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1.  Evidence for Community Transmission of Community-Associated but Not Health-Care-Associated Methicillin-Resistant Staphylococcus Aureus Strains Linked to Social and Material Deprivation: Spatial Analysis of Cross-sectional Data 
PLoS Medicine  2016;13(1):e1001944.
Background
Identifying and tackling the social determinants of infectious diseases has become a public health priority following the recognition that individuals with lower socioeconomic status are disproportionately affected by infectious diseases. In many parts of the world, epidemiologically and genotypically defined community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged to become frequent causes of hospital infection. The aim of this study was to use spatial models with adjustment for area-level hospital attendance to determine the transmission niche of genotypically defined CA- and health-care-associated (HA)-MRSA strains across a diverse region of South East London and to explore a potential link between MRSA carriage and markers of social and material deprivation.
Methods and Findings
This study involved spatial analysis of cross-sectional data linked with all MRSA isolates identified by three National Health Service (NHS) microbiology laboratories between 1 November 2011 and 29 February 2012. The cohort of hospital-based NHS microbiology diagnostic services serves 867,254 usual residents in the Lambeth, Southwark, and Lewisham boroughs in South East London, United Kingdom (UK). Isolates were classified as HA- or CA-MRSA based on whole genome sequencing. All MRSA cases identified over 4 mo within the three-borough catchment area (n = 471) were mapped to small geographies and linked to area-level aggregated socioeconomic and demographic data. Disease mapping and ecological regression models were used to infer the most likely transmission niches for each MRSA genetic classification and to describe the spatial epidemiology of MRSA in relation to social determinants. Specifically, we aimed to identify demographic and socioeconomic population traits that explain cross-area extra variation in HA- and CA-MRSA relative risks following adjustment for hospital attendance data. We explored the potential for associations with the English Indices of Deprivation 2010 (including the Index of Multiple Deprivation and several deprivation domains and subdomains) and the 2011 England and Wales census demographic and socioeconomic indicators (including numbers of households by deprivation dimension) and indicators of population health. Both CA-and HA-MRSA were associated with household deprivation (CA-MRSA relative risk [RR]: 1.72 [1.03–2.94]; HA-MRSA RR: 1.57 [1.06–2.33]), which was correlated with hospital attendance (Pearson correlation coefficient [PCC] = 0.76). HA-MRSA was also associated with poor health (RR: 1.10 [1.01–1.19]) and residence in communal care homes (RR: 1.24 [1.12–1.37]), whereas CA-MRSA was linked with household overcrowding (RR: 1.58 [1.04–2.41]) and wider barriers, which represent a combined score for household overcrowding, low income, and homelessness (RR: 1.76 [1.16–2.70]). CA-MRSA was also associated with recent immigration to the UK (RR: 1.77 [1.19–2.66]). For the area-level variation in RR for CA-MRSA, 28.67% was attributable to the spatial arrangement of target geographies, compared with only 0.09% for HA-MRSA. An advantage to our study is that it provided a representative sample of usual residents receiving care in the catchment areas. A limitation is that relationships apparent in aggregated data analyses cannot be assumed to operate at the individual level.
Conclusions
There was no evidence of community transmission of HA-MRSA strains, implying that HA-MRSA cases identified in the community originate from the hospital reservoir and are maintained by frequent attendance at health care facilities. In contrast, there was a high risk of CA-MRSA in deprived areas linked with overcrowding, homelessness, low income, and recent immigration to the UK, which was not explainable by health care exposure. Furthermore, areas adjacent to these deprived areas were themselves at greater risk of CA-MRSA, indicating community transmission of CA-MRSA. This ongoing community transmission could lead to CA-MRSA becoming the dominant strain types carried by patients admitted to hospital, particularly if successful hospital-based MRSA infection control programmes are maintained. These results suggest that community infection control programmes targeting transmission of CA-MRSA will be required to control MRSA in both the community and hospital. These epidemiological changes will also have implications for effectiveness of risk-factor-based hospital admission MRSA screening programmes.
Community associated MRSA variants, rather than hospital associated ones, are more readily transmitted and this is where control programs should focus to limit both hospital and community infections.
