{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T01:45:56Z","timestamp":1794015956167,"version":"4.8.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2010,10,4]],"date-time":"2010-10-04T00:00:00Z","timestamp":1286150400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>\n              <jats:italic>Cryptococcus neoformans<\/jats:italic> is commonly associated with meningoencephalitis in immunocompromised patients and occasionally in apparently healthy individuals. Recurrence of infection after initial treatment is not uncommon. We studied <jats:italic>C. neoformans<\/jats:italic> isolates from 7 Cuban patients with recurrent cryptococcal meningitis. Antifungal susceptibility and genotyping with microsatellite molecular typing were carried out.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Isolates (n = 19) were recovered from cerebrospinal fluid, blood, urine and semen. Antifungal susceptibilities for amphotericin B, fluconazole, flucytosine, itraconazole, voriconazole, posaconazole and isavuconazole were tested by CLSI M27A3 broth microdilution method. Genotyping was done using a panel of 9 microsatellite (STR) markers: (CT)n, (TG)n, (TA)n, (CTA)n, (TCT)n, (CCA)n, (TTAT)n, (ATCC)n and (TATT)n.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The average number of isolates\/patient was 2.71. The mean time interval between the collection of any two isolates was 52.5 days. All strains were identified as <jats:italic>C. neoformans<\/jats:italic> var. <jats:italic>grubii<\/jats:italic> (serotype A\u03b1). Although none of the strains were resistant to the studied drugs, in serial isolates from two patients, MICs values of triazoles increased 4-5 log<jats:sub>2<\/jats:sub> dilutions over time. STR patterns showed 14 distinctive profiles. In three patients the recurrent infection was associated with genotypically identical isolates. The four other patients had relapse isolates which were genotypically different from the initial infecting strain.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Recurrences of cryptococcal meningitis in our series of patients was not associated with development of drug resistance of the original strain but by an initial infection with different strains or a reinfection with a new strain.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2334-10-289","type":"journal-article","created":{"date-parts":[[2010,10,15]],"date-time":"2010-10-15T18:16:04Z","timestamp":1287166564000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Microsatellite typing and susceptibilities of serial Cryptococcus neoformansisolates from Cuban patients with recurrent cryptococcal meningitis"],"prefix":"10.1186","volume":"10","author":[{"given":"Mar\u00eda T","family":"Illnait-Zaragoz\u00ed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo F","family":"Mart\u00ednez-Mach\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos M","family":"Fern\u00e1ndez-Andreu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferry","family":"Hagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teun","family":"Boekhout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corn\u00e9 HW","family":"Klaassen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques F","family":"Meis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,10,4]]},"reference":[{"key":"1269_CR1","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1093\/bmb\/ldh043","volume":"72","author":"T Bicanic","year":"2005","unstructured":"Bicanic T, Harrison TS: Cryptococcal meningitis. Br Med Bull. 2005, 72: 99-118. 10.1093\/bmb\/ldh043.","journal-title":"Br Med Bull"},{"key":"1269_CR2","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1097\/QAD.0b013e328322ffac","volume":"23","author":"BJ Park","year":"2009","unstructured":"Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM: Estimation of the current global burden of cryptococcal meningitis among persons living with HIV\/AIDS. AIDS. 2009, 23: 525-30. 10.1097\/QAD.0b013e328322ffac.","journal-title":"AIDS"},{"key":"1269_CR3","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/0140-6736(93)90354-J","volume":"341","author":"ED Spitzer","year":"1993","unstructured":"Spitzer ED, Spitzer SG, Freundlich LF, Casadevall A: Persistence of initial infection in recurrent Cryptococcus neoformans meningitis. Lancet. 