Systematic Surveillance Detects Multiple Silent Introductions and Household Transmission of Methicillin-Resistant Staphylococcus aureus USA300 in the East of England

Abstract

Background: The spread of USA300 methicillin-resistant Staphylococcus aureus (MRSA) across the United States resulted in an epidemic of infections. In Europe, only sporadic cases or small clusters of USA300 infections are described, and its prevalence in England is unknown. We conducted prospective surveillance for USA300 in the east of England.

Methods: We undertook a 12-month prospective observational cohort study of all individuals with MRSA isolated from community and hospital samples submitted to a microbiology laboratory. At least 1 MRSA isolate from each individual underwent whole-genome sequencing. USA300 was identified on the basis of sequence analysis, and phylogenetic comparisons were made between these and USA300 genomes from the United States.

Results: Between April 2012 and April 2013, we sequenced 2283 MRSA isolates (detected during carriage screening and in clinical samples) from 1465 individuals. USA300 was isolated from 24 cases (1.6%). Ten cases (42%) had skin and soft tissue infection, and 2 cases had invasive disease. Phylogenetic analyses identified multiple introductions and household transmission of USA300.

Conclusions: Use of a diagnostic laboratory as a sentinel for surveillance has identified repeated introductions of USA300 in eastern England in 2012-2013, with evidence for limited transmission. Our results show how systematic surveillance could provide an early warning of strain emergence and dissemination.

Keywords: MRSA; Staphylococcus aureus; USA300; molecular epidemiology; whole-genome sequencing.

Figure 1.

A, Phylogenetic, midpoint-rooted tree of study CC8 isolates, with USA300 isolates highlighted. A total of 56 isolates residing in the subclade within the gray box were phylogenetically identified as USA300 isolates. B, Detailed USA300 phylogenetic tree rooted on the isolate from P01, with a summary of metadata for each isolate. Person (P) numbers represent the study identifier of each individual from whom the sample was from, with gray boxes indicating pairs or clusters with presumptive epidemiological links. ±Red, resistant; yellow, intermediate; blue, susceptible. *Ciprofloxacin: red, S80Y and S84L; blue, S80F only; white, none identified; gray, not done. Staphylococcal cassette chromosome mec (SCCmec) IVa, Panton-Valentine leukocidin (PVL), arginine catabolic mobile element (ACME), staphylococcal pathogenicity island 5 (SAPI5): red, present; black, absent. ^Red, 4 mutations associated with the CAP5 locus were identified. Abbreviation: SNP, single-nucleotide polymorphism.

Figure 2.

Comparison of the first USA300 isolate from each study case (n = 24, circles) relative to previously published USA300 isolates from the United States (n = 348) [6]. Mid-point rooted maximum likelihood tree based on single-nucleotide polymorphisms (SNPs) in the core genome of methicillin-resistant Staphylococcus aureus with branch colors representing fluoroquinolone genotypes. Red branches: S80F/Y and S84A/L; yellow: S80F only; blue branches: nil; black branch: reference genome FPR3757. Letters alongside circles indicate epidemiologically linked pairs or clusters.