Editors' Summary
Background
Addressing health inequality requires understanding the social determinants of poor health. Previous studies have suggested a link between deprived living conditions and infections with methicillin-resistant Staphylococcus aureus (MRSA), that is, strains of the common bacterium S. aureus that have acquired antibiotic resistance and are therefore more difficult to treat. MRSA was first identified in the 1960s and for years thought of as a dangerous health-care-associated (HA-) pathogen that infects hospital patients who are predominantly older, sick, or undergoing invasive procedures. In the late 1990s, however, community-associated MRSA (CA-MRSA) emerged as pathogen infecting healthy individuals of all ages and without recent hospital contact. Most CA-MRSA cases are contagious skin infections, and numerous outbreaks have been reported in different communities. The traditional distinction between HA-MRSA and CA-MRSA based on where transmission occurred has become problematic in recent years, because CA-MRSA transmission has also been reported in health care settings. However, as HA- and CA-MRSA strains are genetically distinct, cases can be classified by DNA sequencing regardless of where a patient got infected.
Why Was This Study Done?
With hospitals historically considered the only place of MRSA transmission, prevention efforts remain focused on health care settings. Given the changing patterns of MRSA infections, however, the need to consider HA and CA transmission settings together has been recognized. This study was designed to take a closer look at the relationship between both HA- and CA-MRSA and socioeconomic deprivation, with the ultimate aim to inform prevention efforts. The researchers selected three boroughs in South East London with a highly diverse population of approximately 850,000 residents for whom socioeconomic and demographic data were available at a high level of spatial resolution. They also had data on hospital attendance for the residents and were therefore able to account for this factor in their analysis. The study addressed the following questions: is there a link between socioeconomic deprivation and both HA- and CA-MRSA cases among the residents? What social determinants are associated with HA- and CA-MRSA cases? What are the transmission settings (i.e., community versus health care) for HA- and CA-MRSA?
What Did the Researchers Do and Find?
They analyzed data on all MRSA samples collected over 4 consecutive mo in late 2011 and early 2012 by microbiology laboratories that serve the three boroughs. Of 471 MRSA cases that occurred in residents, 392 could be classified based on genome sequencing. Of these, approximately 72% were HA-MRSA, and 26% were CA-MRSA. Approximately 2% of residents carried both HA- and CA-MRSA. All MRSA cases were mapped to 513 smaller areas (called Lower Layer Super Output Areas, or LSOAs) in the three boroughs for which extensive socioeconomic and demographic data existed. The former included data on income, employment, health, and education, the latter data on number individuals per household, their ages and gender, and length of residence in the UK. MRSA cases were detected in just over half of the LSOAs in the study area. The researchers then used mathematical models to determine the most likely transmission settings for each MRSA genetic classification. They also described the spatial distributions of the two in relation to socioeconomic and demographic determinants. Both CA-and HA-MRSA were associated with household deprivation, which was itself correlated with hospital attendance. HA-MRSA was also associated with poor health and with living in communal care homes, whereas CA-MRSA was linked with household overcrowding and a combination of household overcrowding, low income, and homelessness. CA-MRSA was also associated with recent immigration to the UK. Around 27% of local variation in CA-MRSA could be explained by the spatial arrangement of LSOAs, meaning areas of high risk tended to cluster. No such clustering was observed for HA-MRSA.
What Do these Findings Mean?
The results show that residents in the most deprived areas are at greater risk for MRSA. The absence of spatial clusters of HA-MRSA suggests that transmission of genetically determined HA-MRSA occurs in hospitals, with little or no transmission in the community. The most important risk factor for acquiring HA-MRSA is therefore likely to be hospital attendance as a result of deprivation. In contrast, genetically determined CA-MRSA both affects deprived areas disproportionately, and—as the clusters imply—spreads from such areas in the community. This suggests that living in deprived conditions itself is a risk factor for acquiring CA-MRSA, as is living near deprived neighbors. Some of the CA-MRSA cases are also likely imported by recent immigrants. Whereas transmission of CA-MRSA in health care settings has been reported in a number of other studies, data from this study cannot answer whether or to what extent this is the case here. However, because of ongoing transmission in the community, and because deprived residents are both more likely to have CA-MRSA and to attend a hospital, importation of CA-MRSA strains into hospitals is an obvious concern. While the researchers intentionally located the study in an area with a very diverse population, it is not clear how generalizable the findings are to other communities, either in the UK or in other countries. Nonetheless, the results justify special focus on deprived populations in the control of MRSA and are useful for the design of specific strategies for HA-MRSA and CA-MRSA.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001944.
