{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:04:14Z","timestamp":1760234654021,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T00:00:00Z","timestamp":1621987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Cutaneous leishmaniasis (CL) caused by Leishmania (Leishmania) infantum is endemic in the Mediterranean basin. Here we report an autochthonous case of CL in a patient living in central Italy with an unsatisfactory response to treatment with intralesional Meglumine Antimoniate and in vitro demonstration of reduced susceptibility to SbIII. Parasitological diagnosis was first achieved by histopathology on tissue biopsy and the patient was treated with a local infiltration of Meglumine Antimoniate. Since the clinical response at 12 weeks from the treatment\u2019s onset was deemed unsatisfactory, two further skin biopsies were taken for histopathological examination, DNA extraction and parasite isolation. L. (L.) infantum was identified by molecular typing. The low susceptibility to Meglumine Antimoniate was confirmed in vitro: the promastigotes from the patient strain showed significantly lower susceptibility to SbIII (the active trivalent form of antimonial) compared to the reference strain MHOM\/TN\/80\/IPT1. The patient underwent a new treatment course with intravenous liposomal Amphotericin B, reaching complete healing of the lesion. Additional studies are needed to confirm the epidemiological and clinical relevance of reduced susceptibility to SbIII of human L. (L.) infantum isolate in Italy.<\/jats:p>","DOI":"10.3390\/microorganisms9061147","type":"journal-article","created":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T21:56:44Z","timestamp":1622066204000},"page":"1147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In Vitro Reduced Susceptibility to Pentavalent Antimonials of a Leishmania infantum Isolate from a Human Cutaneous Leishmaniasis Case in Central Italy"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5456-1821","authenticated-orcid":false,"given":"Aurora","family":"Diotallevi","sequence":"first","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino \u201cCarlo Bo\u201d, 61029 Urbino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Buffi","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino \u201cCarlo Bo\u201d, 61029 Urbino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Corbelli","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Marche Nord Hospital, 61122 Pesaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcello","family":"Ceccarelli","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino \u201cCarlo Bo\u201d, 61029 Urbino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margherita","family":"Ortalli","sequence":"additional","affiliation":[{"name":"Unit of Microbiology, IRCCS Polyclinic S.Orsola-Malpighi, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0862-4937","authenticated-orcid":false,"given":"Stefania","family":"Varani","sequence":"additional","affiliation":[{"name":"Unit of Microbiology, IRCCS Polyclinic S.Orsola-Malpighi, 40138 Bologna, Italy"},{"name":"Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6456-6626","authenticated-orcid":false,"given":"Mauro","family":"Magnani","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino \u201cCarlo Bo\u201d, 61029 Urbino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1747-526X","authenticated-orcid":false,"given":"Luca","family":"Galluzzi","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino \u201cCarlo Bo\u201d, 61029 Urbino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200407","DOI":"10.1098\/rsob.200407","article-title":"Euglenozoa: Taxonomy, diversity and ecology, symbioses and viruses","volume":"11","author":"Kostygov","year":"2021","journal-title":"Open Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S1473-3099(07)70209-8","article-title":"Cutaneous leishmaniasis","volume":"7","author":"Reithinger","year":"2007","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1128\/CMR.00104-14","article-title":"Species Typing in Dermal Leishmaniasis","volume":"28","author":"Dujardin","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Heras-Mosteiro, J., Monge-Maillo, B., Pinart, M., Lopez Pereira, P., Reveiz, L., Garcia-Carrasco, E., Campuzano Cuadrado, P., Royuela, A., Mendez Roman, I., and L\u00f3pez-V\u00e9lez, R. (2017). Interventions for Old World cutaneous leishmaniasis. Cochrane Database Syst. Rev., 2017.","DOI":"10.1002\/14651858.CD005067.pub5"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/j.1365-2915.2012.01034.x","article-title":"Phlebotomine sandflies and the spreading of leishmaniases and other diseases of public health concern","volume":"27","author":"Maroli","year":"2013","journal-title":"Med. Vet. Entomol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0304-4017(02)00115-2","article-title":"Chemotherapy of canine leishmaniosis","volume":"106","author":"Baneth","year":"2002","journal-title":"Vet. Parasitol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ponte-Sucre, A., Gamarro, F., Dujardin, J.-C.C., Barrett, M.P., L\u00f3pez-V\u00e9lez, R., Garc\u00eda-Hern\u00e1ndez, R., Pountain, A.W., Mwenechanya, R., and Papadopoulou, B. (2017). Drug resistance and treatment failure in leishmaniasis: A 21st century challenge. