{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:20:21Z","timestamp":1791933621010,"version":"4.3.4"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T00:00:00Z","timestamp":1640649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Management of cryptococcal infections among patients suffering from acquired immunodeficiency syndrome (AIDS) represents a medical challenge. This retrospective study aims to describe the disease management and outcomes among 24 AIDS patients who suffered from Cryptococcus neoformans meningitis. The parameters evaluated from our patients\u2019 database records include epidemiological data, clinical manifestations, biochemical and microbiological analysis of patients\u2019 cerebrospinal fluid (CSF), treatment profiles, and disease outcomes. All patients included in the study had a lymphocyte count of less than 200 CD4\/mm3. Of the 24 patients included in this study, five had been diagnosed with HIV infection since childhood, after receiving HIV-infected blood transfusions. The most prominent symptom was fatigue in 62.5% of patients, followed by nausea\/vomiting and headache. Seven patients had liver cirrhosis due to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, while Kaposi sarcoma and cerebral toxoplasmosis were found in two patients. Six out of 24 patients died due to bacterial sepsis and acute respiratory distress syndrome (ARDS). High intracranial pressure was the strongest predictive factor for mortality (OR = 2.9), followed by ARDS (OR = 1.8), seizures at disease onset (OR = 1.4), and diabetes mellitus (OR = 1.2). Interestingly, patients younger than 40 years old had a significantly lower survival rate than that of the older patients. Before developing Cryptococcal meningitis, all patients had low adherence to the early ART treatment scheme and skipped the follow-up visits. All patients received a combination of amphotericin B and flucytosine as induction therapy, adding fluconazole for maintenance. Simultaneously, AIDS HAART was initiated at diagnosis of the cryptococcal infection. A combined regimen of antifungals and highly active antiretroviral therapy showed improved patient recovery with minor side effects.<\/jats:p>","DOI":"10.3390\/diagnostics12010054","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T01:18:15Z","timestamp":1640654295000},"page":"54","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical Profile of 24 AIDS Patients with Cryptococcal Meningitis in the HAART Era: A Report from an Infectious Diseases Tertiary Hospital in Western Romania"],"prefix":"10.3390","volume":"12","author":[{"given":"Iosif","family":"Marincu","sequence":"first","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosmin","family":"Citu","sequence":"additional","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iulia","family":"Vidican","sequence":"additional","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4711-4315","authenticated-orcid":false,"given":"Felix","family":"Bratosin","sequence":"additional","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3103-4954","authenticated-orcid":false,"given":"Mihai","family":"Mares","sequence":"additional","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Suciu","sequence":"additional","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7469-6755","authenticated-orcid":false,"given":"Stefan","family":"Frent","sequence":"additional","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0287-5938","authenticated-orcid":false,"given":"Adrian Vasile","family":"Bota","sequence":"additional","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalina","family":"Timircan","sequence":"additional","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania Lavinia","family":"Bratu","sequence":"additional","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Department of Psychology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirela Loredana","family":"Grigoras","sequence":"additional","affiliation":[{"name":"Methodological and Infectious Diseases Research Center, Department of Infectious Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Spadari, C.d.C., Wirth, F., Lopes, L.B., and Ishida, K. (2020). New approaches for cryptococcosis treatment. Microorganisms, 8.","DOI":"10.3390\/microorganisms8040613"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1097\/QAD.0b013e328322ffac","article-title":"Estimation of the current global burden of cryptococcal meningitis among persons living with HIV\/AIDS","volume":"23","author":"Park","year":"2009","journal-title":"AIDS"},{"key":"ref_3","unstructured":"Situational Analysis (2021, March 14). World AIDS Day. Available online: https:\/\/www.dsptimis.ro\/promovare\/zml_hiv_19_analiza.pdf2018."},{"key":"ref_4","unstructured":"Comisia Na\u021bional\u0103 de Lupt\u0103 Anti-SIDA\u2013Date Statistice (2021, March 14). Evolu\u021bia Infec\u021biei HIV\/SIDA \u00een Rom\u00e2nia. Available online: http:\/\/cnlas.ro\/images\/doc\/31122017_rom.pdf2017."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1097\/QAD.0b013e32832605fe","article-title":"Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures","volume":"23","author":"Bicanic","year":"2009","journal-title":"AIDS"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1093\/bmb\/ldh043","article-title":"Cryptococcal meningitis","volume":"72","author":"Bicanic","year":"2004","journal-title":"Br. Med. Bull."