Online information on MRSA from the UK National Health Service: http://www.nhs.uk/conditions/MRSA/Pages/Introduction.aspx
MRSA webpage from the US Centers of Disease Control and Prevention: http://www.cdc.gov/mrsa/
MRSA page from the San Francisco Department of Public Health: http://www.sfcdcp.org/mrsa.html
MedlinePlus provides links to information about MRSA, including sources in languages other than English: https://www.nlm.nih.gov/medlineplus/mrsa.html
doi:10.1371/journal.pmed.1001944
PMCID: PMC4727805  PMID: 26812054
2.  Geographic Distribution of Staphylococcus aureus Causing Invasive Infections in Europe: A Molecular-Epidemiological Analysis 
PLoS Medicine  2010;7(1):e1000215.
Hajo Grundmann and colleagues describe the development of a new interactive mapping tool for analyzing the spatial distribution of invasive Staphylococcus aureus clones.
Background
Staphylococcus aureus is one of the most important human pathogens and methicillin-resistant variants (MRSAs) are a major cause of hospital and community-acquired infection. We aimed to map the geographic distribution of the dominant clones that cause invasive infections in Europe.
Methods and Findings
In each country, staphylococcal reference laboratories secured the participation of a sufficient number of hospital laboratories to achieve national geo-demographic representation. Participating laboratories collected successive methicillin-susceptible (MSSA) and MRSA isolates from patients with invasive S. aureus infection using an agreed protocol. All isolates were sent to the respective national reference laboratories and characterised by quality-controlled sequence typing of the variable region of the staphylococcal spa gene (spa typing), and data were uploaded to a central database. Relevant genetic and phenotypic information was assembled for interactive interrogation by a purpose-built Web-based mapping application. Between September 2006 and February 2007, 357 laboratories serving 450 hospitals in 26 countries collected 2,890 MSSA and MRSA isolates from patients with invasive S. aureus infection. A wide geographical distribution of spa types was found with some prevalent in all European countries. MSSA were more diverse than MRSA. Genetic diversity of MRSA differed considerably between countries with dominant MRSA spa types forming distinctive geographical clusters. We provide evidence that a network approach consisting of decentralised typing and visualisation of aggregated data using an interactive mapping tool can provide important information on the dynamics of MRSA populations such as early signalling of emerging strains, cross border spread, and importation by travel.
Conclusions
In contrast to MSSA, MRSA spa types have a predominantly regional distribution in Europe. This finding is indicative of the selection and spread of a limited number of clones within health care networks, suggesting that control efforts aimed at interrupting the spread within and between health care institutions may not only be feasible but ultimately successful and should therefore be strongly encouraged.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The bacterium Staphylococcus aureus lives on the skin and in the nose of about a third of healthy people. Although S. aureus usually coexists peacefully with its human carriers, it is also an important disease-causing organism or pathogen. If it enters the body through a cut or during a surgical procedure, S. aureus can cause minor infections such as pimples and boils or more serious, life-threatening infections such as blood poisoning and pneumonia. Minor S. aureus infections can be treated without antibiotics—by draining a boil, for example. Invasive infections are usually treated with antibiotics. Unfortunately, many of the S. aureus clones (groups of bacteria that are all genetically related and descended from a single, common ancestor) that are now circulating are resistant to methicillin and several other antibiotics. Invasive methicillin-resistant S. aureus (MRSA) infections are a particular problem in hospitals and other health care facilities (so-called hospital-acquired MRSA infections), but they can also occur in otherwise healthy people who have not been admitted to a hospital (community-acquired MRSA infections).
