Vancomycin-resistant Staphylococcus aureus (VRSA) infection is a rare occurrence thought to arise from independent acquisitions of the vanA operon by methicillin-resistant S. aureus (MRSA). ^{Reference Cong, Yang and Rao1} Vancomycin resistance makes treatment of MRSA infections more difficult, hence detection and prevention of transmission ^{Reference Walters, Lonsway and Rasheed2} are critical for public health.

In May 2021, the Michigan Department of Health and Human Services (MDHHS) Bureau of Laboratories (BOL) detected a VRSA isolate [vancomycin minimum inhibitory concentration (MIC) of ≥16 µg/mL] harboring a vanA gene. This was confirmed by CDC as the 15^th VRSA case (VRSA15) in the United States and the first since 2015. Upon notification, MDHHS in collaboration with the CDC, launched an investigation including collecting clinical and healthcare exposure data, screening healthcare contacts, conducting onsite assessments of infection prevention and control (IPC) practices, and performing whole genome sequencing (WGS) of VRSA isolates. ^{Reference Walters, Lonsway and Rasheed2} A case was defined as VRSA isolated from any source from February 2021 to September 2021. The investigation focused on healthcare facilities that cared for the index case-patient during the exposure window period, February 2021 – May 2021.

VRSA15 was isolated from a heel wound of a >85-year-old resident of a skilled nursing facility (SNF) with multiple comorbid conditions, including diabetes mellitus, chronic venous insufficiency, and chronic lower extremity wounds. The case-patient developed a new heel wound in February 2021 and wound cultures yielded multiple organisms, including vancomycin-susceptible MRSA and Enterococcus faecalis. In May 2021, wound healing was not progressing, and another culture was obtained, which grew VRSA (confirmed at MDHHS BOL by broth microdilution as vancomycin MIC >128 µg/mL; daptomycin ≤ 0.5 µg/mL) and vancomycin-resistant E. faecalis (VRE). Intravenous meropenem and daptomycin were started and the wound improved after 58 days of treatment. Three sets of post-treatment surveillance cultures were collected a week apart, from nares, throat, axilla, groin, perirectal, and heel wound sites. Final VRSA-negative post-treatment surveillance cultures were collected in July 2021. No further surveillance cultures were obtained.

To assess VRSA transmission, swabs from nares, axilla/groin, and wounds (if present) from healthcare contacts with extensive and moderate interactions was recommended. ^{Reference Walters, Lonsway and Rasheed2} Contacts were defined as SNF residents or ACH patients who overlapped on the same unit(s) or received wound care from the same provider, and any healthcare personnel (HCP) that provided direct care to the case-patient.

In total, 369 contacts were identified at 3 ACHs and 2 SNFs, of which, 144 agreed to screening, including 9 contacts at ACHs (2 patients and 7 HCP) and 135 contacts at SNFs (65 residents and 70 HCP). Overall, 138 nares, 91 axilla/groin, and 10 wound culture screens were collected by MDHHS staff (SNFs) or facility staff (ACHs), and tested by the MDHHS BOL. All screens were negative for VRSA, however 23 individuals at SNFs were positive for MRSA (19 residents and 4 HCP) all with vancomycin MIC ≤ 1 µg/mL

All facilities were provided recommendations on identifying VRSA and preventing transmission. An onsite IPC assessment was conducted at the SNF where the case-patient resided at the time of VRSA infection., which identified several gaps, including missed opportunities for hand hygiene and personal protective equipment (PPE) use, appropriate PPE use during supply shortages, ³ and effective disinfection of medical equipment between residents. Findings and recommendations were communicated back to the SNF and additional PPE was supplied.

VRSA15 demonstrated resistance to oxacillin, cefoxitin, clindamycin, erythromycin, levofloxacin, and vancomycin (MIC 1024 µg/mL), but remained susceptible to trimethoprim-sulfamethoxazole, daptomycin, linezolid, and ceftaroline. WGS confirmed the presence of mecA and vanA genes. The vanA operon was encoded on the enterococcal transposon Tn1546. ^{Reference Kos, Desjardins and Griggs4} Similar to previous U.S. VRSA isolates, including those from Michigan, VRSA15 was sequence type 5 (ST5), belonging to clonal complex 5, but was genetically distinct by whole genome multilocus sequence typing (wgMLST) (Figure 1). The isolate clustered with VRSA previously classified as pulsed-field gel electrophoresis type USA100, which are associated with healthcare infections. ^{Reference Klevens, Morrison and Nadle5}

Figure 1.

Whole genome multi-locus sequence typing of U.S. Clonal Complex 5 VRSA Isolates. Unweighted pair group method with arithmetic mean dendrogram showing the relationship of VRSA15 and VRSA 1–11 genomes that were previously sequenced ^{Reference Walters, Lonsway and Rasheed2} ; sequences for VRSA 12–14 were not available. The date of isolation (year), pulsed-field gel electrophoresis (PFGE) type, and geographic location of each VRSA isolate is indicated.

This investigation of the 15^th U.S. case of VRSA identified no evidence of onward transmission. Rapid laboratory identification, communication to public health authorities for investigation enabled implementation of Transmission Based Precautions (TBP), assessment of IPC practices, and contact screening, which may have helped prevent spread.

However, Michigan remains at risk for future VRSA cases. Notably, 8 of the prior 14 VRSA cases also occurred in Michigan. Similar to previous VRSA cases, ⁶ the affected patient had a history of chronic wounds, multiple underlying medical conditions, and healthcare exposures. These factors, along with microbiological characteristics of circulating VRE strains with Tn1546 carrying Inc18-like conjugative plasmids which may act as vanA donors to receptive clonal complex 5 S. aureus strains, ^{Reference Kos, Desjardins and Griggs4,Reference Zhu, Clark, McDougal, Hageman, McDonald and Patel7} has likely contributed to the emergence of VRSA strains and the high proportion of U.S. VRSA cases that have occurred in Michigan. ^{Reference Sievert, Rudrik, Patel, McDonald, Wilkins and Hageman8} WGS analysis of VRSA15 demonstrated that, while grouped with other USA100 VRSA isolates, the wgMLST profile was distinct from those of previous VRSA from Michigan, suggesting de novo acquisition of vanA from a co-infecting VRE strain, which is also believed to have occurred in the past, ^{Reference Kos, Desjardins and Griggs4} and not expansion of a previous VRSA strain.

Although transmission of VRSA has not yet been documented, ^{Reference Kos, Desjardins and Griggs4} identification of potential VRSA isolates ⁶ is critical for timely initiation of IPC measures and public health response. Clinical laboratories should remain vigilant to identify suspected VRSA isolates, and healthcare facilities should take steps to ensure adherence to recommended IPC practices and communication of multidrug-resistant organism status to limit the opportunities for spread.