Amphotericin B plus fluorocytosine combined with voriconazole for the treatment of non-HIV and non-transplant-associated cryptococcal meningitis: a retrospective study
Open accessAbstract
Background: Our previous study explored Amphotericin B (AMB) plus 5-flucytosine (5-FC) combined with fluconazole (FLU) therapy in the induction period, which seemed to be better than the previous AMB + 5-FC antifungal therapy in non-HIV and non-transplant-associated CM. However, based on our clinical finding, the outcomes of some CM patients who received AMB plus 5-FC combined with FLU antifungal therapy were still poor. Therefore, we need to explore new antifungal methods in non-HIV and non-transplant-associated CM during the induction period. Methods: Clinical data from 148 patients admitted to the Third Affiliated Hospital of Sun Yat Sen University from January 2011 to December 2020 were collected. These patients were stratified based on antifungal treatment methods in the induction period (group I with AMB + 5-FC + VOR, group II with AMB + 5-FC + FLU, group III with AMB + 5-FC). Results: The first hospitalization time of Group I (median: 25 days, IQR: 20–34.5) was significantly shorter than that of Group II (median: 43 days, IQR: 29–62) (p < 0.001) and Group III (median: 50.5 days, IQR: 43–77.5) (p < 0.001). After 2 weeks of follow-up, Group I (26/49) had more patients reaching CSF clearance (p = 0.004) than Group II (18/71) and Group III (7/28). In multivariable analysis, Group II (OR: 3.35, 95%CI 1.43–7.82, p = 0.005) and Group III (OR: 3.8, 95%CI 1.23–11.81, p = 0.021) were associated with higher risk about CSF clearance failure at 2 weeks follow-up than Group I. After 10 weeks of follow-up, the incidence of hypokalemia in Group I was significantly lower than that in Group II (p = 0.003) and Group III (p = 0.004), and the incidence of gastrointestinal discomfort in Group I was significantly lower than that in Group II (p = 0.004). Conclusion: AMB plus 5-FC combined with VOR may rapidly improve clinical manifestation, decrease CSF OP and clear the cryptococci in CSF during the early phase, substantially shorten the hospitalization time, and reduce the incidences of hypokalemia and gastrointestinal discomfort.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Expanding scope to all failed antifungal treatments, such as adding 5-FC or amphotericin B to fluconazole monotherapy, alleviates mortality rate and achieves up to 90% efficacy.
“Expanding the scope to all failed antifungal treatments, such as adding 5-FC or amphotericin B to fluconazole monotherapy, alleviates mortality rate and achieves up to 90% efficacy [177,178,179].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [179]
The Methods (Treatment strategies) and Results compare combination regimens, and the Results report better early CSF clearance with amphotericin B, 5-FC and voriconazole. But the study does not compare either addition against fluconazole monotherapy, show reduced mortality, or report 90% treatment efficacy; the Results state that treatment response did not differ significantly among groups. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
How to develop a more accurate risk prediction model when there are few events
Pavlou, M., Ambler, G., Seaman, S. R., Guttmann, O. P., Elliot, P. M., King, M., & Omar, R. (2015) · BMJ · doi:10.1136/bmj.h3868 · Cited by 668 · see citing works
Evaluation and accurate diagnoses of pediatric diseases using artificial intelligence
Liang, H., Tsui, B., Ni, H., Valentim, C. C. S., Baxter, S. L., Liu, G., Cai, W., Kermany, D., Sun, X., Chen, J., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0335-9 · Cited by 661 · see citing works
Combination Antifungal Therapy for Cryptococcal Meningitis
Day, J., Chau, T. T., Wolbers, M., Mai, P. P., Dung, N. T., Mai, N. H., Phu, N. H., Nghia, H. D. T., Phong, N. D., Cao, Q. T., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1110404 · Cited by 542 · see citing works