Why Was This Study Done?
The severity and outcome of an S. aureus infection in an individual depends in part on the ability of the bacterial clone with which the individual is infected to cause disease—the clone's “virulence.” Public-health officials and infectious disease experts would like to know the geographic distribution of the virulent S. aureus clones that cause invasive infections, because this information should help them understand how these pathogens spread and thus how to control them. Different clones of S. aureus can be distinguished by “molecular typing,” the determination of clone-specific sequences of nucleotides in variable regions of the bacterial genome (the bacterium's blueprint; genomes consist of DNA, long chains of nucleotides). In this study, the researchers use molecular typing to map the geographic distribution of MRSA and methicillin-sensitive S. aureus (MSSA) clones causing invasive infections in Europe; a MRSA clone emerges when an MSSA clone acquires antibiotic resistance from another type of bacteria so it is useful to understand the geographic distribution of both MRSA and MSSA.
What Did the Researchers Do and Find?
Between September 2006 and February 2007, 357 laboratories serving 450 hospitals in 26 European countries collected almost 3,000 MRSA and MSSA isolates from patients with invasive S. aureus infections. The isolates were sent to the relevant national staphylococcal reference laboratory (SRL) where they were characterized by quality-controlled sequence typing of the variable region of a staphylococcal gene called spa (spa typing). The spa typing data were entered into a central database and then analyzed by a public, purpose-built Web-based mapping tool (SRL-Maps), which provides interactive access and easy-to-understand illustrations of the geographical distribution of S. aureus clones. Using this mapping tool, the researchers found that there was a wide geographical distribution of spa types across Europe with some types being common in all European countries. MSSA isolates were more diverse than MRSA isolates and the genetic diversity (variability) of MRSA differed considerably between countries. Most importantly, major MRSA spa types occurred in distinct geographical clusters.
What Do These Findings Mean?
These findings provide the first representative snapshot of the genetic population structure of S. aureus across Europe. Because the researchers used spa typing, which analyzes only a small region of one gene, and characterized only 3,000 isolates, analysis of other parts of the S. aureus genome in more isolates is now needed to build a complete portrait of the geographical abundance of the S. aureus clones that cause invasive infections in Europe. However, the finding that MRSA spa types occur mainly in geographical clusters has important implications for the control of MRSA, because it indicates that a limited number of clones are spreading within health care networks, which means that MRSA is mainly spread by patients who are repeatedly admitted to different hospitals. Control efforts aimed at interrupting this spread within and between health care institutions may be feasible and ultimately successful, suggest the researchers, and should be strongly encouraged. In addition, this study shows how, by sharing typing results on a Web-based platform, an international surveillance network can provide clinicians and infection control teams with crucial information about the dynamics of pathogens such as S. aureus, including early warnings about emerging virulent clones.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000215.
This study is further discussed in a PLoS Medicine Perspective by Franklin D. Lowy
The UK Health Protection Agency provides information about Staphylococcus aureus
The UK National Health Service Choices Web site has pages on staphylococcal infections and on MRSA
The US National Institute of Allergy and Infectious Disease has information about MRSA
The US Centers for Disease Control and Infection provides information about MRSA for the public and professionals
MedlinePlus provides links to further resources on staphylococcal infections and on MRSA (in English and Spanish)
SRL-Maps can be freely accessed
doi:10.1371/journal.pmed.1000215
PMCID: PMC2796391  PMID: 20084094
3.  Identification of a Highly Transmissible Animal-Independent Staphylococcus aureus ST398 Clone with Distinct Genomic and Cell Adhesion Properties 
mBio  2012;3(2):e00027-12.