1993, 341: 595-596. 10.1016\/0140-6736(93)90354-J.","journal-title":"Lancet"},{"key":"1269_CR4","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1128\/AAC.37.6.1383","volume":"37","author":"A Casadevall","year":"1993","unstructured":"Casadevall A, Spitzer ED, Webb D, Rinaldi MG: Susceptibilities of serial Cryptococcus neoformans isolates from patients with recurrent cryptococcal meningitis to amphotericin B and fluconazole. Antimicrob Agents Chemother. 1993, 37: 1383-1386.","journal-title":"Antimicrob Agents Chemother"},{"key":"1269_CR5","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/S0732-8893(98)00095-9","volume":"32","author":"M Pfaller","year":"1998","unstructured":"Pfaller M, Zhang J, Messer S, Tumberland M, Mbidde E, Jessup C, Ghannoum M: Molecular epidemiology and antifungal susceptibility of Cryptococcus neoformans isolates from Ugandan AIDS patients. Diagn Microbiol Infect Dis. 1998, 32: 191-199. 10.1016\/S0732-8893(98)00095-9.","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"8","key":"1269_CR6","doi-asserted-by":"publisher","first-page":"e2870","DOI":"10.1371\/journal.pone.0002870","volume":"3","author":"F Dromer","year":"2008","unstructured":"Dromer F, Bernede-Bauduin C, Guillemot D, Lortholary O, French Cryptococcosis Study Group: Major role for amphotericin B-flucytosine combination in severe cryptococcosis. PLoS One. 2008, 3 (8): e2870-10.1371\/journal.pone.0002870.","journal-title":"PLoS One"},{"key":"1269_CR7","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1086\/649858","volume":"50","author":"JR Perfect","year":"2010","unstructured":"Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC: Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2010, 50: 291-322. 10.1086\/649858.","journal-title":"Clin Infect Dis"},{"key":"1269_CR8","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1086\/649861","volume":"50","author":"JC Nussbaum","year":"2010","unstructured":"Nussbaum JC, Jackson A, Namarika D, Phulusa J, Kenala J, Kanyemba C, Jarvis JN, Jaffar S, Hosseinipour MC, Kamwendo D, van der Horst CM, Harrison TS: Combination flucytosine and high-dose fluconazole compared with fluconazole monotherapy for the treatment of cryptococcal meningitis: a randomized trial in Malawi. Clin Infect Dis. 2010, 50: 338-344. 10.1086\/649861.","journal-title":"Clin Infect Dis"},{"key":"1269_CR9","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1111\/j.1567-1364.2006.00128.x","volume":"7","author":"AM Fusco-Almeida","year":"2007","unstructured":"Fusco-Almeida AM, Teruyuki-Matsumoto M, Baeza LC, Bellan de Oliveira R, Pizzirani-Kleiner AA, de Souza Carvalho-Melhem M, Mendes-Giannini MJS: Molecular typing and antifungal susceptibility of clinical sequential isolates of Cryptococcus neoformans from Sao Paulo State, Brazil. FEMS Yeast Res. 2007, 7: 152-164. 10.1111\/j.1567-1364.2006.00128.x.","journal-title":"FEMS Yeast Res"},{"key":"1269_CR10","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1128\/jcm.33.1.99-102.1995","volume":"33","author":"KA Haynes","year":"1995","unstructured":"Haynes KA, Sullivan DJ, Coleman DC, Clarke JC, Emilianus R, Atkinson C, Cann KJ: Involvement of multiple Cryptococcus neoformans strains in a single episode of cryptococcosis and reinfection with novel strains in recurrent infection demonstrated by random amplification of polymorphic DNA and DNA fingerprinting. J Clin Microbiol. 1995, 33: 99-102.","journal-title":"J Clin Microbiol"},{"key":"1269_CR11","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1128\/jcm.34.7.1739-1744.1996","volume":"34","author":"D Sullivan","year":"1996","unstructured":"Sullivan D, Haynes K, Moran G, Shanley D, Coleman D: Persistence, replacement, and microevolution of Cryptococcus neoformans strains in recurrent meningitis in AIDS patients. J Clin Microbiol. 