Table 2 Summary of statements on the use of systemic LAMB in ICU
From: Role of liposomal amphotericin B in intensive care unit: an expert opinion paper
Pharmacology | The recommended dose of L-AmB for most indications in critically ill septic patients is 3 mg/kg, with a maximum of 5 mg/kg/day (a dose ceiling of 500 mg is recommended in patients weighing > 100 kg). Daily doses of L-AmB > 5 mg/kg are not associated with a significant benefit in terms of clinical outcome in any type of fungal infection and could increase the risk of nephrotoxicity and hypokalemia. However, a single 10 mg/kg dose could be considered for treating visceral leishmaniasis and/or cryptococcal meningitis |
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The risk of nephrotoxicity of L-AmB at a dose of 3–5 mg/kg/day is much lower than that of amphotericin B deoxycholate | |
In critically ill patients with renal dysfunction and/or requiring hemodialysis or continuous renal replacement, no dosing adjustment of L-AmB is necessary due to the fact that its elimination is non-renal and the incidence of adverse events did not markedly differ from non-RRT groups | |
Therapeutic approach to mold infections in patients with severe viral pneumonia, chronic corticosteroids or immunomodulatory therapy, COPD, diabetes, and end-stage liver disease | Anti-mold therapy with L-AmB could be preferable over azoles in case of treatment failure and could be proposed as the first-line option (i) in geographic areas with a high prevalence of azole resistance (ii) in patients at higher risk for hepatotoxicity (i.e., end-stage liver disease) in subjects taking drugs having clinically relevant drug-drug interactions vs. azoles (iv) in setting having no possibility of performing voriconazole TDM |
The interindividual pharmacokinetic variability of L-AmB in critically ill patients is expected to be limited so that TDM is not needed | |
L-AmB demonstrated efficacy in the treatment of mucormycosis with various organ involvement patterns. The daily dose should be 5Â mg/kg per day | |
SOT | In SOT recipients, a targeted (risk-based) approach to antifungal prophylaxis is recommended. Clinically relevant drug-drug interactions, safety concerns, and rates of breakthrough infections are all issues to be taken into account when choosing an antifungal agent for prophylaxis. In this regard, L-AmB may be considered a suitable option |
Drug-drug interactions with immunosuppressive drugs could sometimes represent a relevant issue when treating IFI with azole antifungals after SOT. In this regard, L-AmB could be a valuable alternative option for the empirical treatment of IFI | |
Regarding IC in SOT recipients, L-AmB could be considered a reasonable alternative to echinocandins | |
Hematologic malignancy | Patients with hematologic malignancies receiving mold-active azole prophylaxis who develop suspected or documented breakthrough IFI should receive treatment with L-AmB and promptly undergo a complete diagnostic work-up |
Patients with hematologic malignancies admitted to the ICU and having IFI with no possibility for TDM for azoles and/or at high risk of azole-related drug–drug interactions should receive treatment with L-AmB | |
Considering the high risk of IFI and wide spectrum of fungal pathogens in certain hematology patients (with prolonged neutropenia or after allogeneic HSCT), empirical therapy with L-AmB can be useful in patients admitted in ICU with clinical suspicion of IFIs while completing diagnostic work-up and it should be discontinued if the suspicion of IFI is not confirmed | |
Abdominal surgery | In patients with IAC, the choice of empirical antifungal therapy should be guided by host, microbiological ad epidemiological variables. L-AmB could be considered first-line therapy in cases of intra-abdominal infection with sepsis/septic shock, the risk for N. glabratus and C. parapsilosis infections, or previous therapy with echinocandins |
Echinocandins could be used as a first-choice treatment in non critically ill patients. However, recent pharmacokinetic/pharmacodynamic evidence suggested that exposure to the ascitic fluid may be suboptimal and may cause breakthrough resistance, especially in the case of non-albicans etiology | |
Combination therapy with L-AmB and an echinocandin should be considered a rescue therapy in the case of C. auris etiology |