ABSTRACT
A methicillin-resistant Staphylococcus aureus (MRSA) clone known as ST398 has emerged as a major cause of acute infections in individuals who have close contact with livestock. More recently, the emergence of an animal-independent ST398 methicillin-sensitive S. aureus (MSSA) clone has been documented in several countries. However, the limited surveillance of MSSA has precluded an accurate assessment of the global spread of ST398 and its clinical relevance. Here we provide evidence that ST398 is a frequent source of MSSA infections in northern Manhattan and is readily transmitted between individuals in households. This contrasts with the limited transmissibility of livestock-associated ST398 (LA-ST398) MRSA strains between humans. Our whole-genome sequence analysis revealed that the chromosome of the human-associated ST398 MSSA clone is smaller than that of the LA-ST398 MRSA reference strain S0385, due mainly to fewer mobile genetic elements (MGEs). In contrast, human ST398 MSSA isolates harbored the prophage φ3 and the human-specific immune evasion cluster (IEC) genes chp and scn. While most of the core genome was conserved between the human ST398 MSSA clone and S0385, these strains differed substantially in their repertoire and composition of intact adhesion genes. These genetic changes were associated with significantly enhanced adhesion of human ST398 MSSA isolates to human skin keratinocytes and keratin. We propose that the human ST398 MSSA clone can spread independent of animal contact using an optimized repertoire of MGEs and adhesion molecules adapted to transmission among humans.
IMPORTANCE
Staphylococcus aureus strains have generally been considered to be species specific. However, cross-species transfers of S. aureus clones, such as ST398 methicillin-resistant S. aureus (MRSA), from swine to humans have been reported. Recently, we observed the emergence of ST398 methicillin-susceptible S. aureus (MSSA) as a colonizing strain of humans in northern Manhattan. Here we report that ST398 is a frequent cause of MSSA infections in this urban setting. The ST398 MSSA clone was readily transmitted within households, independent of animal contact. We discovered that human ST398 MSSA genomes were smaller than that of the LA-ST398 strain S0385 due to fewer mobile genetic elements. Human and LA-ST398 strains also differed in their composition of adhesion genes and their ability to bind to human skin keratinocytes, providing a potential mechanism of S. aureus host adaptation. Our findings illustrate the importance of implementing molecular surveillance of MSSA given the evidence for the rapid and clinically undetected spread of ST398 MSSA.
doi:10.1128/mBio.00027-12
PMCID: PMC3302565  PMID: 22375071
4.  Next-Generation Sequencing Confirms Presumed Nosocomial Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus in the Netherlands 
Applied and Environmental Microbiology  2016;82(14):4081-4089.
ABSTRACT
Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) was detected in 2003 and rapidly became the predominant MRSA clade in the Netherlands. Studies have shown that transmissions are difficult to identify, since this MRSA variant represents a genetically homogenous clade when current typing techniques are used. Here, next-generation sequencing was performed on 206 LA-MRSA isolates to assess the capability of LA-MRSA to be transmitted between humans. The usefulness of single nucleotide variants (SNVs), the composition of the SCCmec region, and the presence of plasmids to identify transmission of LA-MRSA were assessed. In total, 30 presumed putative nosocomial transmission events and 2 LA-MRSA outbreaks were studied; in most cases, SNV analysis revealed that the isolates of the index patient and the contact(s) clustered closely together. In three presumed events, the isolates did not cluster together, indicating that transmission was unlikely. The composition of the SCCmec region corroborated these findings. However, plasmid identification did not support our SNV analysis, since different plasmids were present in several cases where SNV and SCCmec analysis suggested that transmission was likely. Next-generation sequencing shows that transmission of LA-MRSA does occur in Dutch health care settings. Transmission was identified based on SNV analysis combined with epidemiological data and in the context of epidemiologically related and unrelated isolates. Analysis of the SCCmec region provided limited, albeit useful, information to corroborate conclusions on transmissions, but plasmid identification did not.
