Stealthy Superbug Emerges in Austria as New Vancomycin-Resistant E. faecium Clone Evades Standard Tests

A potentially landmark threat in hospital infection control has surfaced in South-Eastern Austria, where microbiologists have documented the abrupt emergence of a genetically distinct and diagnostically elusive clone of vancomycin-resistant Enterococcus faecium. The strain, assigned the sequence type ST117 and the novel complex type CT7799, was responsible for a rapid increase in invasive infections at the University Hospital of Graz and its surrounding network of more than 1,600 medical practices. What makes the clone especially alarming is not merely its virulence potential but the fact that it slips past most of the conventional laboratory tests that hospitals around the world depend upon to detect vancomycin resistance, raising the prospect that similar strains could already be circulating undetected elsewhere.

Enterococci are gram-positive bacteria that normally colonize the intestinal tracts of humans and animals, where they usually live as harmless commensals. Yet two species in particular, Enterococcus faecalis and Enterococcus faecium, are among the most important causes of opportunistic and healthcare-associated infections. Enterococcus faecium is notorious for its capacity to acquire resistance to penicillins and, increasingly, to glycopeptides such as vancomycin, an antibiotic class introduced in 1955 that kills bacteria by binding to peptidoglycan precursors and blocking cell wall synthesis. Vancomycin-resistant enterococci were first described more than two decades after the drug’s introduction, and among resistant E. faecium isolates the vanB genotype has become the most prevalent in several European countries. VanB-type resistance is known for phenotypic variability, meaning that laboratory phenotype does not always reliably reflect the underlying resistance genes, a property that has now proven consequential in a dramatic way.

The public health stakes are considerable. The World Health Organization’s 2024 Bacterial Priority Pathogens List classifies vancomycin-resistant E. faecium as a high-priority pathogen, and according to the European Centre for Disease Prevention and Control the mean vancomycin resistance rate among European E. faecium isolates stands at roughly 20 percent. Austria had long reported comparatively low figures, with the national action program on antibiotic resistance documenting a resistance rate of just 3 percent among invasive isolates in 2023. That picture changed abruptly. After years without any invasive vancomycin-resistant E. faecium infections, the diagnostic laboratory serving Graz and the wider region observed the resistance rate among E. faecium-positive blood cultures climb to 6 percent in 2024 and then to 20 percent in the first half of 2025. By June 2025, thirty-one resistant isolates had been collected, and virtually all could be attributed to a single previously unreported lineage, ST117/CT7799.

The outbreak’s first signal appeared in February 2024, when automated VITEK2 susceptibility testing flagged vancomycin resistance in a clinical E. faecium isolate even though disk diffusion, gradient testing, and broth microdilution all failed to confirm it under routine conditions. When the laboratory reorganized its workflow to route all enterococcal isolates through automated testing and systematically re-examined results, five further isolates with the same distinctive phenotype emerged within months. All came from specimens obtained for genuine infection diagnostics rather than screening, and every case was confirmed as vanB-type resistance by molecular PCR. Retrospective review of raw instrument data found no evidence of this phenotype in the laboratory’s records before 2024, strongly suggesting a genuinely new arrival. Early cases clustered around invasive procedures performed at a single hospital, and a second transmission chain later surfaced among urology patients who had undergone double-J catheterization in an operating room shared with surgeons. Notably, environmental surface sampling by the hospital infection control team failed to locate the organism, and nearly all affected patients had either been hospitalized for at least four days or had recent inpatient care history with the same provider.

To characterize the outbreak, the team subjected twenty non-duplicate isolates to whole genome sequencing using both Illumina short-read and Oxford Nanopore long-read platforms, achieving highly concordant results between technologies. Core genome multilocus sequence typing based on 1,423 loci revealed a strikingly homogeneous cluster: even isolates sampled sixteen months apart differed by no more than six alleles, far below the cluster threshold of three alleles used for assignment once the clonal relationship was established. The nearest local control strain, isolated at the same site during the same period, differed by 159 alleles, and the closest reference strain from the Robert Koch Institute collection differed by 142 alleles. Searches of the cross-national surveillance platform MiGenomeSurv showed the next closest relative still 76 alleles away, confirming that CT7799 represents an entirely novel lineage. The clone was provisionally named VREfmstyr, after Styria, the Austrian federal state where it was first isolated.

Genomic analysis also illuminated the genetic architecture of resistance. All outbreak isolates carried a complete copy of the transposon Tn1549, the mobile element responsible for vanB-mediated vancomycin resistance, inserted into the chromosome. Long-read assemblies proved essential: short-read assemblies fragmented the transposon across three contigs, obscuring its structure, whereas long reads revealed three matching blocks separated by two intervening regions of 1,494 and 1,417 base pairs containing insertion sequence elements, including an ISL3-like transposase of the ISEfa11 family and an IS3-like ISEnfa3-family transposase alongside a helix-turn-helix domain protein. An additional IS91 transposase was found inserted in a YodL domain protein upstream of the vanB gene cluster. All seven vancomycin resistance genes, vanB, vanY-B, vanW-B, vanH-B, vanX-B, vanR-B, and vanS-B, were identical across every outbreak isolate, underscoring the clone’s remarkable genetic stability despite months of circulation. Based on the classification scheme of the Norwegian VRE study group, the vanB cassette appears to be a hybrid between variants typically associated with different sequence types, hinting at a recombination event in the strain’s recent history.