1996, 34: 1739-1744.","journal-title":"J Clin Microbiol"},{"issue":"2","key":"1269_CR12","doi-asserted-by":"publisher","first-page":"e9124","DOI":"10.1371\/journal.pone.0009124","volume":"9;5","author":"MT Illnait-Zaragozi","year":"2010","unstructured":"Illnait-Zaragozi MT, Mart\u00ednez-Mach\u00edn GF, Fern\u00e1ndez-Andreu CM, Boekhout T, Meis JF, Klaassen CH: Microsatellite typing of clinical and environmental Cryptococcus neoformans var. grubii isolates from Cuba shows multiple genetic lineages. PLoS One. 2010, 9;5 (2): e9124-10.1371\/journal.pone.0009124.","journal-title":"PLoS One"},{"key":"1269_CR13","volume-title":"M27-A3. Clinical and Laboratory Standards Institute, Wayne, PA","author":"Clinical and Laboratory Standards Institute","year":"2008","unstructured":"Clinical and Laboratory Standards Institute: Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard. M27-A3. Clinical and Laboratory Standards Institute, Wayne, PA. 2008, 3","edition":"3"},{"key":"1269_CR14","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1128\/JCM.42.3.1356-1359.2004","volume":"42","author":"MT Barreto de Oliveira","year":"2004","unstructured":"Barreto de Oliveira MT, Boekhout T, Theelen B, Hagen F, Baroni FA, Lazera MS, Lengeler KB, Heitman J, Rivera IN, Paula CR: Cryptococcus neoformans shows a remarkable genotypic diversity in Brazil. J Clin Microbiol. 2004, 42: 1356-1359. 10.1128\/JCM.42.3.1356-1359.2004.","journal-title":"J Clin Microbiol"},{"key":"1269_CR15","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.diagmicrobio.2003.09.008","volume":"48","author":"MA Pfaller","year":"2004","unstructured":"Pfaller MA, Messer SA, Boyken L, Hollis RJ, Rice C, Tendolkar S, Diekema DJ: In vitro activities of voriconazole, posaconazole, and fluconazole against 4,169 clinical isolates of Candida spp. and Cryptococcus neoformans collected during 2001 and 2002 in the ARTEMIS global antifungal surveillance program. Diagn Microbiol Infect Dis. 2004, 48: 201-205. 10.1016\/j.diagmicrobio.2003.09.008.","journal-title":"Diagn Microbiol Infect Dis"},{"key":"1269_CR16","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.1128\/JCM.02434-08","volume":"47","author":"SA Messer","year":"2009","unstructured":"Messer SA, Moet GJ, Kirby J, Jones RN: Activity of contemporary antifungal agents, including the novel echinocandin anidulafungin, tested against Candida spp., Cryptococcus spp., and Aspergillus spp.: Report from the SENTRY Antimicrobial Surveillance Program (2006 to 2007). J Clin Microbiol. 2009, 47: 1942-1946. 10.1128\/JCM.02434-08.","journal-title":"J Clin Microbiol"},{"key":"1269_CR17","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1128\/AAC.01384-07","volume":"52","author":"MT Illnait-Zaragozi","year":"2008","unstructured":"Illnait-Zaragozi MT, Mart\u00ednez FG, Curfs-Breuker I, Fern\u00e1ndez CM, Boekhout T, Meis JF: In vitro activity of the new azole isavuconazole (BAL4815) compared with six other antifungal agents against 162 Cryptococcus neoformans isolates from Cuba. Antimicrob Agents Chemother. 2008, 52: 1580-1582. 10.1128\/AAC.01384-07.","journal-title":"Antimicrob Agents Chemother"},{"key":"1269_CR18","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1128\/JCM.36.10.2817-2822.1998","volume":"36","author":"M Lozano-Chiu","year":"1998","unstructured":"Lozano-Chiu M, Paetznick VL, Ghannoum MA, Rex JH: Detection of resistance to amphotericin B among Cryptococcus neoformans clinical isolates: performances of three different media assessed by using E-test and National Committee for Clinical Laboratory Standards M27-A methodologies. J Clin Microbiol. 1998, 36: 2817-2822.","journal-title":"J Clin Microbiol"},{"key":"1269_CR19","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1128\/AAC.44.6.1544-1548.2000","volume":"44","author":"AI Aller","year":"2000","unstructured":"Aller AI, Martin-Mazuelos E, Lozano F, Gomez-Mateos J, Steele-Moore L, Holloway WJ, Gutierrez MJ, Recio FJ, Espinel-Ingroff A: Correlation of fluconazole MICs with clinical outcome in cryptococcal infection. Antimicrob Agents Chemother. 2000, 44: 1544-1548. 10.1128\/AAC.44.6.1544-1548.2000.","journal-title":"Antimicrob Agents Chemother"},{"key":"1269_CR20","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1128\/AAC.43.8.1856","volume":"43","author":"P Mondon","year":"1999","unstructured":"Mondon P, Petter R, Amalfitano G, Luzzati R, Concia E, Polacheck I, Kwon-Chung KJ: Heteroresistance to fluconazole and voriconazole in Cryptococcus neoformans. Antimicrob Agents Chemother. 1999, 43: 856-861.","journal-title":"Antimicrob Agents Chemother"},{"key":"1269_CR21","doi-asserted-by":"publisher","first-page":"603","DOI":"10.2217\/17460913.3.6.603","volume":"3","author":"J Guinea","year":"2008","unstructured":"Guinea J, Bouza E: Isavuconazole: a new and promising antifungal triazole for the treatment of invasive fungal infections. Future Microbiol. 