Comparative genomics and antimicrobial resistance profiling of Elizabethkingia isolates reveals nosocomial transmission and in vitro susceptibility to fluoroquinolones, tetracyclines and trimethoprim-sulfamethoxazole
Authors: Burnard Delaney , Gore Letitia , Henderson Andrew , Ranasinghe Ama , Bergh Haakon , Cottrell Kyra , Sarovich Derek S. , Price Erin P. , Paterson David L. , Harris Patrick N. A. 
Published: March 2020

The Elizabethkingia genus has gained global attention in recent years as a nosocomial pathogen. Elizabethkingia spp. are intrinsically multidrug resistant, primarily infect immunocompromised individuals, and are associated with high mortality (∼20-40%). Although Elizabethkingia infections appear sporadically worldwide, gaps remain in our understanding of transmission, global strain relatedness and patterns of antimicrobial resistance. To address these knowledge gaps, 22 clinical isolates collected in Queensland, Australia, over a 16-year period along with six hospital environmental isolates were examined using MALDI-TOF MS (VITEK® MS) and whole-genome sequencing to compare with a global strain dataset. Phylogenomic reconstruction against all publicly available genomes (n=100) robustly identified 22 E. anophelis, three E. miricola, two E. meningoseptica and one E. bruuniana from our isolates, most with previously undescribed diversity. Global relationships show Australian E. anophelis isolates are genetically related to those from the USA, England and Asia, suggesting shared ancestry. Genomic examination of clinical and environmental strains identified evidence of nosocomial transmission in patients admitted several months apart, indicating probable infection from a hospital reservoir. Furthermore, broth microdilution of the 22 clinical Elizabethkingia spp. isolates against 39 antimicrobials revealed almost ubiquitous resistance to aminoglycosides, carbapenems, cephalosporins and penicillins, but susceptibility to minocycline, levofloxacin and trimethoprim/sulfamethoxazole. Our study demonstrates important new insights into the genetic diversity, environmental persistence and transmission of Australian Elizabethkingia species. Furthermore, we show that Australian isolates are highly likely to be susceptible to minocycline, levofloxacin and trimethoprim/sulfamethoxazole, suggesting that these antimicrobials may provide effective therapy for Elizabethkingia infections.

Importance

Elizabethkingia are a genus of environmental Gram-negative, multidrug resistant, opportunistic pathogens. Although an uncommon cause of nosocomial and community-acquired infections, Elizabethkingia spp. are known to infect those with underlying co-morbidities and/or immunosuppression, with high mortality rates of ∼20-40%. Elizabethkingia have a presence in Australian hospitals and patients; however, their origin, epidemiology, and antibiotic resistance profile of these strains is poorly understood. Here, we performed phylogenomic analyses of clinical and hospital environmental Australian Elizabethkingia spp., to understand transmission and global relationships. Next, we performed extensive minimum inhibitory concentration testing to determine antimicrobial susceptibility profiles. Our findings identified a highly diverse Elizabethkingia population in Australia, with many being genetically related to international strains. A potential transmission source was identified within the hospital environment where two transplant patients were infected and three E. anophelis strains formed a clonal cluster within the phylogeny. Furthermore, near ubiquitous susceptibility to tetracyclines, fluoroquinolones and trimethoprim/sulfamethoxazole was observed in clinical isolates. We provide new insights into the origins, transmission and epidemiology of Elizabethkingia spp., in addition to understanding their intrinsic resistance profiles and potential effective treatment options, which has implications to managing infections and detecting outbreaks globally.