Clinical evaluation of the antifungal effect of sertraline in the treatment of cryptococcal meningitis in HIV patients: A single Mexican center experience
Abstract
Purpose Cryptococcal meningitis is a potentially fatal fungal infection associated with a significant attributable morbidity and mortality, especially among HIV/AIDS patients. The first-line therapy for the treatment of this clinical entity is the combinatory therapy of amphotericin B plus flucytosine. However, the high cost, toxic effects, and limited repertoire of effective antifungal drugs have led to the investigation of novel molecules. This is a prospective, double-blinded, and randomized study performed in a Mexican tertiary care center to evaluate the antifungal activity of sertraline in the treatment of cryptococcal meningitis in HIV patients.Methods During June 2015-December 2016, patients were recruited and included in one of two study groups: group A was given standard antifungal treatment plus sertraline 200 mg/day, while group B was given standard antifungal plus placebo. Lumbar punctures were performed on days 0, 7, and 14 of the study, and cryptococcal antigenemia and quantitative fungal culture in cerebrospinal fluid at each time point were evaluated to measure the rate of fungal clearance.Results The fungal loads and cryptococcal antigenemia titers showed a marked tendency to decrease by day 14 in both groups. Otherwise, group B exhibited a slightly higher nonstatistical rate of fungal clearance (-0.2868 ± 0.08275 log CFU/ml/day) than group A (-0.2496 ± 0.08340 log CFU/ml/day).Conclusions A statistical difference between study groups was not found. This is the first study in Latin America that reports the experience of using sertraline as an adjuvant in the antifungal management of cryptococcal meningitis in HIV patients.
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In a Phase II study and follow-up Phase III study in HIV patients infected by cryptococcal meningitis, sertraline had no convincing results.
“Sertraline was initially demonstrated to be able to potentiate the action of azoles against cryptococcal microbes [60]; later, it was tested in a Phase II study [94] and a follow-up Phase III study in HIV patients infected by this fungus, but with no convincing results [95].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [95]
Cites
Perfect, J. R., Dismukes, W. E., Dromer, F., Goldman, D. L., Graybill, J. R., Hamill, R. J., Harrison, T. S., Larsen, R. A., Lortholary, O., Nguyen, M.-H., et al. (2010) · Clinical Infectious Diseases · doi:10.1086/649858 · Cited by 2,660 · see citing works
Park, B. J., Wannemuehler, K. A., Marston, B. J., Govender, N. P., Pappas, P. G., & Chiller, T. M. (2009) · AIDS · doi:10.1097/qad.0b013e328322ffac · Cited by 2,013 · see citing works
Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis
Rajasingham, R., Smith, R. M., Park, B. J., Jarvis, J. N., Govender, N. P., Chiller, T. M., Denning, D. W., Loyse, A., & Boulware, D. R. (2017) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(17)30243-8 · Cited by 1,861 · see citing works
Treatment of Cryptococcal Meningitis Associated with the Acquired Immunodeficiency Syndrome
van der Horst, C. M., Saag, M. S., Cloud, G. A., Hamill, R. J., Graybill, J. R., Sobel, J. D., Johnson, P. C., Tuazon, C. U., Kerkering, T. M., Moskovitz, B. L., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199707033370103 · Cited by 808 · see citing works
Maziarz, E. K., & Perfect, J. R. (2016) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2015.10.006 · Cited by 698 · see citing works
Graybill, J. R., Sobel, J. D., Saag, M. S., van der Horst, C., Powderly, W. G., Cloud, G., Riser, L., Hamill, R. J., Dismukes, W. E., & NIAID Mycoses Study Group and AIDS Cooperative Treatment Groups (2000) · Clinical Infectious Diseases · doi:10.1086/313603 · Cited by 484 · see citing works
Dismukes, W. E., Cloud, G. A., Gallis, H. A., Kerkering, T. M., Medoff, G., Craven, P. C., Kaplowitz, L. G., Fisher, J. F., Gregg, C. R., Bowles, C. A., et al. (1987) · New England Journal of Medicine · doi:10.1056/nejm198708063170602 · Cited by 416 · see citing works
Jarvis, J. N., Bicanic, T., Loyse, A., Namarika, D., Jackson, A., Nussbaum, J. C., Longley, N., Muzoora, C., Phulusa, J., Taseera, K., et al. (2014) · Clinical Infectious Diseases · doi:10.1093/cid/cit794 · Cited by 367 · see citing works
Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections.
