How low can you go? Use of low- and standard-dose liposomal amphotericin B for treatment of invasive fungal infections

Kassamali, Zahra; Danziger, Larry H.; Glowacki, Robert C.; Schwartz, David N.

doi:10.1016/j.ijid.2013.01.015

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…Compared to dosages of AmB 0.6–0.7 mg/kg/d, dosages of AmB 0.4–0.5 mg/kg/d were not related to increased mortality in CM patients but were related to a lower incidence of adverse effects such as hypokalemia and creatinine elevation. It was noted that a low dosage of AmB (including liposomal AmB) produced more safety and similar efficacy to prevent or treat fungal infections (Koh et al, 2002; Lequaglie, 2002; Kassamali et al, 2013; Yasu et al, 2018). The possible reason that a low dosage of AmB achieved comparable efficacy to a standard dosage of AmB may be that first, AmB is a fungicidal medicine with a long half-life.…”

Section: Discussionmentioning

confidence: 99%

Short-Course Rather Than Low-Dose Amphotericin B May Exert Potential Influence on Mortality in Cryptococcal Meningitis Patients Treated With Amphotericin B Plus Flucytosine Alone or in Combination With Fluconazole

Tao

et al. 2019

Front. Microbiol.

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BackgroundThe influence of Amphotericin B (AmB) dose and the addition of fluconazole (Flu) on the AmB + 5-flucytosine (5FC) regimen for cryptococcal meningitis (CM) treatment remain debatable.MethodsA retrospective study was conducted to compare 44 CM patients treated with AmB + 5FC and 78 CM patients treated with AmB + 5FC + Flu using the propensity score matching method. The effects of AmB dosage, AmB course and Flu addition on the cerebrospinal fluid (CSF) chemical profile recovery, adverse effects, and 90-day mortality were compared between the groups.ResultsNo differences in adverse effects, the rate of the 14-day CSF chemical profile recovery and 90-day cumulative survival rate (91.2% vs. 87.5%, P = 0.637) were observed between the AmB + 5FC group and the AmB + 5FC + Flu group. However, the incidence rates of hypokalemia (33.9%) and creatinine elevation (7.1%) in patients treated with an AmB dosage of 0.4–0.5 mg/kg/d were less than those (53.0 and 22.7%, respectively) treated with an AmB dosage of 0.6–0.7 mg/kg/d (P = 0.034 and P = 0.018, respectively). The 90-day cumulative survival rate was 70.1% for patients treated with AmB for <14 days and 96.4% for patients treated with AmB for ≥14 days (log-rank P < 0.001). Multivariate Cox proportional hazards models suggested the hazard ratio was 26.8 (95% CI: 3.9–183.2) for patients treated with AmB < 14 days than those treated with AmB ≥ 14 days (P = 0.001).ConclusionTreatment with AmB less than 14 days was associated with a higher 90-day mortality in CM patients. A relative lower dosage but prolonged course of AmB in the +5FC ± Flu regimen led to favorable trends of fewer adverse effects and comparable clinical efficacy.

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Section: Discussionmentioning

confidence: 99%

Short-Course Rather Than Low-Dose Amphotericin B May Exert Potential Influence on Mortality in Cryptococcal Meningitis Patients Treated With Amphotericin B Plus Flucytosine Alone or in Combination With Fluconazole

Tao

et al. 2019

Front. Microbiol.

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“…However, Ellis et al reported a prospective randomized trial that compared the efficacy of two dosages of L-AMB for treatment of invasive aspergillosis and found that a daily dose of 1 mg/kg was as effective as a dose of 4 mg/kg (10). Moreover, although the optimal dose of L-AMB for empirical or preemptive therapy during neutropenia remains unclear, several prospective and retrospective studies have suggested that a daily dose of L-AMB as low as 1 mg/kg is effective for empirical therapy and for prevention of IFIs during neutropenia (9)(10)(11)(12)(13)(14). Among those studies, Prentice et al reported a prospective randomized trial that compared the efficacy of two dosages of L-AMB and conventional D-AMB for empirical therapy during neutro- penia and found that a daily dose of L-AMB of 1 mg/kg could provide an efficacy similar to that of 3 mg/kg L-AMB (9).…”

