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Multicenter Study
. 2020 Oct 1;58(7):874-880.
doi: 10.1093/mmy/myz134.

Outpatient parenteral antifungal therapy (OPAT) for invasive fungal infections with intermittent dosing of liposomal amphotericin B

Robert J van de Peppel  1   2 , Alexander Schauwvlieghe  3 , Ruth Van Daele  4 , Isabel Spriet  4 , Jan W Van't Wout  1 , Roger J Brüggemann  5 , Bart J A Rijnders  3 , Bart J C Hendriks  6 , Mark G J de Boer  1
Affiliations
Multicenter Study

Outpatient parenteral antifungal therapy (OPAT) for invasive fungal infections with intermittent dosing of liposomal amphotericin B

Robert J van de Peppel et al. Med Mycol. .

Abstract

Triazole resistant A. fumigatus has been documented in many parts of the world. In the Netherlands, incidence is now above 10% and results in the need for long-term parenteral therapy with liposomal amphotericin B (LAmB). The long terminal half-life of LAmB suggests that intermittent dosing could be effective, making the application of outpatient antifungal therapy (OPAT) possible. Here, we report our experience with the use of OPAT for Invasive Fungal Infections (IFI). All adult patients treated with LAmB with a 2 or 3 times weekly administration via the outpatient departments in four academic tertiary care centers in the Netherlands and Belgium since January 2010 were included in our analysis. Patient characteristics were collected, as well as information about diagnostics, therapy dose and duration, toxicity, treatment history and outcome of the IFI. In total, 18 patients were included. The most frequently used regimen (67%) was 5 mg/kg 3 times weekly. A partial response to the daily treatment prior to discharge was confirmed by CT-scan in 17 (94%) of patients. A favorable outcome was achieved in 13 (72%) patients. Decrease in renal function occurred in 10 (56%) cases but was reversible in all and was treatment limiting in one patient only. The 100-day mortality and 1-year mortality after initiation of OPAT were 0% and 6%, respectively. In a selected population, and after confirmation of initial response to treatment, our data support the use of OPAT with LAmB for treatment of IFI in an intermittent dosing regimen.

Keywords: Invasive fungal infection; antifungal stewardship; liposomal amphotericin B; outpatient parenteral antibiotic treatment; triazole resistance.

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Figures

Figure 1.
Figure 1.
Overall survival from start of intermittent treatment. Censored cases were lost to follow-up. LAmB, liposomal amphotericin B; OPAT, outpatient antifungal therapy.
Figure 2.
Figure 2.
Time to resolution of IFI after start of intermittent therapy. Censored cases stopped intermittent treatment before resolution of infection. Resolution of IFI was defined as clinically observed absence of symptoms that are likely to be caused by IFI in combination with findings concordant with resolution of IFI on high-resolution CT scan. IFI, invasive fungal infection; LAmB, liposomal amphotericin B; OPAT, outpatient antifungal therapy.
Figure 3.
Figure 3.
Occurrence of nephrotoxicity from start of intermittent treatment. Censored cases stopped intermittent treatment before nephrotoxicity occurred. Nephrotoxicity was defined as a >1.5 times increase of baseline serum creatinine levels resulting in an eGFR of < 40 ml/min/1.73 m2 during treatment or as electrolyte disorders suspected to be the result of renal damage and requiring cessation of treatment with LAmB at the discretion of the treating clinician. LAmB, liposomal amphotericin B; OPAT, outpatient antifungal therapy.
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