Treatment of Cutaneous <i>Balamuthia mandrillaris</i> Infection With Diminazene Aceturate: A Report of 4 Cases

Wang, Lei; Li, Bing; Ting, Zhao; Wang, Lu; Jian, Zhe; Cheng, Wenjing; Chen, Jiaxi; Li, Chunying; Wang, Gang; Gao, Tianwen

doi:10.1093/cid/ciac356

Cited by 4 publications

(2 citation statements)

References 11 publications

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“…For example, a 57-year-old cutaneous B. mandrillaris infected patient died with severe liver damage potentially due to complications of the diminazene aceturate treatment they received. 41 Another patient with B. mandrillaris GAE was treated for more than 2 months with the recommended multiple-drug regimen (flucytosine, pentamidine, fluconazole, sulfadiazine, azithromycin, miltefosine, and albendazole) and developed adverse effects, including acute kidney injury and myelosuppression. 35,42 These examples indicate that new treatments with lower toxicities are needed for B. mandrillaris .…”

Section: Resultsmentioning

confidence: 99%

Discovery of cyclic peptide natural product inhibitors ofBalamuthia mandrillaris

Lu,

Nelson,

Coy

et al. 2024

Preprint

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Balamuthia mandrillaris is a pathogenic free-living amoeba that causes infection of central nervous system, called Balamuthia amoebic encephalitis (BAE), as well as cutaneous and systemic diseases. Patients infected with B. mandrillaris have a high mortality rate due to the lack of effective treatments. A combination of non-optimized antimicrobial drug regimen is typically recommended; however, they have poor parasite activity and can cause various severe side effects. Cyclic peptides exhibit a broad spectrum of antimicrobial activities and lower cytotoxicity. In this study, we evaluated the anti-B. mandrillaris effect of cyclic peptides. The predicted natural product-43 (pNP-43), identified from the SNaPP (Synthetic Natural Product Inspired Cyclic Peptides) library, and its derivates displayed a significant inhibition for B. mandrillaris trophozoites. Eight pNPs had IC50s <5 μM. Furthermore, all hit pNPs demonstrated minimal hemolytic and cytotoxic effects on human cells. Our study first indicates the anti-B. mandrillaris effect of cyclic peptides, which provides a new direction for drug development. Further studies of the mechanism of action and in vivo effects will be elucidated to confirm the potency as a treatment for B. mandrillaris infection in the future.

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Section: Resultsmentioning

confidence: 99%

Discovery of cyclic peptide natural product inhibitors ofBalamuthia mandrillaris

Lu,

Nelson,

Coy

et al. 2024

Preprint

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“…A previous study examined the effects of the conjugation of amphotericin B on N. fowleri, revealing encouraging results; however, in this study, silver nanoparticles were utilized for the conjugation, and the cytotoxicity of the compounds alone was not evaluated [ 8 ]. Furthermore, until now, conjugated curcumin and amphotericin B have not been evaluated on B. mandrillaris , for which the number of reported cases is evident [ 45 , 46 , 47 ]. The nanocarriers utilized in this study also revealed greater drug loading efficiency, thus showing their capability for higher drug release to the desired target site [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Nanocarrier Drug Conjugates Exhibit Potent Anti-Naegleria fowleri and Anti-Balamuthia mandrillaris Properties

et al. 2023

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Given the opportunity and access, pathogenic protists (Balamuthia mandrillaris and Naegleria fowleri) can produce fatal infections involving the central nervous system. In the absence of effective treatments, there is a need to either develop new antimicrobials or enhance the efficacy of existing compounds. Nanocarriers as drug delivery systems are gaining increasing attention in the treatment of parasitic infections. In this study, novel nanocarriers conjugated with amphotericin B and curcumin were evaluated for anti-amoebic efficacy against B. mandrillaris and N. fowleri. The results showed that nanocarrier conjugated amphotericin B exhibited enhanced cidal properties against both amoebae tested compared with the drug alone. Similarly, nanocarrier conjugated curcumin exhibited up to 75% cidal effects versus approx. 50% cidal effects for curcumin alone. Cytopathogenicity assays revealed that the pre-treatment of both parasites with nanoformulated-drugs reduced parasite-mediated host cellular death compared with the drugs alone. Importantly, the cytotoxic effects of amphotericin B on human cells alone were reduced when conjugated with nanocarriers. These are promising findings and further suggest the need to explore nanocarriers as a means to deliver medicine against parasitic infections.

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Diminazene

2023

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Treatment of Cutaneous Balamuthia mandrillaris Infection With Diminazene Aceturate: A Report of 4 Cases

Cited by 4 publications

References 11 publications

Discovery of cyclic peptide natural product inhibitors ofBalamuthia mandrillaris

Discovery of cyclic peptide natural product inhibitors ofBalamuthia mandrillaris

Nanocarrier Drug Conjugates Exhibit Potent Anti-Naegleria fowleri and Anti-Balamuthia mandrillaris Properties

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