Segal, B. H., Herbrecht, R., Stevens, D. A., Ostrosky‐Zeichner, L., Sobel, J. D., Viscoli, C., Walsh, T. J., Maertens, J. A., Patterson, T. F., Perfect, J. R., et al. (2008) · Clinical Infectious Diseases · doi:10.1086/590566 · Cited by 467 · see citing works
Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa
Molloy, S. F., Kanyama, C., Heyderman, R. S., Loyse, A., Kouanfack, C., Chanda, D. M., Mfinanga, S., Temfack, E., Lakhi, S., Kivuyo, S. L., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1710922 · Cited by 397 · see citing works
Determinants of Disease Presentation and Outcome during Cryptococcosis: The CryptoA/D Study
Dromer, F., Mathoulin-Pélissier, S., Launay, O., Lortholary, O., & the French Cryptococcosis Study Group (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040021 · Cited by 374 · see citing works
Singh, N., Dromer, F., Perfect, J. R., & Lortholary, O. (2008) · Clinical Infectious Diseases · doi:10.1086/592690 · Cited by 220 · 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
Cryptococcal meningitis in non-HIV-infected patients in a Chinese tertiary care hospital, 1997–2007
Zhu, L., Wu, J., Xu, B., Ou, X., Zhang, Q., & Weng, X. (2010) · Medical Mycology · doi:10.3109/13693780903437876 · Cited by 137 · see citing works
Effect of salt supplementation on amphotericin B nephrotoxicity
Llanos, A., Cieza, J. A., Bernardo, J., Echevarría, J., Biaggioni, I., Sabra, R., & Branch, R. A. (1991) · Kidney International · doi:10.1038/ki.1991.214 · Cited by 129 · see citing works
George, I. A., Spec, A., Powderly, W. G., & Santos, C. A. Q. (2017) · Clinical Infectious Diseases · doi:10.1093/cid/cix867 · Cited by 116 · see citing works
Pfaller, M. A., Zhang, J., Messer, S. A., Brandt, M. E., Hajjeh, R. A., Jessup, C. J., Tumberland, M., Mbidde, E. K., & Ghannoum, M. A. (1999) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.43.1.169 · Cited by 114 · see citing works
The search for new triazole antifungal agents
Koltin, Y., & Hitchcock, C. A. (1997) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(97)80007-5 · Cited by 110 · see citing works
Methods of Rapid Diagnosis for the Etiology of Meningitis in Adults
Bahr, N. C., & Boulware, D. R. (2014) · Biomarkers in Medicine · doi:10.2217/bmm.14.67 · Cited by 108 · see citing works
Cryptococcosis and Idiopathic CD4 Lymphocytopenia
Zonios, D. I., Falloon, J., Huang, C. Y., Chaitt, D. G., & Bennett, J. E. (2007) · Medicine · doi:10.1097/md.0b013e31803b52f5 · Cited by 97 · see citing works
Effects of Voriconazole on Cryptococcus neoformans
van Duin, D., Cleare, W., Zaragoza, Ó., Casadevall, A., & Nosanchuk, J. D. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.6.2014-2020.2004 · Cited by 79 · see citing works
Epidemiology and management of cryptococcal meningitis: developments and challenges
Pukkila-Worley, R., & Mylonakis, E. E. (2008) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.9.4.551 · Cited by 77 · see citing works
STREPTOMYCIN treatment of tuberculous meningitis.
(1948) · PubMed · Cited by 71 · see citing works
Amphotericin B Use in a Community Hospital, with Special Emphasis on Side Effects
Pathak, A. B., Pien, F. D., & de Carvalho, L. V. (1998) · Clinical Infectious Diseases · doi:10.1086/516321 · Cited by 70 · see citing works
Antinori, S., Ridolfo, A., Fasan, M., Magni, C. F., Galimberti, L., Milazzo, L., Sollima, S., Adorni, F., Giuliani, G., Galli, M., et al. (2008) · HIV Medicine · doi:10.1111/j.1468-1293.2008.00645.x · Cited by 61 · see citing works
Efficacy of voriconazole in a murine model of cryptococcal central nervous system infection
Serena, C., Pastor, F. J., Mariné, M., Rodríguez, M. M., & Guarro, J. (2007) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkm123 · Cited by 37 · see citing works
[Expert consensus on the diagnosis and treatment of cryptococcal meningitis].
