Rapid expansion and international spread of M1UK in the post-pandemic UK upsurge of Streptococcus pyogenes.

The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1global strains, invasive M1UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks.

Whole-genome sequencing reveals widespread presence of Staphylococcus capitis NRCS-A clone in neonatal units across the United Kingdom.

OBJECTIVE: Increased incidence of neonatal Staphylococcus capitis bacteraemia in summer 2020, London, raised suspicion of widespread multidrug-resistant clone NRCS-A. We set out to investigate the molecular epidemiology of this clone in neonatal units (NNUs) across the UK. METHODS: We conducted whole-genome sequencing (WGS) on presumptive S. capitis NRCS-A isolates collected from infants admitted to nationwide NNUs and from environmental sampling in two distinct NNUs in 2021. Previously published S. capitis genomes were added for comparison. Genetic clusters of NRCS-A isolates were defined based on core-genome single-nucleotide polymorphisms. RESULTS: We analysed WGS data of 838 S. capitis isolates and identified 750 NRCS-A isolates. We discovered a possible UK-specific NRCS-A lineage consisting of 611 isolates collected between 2005 and 2021. We determined 28 genetic clusters of NRCS-A isolates, which covered all geographical regions in the UK, and isolates of 19 genetic clusters were found in ≥2 regions, suggesting inter-regional spread. Within the NRCS-A clone, strong genetic relatedness was identified between contemporary clinical and incubator-associated fomite isolates and between clinical isolates associated with inter-hospital infant transfer. CONCLUSIONS: This WGS-based study confirms the dispersion of S. capitis NRCS-A clone amongst NNUs across the UK and urges research on improving clinical management of neonatal S. capitis infection.

Is Panton-Valentine leucocidin (PVL) toxin associated with poor clinical outcomes in patients with community-acquired Staphylococcus aureus bacteraemia?

Introduction. Panton-Valentine leucocidin (PVL) toxin is a potential determinant of virulence associated with S. aureus infection.Gap Statement. The contribution of PVL to S. aureus pathogenicity remains unclear.Aim. To compare clinical outcomes in hospitalized patients with PVL-positive and PVL-negative community-acquired (CA) S. aureus bacteraemia.Methods. Three national datasets were combined to provide clinical and mortality data for patients with CA S. aureus blood culture isolates sent to the UK reference laboratory for PVL testing, August 2018 to August 2021. Multivariable logistic regression models were built for the effect of PVL positivity on 30 day all-cause mortality and 90 day readmission.Results. In 2191 cases of CA S. aureus bacteraemia, there was no association between PVL and mortality (adjusted odds ratio, aOR: 0·90, 95 % confidence interval, CI: 0·50-1·35, P=0·602) and no difference in median LOS (14 versus 15 days, P=0.169). PVL-positive cases had lower odds of readmission (aOR 0·74, CI 0·55-0.98, P=0·038). There was no evidence that MRSA status modified this effect (P=0·207).Conclusions. In patients with CA S. aureus bacteraemia PVL toxin detection was not associated with worse outcomes.

High clonal heterogeneity of Panton-Valentine leukocidin-positive meticillin-resistant Staphylococcus aureus strains from skin and soft-tissue infections in the Province of Bolzano, Northern Italy.

Panton-Valentine leukocidin (PVL)-positive community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) isolates are widespread in many countries, with varying distribution and epidemiology. The aim of this study was to characterise 10 PVL-positive MRSA isolates collected during February 2010 to January 2011 from skin and soft-tissue infections in the North Italian Province of Bolzano. Accessory gene regulator (agr) typing, staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) gene typing, multilocus sequence typing, toxin gene profiling, polymerase chain reaction for type I arginine catabolic mobile element (ACME) and antimicrobial resistance typing were applied to the isolates. Eight different CA-MRSA clones were identified, including ST30-IVc, ST772-V, ST80-IVc, ST5-IVc, ST88-IVa, ST93-IVa, ST8-IVc and the type I ACME-positive ST8-IVa. The high heterogeneity of PVL-positive MRSA probably reflects the introduction of different clones by international travellers or immigrants.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus from bacteraemia in northern Italy.

