{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T08:53:36Z","timestamp":1782982416718,"version":"3.54.5"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Cryptococcosis is one of the most serious opportunistic diseases in patients living with HIV. For this reason, early diagnosis and appropriate treatment are important. Objectives. The aim of the study was to understand the development of patients diagnosed with cryptococcosis by detection of Cryptococcus antigen in serum by lateral flow assay (CrAg LFA) without nervous system involvement and with treatment in accordance with the results. Materials and Methods. A retrospective, longitudinal, analytical study was performed. Seventy patients with cryptococcosis initially diagnosed by serum CrAg LFA without meningeal involvement between January 2019 and April 2022 were analyzed for medical records. The treatment regimen was adapted to the results of blood culture, respiratory material, and pulmonary tomography imaging. Results. Seventy patients were included, 13 had probable pulmonary cryptococcosis, 4 had proven pulmonary cryptococcosis, 3 had fungemia, and 50 had preemptive therapy without microbiological or imaging findings compatible with cryptococcosis. Among the 50 patients with preemptive therapy, none had meningeal involvement or cryptococcosis recurrences to date. Conclusion. Preemptive therapy avoided progression to meningitis in CrAg LFA-positive patients. Preemptive therapy with dose adjustment of fluconazole in patients with the mentioned characteristics was useful despite the use of lower doses than recommended.<\/jats:p>","DOI":"10.3390\/jof9060631","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T02:57:10Z","timestamp":1685501830000},"page":"631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Preemptive Therapy in Cryptococcosis Adjusted for Outcomes"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3062-7851","authenticated-orcid":false,"given":"Fernando","family":"Messina","sequence":"first","affiliation":[{"name":"Mycology Unit, Infectious Diseases Hospital F.J. Mu\u00f1iz, Buenos Aires C1282AEN, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Santiso","sequence":"additional","affiliation":[{"name":"Mycology Unit, Infectious Diseases Hospital F.J. Mu\u00f1iz, Buenos Aires C1282AEN, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4335-6552","authenticated-orcid":false,"given":"Alicia","family":"Arechavala","sequence":"additional","affiliation":[{"name":"Mycology Unit, Infectious Diseases Hospital F.J. Mu\u00f1iz, Buenos Aires C1282AEN, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Romero","sequence":"additional","affiliation":[{"name":"Mycology Unit, Infectious Diseases Hospital F.J. Mu\u00f1iz, Buenos Aires C1282AEN, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Depardo","sequence":"additional","affiliation":[{"name":"Mycology Unit, Infectious Diseases Hospital F.J. Mu\u00f1iz, Buenos Aires C1282AEN, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1925-9835","authenticated-orcid":false,"given":"Emmanuel","family":"Marin","sequence":"additional","affiliation":[{"name":"Mycology Unit, Infectious Diseases Hospital F.J. Mu\u00f1iz, Buenos Aires C1282AEN, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.idc.2021.03.001","article-title":"Recent Trends in the epidemiology of fungal infections","volume":"35","author":"Seagle","year":"2021","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Firacative, C., Meyer, W., and Casta\u00f1eda, E. (2021). Cryptococcus neoformans and Cryptococcus gattii species complexes in Latin America: A map of molecular types, genotypic diversity, and antifungal susceptibility as reported by the Latin American Cryptococcal Study Group. J. Fungi, 7.","DOI":"10.3390\/jof7040282"},{"key":"ref_3","unstructured":"World Health Organization (2011). Rapid Advice: Diagnosis, Prevention, and Management of Cryptococcal Disease in HIV-Infected Adults, Adolescents and Children, World Health Organization."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1093\/cid\/cir613","article-title":"Evaluation of a novel point-of-care cryptococcal antigen test on serum, plasma, and urine from patients with HIV-associated cryptococcal meningitis","volume":"53","author":"Jarvis","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1128\/CVI.00446-12","article-title":"Comparison of four assays for the detection of cryptococcal antigen","volume":"19","author":"Binnicker","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rick, F., Niyibizi, A.A., Shroufi, A., Onami, K., Steele, S.J., Kuleile, M., Muleya, I., Chiller, T., Walker, T., and Van Cutsem, G. (2017). Cryptococcal antigen screening by lay cadres using a rapid test at the point of care: A feasibility study in rural Lesotho. