Case Report: Combination Therapy with Liposomal Amphotericin B, N-Methyl Meglumine Antimoniate, and Pentamidine Isethionate for Disseminated Visceral Leishmaniasis in a Splenectomized Adult Patient

Vechi, Hareton Teixeira; Sousa, Ana Solange Vasconcelos de; Cunha, Mirella Alves; Shaw, Jeffrey Jon; Luz, Kléber Giovanni

doi:10.4269/ajtmh.18-0999

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…However, because TCBZ has already shown successful repurposing as a bactericidal (Pi et al, 2021) and as a fasciolosis treatment in sheep, when used combined with other drugs, even in resistant parasites (Tabari et al, 2022), this specific combination may lead to desirable results. AmpB has already been used in successful treatments in combination with miltefosine, meglumine antimoniate, and pentamidine (Goswami et al, 2020;Ramesh et al, 2020;Vechi et al, 2020). Indeed, we found that TCBZ and AmpB have synergic effects in vitro when administrated in combination, and no interaction between these two drugs was found by the DrugBank prediction in silico, indicating that it is safe to combine them.…”

Section: Discussionmentioning

confidence: 71%

Strategies in the drug discovery and development for leishmaniasis: immunomodulators, natural products, synthetic compounds, and drug repositioning

2024

Frontiers Research Topics

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Frontiers is more than just an open access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers journal seriesThe Frontiers journal series is a multi-tier and interdisciplinary set of openaccess, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers journal series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to qualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews. Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view. By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation. What are Frontiers Research Topics?Frontiers Research Topics are very popular trademarks of the Frontiers journals series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area.

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Section: Discussionmentioning

confidence: 71%

Strategies in the drug discovery and development for leishmaniasis: immunomodulators, natural products, synthetic compounds, and drug repositioning

2024

Frontiers Research Topics

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“…However, because TCBZ has already shown successful repurposing as a bactericidal ( Pi et al., 2021 ) and as a fasciolosis treatment in sheep, when used combined with other drugs, even in resistant parasites ( Tabari et al., 2022 ), this specific combination may lead to desirable results. AmpB has already been used in successful treatments in combination with miltefosine, meglumine antimoniate, and pentamidine ( Goswami et al., 2020 ; Ramesh et al., 2020 ; Vechi et al., 2020 ). Indeed, we found that TCBZ and AmpB have synergic effects in vitro when administrated in combination, and no interaction between these two drugs was found by the DrugBank prediction in silico , indicating that it is safe to combine them.…”

Section: Discussionmentioning

confidence: 99%

In vitro anti-Leishmania activity of triclabendazole and its synergic effect with amphotericin B