IMPORTANCE In 2003, a variant of methicillin-resistant Staphylococcus aureus (MRSA) isolated from pigs was also found in pig farmers in France and the Netherlands. Soon thereafter, this livestock-associated MRSA (LA-MRSA) was identified in many other countries. Transmission of LA-MRSA between humans, particularly in the health care setting, is regarded to occur sporadically. Moreover, studies that describe LA-MRSA transmission used molecular characterization of isolates with limited discriminatory power, making the validity of the conclusion that transmission occurred questionable. In our study, we sequenced the complete genomes of 206 LA-MRSA isolates, obtained from more than 30 presumed LA-MRSA transmission events. Analysis of the data showed that transmission of LA-MRSA between humans had indeed occurred in more than 90% of these events. We conclude that transmission of LA-MRSA between humans does occur in Dutch health care settings; therefore, a decision to discontinue the search and destroy policy for LA-MRSA should be taken with caution.
doi:10.1128/AEM.00773-16
PMCID: PMC4959200  PMID: 27129960
5.  Transmission and Persistence of Livestock-Associated Methicillin-Resistant Staphylococcus aureus among Veterinarians and Their Household Members 
After the first isolation of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in 2003, this MRSA variant quickly became the predominant MRSA obtained from humans as part of the Dutch national MRSA surveillance. Previous studies have suggested that human-to-human transmission of LA-MRSA, compared to that of other MRSA lineages, rarely occurs. However, these reports describe the transmission of LA-MRSA based on epidemiology and limited molecular characterization of isolates, making it difficult to assess whether transmission actually occurred. In this study, we used whole-genome maps (WGMs) to identify possible transmission of LA-MRSA between humans. For this, we used LA-MRSA isolates originating from a 2-year prospective longitudinal cohort study in which livestock veterinarians and their household members were repeatedly sampled for the presence of S. aureus. A considerable degree of genotypic variation among LA-MRSA strains was observed. However, there was very limited variability between the maps of the isolates originating from the same veterinarian, indicating that each of the veterinarians persistently carried or had reacquired the same LA-MRSA strain. Comparison of WGMs revealed that LA-MRSA transmission had likely occurred within virtually every veterinarian household. Yet only a single LA-MRSA strain per household appeared to be involved in transmission. The results corroborate our previous finding that LA-MRSA is genetically diverse. Furthermore, this study shows that transmission of LA-MRSA between humans occurs and that carriage of LA-MRSA can be persistent, thus posing a potential risk for spread of this highly resistant pathogen in the community.
doi:10.1128/AEM.02803-14
PMCID: PMC4272725  PMID: 25326300
6.  Hospital-Community Interactions Foster Coexistence between Methicillin-Resistant Strains of Staphylococcus aureus 
PLoS Pathogens  2013;9(2):e1003134.
Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of morbidity and mortality in both hospitals and the community. Traditionally, MRSA was mainly hospital-associated (HA-MRSA), but in the past decade community-associated strains (CA-MRSA) have spread widely. CA-MRSA strains seem to have significantly lower biological costs of resistance, and hence it has been speculated that they may replace HA-MRSA strains in the hospital. Such a replacement could potentially have major consequences for public health, as there are differences in the resistance spectra of the two strains as well as possible differences in their clinical effects. Here we assess the impact of competition between HA- and CA-MRSA using epidemiological models which integrate realistic data on drug-usage frequencies, resistance profiles, contact, and age structures. By explicitly accounting for the differing antibiotic usage frequencies in the hospital and the community, we find that coexistence between the strains is a possible outcome, as selection favors CA-MRSA in the community, because of its lower cost of resistance, while it favors HA-MRSA in the hospital, because of its broader resistance spectrum. Incorporating realistic degrees of age- and treatment-structure into the model significantly increases the parameter ranges over which coexistence is possible. Thus, our results indicate that the large heterogeneities existing in human populations make coexistence between hospital- and community-associated strains of MRSA a likely outcome.
Author Summary
One of the most notorious cases of antibiotic-resistant bacteria is methicillin-resistant Staphylococcus aureus (MRSA), which causes diseases ranging from skin and soft-tissue infections to pneumonia and septicemia. Traditionally, MRSA was mainly hospital-associated, but in the past decade community-associated strains have spread widely. Typically drug-resistant bacteria have lower reproduction or transmission rates, called a fitness cost. Because this cost is estimated to be significantly lower for community-associated strains, it has been predicted that these will eventually replace the hospital-associated strains. However, hospital-associated strains are resistant against a greater variety of antibiotics, which may compensate for the higher fitness cost. Here, we integrate realistic data on drug-usage, resistance profiles, contact, and age structures into a mathematical model of MRSA transmission to predict the competition between hospital- and community-associated strains. We find that for a realistic degree of population structure it is likely that both strains of MRSA will coexist in the long term. This results from significantly different hospitalization and antibiotic consumption rates between age groups. In particular, elderly individuals have much higher rates of antibiotic usage and hospitalizations than other age groups. This generates a situation where community-associated strains can predominate in the community but are outcompeted in the hospital, resulting in coexistence in the population.
