{"doi":"10.1371/journal.pntd.0008137","title":"Decreasing fluconazole susceptibility of clinical South African Cryptococcus neoformans isolates over a decade","abstract":"BACKGROUND: Fluconazole is used in combination with amphotericin B for induction treatment of cryptococcal meningitis and as monotherapy for consolidation and maintenance treatment. More than 90% of isolates from first episodes of cryptococcal disease had a fluconazole minimum inhibitory concentration (MIC) ≤4 μg/ml in a Gauteng population-based surveillance study of Cryptococcus neoformans in 2007-2008. We assessed whether fluconazole resistance had emerged in clinical cryptococcal isolates over a decade. METHODOLOGY AND PRINCIPAL FINDINGS: We prospectively collected C. neoformans isolates from 1 January through 31 March 2017 from persons with a first episode of culture-confirmed cryptococcal disease at 37 South African hospitals. Isolates were phenotypically confirmed to C. neoformans species-complex level. We determined fluconazole MICs (range: 0.125 μg/ml to 64 μg/ml) of 229 C. neoformans isolates using custom-made broth microdilution panels prepared, inoculated and read according to Clinical and Laboratory Standards Institute M27-A3 and M60 recommendations. These MIC values were compared to MICs of 249 isolates from earlier surveillance (2007-2008). Clinical data were collected from patients during both surveillance periods. There were more males (61% vs 39%) and more participants on combination induction antifungal treatment (92% vs 32%) in 2017 compared to 2007-2008. The fluconazole MIC50, MIC90 and geometric mean MIC was 4 μg/ml, 8 μg/ml and 4.11 μg/ml in 2017 (n = 229) compared to 1 μg/ml, 2 μg/ml and 2.08 μg/ml in 2007-2008 (n = 249) respectively. Voriconazole, itraconazole and posaconazole Etests were performed on 16 of 229 (7%) C. neoformans isolates with a fluconazole MIC value of ≥16 μg/ml; only one had MIC values of >32 μg/ml for these three antifungal agents. CONCLUSIONS AND SIGNIFICANCE: Fluconazole MIC50 and MIC90 values were two-fold higher in 2017 compared to 2007-2008. Although there are no breakpoints, higher fluconazole doses may be required to maintain efficacy of standard treatment regimens for cryptococcal meningitis.","journal":"PLoS neglected tropical diseases","year":2020,"id":95220,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":473349,"name":"Ruth Mpembe","orcid":"0000-0001-6510-7288","position":1,"is_corresponding":false},{"id":473350,"name":"Tsidiso G. Maphanga","orcid":"0000-0002-6117-4309","position":2,"is_corresponding":false},{"id":474249,"name":"Thokozile G. Zulu","orcid":null,"position":3,"is_corresponding":false},{"id":473351,"name":"Daniel DeSanto","orcid":"0000-0002-7318-0079","position":4,"is_corresponding":false},{"id":474250,"name":"Jeannette Wadula","orcid":null,"position":5,"is_corresponding":false},{"id":473352,"name":"Nomonde R. Mvelase","orcid":"0000-0002-5298-5556","position":6,"is_corresponding":false},{"id":473353,"name":"Caroline Maluleka","orcid":"0000-0003-3700-9669","position":7,"is_corresponding":false},{"id":473354,"name":"Kessendri Reddy","orcid":"0000-0002-6701-9764","position":8,"is_corresponding":false},{"id":473355,"name":"Halima Dawood","orcid":"0000-0001-8180-6791","position":9,"is_corresponding":false},{"id":473356,"name":"Motlatji Reratilwe Bonnie Maloba","orcid":"0000-0003-4566-0742","position":10,"is_corresponding":false},{"id":239834,"name":"Nelesh P. Govender","orcid":"0000-0001-7869-9462","position":11,"is_corresponding":false},{"id":474251,"name":"for GERMS-SA","orcid":null,"position":12,"is_corresponding":false},{"id":473348,"name":"Serisha D. Naicker","orcid":"0000-0002-4445-1482","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":null,"created_at":"2026-07-18T22:33:30.364261Z","pmid":"32231354","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}