Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis

Mihara, Tomo; Kakeya, Hiroshi; Izumikawa, Koichi; Obata, Yoko; Nishino, Tomoya; Takazono, Takahiro; Kosai, Kosuke; Morinaga, Yoshitomo; Kurihara, Shintaro; Nakamura, Shigeki; Imamura, Yoshifumi; Miyazaki, Taiga; Tsukamoto, Misuzu; Yamamoto, Yoshihiro; Yanagihara, Katsunori; Tashiro, Takayoshi; Kohno, Shigeru

doi:10.1016/j.jiac.2013.09.002

Cited by 13 publications

(11 citation statements)

References 16 publications

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“…n-AmB prophylaxis have been studied in animal models of aspergillosis, on rats [ 35 , 37 , 56 , 88 , 89 ], mice [ 36 ], and guinea pigs [ 90 ]. The only study assessing n-AmB for mucormycosis prophylaxis showed negative results with n-L-AmB [ 91 ].…”

Section: Resultsmentioning

confidence: 99%

Inhaled Antifungal Agents for Treatment and Prophylaxis of Bronchopulmonary Invasive Mold Infections

et al. 2022

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Pulmonary mold infections are life-threatening diseases with high morbi-mortalities. Treatment is based on systemic antifungal agents belonging to the families of polyenes (amphotericin B) and triazoles. Despite this treatment, mortality remains high and the doses of systemic antifungals cannot be increased as they often lead to toxicity. The pulmonary aerosolization of antifungal agents can theoretically increase their concentration at the infectious site, which could improve their efficacy while limiting their systemic exposure and toxicity. However, clinical experience is poor and thus inhaled agent utilization remains unclear in term of indications, drugs, and devices. This comprehensive literature review aims to describe the pharmacokinetic behavior and the efficacy of inhaled antifungal drugs as prophylaxes and curative treatments both in animal models and humans.

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Section: Resultsmentioning

confidence: 99%

Inhaled Antifungal Agents for Treatment and Prophylaxis of Bronchopulmonary Invasive Mold Infections

et al. 2022

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“…The dose of NAB for the treatment of pulmonary mucormycosis remains unclear 14 . Most data are from case reports where both lipid and non‐lipid formulations of amphotericin B have been used in varying doses 11,12,26 .…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, all the available amphotericin B formulations achieve therapeutic concentrations in the alveolar lining fluid but negligible systemic levels, thereby avoiding serious systemic adverse events 10,13 . Data from murine models and a few case reports suggest a possible role of NAB in managing PM 14,15 . We hypothesized that combining inhalational and intravenous amphotericin B would result in better outcomes than intravenous amphotericin B alone in PM.…”

Section: Introductionmentioning

confidence: 99%

Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin B (MUCONAB trial): Results of an open‐label randomized controlled trial

Muthu

Gogineni

Agarwal

et al. 2023

Mycoses

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Background:The role of nebulized amphotericin B (NAB) in managing pulmonary mucormycosis (PM) is unknown. Methods:In this open-label trial, we randomized PM subjects to receive either intravenous liposomal amphotericin B (control arm, 3-5 mg/kg/day) alone or along with nebulized amphotericin B deoxycholate (NAB, 10 mg twice a day, every alternate day).The primary outcomes were: (1) overall response ('success' [complete or partial response] or 'failure' [stable disease, progressive disease, or death]) at 6 weeks; and (2) the proportion of subjects with adverse events (AE). The key secondary outcome was 90-day mortality. We performed a modified intention-to-treat (mITT) analysis where we included only subjects receiving at least a single dose of NAB.Results: Fifteen and 17 subjects were randomized to the control and NAB arms; two died before the first dose of NAB. Finally, we included 30 subjects (15 in each arm; mean age 49.8 years; 80% men) for the mITT analysis. Diabetes mellitus (n = 27; 16/27 were COVID-19-associated PM) was the most common predisposing factor. The overall treatment success was not significantly different between the control and the NAB arms (71.4% vs. 53.3%; p = .45). Twenty-nine subjects experienced any AE, but none discontinued treatment. The 90-day mortality was not significantly different between the control (28.6%) and NAB arm (53.3%; p = .26). Conclusion:Adjunctive NAB was safe but did not improve overall response at 6 weeks.A different dosing schedule or nebulized liposomal amphotericin B may still need evaluation. More research is needed to explore other treatment options for PM.

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“…To the best of our knowledge, only one experimental study was dedicated to prophylaxis with L-AmB treatment (30). This study used nebulized L-AmB in a mouse model of R. oryzae pulmonary infection.…”

Section: Lung Decolonization To Prevent Mucormycosismentioning

confidence: 99%

Lichtheimia corymbifera Colonization Leading to Pulmonary Infection Can Be Prevented with Liposomal Amphotericin B in a New Murine Model

Brunet

Jouvion

et al. 2019

Antimicrob Agents Chemother

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The incidence of pulmonary mucormycosis is constantly increasing, especially in hematological patients staying in high-efficiency particulate air-filtered rooms. Pulmonary inhalation of spores may occur outside the hospital, leading to invasive disease once patients received chemotherapies. We developed a new pulmonary mucormycosis mouse model mimicking the expected pathophysiology in human to study antifungal drugs. Naive mice were inoculated intratracheally with Lichtheimia corymbifera spores. After 3 days, mice received corticosteroids and cyclophosphamide and secondarily developed the disease, while only 5% of the initial inoculum was present in the lungs at day 3. Lung colonization with L. corymbifera spores in immunocompetent mice can last at least 44 days. Antifungal drug was administered the day of immunosuppression. Injection of a single 15 mg/kg of body weight dose of liposomal amphotericin B significantly improved survival and pulmonary fungal burden compared with controls, whereas 80 mg/kg oral posaconazole did not. These results show that a unique dose of liposomal amphotericin B offers a real potential decolonization treatment to prevent infection in our mouse model of L. corymbifera lung colonization followed by lung infection.

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Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis

Cited by 13 publications

References 16 publications

Inhaled Antifungal Agents for Treatment and Prophylaxis of Bronchopulmonary Invasive Mold Infections

Inhaled Antifungal Agents for Treatment and Prophylaxis of Bronchopulmonary Invasive Mold Infections

Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin B (MUCONAB trial): Results of an open‐label randomized controlled trial

Lichtheimia corymbifera Colonization Leading to Pulmonary Infection Can Be Prevented with Liposomal Amphotericin B in a New Murine Model

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