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183656"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Li, Y., Huang, X., Chen, H., Qin, Y., Hou, J., Li, A., Wu, H., Yan, X., and Chen, Y. (2020). The prevalence of cryptococcal antigen (CrAg) and benefits of pre-emptive antifungal treatment among HIV-infected persons with CD4+ T-cell counts <200 cells\/\u03bcL: Evidence based on a meta-analysis. BMC Infect. Dis., 20, Erratum in BMC Infect. Dis.2021, 21, 604.","DOI":"10.1186\/s12879-020-05126-z"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/14787210.2020.1785871","article-title":"Cryptococcal meningitis: A review of cryptococcal antigen screening programs in Africa","volume":"19","author":"Greene","year":"2021","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_9","unstructured":"WHO\u2014World Health Organization (2023, April 27). Guidelines for Diagnosing, Preventing and Managing Cryptococcal Disease among adults, Adolescents and Children Living with HIV June 2022. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240052178."},{"key":"ref_10","first-page":"25","article-title":"Alternativas terap\u00e9uticas de la criptococosis men\u00edngea","volume":"23","author":"Messina","year":"2015","journal-title":"Actual. Sida Infectolog\u00eda"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.riam.2017.04.003","article-title":"Cryptococcosis in an Infectious Diseases Hospital of Buenos Aires, Argentina. Revision of 2041 cases: Diagnosis, clinical features, and therapeutics","volume":"35","author":"Arechavala","year":"2018","journal-title":"Rev. Iberoam. Micol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1590\/S0036-46651993000200008","article-title":"Valor de los m\u00e9todos directos e indirectos de diagn\u00f3stico en las micosis sist\u00e9micas asociadas al sida","volume":"35","author":"Arechavala","year":"1993","journal-title":"Rev. Inst. Med. Trop. S\u00e3o Paulo"},{"key":"ref_13","first-page":"30","article-title":"Manual pr\u00e1ctico de Micolog\u00eda M\u00e9dica","volume":"S1","author":"Guelfand","year":"2015","journal-title":"Acta Bioquim Clin. Lat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1080\/mmy.38.1.77.80","article-title":"The usefulness of blood culture in diagnosing HIV-related systemic mycoses: Evaluation of a manual lysis centrifugation method","volume":"38","author":"Bianchi","year":"2000","journal-title":"Med. Mycol."},{"key":"ref_15","unstructured":"Negroni, R., and Arechavala, A. (2019). Lecciones de Clinica Micol\u00f3gica, Editorial Ascune. [2nd ed.]. Available online: www.editorialascune.com\/ebookdetalle\/4-lecciones-de-clinica-micologica."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3201\/eid0902.020246","article-title":"Molecular typing of Ibero American Cryptococcus neoformans isolates","volume":"9","author":"Meyer","year":"2003","journal-title":"Emerg. Infect. Dis."},{"key":"ref_17","unstructured":"CLSI (2017). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeast, Approved Standard, CLSI M27-A, Clinical and Laboratory Standards Institute. [4th ed.]."},{"key":"ref_18","unstructured":"CLSI (2022). Principles and Procedures for the Development of Epidemiological Cutoff Values for Antifungal Susceptibility Testing, Clinical and Laboratory Standards Institute. [4th ed.]. M57S."},{"key":"ref_19","unstructured":"CLSI (2022). Epidemiological Cutoff Values for Antifungal Susceptibility Testing, Clinical and Laboratory Standards Institute. [4th ed.]. M59S."},{"key":"ref_20","unstructured":"CLSI (2020). Performance Standards for Antifungal Susceptibility Testing of Yeasts, Clinical and Laboratory Standards Institute. [2nd ed.]. CLSI supplement M60."},{"key":"ref_21","unstructured":"(2020, January 12). Immy CrAg Lateral Flow Assay REF CR2003. Available online: www.immy.com."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.riam.2020.10.004","article-title":"Problemas cl\u00ednicos en Micolog\u00eda M\u00e9dica: Problema n\u00famero 55 [Clinical problems in Medical Mycology: Problema number 55]","volume":"38","author":"Romero","year":"2021","journal-title":"Rev. Iberoam. Micol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1111\/ajt.14208","article-title":"Infection in organ transplantation","volume":"17","author":"Fishman","year":"2017","journal-title":"Am. J. Transpl."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1093\/cid\/ciaa1243","article-title":"Cryptococcal antigen in serum and cerebrospinal fluid for detecting cryptococcal meningitis in adults living with HIV: Systematic review and meta-analysis of diagnostic test accuracy studies","volume":"2","author":"Temfack","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","first-page":"16","article-title":"Sensitivity and specificity of a new cryptococcal antigen lateral flow assay in serum and cerebrospinal fluid","volume":"45","author":"Vijayan","year":"2013","journal-title":"MLO Med. Lab. Obs."