Molecular characterization of Candida auris outbreak isolates in Qatar from patients with COVID-19 reveals the emergence of isolates resistant to three classes of antifungal drugs.

OBJECTIVES: During the COVID-19 pandemic in Qatar, many patients who were severely ill were colonized and infected by Candida auris, an invasive multidrug-resistant yeast pathogen that spreads through nosocomial transmission within healthcare facilities. Here, we investigated the molecular epidemiology of these C. auris isolates and the mechanisms associated with antifungal drug resistance. METHODS: Whole genomes of 76 clinical C. auris isolates, including 65 from patients with COVID-19 collected from March 2020 to June 2021, from nine major hospitals were sequenced on Illumina NextSeq. Single nucleotide polymorphisms were used to determine their epidemiological patterns and mechanisms for antifungal resistance. The data were compared with those published prior to the COVID-19 pandemic from 2018 to 2020 in Qatar. RESULTS: Genomic analysis revealed low genetic variability among the isolates from patients with and without COVID-19, confirming a clonal outbreak and ongoing dissemination of C. auris among various healthcare facilities. Based on antifungal susceptibility profiles, more than 70% (22/28) of isolates were resistant to both fluconazole and amphotericin B. Variant analysis revealed the presence of multi-antifungal resistant isolates with prominent amino acid substitutions: Y132F in ERG11 and V704L in CDR1 linked to reduced azole susceptibility and the emergence of echinocandin resistance samples bearing mutations in FKS1 in comparison with pre-COVID-19 pandemic samples. One sample (CAS109) was resistant to three classes of antifungal drugs with a unique premature stop codon in ERG3 and novel mutations in CDR2, which may be associated with elevated amphotericin B and azole resistance. DISCUSSION: Candida auris isolates from patients with COVID-19 and from most patient samples without COVID-19 in Qatar were highly clonal. The data demonstrated the emergence of multidrug-resistant strains that carry novel mutations linked to enhanced resistance to azoles, echinocandins, and amphotericin B. Understanding the epidemiology and drug resistance will inform the infection control strategy and drug therapy.

Molecular characterization of clinical carbapenem-resistant Enterobacterales from Qatar.

One hundred forty-nine carbapenem-resistant Enterobacterales from clinical samples obtained between April 2014 and November 2017 were subjected to whole genome sequencing and multi-locus sequence typing. Klebsiella pneumoniae (81, 54.4%) and Escherichia coli (38, 25.5%) were the most common species. Genes encoding metallo-ß-lactamases were detected in 68 (45.8%) isolates, and OXA-48-like enzymes in 60 (40.3%). blaNDM-1 (45; 30.2%) and blaOXA-48 (29; 19.5%) were the most frequent. KPC-encoding genes were identified in 5 (3.6%) isolates. Most common sequence types were E. coli ST410 (8; 21.1%) and ST38 (7; 18.4%), and K. pneumoniae ST147 (13; 16%) and ST231 (7; 8.6%).

Adult tuberculous meningitis in Qatar: a descriptive retrospective study from its referral center.

BACKGROUND: Tuberculous meningitis is the severest and commonest form of central nervous system tuberculosis causing high mortality and morbidity. We aim to study the clinical, biochemical, and radiological characteristics of tuberculous meningitis in adult patients in Qatar and to calculate the incidence. METHODS: A descriptive retrospective 7-year study was conducted at the Hamad General Hospital (the only tertiary referral center and sole health care provider for tuberculosis in Qatar) between the 1st of January 2006 and the 31st of December 2012, to describe the clinical presentation, diagnosis, treatment, outcome, and the incidence of adult tuberculous meningitis in Qatar. RESULTS: Tuberculous meningitis was diagnosed in 80 patients (65 male, 15 female), with a mean age of 30.3 ± 8.9. The majority of patients (76.3%) were from the Indian subcontinent. The commonest clinical features were fever (79%), headache (71%), and meningism (56%). Cerebrospinal fluid tuberculosis culture was positive in 44% of patients. Almost 39% of patients were in Stage I, 46% in Stage II and 15% in Stage III of the disease. The commonest neuroimaging features were leptomeningeal enhancement (34%) and hydrocephalus (33%). Cranial nerve palsy, limb weakness, and an elevated C-reactive protein were associated with a poorer outcome. Sixty eight percent had complete recovery, 10% had residual neurological sequelae without disability, 17% had disability, and 5% died. The average incidence of tuberculous meningitis over 7 years was 0.9 per 100,000 adult population. CONCLUSION: The characteristics of tuberculous meningitis were described in our population. Our data indicate that the incidence of tuberculosis meningitis in Qatar has increased. Tuberculous meningitis in Qatar is mainly an imported disease.