doi:10.1371/journal.ppat.1003134
PMCID: PMC3585153  PMID: 23468619
7.  What Is the Origin of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Clonal Complex 398 Isolates from Humans without Livestock Contact? An Epidemiological and Genetic Analysis 
Journal of Clinical Microbiology  2015;53(6):1836-1841.
Fifteen percent of all methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) human carriers detected in The Netherlands had not been in direct contact with pigs or veal calves. To ensure low MRSA prevalence, it is important to investigate the likely origin of this MRSA of unknown origin (MUO). Recently, it was shown that CC398 strains originating from humans and animals differ in the presence of specific mobile genetic elements (MGEs). We hypothesized that determining these specific MGEs in MUO isolates and comparing them with a set of CC398 isolates of various known origin might provide clues to their origin. MUO CC398 isolates were compared to MRSA CC398 isolates obtained from humans with known risk factors, a MRSA CC398 outbreak isolate, livestock associated (LA) MRSA CC398 isolates from pigs, horses, chickens, and veal calves, and five methicillin-susceptible Staphylococcus aureus (MSSA) CC398 isolates of known human origin. All strains were spa typed, and the presence or absence of, scn, chp, φ3 int, φ6 int, φ7 int, rep7, rep27, and cadDX was determined by PCRs. The MRSA CC398 in humans, MUO, or MRSA of known origin (MKO) resembled MRSA CC398 as found in pigs and not MSSA CC398 as found in humans. The distinct human MSSA CC398 spa type, t571, was not present among our MRSA CC398 strains; MRSA CC398 was tetracycline resistant and carried no φ3 bacteriophage with scn and chp. We showed by simple PCR means that human MUO CC398 carriers carried MRSA from livestock origin, suggestive of indirect transmission. Although the exact transmission route remains unknown, direct human-to-human transmission remains a possibility as well.
doi:10.1128/JCM.02702-14
PMCID: PMC4432056  PMID: 25809975
8.  Key Role for Clumping Factor B in Staphylococcus aureus Nasal Colonization of Humans 
PLoS Medicine  2008;5(1):e17.
Background
Staphylococcus aureus permanently colonizes the vestibulum nasi of one-fifth of the human population, which is a risk factor for autoinfection. The precise mechanisms whereby S. aureus colonizes the nose are still unknown. The staphylococcal cell-wall protein clumping factor B (ClfB) promotes adhesion to squamous epithelial cells in vitro and might be a physiologically relevant colonization factor.
Methods and Findings
We define the role of the staphylococcal cytokeratin-binding protein ClfB in the colonization process by artificial inoculation of human volunteers with a wild-type strain and its single locus ClfB knock-out mutant. The wild-type strain adhered to immobilized recombinant human cytokeratin 10 (CK10) in a dose-dependent manner, whereas the ClfB− mutant did not. The wild-type strain, when grown to the stationary phase in a poor growth medium, adhered better to CK10, than when the same strain was grown in a nutrient-rich environment. Nasal cultures show that the mutant strain is eliminated from the nares significantly faster than the wild-type strain, with a median of 3 ± 1 d versus 7 ± 4 d (p = 0.006). Furthermore, the wild-type strain was still present in the nares of 3/16 volunteers at the end of follow-up, and the mutant strain was not.
Conclusions
The human colonization model, in combination with in vitro data, shows that the ClfB protein is a major determinant of nasal-persistent S. aureus carriage and is a candidate target molecule for decolonization strategies.
Heiman Wertheim and colleagues investigate the role ofStaphylococcus aureus clumping factor B, a cell wall protein, in bacterial adherence to epithelial cells and persistent colonization of human nostrils.