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1093\/cid\/cix872","article-title":"High cryptococcal antigen titers in blood are predictive of subclinical cryptococcal meningitis among human immunodeficiency virus-infected patients","volume":"66","author":"Wake","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Skipper, C., Abassi, M., and Boulware, D.R. (2019). Diagnosis, and management of central nervous system cryptococcal infections in HIV-infected adults. J. Fungi, 5.","DOI":"10.3390\/jof5030065"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1097\/QAI.0000000000001894","article-title":"Reflexive laboratory-bases cryptococcal antigen screening and preemptive fluconazole therapy for cryptococcal antigenemia in HIV-infected individuals with CD4 <100 cell\/\u00b5L: A stepped-wedge, cluster-randomized trial","volume":"80","author":"Meya","year":"2019","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Montoya, M.C., Magwene, P.M., and Perfect, J.R. (2021). Associations between Cryptococcus genotypes, phenotypes, and clinical parameters of human disease: A review. J. Fungi, 7.","DOI":"10.3390\/jof7040260"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e170554","DOI":"10.1590\/0074-02760170554","article-title":"The status of cryptococcosis in Latin America","volume":"113","author":"Firacative","year":"2018","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S331","DOI":"10.1097\/QAI.0000000000000484","article-title":"Cryptococcal antigen screening and early antifungal treatment to prevent cryptococcal meningitis: A review of the literature","volume":"68","author":"Kaplan","year":"2015","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1093\/cid\/ciz485","article-title":"Cryptococcal-related mortality despite fluconazole preemptive treatment in a cryptococcal antigen screen-and-treat program","volume":"70","author":"Wake","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1093\/cid\/civ936","article-title":"Cryptococcal Antigen Screening in Patients Initiating ART in South Africa: A Prospective Cohort Study","volume":"62","author":"Longley","year":"2016","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_34","first-page":"1","article-title":"Caracter\u00edsticascl\u00ednicas, m\u00e9todosdiagn\u00f3sticos y evoluci\u00f3n de la criptococosis extramen\u00edngea en personas viviendo con VIH","volume":"30","author":"Messina","year":"2022","journal-title":"Actual. Sida Infectolog\u00eda"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rothe, C., Sloan, D.J., Goodson, P., Chikafa, J., Mukaka, M., Denis, B., Harrison, T., van Oosterhout, J.J., Heyderman, R.S., and Lalloo, D.G. (2013). A Prospective longitudinal study of the clinical outcomes from cryptococcal meningitis following treatment induction with 800 mg oral fluconazole in Blantyre, Malawi. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067311"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1093\/cid\/ciz488","article-title":"Cryptococcal antigen screening and preemptive treatment-how can we improve survival?","volume":"70","author":"Rajasingham","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S152","DOI":"10.1093\/cid\/cix1143","article-title":"CD4 cell count threshold for cryptococcal antigen screening of HIV-infected individuals: A systematic review and meta-analysis","volume":"66","author":"Ford","year":"2018","journal-title":"Clin. Infect. Dis. Off. Public Infect. Dis. Soc. Am."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.ccm.2017.04.002","article-title":"When to consider the possibility of a fungal infection: An overview of clinical diagnosis and laboratory approaches","volume":"38","author":"Batzlaff","year":"2017","journal-title":"Clin. Chest Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1093\/cid\/ciac675","article-title":"Cryptococcal antigenemia in advanced human immunodeficiency virus disease: Pathophysiology, epidemiology, and clinical implications","volume":"76","author":"Wake","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Borges, M.A.S.B., de Ara\u00fajo Filho, J.A., Oliveira, B.D.J.S., Moreira, I.S., de Paula, V.V., de Bastos, A.L., Soares, R.D.B.A., and Turchi, M.D. (2019). Prospective cohort of AIDS patients screened for cryptococcal antigenaemia, pre-emptively treated and followed in Brazil. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0219928"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1097\/QAD.0000000000000872","article-title":"Sixmonth outcomes of HIV-infected patients given short-course fluconazole therapy for asymptomatic cryptococcal antigenemia","volume":"29","author":"Kapoor","year":"2015","journal-title":"AIDS"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.ccm.2017.04.007","article-title":"Cryptococcal lung infections","volume":"38","author":"Skolnik","year":"2017","journal-title":"Clin. Chest Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1093\/infdis\/jiy447","article-title":"Association between plasma antibody responses and risk for Cryptococcus-associated immune reconstitution inflammatory syndrome","volume":"219","author":"Yoon","year":"2019","journal-title":"J. Infect. Dis."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/6\/631\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:45:32Z","timestamp":1760125532000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/6\/631"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,30]]},"references-count":43,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["jof9060631"],"URL":"https:\/\/doi.org\/10.3390\/jof9060631","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,30]]}}}