BACKGROUND: Vancomycin is frequently used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia; reduced susceptibility to vancomycin is therefore disturbing. METHODS: molecular epidemiological analysis of 81 MRSA bacteraemia isolates collected during 2002-10 in the province of Bolzano, northern Italy was performed. MICs of a range of antimicrobials were determined by agar microdilution, screening for hGISA was by Macro-Etest and Etest GRD and confirmed by PAP-AUC with vancomycin and teicoplanin. All isolates were characterised by toxin gene profiling, agr, spa, and SCCmec-typing; MLST and PFGE were carried out on representative strains. RESULTS: The dominant clones identified were ST8-MRSA-IVc (55%) and ST228- and ST111-MRSA-I (25%); most of the latter two lineages (19/20; 95%) were GISA or PAP-AUC confirmed hGISA. One ST8-MRSA-IVc isolate harboured ccrA2B2 together with ccrA4B4. The remainder were diverse genotypically and belonged to MLST clonal complexes 1, 22, 45 and 398. CONCLUSIONS: Diverse lineages of MRSA were identified as causing bacteraemia in a province in northern Italy. The association of a specific genotype with the hGISA and GISA phenotypes among representatives of the second most common lineage identified is of clinical concern.

Polyclonal multiply antibiotic-resistant methicillin-resistant Staphylococcus aureus with Panton-Valentine leucocidin in England.

OBJECTIVES: Community-associated methicillin-resistant Staphylococcus aureus (MRSA) including those encoding Panton-Valentine leucocidin (PVL) are often described as more susceptible to a range of antibiotics than their hospital-associated counterparts. Recent scattered reports of the emergence of multiresistant PVL-MRSA have highlighted the potential for resistance to emerge. Here we detail polyclonal multiply antibiotic-resistant PVL-MRSA occurring in England. METHODS: PVL-MRSA from community-based and hospitalized patients located across England were identified by PCR. Isolates were characterized via MIC determinations, toxin gene profiling, PFGE, SCCmec, spa and agr typing. Multilocus sequence typing (MLST) was performed on selected isolates. Patient demographic and available disease data were retained for analysis. RESULTS: Seventy-six PVL-MRSA isolates resistant to three further classes of antibiotic were identified between 2005 and 2008 from centres in each of the Health Protection Agency's geographic regions in England. Patient demographics were typical for PVL-MRSA, and some travel associations were identified along with clonal spread. One instance of familial transmission in the community was detected. PVL-MRSA belonging to MLST clonal complex (CC) 1 (sequence type 772) were consistently highly resistant; multiply antibiotic-resistant representatives of CCs 5, 8, 22, 59 and 80 were also identified. Ciprofloxacin resistance was common amongst the study isolates (51 of 76 isolates). CONCLUSIONS: Genetically diverse multiply antibiotic-resistant PVL-MRSA were identified, and included representatives of a recently emerged multiresistant clone (dubbed the Bengal Bay clone). Risk factors and disease presentations were typical for PVL-MRSA infections. This work highlights the diminishing utility of ciprofloxacin susceptibility for putative identification of PVL-MRSA.

Distribution of the ACME-arcA gene among methicillin-resistant Staphylococcus aureus from England and Wales.

BACKGROUND: The ST8-SCCmecIVa (USA300) methicillin-resistant Staphylococcus aureus (MRSA) clone can harbour the arginine catabolic mobile element (ACME). The arc gene cluster within the ACME may function as a virulence or strain survival factor. We determined the distribution of the ACME-associated arcA gene among genetically diverse MRSA from around England and Wales. METHODS: MRSA isolates (n = 203) of diverse genetic types, referred to the England and Wales Staphylococcus reference laboratory, were tested for the presence of the ACME-arcA gene. ACME-arcA-positive isolates were characterized by toxin gene profiling, PFGE and spa sequence typing. MICs of a range of antimicrobials were also determined. RESULTS: The ACME-arcA gene was detected in 17 isolates. Twelve were related to known ST8-MRSA-SCCmecIVa isolates of the USA300 lineage by pulsotype and were resistant to oxacillin, with variable ciprofloxacin and erythromycin resistance. Outside the USA300 lineage, four of the remaining five ACME-arcA isolates were closely related ST97-MRSA-SCCmecV, Panton-Valentine leucocidin (PVL)-negative, resistant to oxacillin and variously resistant to erythromycin, ciprofloxacin, clindamycin, gentamicin, tetracycline and fusidic acid. The remaining isolate was ST1, PVL-positive and resistant to fusidic acid as well as oxacillin. Thirteen out of the 17 isolates were associated with skin and soft tissue infections. CONCLUSIONS: The detection of ACME-arcA in diverse MRSA types highlights the mobility of the elements encoding ACME-arcA genes. The diversity of strain types and resistance profiles among ACME-arcA-encoding MRSA is a cause for public-health concern and demands continued surveillance and close monitoring.