Borges

Bueno

Tomiotto-Pellissier

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionLeishmaniasis is a neglected tropical disease, with approximately 1 million new cases and 30,000 deaths reported every year worldwide. Given the lack of adequate medication for treating leishmaniasis, drug repositioning is essential to save time and money when searching for new therapeutic approaches. This is particularly important given leishmaniasis’s status as a neglected disease. Available treatments are still far from being fully effective for treating the different clinical forms of the disease. They are also administered parenterally, making it challenging to ensure complete treatment, and they are extremely toxic, in some cases, causing death. Triclabendazole (TCBZ) is a benzimidazole used to treat fasciolosis in adults and children. It presents a lower toxicity profile than amphotericin B (AmpB) and is administered orally, making it an attractive candidate for treating other parasitoses. The mechanism of action for TCBZ is not yet well understood, although microtubules or polyamines could potentially act as a pharmacological target. TCBZ has already shown antiproliferative activity against T. cruzi, T. brucei, and L. infantum. However, further investigations are still necessary to elucidate the mechanisms of action of TCBZ.MethodsCytotoxicity assay was performed by MTT assay. Cell inhibition (CI) values were obtained according to the equation CI = (O.D treatment x 100/O.D. negative control). For Infection evaluation, fixated cells were stained with Hoechst and read at Operetta High Content Imaging System (Perkin Elmer). For growth curves, cell culture absorbance was measured daily at 600 nm. For the synergism effect, Fractional Inhibitory Concentrations (FICs) were calculated for the IC50 of the drugs alone or combined. Mitochondrial membrane potential (DYm), cell cycle, and cell death analysis were evaluated by flow cytometry. Reactive oxygen species (ROS) and lipid quantification were also determined by fluorimetry. Treated parasites morphology and ultrastructure were analyzed by electron microscopy.ResultsThe selectivity index (SI = CC50/IC50) of TCBZ was comparable with AmpB in promastigotes and amastigotes of Leishmania amazonensis. Evaluation of the cell cycle showed an increase of up to 13% of cells concentrated in S and G2, and morphological analysis with scanning electron microscopy showed a high frequency of dividing cells. The ultrastructural analysis demonstrated large cytoplasmic lipid accumulation, which could suggest alterations in lipid metabolism. Combined administration of TCBZ and AmpB demonstrated a synergistic effect in vitro against intracellular amastigote forms with cSFICs of 0.25.ConclusionsConsidering that TCBZ has the advantage of being inexpensive and administrated orally, our results suggest that TCBZ, combined with AmpB, is a promising candidate for treating leishmaniasis with reduced toxicity.

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“…Recent findings suggest that a combination of anti-Leishmania therapy with locally available drugs should be tried first. 40,41 Furthermore, the decision to perform splenectomy should only be made after patients' informed consent.…”

Section: Discussionmentioning

confidence: 99%

Splenectomy in Patients with Visceral Leishmaniasis Resistant to Conventional Therapy and Secondary Prophylaxis: A Retrospective Cohort

reinaldo

Araújo-Júnior

Diniz

et al. 2022

The American Journal of Tropical Medicine and Hygiene

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Some patients with visceral leishmaniasis (VL), or kala-azar, suffer relapses and low quality of life despite adequate drug therapy, especially those co-infected with HIV. Occasionally, physicians indicate splenectomy, but the benefit of the procedure needs to be analyzed systematically. Therefore, a retrospective open cohort study was conducted in Teresina, Brazil. Inpatients from a reference hospital with relapsing VL who had a rescue splenectomy between 2012 and 2019 after the nationally recommended drug therapy failed were studied. The procedure’s risks and benefits were assessed in a limited-resource setting. The primary outcomes were surgical complications, complete blood count, CD4+ cell count, hospitalizations, survival time, and medical complications preceding death. Thirteen adult patients received medical and surgical indications of splenectomy (12 men and one woman). Eleven had HIV infection. Two had early and two had late complications. Four died, all of whom were infected with HIV. An additional HIV-coinfected patient, apart from the cohort, died just before surgery. The death rate after surgery was 13.3 overall and 22.1 per 100 person-years among HIV-infected patients (31% overall and 36%, respectively). The impressive rise of complete blood counts and reduction of blood transfusions and hospitalizations were observed among all patients. Also, a meaningful increase in CD4+ cells in HIV-infected patients was noted. Splenectomy may benefit patients with relapsing VL. However, before performing splenectomy, available combined drug therapy should be tried for relapsing VL.

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Case Report: Combination Therapy with Liposomal Amphotericin B, N-Methyl Meglumine Antimoniate, and Pentamidine Isethionate for Disseminated Visceral Leishmaniasis in a Splenectomized Adult Patient

Cited by 7 publications

References 31 publications

Strategies in the drug discovery and development for leishmaniasis: immunomodulators, natural products, synthetic compounds, and drug repositioning

Strategies in the drug discovery and development for leishmaniasis: immunomodulators, natural products, synthetic compounds, and drug repositioning

In vitro anti-Leishmania activity of triclabendazole and its synergic effect with amphotericin B

Splenectomy in Patients with Visceral Leishmaniasis Resistant to Conventional Therapy and Secondary Prophylaxis: A Retrospective Cohort

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