Liu, Z. Y., Wang, G. Q., Zhu, L., Lyu, X., Zhang, Q. Q., Yu, Y., Zhou, Z., Liu, Y. B., Cai, W. P., Li, R. Y., et al. (2018) · PubMed · doi:10.3760/cma.j.issn.0578-1426.2018.05.003 · Cited by 36 · see citing works
Chang, H. H., Lee, N., Ko, W., Lee, H., Yang, Y.-H. K., Wu, C.-J., & Chang, C. (2009) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2009.04.012 · Cited by 25 · see citing works
Carbonara, S., Regazzi, M. B., Ciracì, E., Villani, P., Stano, F., Cusato, M. P., Heichen, M., & Monno, L. (2009) · Annals of Pharmacotherapy · doi:10.1345/aph.1l607 · Cited by 24 · see citing works
Liu, Y., Peng, X., Weng, W., Zhu, J., Cao, H., & Xie, S.-B. (2019) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2019.08.034 · Cited by 18 · see citing works
Motoa, G., Pate, A., Chastain, D. B., Mann, S., Canfield, G. S., Franco‐Paredes, C., & Henao‐Martínez, A. F. (2020) · Therapeutic Advances in Infectious Disease · doi:10.1177/2049936120940881 · Cited by 18 · see citing works
Li, Z., Liu, Y., Chong, Y., Li, X., Jie, Y., Zheng, X., & Yan, Y. (2019) · Mycoses · doi:10.1111/myc.12944 · Cited by 14 · see citing works
Voriconazole in an infant with cryptococcal meningitis
Shen, Y., Wang, J., & Lu, H. (2008) · Chinese Medical Journal · doi:10.1097/00029330-200802010-00024 · Cited by 13 · see citing works
Xu, L., Liu, J., Zhang, Q., Li, M., Liao, J., Kuang, W., Zhu, C., Yi, H., & Peng, F. (2018) · Neurological Research · doi:10.1080/01616412.2018.1447319 · Cited by 12 · see citing works
Self-citationMolloy, S. F., Ross, B., Kanyama, C., Mfinanga, S., Kivuyo, S. L., Heyderman, R. S., Kalata, N. L., Ellis, J. P., Kouanfack, C., Chanda, D. M., et al. (2021) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofab066 · Cited by 11 · see citing works
Voriconazole-induced Severe Hyperkalemia Precipitated by Multiple Drug Interactions
Choi, J. Y., Cho, S. G., Jang, K.-S., & Kim, G. (2020) · Electrolytes & Blood Pressure · doi:10.5049/ebp.2020.18.1.10 · Cited by 8 · see citing works
Chen, C., Li, H., Chen, H.-M., Chen, Y.-M., Chang, Y., Lin, P., Hsu, C., Tseng, P., Lin, K.-H., & Tu, Y. (2021) · Scientific Reports · doi:10.1038/s41598-021-87726-6 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance
Su, Y., Li, Y., Yi, Q., Xu, Y., Sun, T., & Li, Y. (2025) · Journal of Fungi · doi:10.3390/jof11020143 · Cited by 18 · see citing works
“Expanding the scope to all failed antifungal treatments, such as adding 5-FC or amphotericin B to fluconazole monotherapy, alleviates mortality rate and achieves up to 90% efficacy [177–179].”
