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BACKGROUND: The emerging fungal pathogen Candida auris poses a serious threat to global public health due to its worldwide distribution, multidrug resistance, high transmissibility, propensity to cause outbreaks, and high mortality. We aimed to characterise three unusual C auris isolates detected in Singapore, and to determine whether they constitute a novel clade distinct from all previously known C auris clades (I-V). METHODS: In this genotypic and phenotypic study, we characterised three C auris clinical isolates, which were cultured from epidemiologically unlinked inpatients at a large tertiary hospital in Singapore. The index isolate was detected in April, 2023. We performed whole-genome sequencing (WGS) and obtained hybrid assemblies of these C auris isolates. The complete genomes were compared with representative genomes of all known C auris clades. To provide a global context, 3651 international WGS data from the National Center for Biotechnology Information (NCBI) database were included in a high-resolution single nucleotide polymorphism (SNP) analysis. Antifungal susceptibility testing was done and antifungal resistance genes, mating-type locus, and chromosomal rearrangements were characterised from the WGS data of the three investigated isolates. We further implemented Bayesian logistic regression models to classify isolates into known clades and simulate the automatic detection of isolates belonging to novel clades as their WGS data became available. FINDINGS: The three investigated isolates were separated by at least 37 000 SNPs (range 37 000-236 900) from all existing C auris clades. These isolates had opposite mating-type allele and different chromosomal rearrangements when compared with their closest clade IV relatives. The isolates were susceptible to all tested antifungals. Therefore, we propose that these isolates represent a new clade of C auris, clade VI. Furthermore, an independent WGS dataset from Bangladesh, accessed via the NCBI Sequence Read Archive, was found to belong to this new clade. As a proof-of-concept, our Bayesian logistic regression model was able to flag these outlier genomes as a potential new clade. INTERPRETATION: The discovery of a new C auris clade in Singapore and Bangladesh in the Indomalayan zone, showing a close relationship to clade IV members most commonly found in South America, highlights the unknown genetic diversity and origin of C auris, particularly in under-resourced regions. Active surveillance in clinical settings, along with effective sequencing strategies and downstream analysis, will be essential in the identification of novel strains, tracking of transmission, and containment of adverse clinical effects of C auris infections. FUNDING: Duke-NUS Academic Medical Center Nurturing Clinician Researcher Scheme, and the Genedant-GIS Innovation Program.
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We report a case of intractable Aspergillus otomycosis with multiple relapses despite conventional topical and systemic antifungal treatment, and adjunctive usage of hyperbaric oxygen therapy. Of note, otomycosis relapsed even after six months of continuous systemic antifungal treatment with therapeutic drug levels and without treatment interruption; and only resolved after application of topical voriconazole. (max. 75 words).
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BACKGROUND: Cefiderocol is a recently licensed novel siderophore-conjugated cephalosporin stable to hydrolysis by serine and MBLs. It has been successfully used to treat Enterobacterales infections and is approved for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options. OBJECTIVES: To describe the compassionate use of cefiderocol and clinical outcome in a case of prosthetic joint infection due to MDR Acinetobacter baumannii. PATIENTS AND METHODS: This case study follows a 66-year-old woman who sustained an open fracture of the left distal humerus in Pakistan. She underwent open reduction and internal fixation and on return to the UK presented to hospital with a discharging surgical wound. RESULTS: Debridement of her wound cultured NDM carbapenemase-producing A. baumannii susceptible to colistin, tobramycin and tigecycline only. She developed vomiting with acute kidney injury with colistin and tigecycline. Antimicrobial efficacy of cefiderocol was predicted from in vitro and in vivo susceptibility tests. A successful request was made to Shionogi for compassionate use of cefiderocol, which was added to tigecycline. Cefiderocol was well tolerated with no toxicity and improved renal function. In total she received 25 days of cefiderocol and continued on tigecycline for a further 6 weeks in the community. She has well-healed wounds and good range of elbow movement. CONCLUSIONS: Cefiderocol's novel mode of cell entry is effective against MDR Gram-negative bacteria with reduced toxicity compared with other last line antibiotics. Our case demonstrates that cefiderocol may be useful as therapy for patients with limited treatment options due to antimicrobial resistance.