Steinbach, W. J., Reedy, J. L., Cramer, R. A., Perfect, J. R., & Heitman, J. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1680 · Cited by 313 · see citing works
Boulware, D. R., Meya, D. B., Bergemann, T. L., Wiesner, D. L., Rhein, J., Musubire, A. K., Lee, S. J., Kambugu, A. D., Janoff, E. N., & Bohjanen, P. R. (2010) · PLoS Medicine · doi:10.1371/journal.pmed.1000384 · Cited by 280 · see citing works
Bicanic, T. A., Meintjes, G., Wood, R., Hayes, M., Rebe, K. B., Bekker, L., & Harrison, T. S. (2007) · Clinical Infectious Diseases · doi:10.1086/518607 · Cited by 271 · see citing works
Cryptococcosis diagnosis and treatment: What do we know now
Perfect, J. R., & Bicanic, T. A. (2014) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2014.10.003 · Cited by 246 · see citing works
Zhai, B., Wu, C., Wang, L., Sachs, M. S., & Lin, X. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00212-12 · Cited by 205 · see citing works
Bicanic, T. A., Brouwer, A. E., Meintjes, G., Rebe, K. B., Limmathurotsakul, D., Chierakul, W., Teparrakkul, P., Loyse, A., White, N. J., Wood, R., et al. (2009) · AIDS · doi:10.1097/qad.0b013e32832605fe · Cited by 194 · see citing works
Increased Antifungal Drug Resistance in Clinical Isolates of Cryptococcus neoformans in Uganda
Smith, K. D., Achan, B., Hullsiek, K. H., McDonald, T. R., Okagaki, L. H., Alhadab, A. A., Akampurira, A., Rhein, J., Meya, D. B., Boulware, D. R., et al. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01299-15 · Cited by 191 · see citing works
Rhein, J., Morawski, B. M., Hullsiek, K. H., Nabeta, H. W., Kiggundu, R., Tugume, L., Musubire, A., Akampurira, A., Smith, K. D., Alhadab, A., et al. (2016) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(16)00074-8 · Cited by 183 · see citing works
Antifungal Drug Discovery: Something Old and Something New
Butts, A., & Krysan, D. J. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002870 · Cited by 182 · see citing works
Taseera, K., Siedner, M. J., Klausner, J. D., Muzoora, C. K., & Boulware, D. R. (2013) · Clinical Infectious Diseases · doi:10.1093/cid/cit641 · Cited by 137 · see citing works
Cryptococcal therapies and drug targets: the old, the new and the promising
Coelho, C., & Casadevall, A. (2016) · Cellular Microbiology · doi:10.1111/cmi.12590 · Cited by 94 · see citing works
Chen, Y., Chang, T.-Y., Liu, J.-W., Chen, F., Chien, C., Lee, C., & Lu, C. (2015) · BMC Infectious Diseases · doi:10.1186/s12879-015-1023-8 · Cited by 71 · see citing works
Activity of sertraline againstCryptococcus neoformans:in vitroandin vivoassays
Treviño‐Rangel, R. D. J., Villanueva‐Lozano, H., Hernández-Rodríguez, P. A., Martínez‐Reséndez, M. F., García‐Juárez, J., Rodríguez‐Rocha, H., & González, G. M. (2015) · Medical Mycology · doi:10.1093/mmy/myv109 · Cited by 65 · see citing works
Self-citationIntegrated therapy for HIV and cryptococcosis
Srichatrapimuk, S., & D, S. S. M. (2016) · AIDS Research and Therapy · doi:10.1186/s12981-016-0126-7 · Cited by 55 · see citing works
Brouwer, A. E., Teparrukkul, P., Pinpraphaporn, S., Larsen, R. A., Chierakul, W., Peacock, S. J., Day, N., White, N. J., & Harrison, T. S. (2005) · The Journal of Infectious Diseases · doi:10.1086/432073 · Cited by 54 · see citing works
Harrison, T. S., Griffin, G. E., & Levitz, S. M. (2000) · The Journal of Infectious Diseases · doi:10.1086/315649 · Cited by 49 · see citing works
Cryptococcus gattii Infection in Healthy Hosts: A Sentinel for Subclinical Immunodeficiency?
Marr, K. A., Datta, K., Pirofski, L., & Barnes, R. A. (2011) · Clinical Infectious Diseases · doi:10.1093/cid/cir756 · Cited by 40 · see citing works
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Farha, M. A., & Brown, E. D. (2019) · Nature Microbiology · doi:10.1038/s41564-019-0357-1 · Cited by 365 · see citing works
Chang, C. C., Harrison, T. S., Bicanic, T. A., Chayakulkeeree, M., Sorrell, T. C., Warris, A., Hagen, F., Spec, A., Oladele, R. O., Govender, N. P., et al. (2024) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(23)00731-4 · Cited by 339 · see citing works
Rhein, J., Hullsiek, K. H., Tugume, L., Nuwagira, E., Mpoza, E., Evans, E. E., Kiggundu, R., Pastick, K. A., Ssebambulidde, K., Akampurira, A., et al. (2019) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(19)30127-6 · Cited by 124 · see citing works
Fungal Diseases in the 21st Century: The Near and Far Horizons
Gardiner, E. S., & Stanturf, J. A. (2018) · Pathogens and Immunity · doi:10.20411/pai.v3i2.249 · Cited by 109 · see citing works
Treatment of Cryptococcal Meningitis: How Have We Got Here and Where are We Going?
