ArticleAntimicrobial agents and chemotherapy2011
Antimony-resistant clinical isolates of Leishmania donovani are susceptible to paromomycin and sitamaquine.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 35 citations in OpenAlex.
- Isolation, typing, and drug susceptibility of Leishmania (Leishmania) infantum isolates from dogs of the municipality of Embu das Artes, an endemic region for canine leishmaniasis in Brazil.Parasitology research · 2022Article
- Involvement ofFrontiers in cellular and infection microbiology · 2021Review
- Artemisinin-resistant Leishmania parasite modulates host cell defense mechanism and exhibits altered expression of unfolded protein response genes.Parasitology research · 2019Article
- Transcriptome profiling identifies genes/pathways associated with experimental resistance to paromomycin in Leishmania donovani.International journal for parasitology. Drugs and drug resistance · 2017Article
- Increased miltefosine tolerance in clinical isolates of Leishmania donovani is associated with reduced drug accumulation, increased infectivity and resistance to oxidative stress.PLoS neglected tropical diseases · 2017Article
- Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency Virus-Coinfected Patients.Frontiers in immunology · 2017Review
- Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2016Article
- Antimalarial and antimicrobial activities of 8-Aminoquinoline-Uracils metal complexes.EXCLI journal · 2016Article
- Leishmanicidal activities of novel methylseleno-imidocarbamates.Antimicrobial agents and chemotherapy · 2015Article
- Over-Expression of Cysteine Leucine Rich Protein Is Related to SAG Resistance in Clinical Isolates of Leishmania donovani.PLoS neglected tropical diseases · 2015Article
- New trends in aminoglycosides use.MedChemComm · 2014Article
- Elucidation of cellular mechanisms involved in experimental paromomycin resistance in Leishmania donovani.Antimicrobial agents and chemotherapy · 2014Article
- Comparative transcript expression analysis of miltefosine-sensitive and miltefosine-resistant Leishmania donovani.Parasitology research · 2014Article
- Experimental induction of paromomycin resistance in antimony-resistant strains of L. donovani: outcome dependent on in vitro selection protocol.PLoS neglected tropical diseases · 2012Article
- Drug susceptibility in Leishmania isolates following miltefosine treatment in cases of visceral leishmaniasis and post kala-azar dermal leishmaniasis.PLoS neglected tropical diseases · 2012Article
- Interest in paromomycin for the treatment of visceral leishmaniasis (kala-azar).Therapeutics and clinical risk management · 2012Article
- Expression Analysis of Multiple Genes May Involve in Antimony Resistance amongIranian journal of parasitologyArticle
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5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Widespread antimonial resistance in anthroponotic visceral leishmaniasis (VL) makes it critical to monitor the susceptibility of prevailing field isolates to upcoming antileishmanials in order to frame the right treatment policies to protect these drugs against development of resistance. We aimed to generate the baseline data on natural in vitro susceptibility to paromomycin and sitamaquine in Leishmania donovani field isolates from VL patients (n = 20) coming from zones of varying sodium antimony gluconate (SAG) resistance. We further monitored nitric oxide (NO) release in infected macrophages treated with these drugs. Field isolates exhibited variable sensitivity to paromomycin and sitamaquine with respective mean 50% effective dose (ED₅₀) values ± standard error of the mean (SEM) of 3.9 ± 0.3 μM and 2.1 ± 0.2 μM at the intracellular amastigote stage and 29.8 ± 2.5 μM and 17.7 ± 1.0 μM at the promastigote stage. Susceptibilities at the two parasite stages did not correlate for either drug. Isolates from high SAG resistance zones exhibited significantly lower susceptibility to sitamaquine than those from low SAG resistance zones, while isolates from different zones showed similar susceptibilities to paromomycin. NO release was promoted in L. donovani-infected macrophages upon treatment with paromomycin/sitamaquine. NO inhibitors significantly compromised amastigote killing by sitamaquine, but not by paromomycin. In conclusion, SAG-resistant/sensitive VL isolates were susceptible to both paromomycin and sitamaquine. Paromomycin, exhibiting higher efficacy against SAG-resistant parasites and having a distinct mechanism of action, appears to be a promising drug for combination therapy.
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