Is Panton-Valentine leucocidin associated with the pathogenesis of Staphylococcus aureus bacteraemia in the UK?

BACKGROUND: The morbidity and mortality associated with Panton-Valentine leucocidin (PVL)-positive Staphylococcus aureus suggest that this toxin is a key marker of disease severity. Nevertheless, the importance of PVL in the pathogenesis of primary bacteraemia caused by S. aureus is uncertain. We have determined the prevalence of PVL-encoding genes among isolates of S. aureus from bacteraemic patients. METHODS: Consecutive bacteraemia isolates of S. aureus (n=244) from patients hospitalized in 25 centres in the UK and Ireland during 2005 were screened for PVL and mecA genes. PVL-positive isolates were characterized by toxin gene profiling, PFGE, spa-typing and MIC determinations for a range of antimicrobials. RESULTS: Four out of 244 isolates (1.6%) were PVL-positive and susceptible to oxacillin [methicillin-susceptible S. aureus (MSSA)]. Eighty-eight out of 244 (36%) were oxacillin-resistant (methicillin-resistant S. aureus), but none was PVL-positive. The four patients (two males: 30 and 33 years; two females: 62 and 80 years) had infection foci of: skin and soft tissue, unknown, indwelling line, and surgical site, and were located at one centre in Wales, one in England and two in Ireland. One of four PVL-positive isolates was resistant to penicillin and fusidic acid, the remainder were susceptible to all antibiotics tested. Genotypic analyses showed that the four isolates represented three distinct strains; the two isolates from Ireland were related. CONCLUSIONS: We found that 1.6% of S. aureus (all MSSA) from bacteraemic patients were PVL-positive. This low incidence suggests that PVL-positive S. aureus are of no particular significance as causative agents of S. aureus bacteraemia.

A new UK strain of epidemic methicillin-resistant Staphylococcus aureus (EMRSA-17) resistant to multiple antibiotics.

An extensive outbreak in a hospital on the south coast of England in 2000, involving a multi-resistant strain of methicillin-resistant Staphylococcus aureus (MRSA) phenotypically similar to a strain periodically seen in several hospitals in that region since 1996, prompted a study to characterize the strain and determine the extent of its spread. Sixty-nine isolates with related phage patterns obtained between 1997 and 2000 from 19 hospitals were selected for study. Of these, 55 isolates had an identical PFGE profile (designated F1), and eight shared five other PFGE profiles (designated F2-F6), which differed from that of F1 by no more than three bands and were considered related. Six isolates had PFGE profiles that differed from F1-F6 by 9-18 bands and were considered to be distinct strains. The 63 isolates of profiles F1-F6 were considered to comprise a single strain and were phenotypically identical, being urease positive and resistant to multiple antibiotics including methicillin, ciprofloxacin, erythromycin, fusidic acid, rifampicin, gentamicin, kanamycin, neomycin, streptomycin and tetracycline, with or without high- or low-level mupirocin resistance. Borderline resistance to teicoplanin was also commonly noted. All but one of these 63 isolates contained the gene sea, with five also carrying the genes seg and sei, and two carrying tst. The isolates of this strain had been referred from 13 different hospitals, seven of which were on or near the south coast, four from London, one from the Midlands and one from the north of England. The isolates were thus considered to comprise an epidemic MRSA (EMRSA) strain, which has been designated EMRSA-17. The six non-EMRSA-17 isolates identified in the study were sensitive to fusidic acid and rifampicin, and came from six geographically diverse hospitals including three in Northern Ireland.