Pharmacokinetics of high-dose weekly Ambisome (liposomal amphotericin B) antifungal prophylaxis in pediatric bone marrow transplantation (BMT) patients

OBJECTIVE To report the development of nephrogenic diabetes insipidus (NDI) associated with the use of high-dose liposomal amphotericin B. CASE SUMMARY A 38-year-old white man with relapsed acute myelogenous leukemia underwent a matched unrelated donor allogeneic bone marrow transplant with adequate engraftment and mild graft-versus–host disease responding to corticosteroids. Approximately 11 months after transplant, the patient was admitted to the hospital with suspected fungal pneumonia and started on liposomal amphotericin B (baseline serum creatinine 1.4–1.5 mg/dL). The dose was increased due to his immunosuppression and poor response, as the fungal etiology was identified as Torulopsis glabrata. The patient required mechanical ventilation due to biopsy-proven bronchiolitis olbiterans organizing pneumonia. Additionally, he developed diffuse alveolar hemorrhage and received intravenous desmopressin, with a reduction in bloody secretions. He also developed hypernatremia (serum sodium 155 mEq/L) on day 3 of the desmopressin and had an inappropriately increased urine output consistent with NDI. The most likely etiology for the NDI was liposomal amphotericin B and its associated hypokalemia. DISCUSSION The observation of worsening hypernatremia (serum sodium increased from 135 to 164 mEq/L) with polyuria was associated with an increasing cumulative dosage of liposomal amphotericin B for fungal pneumonia despite the concurrent use of intravenous desmopressin. Aggressive water replacement was an effective treatment option in this patient. The Naranjo probability scale classified this as a possible adverse reaction because of the temporal sequence of NDI after high-dose liposomal amphotericin B and previously reported cases of NDI associated with amphotericin B desoxycholate. CONCLUSIONS Amphotericin B desoxycholate has been implicated as an etiology for NDI, and the use of the newer liposomal amphotericin B reportedly avoids this rare complication. We observed the development of NDI despite the use of liposomal amphotericin B in a critically ill patient with bone marrow transplant.

Download Full-text

Safety and Efficacy of Intermittent High-Dose Liposomal Amphotericin B Antifungal Prophylaxis in Haemato-Oncology: An Eight-Year Single-Centre Experience and Review of the Literature

Journal of Fungi ◽

10.3390/jof6040385 ◽

2020 ◽

Vol 6 (4) ◽

pp. 385

Author(s):

Jonathan Youngs ◽

Jen Mae Low ◽

Laura Whitney ◽

Clare Logan ◽

Janice Chase ◽

...

Keyword(s):

Amphotericin B ◽

Liposomal Amphotericin ◽

Fungal Infections ◽

Antifungal Prophylaxis ◽

Liposomal Amphotericin B ◽

High Dose ◽

Single Centre ◽

Antifungal Stewardship ◽

European Organization ◽

Grade 3

Triazoles remain first-line agents for antifungal prophylaxis in high-risk haemato-oncology patients, but their use is increasingly contraindicated due to drug–drug interactions and additive toxicities with novel treatments. In this retrospective, single-centre, observational study, we present our eight-year experience of antifungal prophylaxis using intermittent high-dose liposomal Amphotericin B (L-AmB). All adults identified through our Antifungal Stewardship Programme as receiving L-AmB prophylaxis at 7.5 mg/kg once-weekly between February 2012 and January 2020 were included. Adverse reactions, including infusion reactions, electrolyte loss, and nephrotoxicity, were recorded. ‘Breakthrough’ invasive fungal infection (IFI) occurring within four weeks of L-AmB was classified using European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Moreover, 114 courses of intermittent high-dose L-AmB prophylaxis administered to 92 unique patients were analysed. Hypokalaemia was the most common grade 3–4 adverse event, with 26 (23%) courses. Grade 3 nephrotoxicity occurred in 8 (7%) and reversed in all six patients surviving to 90 days. There were two (1.8%) episodes of breakthrough IFI, one ‘probable’ and one ‘possible’. In this study, the largest evaluation of intermittent high-dose L-AmB prophylaxis conducted to date, toxicity was manageable and reversible and breakthrough IFI was rare. L-AmB prophylaxis represents a viable alternative for patients with a contraindication to triazoles.

Download Full-text