2008, 3: 603-615. 10.2217\/17460913.3.6.603.","journal-title":"Future Microbiol"},{"key":"1269_CR22","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1128\/AAC.01216-08","volume":"53","author":"GR Thompson III","year":"2009","unstructured":"Thompson GR, Wiederhold NP, Fothergill AW, Vallor AC, Wickes BL, Patterson TF: Antifungal susceptibilities among different serotypes of Cryptococcus gattii and Cryptococcus neoformans. Antimicrob Agents Chemother. 2009, 53: 309-311. 10.1128\/AAC.01216-08.","journal-title":"Antimicrob Agents Chemother"},{"key":"1269_CR23","doi-asserted-by":"publisher","first-page":"2464","DOI":"10.1128\/AAC.01520-05","volume":"50","author":"E Dannaoui","year":"2006","unstructured":"Dannaoui E, Abdul M, Arpin M, Nguyen AM, Piens MA, Favel A, Lortholary O, Dromer F: Results obtained with various antifungal susceptibility testing methods do not predict early clinical outcome in patients with cryptococcosis. Antimicrob Agents Chemother. 2006, 50: 2464-2470. 10.1128\/AAC.01520-05.","journal-title":"Antimicrob Agents Chemother"},{"key":"1269_CR24","doi-asserted-by":"publisher","first-page":"5733","DOI":"10.1128\/JCM.43.11.5733-5742.2005","volume":"43","author":"N Jain","year":"2005","unstructured":"Jain N, Wickes BL, Keller SM, Fu J, Casadevall A, Jain P, Ragan MA, Banerjee U, Fries BC: Molecular epidemiology of clinical Cryptococcus neoformans strains from India. J Clin Microbiol. 2005, 43: 5733-5742. 10.1128\/JCM.43.11.5733-5742.2005.","journal-title":"J Clin Microbiol"},{"key":"1269_CR25","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1128\/JCM.43.2.556-564.2005","volume":"43","author":"P Litvintseva A","year":"2005","unstructured":"Litvintseva A P, Kestenbaum L, Vilgalys R, Mitchell TG: Comparative analysis of environmental and clinical populations of Cryptococcus neoformans. J Clin Microbiol. 2005, 43: 556-564. 10.1128\/JCM.43.2.556-564.2005.","journal-title":"J Clin Microbiol"},{"key":"1269_CR26","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1080\/13693780310001644743","volume":"42","author":"RP Igreja","year":"2004","unstructured":"Igreja RP, Dos Santos-Lazera M, Wanke B, Gutierrez-Galhardo MC, Kidd SE, Meyer W: Molecular epidemiology of Cryptococcus neoformans isolates from AIDS patients of the Brazilian City, Rio de Janeiro. Med Mycol. 2004, 42: 229-238. 10.1080\/13693780310001644743.","journal-title":"Med Mycol"},{"key":"1269_CR27","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1086\/314521","volume":"178","author":"BC Fries","year":"1998","unstructured":"Fries BC, Casadevall A: Serial isolates of Cryptococcus neoformans from patients with AIDS differ in virulence for mice. J Infect Dis. 1998, 178: 1761-1766. 10.1086\/314521.","journal-title":"J Infect Dis"},{"key":"1269_CR28","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.1097\/00002030-200111230-00026","volume":"15","author":"G Friese","year":"2001","unstructured":"Friese G, Discher T, F\u00fcssle R, Schmalreck A, Lohmeyer J: Development of azole resistance during fluconazole maintenance therapy for AIDS-associated cryptococcal disease. AIDS. 2001, 15: 2344-2345. 10.1097\/00002030-200111230-00026.","journal-title":"AIDS"},{"key":"1269_CR29","doi-asserted-by":"crossref","unstructured":"Desnos-Ollivier M, Patel S, Spaulding AR, Charlier C, Garcia-Hermoso D, Nielsen K, Dromer F: Mixed infections and in vivo evolution in the human fungal pathogen Cryptococcus neoformans. mBio. 1 (1): pii: e00091-10","DOI":"10.1128\/mBio.00091-10"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2334-10-289.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2334-10-289\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2334-10-289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2334-10-289.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T04:00:58Z","timestamp":1630468858000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/1471-2334-10-289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10,4]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["1269"],"URL":"https:\/\/doi.org\/10.1186\/1471-2334-10-289","relation":{},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,10,4]]},"assertion":[{"value":"20 May 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"289"}}