Section: Discussionmentioning

confidence: 99%

“…Although L-AMB has a significantly improved toxicity profile, compared with conventional amphotericin B deoxycholate (D-AMB), adverse events such as hepatotoxicity, nephrotoxicity, electrolyte abnormalities, and infusion-related reactions also frequently occurred with recommended daily doses of L-AMB ranging between 3 and 6 mg/kg (3,4). However, recent studies have suggested that low doses of L-AMB (less than ϳ2 mg/kg/day) are effective and have less toxicity for patients with hematological malignancies (9)(10)(11)(12)(13)(14). Therefore, the optimal daily dosage of L-AMB is controversial.…”

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confidence: 99%

Efficacy and Safety of Low-Dose Liposomal Amphotericin B in Adult Patients Undergoing Unrelated Cord Blood Transplantation

Yasu

Konuma

Oiwa‐Monna

et al. 2018

Antimicrob Agents Chemother

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Liposomal amphotericin B (L-AMB) is widely used for empirical or preemptive therapy and treatment of invasive fungal infections after cord blood transplantation (CBT). We retrospectively examined the efficacy and safety of low-dose L-AMB in 48 adult patients who underwent CBT between 2006 and 2017 in our institute. Within the entire cohort, 42 patients (88%) received L-AMB as empirical or preemptive therapy. The median daily dose of L-AMB and the median cumulative dose of L-AMB were 1.20 mg/kg/day (range, 0.62 to 2.60 mg/kg/day) and 30.6 mg/kg (range, 0.7 to 241.5 mg/kg), respectively. The median duration of L-AMB administration was 21.5 days (range, 1 to 313 days). A documented breakthrough fungal infection occurred in 1 patient during L-AMB treatment, and 43 patients (90%) survived for at least 7 days after the end of L-AMB treatment. Grade 3 or higher hypokalemia and hepatotoxicity were frequently observed during L-AMB treatment. However, no patient developed an increase in serum creatinine levels of grade 3 or higher. In univariate analyses using a logistic regression model, a duration of L-AMB treatment of more than 21 days and a cumulative dose of L-AMB of more than 30 mg/kg were significantly associated with nephrotoxicity and grade 3 hypokalemia. These data suggest that low-dose L-AMB may be safe and effective in adult patients undergoing CBT.

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“…However, because they used effectiveness measures from the study by Walsh et al (26), who only used doses of 3 mg/kg, cost-effectiveness analysis was not possible. The use of low doses of LAmB has been evaluated, and most studies indicate that there is no significant improvement in major outcomes with higher doses (32)(33)(34)(35). Therefore, conducting economic evaluations based on studies that used low doses of L-AmB (1-2 mg/kg) could provide a new perspective in the pharmacoeconomics of LAmB.…”

Section: Discussionmentioning

confidence: 99%

Cost-effectiveness of caspofungin versus liposomal amphotericin B in the treatment of systemic fungal infections: a systematic review of economic analyses

Mistro

Rosa

Gomes

et al. 2016

Expert Review of Pharmacoeconomics & Outcomes Research

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A systematic search was conducted in PubMed, Scopus, Web of Science, Cochrane Library, Health Economic Evaluation Database, and Centre for Review and Dissemination to find complete economic evaluations that directly compared the two treatment strategies. Expert commentary: Because of the high cost, patients in developing countries experience difficulty accessing highly effective treatments. These data can subsidize a decision for an effective antifungal treatment with reduced costs from all perspectives.

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How low can you go? Use of low- and standard-dose liposomal amphotericin B for treatment of invasive fungal infections

Abstract: Comparable rates of clinical improvement, survival to discharge, and toxicity were identified among low- and standard-dose L-AMB recipients.

Cited by 7 publications

References 22 publications

Short-Course Rather Than Low-Dose Amphotericin B May Exert Potential Influence on Mortality in Cryptococcal Meningitis Patients Treated With Amphotericin B Plus Flucytosine Alone or in Combination With Fluconazole

Short-Course Rather Than Low-Dose Amphotericin B May Exert Potential Influence on Mortality in Cryptococcal Meningitis Patients Treated With Amphotericin B Plus Flucytosine Alone or in Combination With Fluconazole

Efficacy and Safety of Low-Dose Liposomal Amphotericin B in Adult Patients Undergoing Unrelated Cord Blood Transplantation

Cost-effectiveness of caspofungin versus liposomal amphotericin B in the treatment of systemic fungal infections: a systematic review of economic analyses

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