Open AccessDecreasing fluconazole susceptibility of clinical South African Cryptococcus neoformans isolates over a decade
Author(s) -
Serisha D. Naicker,
Ruth Mpembe,
Tsidiso G. Maphanga,
Thokozile G. Zulu,
Daniel J DeSanto,
Jeannette Wadula,
Nomonde R. Mvelase,
Caroline Maluleka,
Kessendri Reddy,
Halima Dawood,
Motlatji Reratilwe Bonnie Maloba,
Nelesh P. Govender,
for Germs-Sa
Publication year - 2020
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0008137
Subject(s) - fluconazole , cryptococcus neoformans , posaconazole , itraconazole , broth microdilution , voriconazole , amphotericin b , microbiology and biotechnology , cryptococcosis , cryptococcus , minimum inhibitory concentration , cryptococcus gattii , population , biology , medicine , antifungal , antibiotics , environmental health
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 MIC 50 , MIC 90 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 MIC 50 and MIC 90 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.