Decreasing fluconazole susceptibility of clinical South African Cryptococcus neoformans isolates over a decade.

BackgroundFluconazole 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 findingsWe 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 significanceFluconazole 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

Large Outbreaks of Fungal and Bacterial Bloodstream Infections in a Neonatal Unit, South Africa, 2012–2016

Candidemia is a major cause of healthcare-associated infections. We describe a large outbreak of Candida krusei bloodstream infections among infants in Gauteng Province, South Africa, during a 4-month period; a series of candidemia and bacteremia outbreaks in the neonatal unit followed. We detected cases by using enhanced laboratory surveillance and audited hospital wards by environmental sampling and epidemiologic studies. During July–October 2014, among 589 patients, 48 unique cases of C. krusei candidemia occurred (8.2% incidence). Risk factors for candidemia on multivariable analyses were necrotizing enterocolitis, birthweight <1,500 g, receipt of parenteral nutrition, and receipt of blood transfusion. Despite initial interventions, outbreaks of bloodstream infection caused by C. krusei, rarer fungal species, and bacterial pathogens continued in the neonatal unit through July 29, 2016. Multiple factors contributed to these outbreaks; the most functional response is to fortify infection prevention and control

Epidemiologic shift in Candidemia driven by Candida auris, South Africa, 2016–2017

Candida auris is an invasive healthcare-associated fungal pathogen. Cases of candidemia, defined as illness in patients with Candida cultured from blood, were detected through national laboratory-based surveillance in South Africa during 2016–2017. We identified viable isolates by using mass spectrometry and sequencing. Among 6,669 cases (5,876 with species identification) from 269 hospitals, 794 (14%) were caused by C. auris. The incidence risk for all candidemia at 133 hospitals was 83.8 (95% CI 81.2–86.4) cases/100,000 admissions. Prior systemic antifungal drug therapy was associated with a 40% increased adjusted odds of C. auris fungemia compared with bloodstream infection caused by other Candida species (adjusted odds ratio 1.4 [95% CI 0.8–2.3]). The crude in-hospital case-fatality ratio did not differ between Candida species and was 45% for C. auris candidemia, compared with 43% for non–C. auris candidemia. C. auris has caused a major epidemiologic shift in candidemia in South Africa.http://wwwnc.cdc.gov/eidam2020School of Health Systems and Public Health (SHSPH