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. 2022 Aug 12;226(1):157-166.
doi: 10.1093/infdis/jiac056.

Genomic Epidemiology Suggests Community Origins of Healthcare-Associated USA300 Methicillin-Resistant Staphylococcus aureus

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Genomic Epidemiology Suggests Community Origins of Healthcare-Associated USA300 Methicillin-Resistant Staphylococcus aureus

Stephanie N Thiede et al. J Infect Dis. .

Abstract

Background: Hospital-onset (HO) methicillin-resistant Staphylococcus aureus (MRSA) infections have declined over the past decade due to infection control strategies; community-onset (CO) and healthcare-associated community-onset (HACO) MRSA, particularly USA300, has declined less. We examined the role of community strains to explain the difference.

Methods: We performed whole-genome sequencing (WGS) on MRSA clinical isolates from Cook County Health patients during 2011-2014. We defined infections as CO, HO, or HACO epidemiologically. We integrated genomic, community exposure, and statewide hospital discharge data to infer MRSA origin.

Results: Among 1020 individuals with available WGS, most were USA300 wound infections (580 CO, 143 HO, 297 HACO). USA300 HO, CO, and HACO infections were intermixed on the USA300 phylogeny, consistent with common strains circulating across community and healthcare settings. Community exposures (eg, substance abuse, incarceration, homelessness) were associated with HACO and HO infections, and genetically linked individuals from both groups had little overlap in healthcare facilities, supporting community origins. Most repeat infections-over months to years-occurred in individuals persistently carrying their own strains. These individuals were more likely to have genetic linkages, suggesting a role of persistent colonization in transmission.

Conclusions: Efforts to reduce presumed nosocomial USA300 spread may require understanding and controlling community sources and transmission networks, particularly for repeat infections.

Keywords: MRSA; community transmission; genomic epidemiology; healthcare-associated community-onset; repeat infection.

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Conflict of interest statement

Potential conflicts of interest. All authors: No reported conflicts of interest.

Figures

Figure 1.
Figure 1.
Summary of data. A, Number of clinical cultures over time. Repeated cultures from the same episode of infection (cultures <30 days apart) are not shown. Repeat infections (infections that occur >30 days apart) are colored in gray. Whole-genome sequences were available for all but 1 culture in 2011, 2013, and 2014 and all but 91 in 2012. B, Per onset type, percentage of clinical cultures of each molecular type. Abbreviations: CO, community-onset; HACO, healthcare-associated community-onset; HO, hospital-onset; NAE, North American epidemic.
Figure 2.
Figure 2.
USA300 phylogeny with onset type and clustering. Maximum likelihood tree of USA300 isolates. One sample per individual shown. Scale bar indicates substitutions per site. Inner ring indicates onset type. Outer ring indicates if the isolate is in a cluster or not defined by a 20 single-nucleotide variant threshold, and if the cluster is of mixed or pure (eg, all community-onset methicillin-resistant Staphylococcus aureus) onset type. Abbreviations: CO, community-onset; HACO, healthcare-associated community-onset; HO, hospital-onset.
Figure 3.
Figure 3.
Exposure to the healthcare system before and after methicillin-resistant Staphylococcus aureus (MRSA) diagnosis. A, Includes only individuals who were diagnosed with MRSA infection in 2013 or 2014 (n = 344). Individuals in transmission clusters (n = 86) do not have more total inpatient or outpatient healthcare exposures than those not in a transmission cluster (n = 258) as indicated by Wilcoxon rank-sum test. Numbers above brackets indicate P values from Wilcoxon-rank sum test. B, Inpatient and outpatient exposures before and after MRSA by onset type (n = 208 community-onset, 94 healthcare-associated community-onset, 42 hospital-onset) reveal that individuals often have exposure to the healthcare system before and after MRSA diagnosis and that some individuals with so-called community-onset MRSA have inpatient exposures outside of Cook County Health before MRSA diagnosis. Abbreviations: CO, community-onset; HACO, healthcare-associated community-onset; HO, hospital-onset; MRSA, methicillin-resistant Staphylococcus aureus.
Figure 4.
Figure 4.
Analysis of repeat infections. A, Individuals with repeat infections, colored by multilocus sequence type. Shape indicates onset type. B, Single-nucleotide variant (SNV) distance between USA300 repeat infections over time. C, Percentage of individuals with repeat USA300 infections that are related to another isolate by 20 SNVs (n = 25) compared to those without repeat infection of the same strain (n = 761). P value from χ2 test indicates significance. D, Number of healthcare exposures before and month of methicillin-resistant Staphylococcus aureus (MRSA) diagnosis and after MRSA diagnosis, colored by repeat adult USA300 infection compared to those with no repeat USA300 infection. Data were subsetted to those infected in 2013 or 2014 (n = 13 repeat USA300 infections of the same strain, n = 331 with no repeat USA300 infection of the same strain). P values from Wilcoxon rank-sum tests indicate significantly higher number of exposures among those with repeat infections across all inpatient, outpatient, before and after MRSA. Abbreviations: CO, community-onset; HACO, healthcare-associated community-onset; HO, hospital-onset; MLST, multilocus sequence type; MRSA, methicillin-resistant Staphylococcus aureus; SNV, single-nucleotide variant.

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