The true significance of the study, however, lies in its systematic evaluation of diagnostic methods, and the results are sobering. Broth microdilution, the reference standard for antimicrobial susceptibility testing, correctly identified only 16 of 31 isolates, or 52 percent, as vancomycin resistant when read after the standard 24 hours of incubation, even though all control strains behaved as expected. Extending incubation to 48 hours eventually pushed minimum inhibitory concentrations above the susceptibility breakpoint for all isolates, but the growth around concentrations of 2 milligrams per liter and above was so sparse that even trained personnel could easily overlook it. Gradient testing from two different manufacturers failed to detect resistance in every single case at 24 hours, and disk diffusion was equally deceptive: all isolates produced inhibition zone diameters clearly wider than the 12-millimeter resistance threshold, and the zone edges lacked the fuzzy appearance that typically signals vancomycin resistance. Only VITEK2 automated testing, which correctly flagged all 31 isolates under routine settings, proved reliable, a finding that diverges from earlier studies reporting only 81 percent sensitivity for low-MIC resistant strains and possibly reflecting improvements in newer test cards and software.

Screening carried a similar message of failure. When seven representative isolates were plated on kanamycin-vancomycin agar and four commercially available chromogenic VRE screening media, three of the four commercial agars yielded no growth at all after 24 hours, and the sole medium showing some activity was only weakly positive for four isolates and negative for the remaining three. Prolonging incubation to 48 and even 72 hours improved results only marginally and inconsistently across manufacturers, while the outbreak strain failed entirely to grow on kanamycin-vancomycin agar. These findings matter because VRE often constitutes only a small fraction of the intestinal enterococcal population, making selective screening media indispensable for controlling transmission, and because prior research has already shown that sensitivity drops sharply for strains with vancomycin minimum inhibitory concentrations below 16 milligrams per liter. Only CHROMagar VRE proved dependable after standard incubation, and even that required confirming results under the study’s specific conditions.

Intriguingly, when a representative isolate was exposed to vancomycin on a gradient strip for more than 100 hours, single colonies eventually grew within the inhibition zone, and after two passages the derivative consistently displayed a minimum inhibitory concentration of at least 32 milligrams per liter. Sequencing revealed that this resistant derivative carried a single nucleotide substitution in the vanS-B gene, the sensor kinase that regulates the vancomycin resistance operon, causing an amino acid change from serine to arginine at position 243. This observation suggests that the outbreak clone’s occult phenotype stems from a regulatory mutation or arrangement that dampens resistance expression, and that vancomycin pressure can select for compensatory variants restoring full resistance. The authors caution, however, that whether the insertion elements or the specific allele differences in vanR-B, vanY-B, and vanW-B are causally responsible for the difficult-to-detect phenotype remains an open question demanding further investigation.

The implications reach well beyond Styria. Because many diagnostic laboratories worldwide rely on 24-hour disk diffusion zone readings to determine vancomycin susceptibility, a strain with this phenotype could spread through hospitals without triggering any alarm, quietly colonizing patients and contaminating environments while appearing fully susceptible on paper. The research team recommends that laboratories verify the adequacy of their screening media and incubation times, and adapt their susceptibility testing protocols by prolonging incubation, adding molecular vanB PCR testing, or employing automated VITEK2 analysis. Given the clone’s demonstrated epidemic potential, its absence from all prior surveillance databases, and the growing proportion of invasive infections it now accounts for in the region, surveillance studies will be essential to determine whether ST117/CT7799 remains a local phenomenon or whether laboratories across Europe and beyond must urgently reassess whether their diagnostic procedures can catch a superbug designed, by evolutionary accident, to stay invisible.

Subject of Research: Emergence and diagnostic challenges of a novel vancomycin-resistant Enterococcus faecium clone (ST117/CT7799) in Austria

Article Title: Emergence of a Novel, Phenotypically Difficult‐to‐Detect Vancomycin‐Resistant Enterococcus faecium Clone (ST117/CT7799)

Article References: Forstner, P., Uitz, C., Dabernig‐Heinz, J., Wagner, G. E., Bender, J., Fischer, M., Siebenhofer, D., Werner, G., Busche, T., Klages, L. J., Rückert‐Reed, C., Steinmetz, I., & Dichtl, K. (2026). Emergence of a Novel, Phenotypically Difficult‐to‐Detect Vancomycin‐Resistant Enterococcus faecium Clone (ST117/CT7799). MicrobiologyOpen, 15(5), Article e70393. https://doi.org/10.1002/mbo3.70393

Image Credits: AI Generated

DOI: 10.1002/mbo3.70393

Keywords: vancomycin-resistant Enterococcus faecium, VRE, ST117/CT7799, hospital outbreak, antimicrobial resistance, vanB operon, Tn1549 transposon, whole genome sequencing, diagnostics, Austria, infection control, cgMLST