Liu, M.-Z., Dai, X.-H., Zeng, M.-T., & Chen, E. (2024) · Journal of Neurology · doi:10.1007/s00415-024-12193-8 · Cited by 9 · see citing works
Qin, J., Nong, L., Zhu, Q., Huang, Z., Wu, F., & Li, S. (2024) · Neurology and Therapy · doi:10.1007/s40120-024-00610-z · Cited by 7 · see citing works
Kang, Y., Zhang, X., Cao, Q., Zheng, Y., Gai, W., Jia, X., Shao, B., Zhang, S., Jiang, H., Huang, X., et al. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1413964 · Cited by 5 · see citing works
Cryptococcosis in Southern China: Insights from a Six-Year Retrospective Study in Eastern Guangdong
Bilal, H., Zhang, D., Shafiq, M., Khan, M. N., Chen, C., Khan, S., Wang, Q., Cai, L., Awais, M., Hu, H., et al. (2023) · Infection and Drug Resistance · doi:10.2147/idr.s417968 · Cited by 5 · see citing works
Modeling and Simulation as a Tool to Assess Voriconazole Exposure in the Central Nervous System
Staudt, K. J., Dias, B. B., Alves, I. A., Lelièvre, B., Bouchara, J., & de Araújo, B. V. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071781 · Cited by 3 · see citing works
Liang, F., Li, R., Yao, M., Wang, J., Li, Y., Lei, L., Guo, J., & Chang, X. (2024) · Medical Mycology · doi:10.1093/mmy/myae092 · Cited by 2 · see citing works
Chippa, V. M., Chenna, S., Gujarathi, R. H., & Candula, N. (2023) · Cureus · doi:10.7759/cureus.37243 · Cited by 2 · see citing works
Tomomatsu, S., Nagai, K., Tsuruta, K., Honma, Y., Kawakami, S., Ochi, F., & Yamamoto, E. (2025) · Journal of Infection and Chemotherapy · doi:10.1016/j.jiac.2025.102876 · Cited by 1 · see citing works
Seo, T., Kim, H. K., & Shin, J.-W. (2023) · encephalitis · doi:10.47936/encephalitis.2023.00038 · Cited by 1 · see citing works
Hu, Z., & Zhou, H. (2022) · Infection and Drug Resistance · doi:10.2147/idr.s374853 · Cited by 1 · see citing works
Effects of fluconazole and amphotericin B in the control of cryptococcal pneumonia in vivo
Yu, Z., Liu, Z., Qian, J., & Qian, Y. (2025) · AMB Express · doi:10.1186/s13568-025-01827-3
Li, Y., Li, D., Liu, J., Lu, Y., Liang, J., Su, X., Li, Z., Liu, Z., Jiang, Y., & Peng, F. (2026) · Mycopathologia · doi:10.1007/s11046-025-01044-3
Self-citationLiu, J., Liu, J., Li, M., Dong, R., Li, D., Chen, J., Zeng, W. R., Li, Z., Xiaofeng, X., Jiang, Y., et al. (2026) · Medical Mycology · doi:10.1093/mmy/myag033
Self-citation
- Authors
- Liu, J., Liu, J., Su, X., Yang, L., Wang, Y., Wang, A., Xu, X., Li, M., Jiang, Y., & Peng, F.
- Affiliations
- Third Affiliated Hospital of Sun Yat-sen University (CN)
- Corresponding author
- Jiang, Ying
- Peng, Fuhua
- ORCID
- Venue
- BMC Neurology
- Published
- 2022-07-22
- Volume
- 22
- Issue
- 1
- Pages
- 274-274
- ISSN
- 1471-2377 (ISSN-L)
- PMC
- PMC9306087
- OpenAlex
- W4286461852
- Cited by
- 14
- References
- 34
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 1
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82071265)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- cryptococcal meningitis, amphotericin B, 5-fluorocytosine, voriconazole, fluconazole, CSF clearance, hypokalemia, treatment duration, risk factors for treatment failure, combination antifungal therapy, cryptococcal antigen serology, cerebrospinal fluid cytology
- MeSH terms
- Amphotericin B, Antifungal Agents, Drug Therapy, Combination, Flucytosine, Humans, Hypokalemia, Retrospective Studies, Fluconazole, Treatment Outcome, Meningitis, Cryptococcal, Voriconazole
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