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0006052"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4866","DOI":"10.1128\/AAC.02521-13","article-title":"Heterogeneity of molecular resistance patterns in antimony-resistant field isolates of Leishmania species from the western mediterranean area","volume":"58","author":"Jeddi","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1111\/j.1365-3156.2008.02144.x","article-title":"Drug regimens for visceral leishmaniasis in Mediterranean countries","volume":"13","author":"Gradoni","year":"2008","journal-title":"Trop. Med. Int. Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1111\/jdv.14309","article-title":"New evidence of cutaneous leishmaniasis in north-eastern Italy","volume":"31","author":"Gaspari","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Galluzzi, L., Diotallevi, A., De Santi, M., Ceccarelli, M., Vitale, F., Brandi, G., and Magnani, M. (2016). Leishmania infantum Induces Mild Unfolded Protein Response in Infected Macrophages. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168339"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.3389\/fmicb.2018.01019","article-title":"Leishmania Infection Induces MicroRNA hsa-miR-346 in Human Cell Line-Derived Macrophages","volume":"9","author":"Diotallevi","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ceccarelli, M., Galluzzi, L., Migliazzo, A., and Magnani, M. (2014). Detection and Characterization of Leishmania (Leishmania) and Leishmania (Viannia) by SYBR Green-Based Real-Time PCR and High Resolution Melt Analysis Targeting Kinetoplast Minicircle DNA. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088845"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1186\/s13071-014-0460-3","article-title":"Application of qPCR in conjunctival swab samples for the evaluation of canine leishmaniasis in borderline cases or disease relapse and correlation with clinical parameters","volume":"7","author":"Ceccarelli","year":"2014","journal-title":"Parasit. Vectors"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ceccarelli, M., Buffi, G., Diotallevi, A., Andreoni, F., Bencardino, D., Vitale, F., Castelli, G., Bruno, F., Magnani, M., and Galluzzi, L. (2020). Evaluation of a kDNA-Based qPCR Assay for the Detection and Quantification of Old World Leishmania Species. Microorganisms, 8.","DOI":"10.3390\/microorganisms8122006"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0732-8893(03)00093-2","article-title":"PCR diagnosis and characterization of Leishmania in local and imported clinical samples","volume":"47","author":"Nasereddin","year":"2003","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_17","first-page":"406","article-title":"The neighbor-joining method: A new method for reconstructing phylogenetic trees","volume":"4","author":"Saitou","year":"1987","journal-title":"Mol. Biol. Evol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1186\/s13071-018-3143-7","article-title":"Exploiting genetic polymorphisms in metabolic enzymes for rapid screening of Leishmania infantum genotypes","volume":"11","author":"Ceccarelli","year":"2018","journal-title":"Parasit. Vectors"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1645\/13-253.1","article-title":"Evaluation of Two Modified Culture Media for Leishmania infantum Cultivation Versus Different Culture Media","volume":"100","author":"Castelli","year":"2014","journal-title":"J. Parasitol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1517\/14656566.2015.973850","article-title":"An update on pharmacotherapy for leishmaniasis","volume":"16","author":"Sundar","year":"2015","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/jtm.12089","article-title":"LeishMan recommendations for treatment of cutaneous and mucosal leishmaniasis in travelers, 2014","volume":"21","author":"Blum","year":"2014","journal-title":"J. Travel Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1007\/s00436-011-2555-5","article-title":"Leishmania antimony resistance: What we know what we can learn from the field","volume":"109","author":"Gazanion","year":"2011","journal-title":"Parasitol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3109\/10715762.2012.668186","article-title":"Leishmania strains causing self-healing cutaneous leishmaniasis have greater susceptibility towards oxidative stress","volume":"46","author":"Sarkar","year":"2012","journal-title":"Free Radic. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1080\/00034983.1992.11812717","article-title":"Decreased sensitivity to meglumine antimoniate (Glucantime) of Leishmania infantum isolated from dogs after several courses of drug treatment","volume":"86","author":"Gramiccia","year":"1992","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.exppara.2013.05.015","article-title":"In vitro drug susceptibility of Leishmania infantum isolated from humans and dogs","volume":"135","author":"Maia","year":"2013","journal-title":"Exp. Parasitol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/6\/1147\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:08:33Z","timestamp":1760162913000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/6\/1147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,26]]},"references-count":25,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["microorganisms9061147"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms9061147","relation":{},"ISSN":["2076-2607"],"issn-type":[{"type":"electronic","value":"2076-2607"}],"subject":[],"published":{"date-parts":[[2021,5,26]]}}}