Schuetz, Audrey N.

Background. Candida tropicalis is a virulent fungal pathogen for which echinocandins are the primary therapy. Emergence of resistance to echinocandins of C. tropicalis carries potentially ominous therapeutic implications. Methods. We describe herein two patients with breakthrough C. tropicalis fungemia during echinocandin therapy, characterize their molecular mechanism of resistance, and systematically review 13 previously reported cases of echinocandin-resistant C. tropicalis bloodstream infections (BSIs) and other diseases. Results. Among these 15 patients with echinocandin-resistant C. tropicalis infections, the median age was 61 years (ages 28–84 years) and 13 (86%) were immunocompromised. Thirteen (86%) of all patients had a history of pervious or concurrent exposure to echinocandins. Isolates of C. tropicalis from 11 cases, including the two index cases, underwent DNA sequencing of the FKS1 gene for mutations known to confer echinocandin resistance. The amino acid substitution Ser654Pro was shown in four cases, while other FKS1 mutations encoded Ser80S/Pro, Phe641Leu, Phe641Ser, Ser80S/Pro substitutions. These mutational events were not associated with collateral increases in minimum inhibitory concentrations to antifungal triazoles and amphotericin B. Overall mortality in patients with echinocandin-resistant C. tropicalis infections was 40%. Among those six patients who died, two received monotherapy with voriconazole, one was treated with fluconazole, one remained on caspofungin, and two were switched to liposomal amphotericin B. Nine patients (60%) survived after being treated with an antifungal agent other than an echinocandin. Conclusions. Emergence of resistance to echinocandins by C. tropicalis, occurs during antifungal therapy, is associated with high mortality, is mediated by a diverse range of FKS1 mutations, retains in vitro susceptibility to triazoles and amphotericin B, and constitutes an emerging threat to patients with hematological malignancies.

Plasmid-mediated colistin resistance (PMCR) is a global public health concern, given its ease of transmissibility. The purpose of this study was to evaluate two methods for the detection of PMCR from bacterial colonies: (i) the NG-Test MCR-1 lateral flow immunoassay (LFA; NG Biotech, Guipry, France) and (ii) the EDTA-colistin broth disk elution (EDTA-CBDE) screening test method. These methods were evaluated using a cohort of contemporary, clinical Gram-negative bacillus isolates from 3 U.S. academic medical centers (126 isolates of the Enterobacterales , 50 Pseudomonas aeruginosa isolates, and 50 Acinetobacter species isolates; 1 isolate was mcr positive) and 12 mcr -positive CDC-FDA Antibiotic Resistance (AR) Isolate Bank isolates for which reference broth microdilution colistin susceptibility results were available.

In this issue of the Journal of Clinical Microbiology , R. E. Bumgarner, D. Harrison, and J. E. Hsu (J Clin Microbiol 58:e00121-19, 2020, https://doi.org/10.1128/JCM.00121-19 ) address in a retrospective analysis that clonality of Cutibacterium acnes isolates from deep tissue specimens obtained from patients during revision shoulder arthroplasty cannot be assumed.

Despite the increasing reliance on polymyxin antibiotics (polymyxin B and colistin) for treatment of multidrug-resistant Gram-negative infections, many clinical laboratories are unable to perform susceptibility testing due to the lack of accurate and reliable methods. Although gradient agar diffusion is commonly performed for other antimicrobials, its use for polymyxins is discouraged due to poor performance characteristics.