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Miltefosine
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Andrew Stewardson, Douglas Johnson
A number of reports describe the successful use of miltefosine for Old World cutaneous leishmaniasis. These include one case due to L. major acquired in Tunisia, treated successfully with a dose of 150 mg daily for 28 days (Stojkovic et al., 2007), treatment of one case of L. major and one case of L. infantum (Dorlo et al., 2011) and two cases due to L. infantum acquired in Spain (Ruiz-Villaverde et al., 2007; Neub et al., 2008). In a retrospective observational study of 34 Dutch military personnel returning from Afghanistan with L. major infection, treatment was successful in 30 patients treated with miltefosine (van Thiel et al., 2010). Keynan et al. (2008) describe the successful treatment of L. tropica with miltefosine among Canadian soldiers returning from Afghanistan.
Lipid-Based Nanocarriers for the Treatment of Infected Skin Lesions
Published in Andreia Ascenso, Sandra Simões, Helena Ribeiro, Carrier-Mediated Dermal Delivery, 2017
Sandra Simöes, Manuela Carvalheiro, Maria Manuela Gaspar
Miltefosine (hexadecylphosphocholine), a structural analogue of alkyllysophospholipids, originally developed as an anticancer drug, is the first efficient oral drug for the treatment of leishmaniasis, essentially used in VL treatment [61,69]. More recently, it has been reported in the treatment of several New World CL species with variable efficacies [66,70]. In Colombia, where L. panamensis is the more frequent specie, the oral administration of miltefosine, at a dose of 2.5 mg/kg/day for 28 days, resulted in over 91% cure rate [25]. Most studies were conducted in Colombia, where the drug is registered for CL treatment. However, in studies conducted in areas with a predominance of L. braziliensis and L. mexicana, cure rates were lower ranging from 35% to 70% [70,71]. Miltefosine is well tolerated and has a half-life of about 8 days after oral administration. Nevertheless, a general concern about severe side effects, including teratogenicity, and the easy appearance of resistant mutants exists [66].
Chemical Hybridization Approaches Applied to Natural and Synthetic Compounds for the Discovery of Drugs Active Against Neglected Tropical Diseases
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Elena Petricci, Paolo Governa, Fabrizio Manetti
Caused by Leishmania parasites, leishmaniasis is a mortal neglected tropical disease that can present cutaneous (CL), mucocutaneous (ML) or visceral (VL) forms depending on the specific Leishmania species involved (i.e., L. aethiopica and L. amazonensis are responsible for CL, while L. donovani is related to VL). More than 12 million people are affected by leishmaniasis with a high mortality level of around 50000 deaths each year in more than 90 countries (Maran et al. 2016). Leishmania are heteroxenous parasites involving an invertebrate and a vertebrate host in their lifecycle. In sandfly vector, the parasite is present in its extracellular promastigote form, while the intracellular amastigote form is the only one observed in the vertebrate host. Amastigotes are absorbed from a vertebrate infected host once a female sandfly bites it, and are transformed into promastigotes in the insect gut where they multiply by binary fission. Formed promastigotes transfer to the proboscis and are transferred by sandfly sting into the vertebrate host where they are phagocytized into macrophages to form amastigotes again. From macrophages, the parasites diffuse in internal organs, especially liver, spleen, lymph nodes, and bone marrow, where they can propagate and suppress the host immune system, thus generating a permanent, eventually lethal infection. Despite many efforts on developing new immunomodulators, immunosuppressive agents, and new antileishmanial compounds, there still is a real need for effective therapies. Pentavalent antimony was developed in 1959, but its current use is limited by its high toxicity. The first line drug is amphotericin B for LV, especially in Bihar State of India where several cases do not respond to antimonium anymore. Pentamidine is the second line treatment with many side effects observed, and it is not active by oral administration. Miltefosine can be considered as a very innovative drug in antileishmania therapy as it is the sole compound that is orally active, though teratogenic. This drug shows a long half-life with an easy induction of resistance.
Severe Inflammatory Response in a Patient on Oral Miltefosine for Acanthamoeba Keratitis
Published in Ocular Immunology and Inflammation, 2022
Zhuangjun Si, Peter B. Veldman, James J. Reidy, Asim V. Farooq
The safety and efficacy of miltefosine use for AK has been demonstrated thus far in case reports.5–9 A potential advantage of oral miltefosine over conventional topical therapies is its proposed cysticidal mechanism. However, as we have seen in two consecutive cases, there can be an increase in inflammation and pain approximately 2–3 weeks into therapy.4,9 The mechanism of this response remains unclear but may represent a Jarisch-Herxheimer-like reaction. Based on our experience and other similar published cases, this exacerbation of symptoms after initiating oral miltefosine can be cautiously treated with topical steroids. It is unclear if it would be beneficial and/or safe to start topical steroids prophylactically for this inflammatory reaction. We hope this case highlights a potential side effect of miltefosine therapy in the setting of AK, which can easily be mistaken for worsening infection. Therefore, when initiating oral miltefosine for AK, both the clinician and patient should be prepared for a potential exacerbation of symptoms approximately 2–3 weeks into treatment.
Combination of infra-red light with nanogold targeting macrophages in the treatment of Leishmania major infected BALB/C mice
Published in Cutaneous and Ocular Toxicology, 2022
Rukiye Yasak Guner, Sibel Berksoy Hayta, Mustafa Tosun, Melih Akyol, Necati Ozpınar, Zubeyde Akın Polat, Reyhan Egilmez, Serkan Celikgün, Selim Cam
After CL formation, 20 µL of Au and Au + MSA nanoparticles were injected subcutaneously into the feet of the mice in the experimental group, and the treatment procedure was applied 24 h later. Positive control groups did not receive treatment, and miltefosine groups were administered orally miltefosine at a dose of 50 mg/kg/day for the first five days and 25 mg/kg/day for the last five days. Due to mouse deaths, doses were reduced in the treatment of miltefosin. NIR was applied with the PL-E Pro 808 nm Infra-red Laser (Jet, China) device in the form of near infra-red radiation at a dose of 5 s/day. Experimental groups were arranged as only Au, Au + NIR, Au + MSA + NIR, NIR as indicated in Table 1. On the 5th and 10th days of the treatment, the mice were evaluated clinically, and on the 10th day histopathologically and immunohistochemically. At the end of the 10-day treatment period, the animals were sacrificed after general anaesthesia.
Recent advances and future perspectives in the pharmacological treatment of Candida auris infections
Published in Expert Review of Clinical Pharmacology, 2021
Daniele R. Giacobbe, Laura Magnasco, Chiara Sepulcri, Malgorzata Mikulska, Philipp Koehler, Oliver A. Cornely, Matteo Bassetti
Miltefosine, which is currently licensed for the treatment of leishmaniasis in several countries [129], has shown fungicidal and post-antifungal effects [130–134]. The mechanism of action postulated for miltefosine is possibly attributable to its detergent properties, able to induce apoptosis in fungal cells [135]. Barreto and colleagues showed an inhibitory effect of miltefosine on C. auris at concentrations ≤2 mg/L, as well as inhibition of biofilm formation and improved survival vs. untreated controls in a G. mellonella model [136]. Of note, alginate-based nanocarriers for drug encapsulation were developed to reduce the toxicity of miltefosine (e.g. serious gastrointestinal effects, nephrotoxicity, liver toxicity, and high hemolytic activity) [132]. Other in vitro studies showed activity of miltefosine against planktonic and biofilm C. auris cells, as well as a possible synergism with amphotericin B [137,138].