Abstract
Infections with multidrug resistant (MDR) Enterococcus faecium (Efm) are a growing problem. Vancomycin resistance in enterococci has long challenged treatment, necessitating the use of linezolid or daptomycin. Subsequently, daptomycin-, linezolid-, vancomycin-resistant Efm (DLVRE) infections have emerged. Case reports and guidelines for treating DLVRE infections are limited. Here, we describe the clinical and laboratory management of an MDR Efm protracted intraabdominal (IA) infection and breakthrough DLVRE bacteremia. Serial Efm resistance was evaluated using whole genome sequencing (WGS), susceptibility testing, and synergy analysis. Prior to in vitro synergy testing, combination antimicrobial therapy with daptomycin (DAP) and ceftaroline (CPT) was employed to treat the patient's central line-associated DLVRE bloodstream infection. In vitro antimicrobial testing revealed no synergy between daptomycin and ceftaroline; however, the patient's bacteremia cleared following initiation of both in conjunction with catheter removal. Sequencing of the DLVRE isolates revealed multiple genomic mutations which explained both linezolid and daptomycin resistance phenotypes and confirmed the presence of a plasmid containing the vanA operon. Sequential WGS of two additional bacterial isolates from the same patient revealed protracted colonization with a single DLVRE clone and suggested the development of bacterial subpopulations. Pairing clinical isolate susceptibilities with WGS and synergy testing should be encouraged in clinical practice to better inform antimicrobial management in cases of multidrug resistance.
| Original language | English (US) |
|---|---|
| Article number | e01593 |
| Journal | IDCases |
| Volume | 29 |
| DOIs | |
| State | Published - Jan 2022 |
Funding
This work was supported by grants from the National Institutes of Health ( NIH )/National Institute of General Medical Sciences ( NIGMS ) ( T32 GM008152 awarded to N.B.P), an American Cancer Society ( ACS ) Clinician Scientist Development Grant ( #134251-CSDG-20-053-01-MPC , awarded to K.E.R.B.), and a Northwestern University Emerging and Re-emerging Pathogen Program ( EREPP ) grant (awarded to K.E.R.B.). This work was also supported by the Northwestern Memorial Clinical Microbiology Laboratory and the NUSeq Core Facility which is generously supported by the NCI CCSG P30 CA060553 award to the Robert H. Lurie Comprehensive Cancer Center. This work was supported in part through the computational resources and staff contributions provided by the Genomics Compute Cluster which is jointly supported by the Feinberg School of Medicine, the Center for Genetic Medicine, Feinberg's Department of Biochemistry and Molecular Genetics , the Office of the Provost , the Office for Research, and Northwestern Information Technology . The Genomics Compute Cluster is part of Quest, Northwestern University's high-performance computing facility, with the purpose to advance research in genomics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords
- Case report
- Daptomycin-resistance
- Linezolid-resistance
- Synergy antimicrobial resistance testing
- Vancomycin-resistant Enterococcus faecium
- Whole genome sequencing
ASJC Scopus subject areas
- Infectious Diseases