Low-dose liposomal amphotericin B for antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell transplantation

Abstract

Background Primary antifungal prophylaxis in paediatric allogeneic HSCT recipients is mainly based on azoles, which can have related toxicity and drug interactions. Low-dose liposomal amphotericin B (L-AmB) is an attractive intravenous alternative because of its low toxicity and lower risk of interactions. Objectives To evaluate the effectiveness and safety of L-AmB (1 mg/kg/day) for primary antifungal prophylaxis in pre-engraftment paediatric HSCT patients. Patients and methods Retrospective, observational study including all consecutive patients aged ≤18 years who underwent HSCT and received antifungal prophylaxis with intravenous L-AmB (1 mg/kg/day, from day −1 to 48 h before discharge) between January 2012 and December 2016. Results In total, 125 HSCT procedures in 118 patients were included, median age 7.2 years (IQR 4.2–11.5). Haematological malignancies were the main underlying condition (63.6%), and 109 (87.2%) were considered at high risk for invasive fungal infection (IFI). Ten patients (7.7%), all high risk, developed breakthrough IFI (three Candida spp., seven invasive mould infections) and tended to have higher overall mortality. The only statistically significant risk factor for IFI was cytomegalovirus co-infection. Adverse events, all grade I, occurred in 25 (20%), requiring L-AmB withdrawal in one case. Overall survival at 30 days was 99.2%. At study completion, one patient had died of IFI. Conclusions The incidence of breakthrough IFI was comparable to that of previous reports, with a very low rate of significant toxicity. Thus, prophylactic L-AmB may be a safe, effective option for antifungal prophylaxis in the pre-engraftment phase for children undergoing HSCT, even those at high risk.

Investigation of the Emerging Nosocomial Wickerhamomyces anomalus Infections at a Chinese Tertiary Teaching Hospital and a Systemic Review: Clinical Manifestations, Risk Factors, Treatment, Outcomes, and Anti-fungal Susceptibility

“…In vivo studies have suggested AMB as an efficacious alternative for patients with infections refractory to echinocandins or those infected with multidrug-resistant isolates (Olson et al, 2005;Binder et al, 2020). Moreover, clinical studies have suggested that LAMB is a safe and efficacious prophylactic option for invasive fungal infections in pediatric patients undergoing hematopoietic stem cell transplantation (Mendoza-Palomar et al, 2020). Systematic reviewing of the literature showed that amphotericin B seems to be the optimal choice for the treatment of W. anomalus infections, and lipid complex amphotericin B could be used in patients with acute renal failure (Goss et al, 1994;Kane et al, 2002).…”

Antifungal stewardship in a tertiary care paediatric hospital: the PROAFUNGI study

“…In terms of the distribution of AF, LAMB was the most prescribed drug in our study, followed by posaconazole. At our hospital, low-dose LAMB is the drug of choice for AF prophylaxis in high-risk cancer patients (relapsed or refractory leukaemia, HSCT preengraftment phase) due to its effectiveness and safety profile as shown in a previous paper by our group [16]. LAMB is also used in critically ill paediatric patients due to its stability with the concomitant use of continuous renal replacement therapy, as opposed to azole elimination [17].…”

The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis

“…Seven studies reported CMV definitions according to the standard definitions and were included in the subgroup analyses. 29,31,33,39,40,42 Both CMV disease and CMV viremia increased the risk of subsequent IFI with pHR of 6.03 (4.04, 9.00), p-value < 0.001, I 2 = 42% and 3.58 (1.75, 7.35), p-value < 0.001, I 2 = 38%, respectively (Figure 3 and S5). Both unadjusted and adjusted effect estimates of CMV increased the risk of subsequent IFIs with pHRs of 1.70 (1.14, 2.55), p = 0.009, I 2 = 14% and 2.99 (1.92, 4.67), p < 0.001, I 2 = 76%, respectively (Figure 3…”

“…A total of 18 studies were extracted for the systematic review. 16,[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] Six articles were excluded from meta-analysis due to lack of HR. 32,34,36,38,41,45 Accordingly, 12 studies were included for meta-analysis of post-transplant CMV and IFIs.…”