Ngan, N. T. T., Flower, B., & Day, J. (2022) · Drugs · doi:10.1007/s40265-022-01757-5 · Cited by 80 · see citing works
Treatment for HIV-associated cryptococcal meningitis
Tenforde, M. W., Shapiro, A. E., Rouse, B., Jarvis, J. N., Li, T., Eshun‐Wilson, I., & Ford, N. P. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005647.pub3 · Cited by 64 · see citing works
Screening Repurposing Libraries for Identification of Drugs with Novel Antifungal Activity
Wall, G., & Lopez-Ribot, J. L. (2020) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00924-20 · Cited by 63 · see citing works
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Henao‐Martínez, A. F., Chastain, D. B., & Franco‐Paredes, C. (2018) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0000000000000458 · Cited by 61 · see citing works
Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications
Caldara, M., & Marmiroli, N. (2021) · Pharmaceuticals · doi:10.3390/ph14090915 · Cited by 54 · see citing works
Yang, S., Yan, D., Li, M., Li, D., Zhang, S., Fan, G., Peng, L., & Pan, S. (2021) · Fungal Biology · doi:10.1016/j.funbio.2021.09.002 · Cited by 55 · see citing works
Update on Drug-Repurposing: Is it Useful for Tackling Antimicrobial Resistance?
Kaul, G., Shukla, M., Dasgupta, A., & Chopra, S. (2019) · Future Microbiology · doi:10.2217/fmb-2019-0122 · Cited by 47 · see citing works
Chang, C. C., Hall, V. G., Cooper, C. M., Grigoriadis, G., Beardsley, J., Sorrell, T. C., & Heath, C. H. (2021) · Internal Medicine Journal · doi:10.1111/imj.15590 · Cited by 43 · see citing works
Ngan, N. T. T., Nhat, L. T. H., Vi, N. N., Van, N. T. T., Hoang, N. T., Anh, D. V., Trieu, P. H., Lan, N. P. H., Phu, N. H., Châu, N. V. V., et al. (2021) · eLife · doi:10.7554/elife.68929 · Cited by 33 · see citing works
Mongia, A., Chouzenoux, É., & Majumdar, A. (2022) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2022.3189879 · Cited by 34 · see citing works
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Is Ferroptosis a Future Direction in Exploring Cryptococcal Meningitis?
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Lawrence, D. S., Leeme, T. B., Mosepele, M., Harrison, T. S., Seeley, J., & Jarvis, J. N. (2021) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0009376 · Cited by 15 · see citing works
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Helou, G. E., & Hellinger, W. C. (2019) · Transplant Infectious Disease · doi:10.1111/tid.13137 · Cited by 12 · see citing works
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- Authors
- Villanueva-Lozano, H., Treviño-Rangel, R. D. J., González, G. M., Hernández-Rodríguez, P. A., Camacho-Ortiz, A., Castillo-Reyna, L., Galindo-Alvarado, S. G., & Martínez-Reséndez, M. F.
- Affiliations
- Universidad Autónoma de Nuevo León (MX)
- ORCID
- González, Gloria M.
- Venue
- Infection
- Published
- 2017-08-16
- Volume
- 46
- Issue
- 1
- Pages
- 25-30
- ISSN
- 0300-8126 (ISSN-L)
- 1439-0973
- OpenAlex
- W2749178799
- Cited by
- 35
- References
- 25
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 5 · 2018: 4
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Infection (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universidad Autónoma de Nuevo León
- Universidad de León
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Pneumocystis jirovecii pneumonia detection and treatment
- Keywords
- sertraline, cryptococcal meningitis, HIV, antifungal activity, adjuvant therapy, cryptococcal antigenemia, amphotericin B, 5-fluorocytosine
- MeSH terms
- Adjuvants, Pharmaceutic, Adult, Aged, Antifungal Agents, Double-Blind Method, Female, Humans, Male, Mexico, Middle Aged, Prospective Studies, HIV Infections, Meningitis, Cryptococcal, AIDS-Related Opportunistic Infections, Sertraline, Young Adult, Tertiary Care Centers
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