fell during treatment and did improve post treatment but did not return to pre-treatment levels by 6 to 8 months follow-up (p<0.001). A similar pattern was observed in patients receiving a second treatment course.
Around 74% of CPA patients receiving a short course of LAmB therapy experienced a clinical response. A deterioration in renal function was observed in the majority of patients with 50% of individuals developing an increased risk of AKI and 25% experiencing an AKI with their first treatment course. Whilst CPA is responsive to LAmB, caution should be exercised with repeated courses of treatment, especially if other treatment options are available.


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7th Advances Against Aspergillosis Conference