{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:51:11Z","timestamp":1789696271663,"version":"4.0.1"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T00:00:00Z","timestamp":1306886400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            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\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">in vitro<\/jats:named-content>\n            susceptibility to paromomycin and sitamaquine in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania donovani<\/jats:named-content>\n            field isolates from VL patients (\n            <jats:italic>n<\/jats:italic>\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 (ED\n            <jats:sub>50<\/jats:sub>\n            ) values \u00b1 standard error of the mean (SEM) of 3.9 \u00b1 0.3 \u03bcM and 2.1 \u00b1 0.2 \u03bcM at the intracellular amastigote stage and 29.8 \u00b1 2.5 \u03bcM and 17.7 \u00b1 1.0 \u03bcM 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\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">L. donovani<\/jats:named-content>\n            -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.\n          <\/jats:p>","DOI":"10.1128\/aac.00812-10","type":"journal-article","created":{"date-parts":[[2011,4,5]],"date-time":"2011-04-05T03:18:51Z","timestamp":1301973531000},"page":"2916-2921","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Antimony-Resistant Clinical Isolates of Leishmania donovani Are Susceptible to Paromomycin and Sitamaquine"],"prefix":"10.1128","volume":"55","author":[{"given":"Arpita","family":"Kulshrestha","sequence":"first","affiliation":[{"name":"Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Singh","sequence":"additional","affiliation":[{"name":"Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhiraj","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narender Singh","family":"Negi","sequence":"additional","affiliation":[{"name":"Safdarjung Hospital and Vardhman Mahavir Medical College, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poonam","family":"Salotra","sequence":"additional","affiliation":[{"name":"Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2000.917307.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2007.12.006"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1748"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2004.10.004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612023396258"},{"key":"e_1_3_2_7_2","first-page":"131","article-title":"Magnitude of unresponsiveness to sodium stibogluconate in the treatment of visceral leishmaniasis in Bihar","volume":"18","author":"Das V. 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