Fatal Breakthrough Candidemia in an Immunocompromised Patient in Kuwait Due to Candida auris Exhibiting Reduced Susceptibility to Echinocandins and Carrying a Novel Mutation in Hotspot-1 of FKS1.

Candida auris is an emerging yeast pathogen that has recently caused major outbreaks in healthcare facilities worldwide. Clinical C. auris isolates are usually resistant to fluconazole and readily develop resistance to echinocandins and amphotericin B (AMB) during treatment. We describe here an interesting case of C. auris infection in an immunocompromised patient who had previously received AMB and caspofungin treatment. Subsequently, C. auris was isolated from tracheal (tracheostomy) secretions and twice from urine and all three isolates were susceptible to AMB and micafungin. The patient received a combination therapy with AMB and caspofungin. Although the C. auris was cleared from the urine, the patient subsequently developed breakthrough candidemia and the bloodstream isolate exhibited a reduced susceptibility to micafungin and also showed the presence of a novel (S639T) mutation in hotspot-1 of FKS1. Interestingly, C. auris from the tracheal (tracheostomy) secretions recovered one and four days later exhibited a reduced susceptibility to micafungin and S639Y and S639T mutations in hotspot-1 of FKS1, respectively. Although the treatment was changed to voriconazole, the patient expired. Our case highlights a novel FKS1 mutation and the problems clinicians are facing to treat invasive C. auris infections due to inherent or developing resistance to multiple antifungal drugs and limited antifungal armamentarium.

First Isolation of Candida nivariensis, an Emerging Fungal Pathogen, in Kuwait.

OBJECTIVE: C. nivariensis is a rare Candida species which is phenotypically closely related to Candida glabrata and Candida bracarensis. The 3 species form the C. glabrata sensu lato complex. Here, we describe the first isolation and characterization of a C. nivariensis isolate cultured from the tracheal aspirate obtained from a young man in Kuwait. MATERIALS AND METHODS: The yeast isolate was initially tested by VITEK 2 followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and multiplex PCR. The identification was confirmed by sequencing of internal transcribed spacer (ITS) region of rDNA. Antifungal susceptibility testing was performed by Etest, and phylogenetic comparison with other international strains was carried out by using MEGA version 7 software. RESULTS: The C. nivariensis isolate was misidentified by VITEK 2, but correctly identified by MALDI-TOF MS with updated software and multiplex PCR. The identity was confirmed by sequence comparisons of ITS region of rDNA. Antifungal susceptibility testing revealed high minimum inhibitory concentration (MIC) against fluconazole, but low MICs against amphotericin B and echinocandins. Phylogenetically, our isolate was closely related to Indian isolates. CONCLUSIONS: This report extends the geographic distribution of C. nivariensis to the Arabian Peninsula. MALDI-TOF MS with updated software and molecular tests are needed to correctly identify C. nivariensis. Since C. nivariensis may exhibit reduced susceptibility to antifungal agents, accurate identification and antifungal susceptibility testing are essential, particularly for isolates from sterile sites, for optimal patient management.

Invasive Candida auris infections in Kuwait hospitals: epidemiology, antifungal treatment and outcome.

PURPOSE: Candida auris is a recently recognized yeast pathogen, which has attracted worldwide attention due to its multidrug-resistant nature and associated high mortality rates. Its persistence in hospital environment and propensity of nosocomial transmission underscores the need of continuous monitoring to prevent outbreaks. Since the first case of C. auris candidemia in May, 2014, we have identified 17 additional invasive cases, which are described here. METHODS: Identity of 17 isolates originating from proven or possible cases of invasive C. auris infection and identified as Candida haemulonii by Vitek 2 yeast identification system was confirmed by PCR-sequencing of rDNA. Information about risk factors, treatment and outcomes were retrospectively retrieved from case files. Antifungal susceptibility testing was performed by Etest. RESULTS: Thirteen cases of candidemia and 4 cases of other invasive infections were detected in 6 hospitals across Kuwait. Major risk factors included adult patients with cancer, diabetes, gastrointestinal/liver diseases and extended (> 25 days) hospital stay. All isolates were resistant to fluconazole. Additionally, 5 and 4 isolates were also resistant to voriconazole and amphotericin B, respectively. Despite antifungal treatment, 9 of 15 patients died. Most patients (n = 12) were hospitalized in 2 hospitals that are in close proximity, whereas 5 other patients were from 3 hospitals that are situated > 10 km apart. CONCLUSIONS: Occurrence of successive cases of invasive C. auris infections with resulting mortality in nine patients suggests persistence of this multidrug-resistant yeast in major hospitals in Kuwait. Early detection by continuous surveillance and enforcement of infection control measures are recommended.