},{"key":"ref_8","unstructured":"CDC (2021, May 19). Preventing Deaths from Cryptococcal Meningitis, Available online: https:\/\/www.cdc.gov\/fungal\/cdc-and-fungal\/cryptococcal-meningitis.html."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","unstructured":"Momin, M., and Webb, G. (2021). The environmental effects on virulence factors and the antifungal susceptibility of Cryptococcus neoformans. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126302"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0966-842X(01)02035-2","article-title":"Intracellular parasitism of macrophages by Cryptococcus neoformans","volume":"9","author":"Feldmesser","year":"2001","journal-title":"Trends Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Alanio, A., Desnos-Ollivier, M., and Dromer, F. (2011). Dynamics of Cryptococcus neoformans\u2014Macrophage interactions reveal that fungal background influences outcome during Cryptococcal Meningoencephalitis in humans. mBio, 2.","DOI":"10.1128\/mBio.00158-11"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1128\/JCM.38.5.1974-1976.2000","article-title":"Prevalence of Cryptococcus neoformans var. neoformans (Serotype D) and Cryptococcus neoformans var. grubii (Serotype A) Isolates in New York City","volume":"38","author":"Steenbergen","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s40475-015-0046-y","article-title":"Cryptococcal Meningitis: Diagnosis and Management Update","volume":"2","author":"Abassi","year":"2015","journal-title":"Curr. Trop. Med. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"198","DOI":"10.18683\/germs.2019.1178","article-title":"Consensus statement on the assessment of comorbidities in people living with HIV in Romania","volume":"9","author":"Mircescu","year":"2019","journal-title":"Germs"},{"key":"ref_16","unstructured":"Comisia Na\u021bional\u0103 de Lupt\u0103 Anti-SIDA\u2013Date Statistice (2021, May 19). Evolu\u021bia Infec\u021biei HIV\/SIDA \u00een Rom\u00e2nia. Available online: https:\/\/www.cnlas.ro\/images\/doc\/31122020_rom.pdf."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Guess, T.E., Rosen, J.A., and McClelland, E.E. (2018). An overview of sex bias in C. neoformans infections. J. Fungi, 4.","DOI":"10.3390\/jof4020049"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/S0255-0857(21)02175-7","article-title":"Prevalence of central nervous system cryptococcosis in human immunodeficiency virus reactive hospitalized patients","volume":"25","author":"Lakshmi","year":"2007","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"444","DOI":"10.4103\/0028-3886.44823","article-title":"Cryptococcal meningitis in HIV infected: Experience from a North Indian tertiary center","volume":"56","author":"Kumar","year":"2008","journal-title":"Neurol. India"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Brizendine, K.D., Baddley, J.W., and Pappas, P.G. (2013). Predictors of mortality and differences in clinical features among patients with Cryptococcosis according to immune status. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060431"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"O\u2019Kelly, B., Mohamed, A., Bergin, C., Lyons, F., Rogers, T.R., O\u2019Connell, B., and Devitt, E. (2021). Successful treatment of Cryptococcal Meningitis and Cryptococcoma with Isavuconazole in a patient living with HIV. J. Fungi, 7.","DOI":"10.3390\/jof7060425"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Manosuthi, W., Athichathanabadi, C., Uttayamakul, S., Phoorisri, T., and Sungkanuparph, S. (2007). Plasma nevirapine levels, adverse events and efficacy of antiretroviral therapy among HIV-infected patients concurrently receiving nevirapine-based antiretroviral therapy and fluconazole. BMC Infect. Dis., 7.","DOI":"10.1186\/1471-2334-7-14"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7197","DOI":"10.1128\/AAC.01299-15","article-title":"Increased antifungal drug resistance in clinical isolates of Cryptococcus neoformans in Uganda","volume":"59","author":"Smith","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1093\/cid\/cix036","article-title":"Primary Prophylaxis for Cryptococcosis with fluconazole in human immunodeficiency virus\u2013infected patients with CD4 T-cell counts < 100 cells\/microL and receiving antiretroviral therapy","volume":"64","author":"Sungkanuparph","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Huang, L., Ye, H., Qu, J., Liu, Y., Zhong, C., Tang, G., Liu, Y., Huang, Y., and Lv, X. (2015). Analysis of cerebrospinal fluid protein concentrations of patients with cryptococcal meningitis treated with antifungal agents. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-1063-0"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rajasingham, R., Meya, D.B., Greene, G.S., Jordan, A., Nakawuka, M., Chiller, T.M., Boulware, D.R., and Larson, B.A. (2019). Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0210105"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1086\/649858","article-title":"Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of America","volume":"50","author":"Perfect","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1086\/313603","article-title":"Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis","volume":"30","author":"Graybill","year":"2000","journal-title":"Clin. Infect. 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