Editors' Summary
Background.
Staphylococcus aureus are common bacteria that normally live on the skin. They also colonize the nostrils of about one in five adults permanently and another one in three adults intermittently. Although these bacteria usually coexist peacefully with their human carriers, they can cause minor infections such as pimples and boils if they enter the skin through a cut or a sore. They can also cause potentially life-threatening infections such as blood poisoning and pneumonia. These serious, invasive infections are often “autoinfections.” That is, they are caused by strains of S. aureus that are present in the patient's nose before they become ill. Minor S. aureus infections can be treated without antibiotics—by draining a boil, for example. Invasive infections are usually treated with antibiotics such as flucloxacillin.
Why Was This Study Done?
There is no effective vaccine against S. aureus infections and these bacteria are becoming increasingly resistant to flucloxacillin, methicillin, and other antibiotics. Worryingly, although methicillin-resistant S. aureus (MRSA) infections occur most frequently among people in health-care facilities who have weakened immune systems, community-acquired MRSA infections among otherwise healthy people are increasingly common. Consequently, new ways to avoid S. aureus infections are urgently needed. Because persistent nasal carriers of S. aureus have an increased risk of infection, one strategy might be to prevent nasal colonization with S. aureus. How these bacteria colonize the nose is poorly understood, but is likely to involve interactions between molecules expressed on the surface of the bacteria and molecules expressed on the surface of the cells lining the nostrils. In this study, the researchers use a new human nasal colonization assay to investigate the involvement of a bacterial surface protein called clumping factor B (ClfB) in the survival of S. aureus in the human nose. ClfB binds to cytokeratin 10, a protein expressed by cells lining the human nose, and has been implicated in the colonization of mouse noses by S. aureus.
What Did the Researchers Do and Find?
The researchers introduced a strain of S. aureus that made ClfB and an otherwise identical, mutant strain that lacked ClfB into the nostrils of healthy human volunteers and measured how long the two strains survived. For safety reasons, the S. aureus strains used in this study have an additional defect that makes them less likely to colonize and persist in the human nose than the strains found in natural S. aureus carriers. Although both strains grew equally well in the laboratory, the mutant strain was eliminated from human noses much quicker than the strain that made ClfB. Mutant bacteria lacking ClfB were cleared from the nostrils of all the volunteers within two weeks, whereas the bacteria that made ClfB were still present in some of the volunteers four weeks after their introduction. When the researchers investigated how well the two strains stuck to a layer of human cytokeratin 10 in a plastic dish, they found that the bacteria that made ClfB stuck to the human protein but the mutant bacteria did not. Furthermore, the strain with ClfB stuck particularly well to cytokeratin 10 when the bacteria had been grown in conditions where nutrients were limiting, a situation that mimics bacterial growth in the human nose.
What Do These Findings Mean?
These findings show that ClfB is an important factor in the establishment of human nasal colonization by S. aureus and suggest that ClfB might be a target for S. aureus decolonization strategies. Furthermore, although ClfB is clearly important in human nasal colonization by S. aureus, it is likely that additional bacterial factors will also be involved in this process. The human nasal colonization model used in this study may be useful in the identification of these additional factors and also as a test bed for potential S. aureus decolonization strategies.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050017.
The MedlinePlus encyclopedia has a page on Staphylococcus aureus and MRSA (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on community-associated MRSA (in English and Spanish)
The UK National Health Service's health website (NHS Direct) provides information about staphylococcal infections and about MRSA
The UK Health Protection Agency provides information about Staphylococcus aureus
doi:10.1371/journal.pmed.0050017
PMCID: PMC2194749  PMID: 18198942
9.  Mortality and Hospital Stay Associated with Resistant Staphylococcus aureus and Escherichia coli Bacteremia: Estimating the Burden of Antibiotic Resistance in Europe 
PLoS Medicine  2011;8(10):e1001104.
The authors calculate excess mortality, excess hospital stay, and related hospital expenditure associated with antibiotic-resistant bacterial bloodstream infections (Staphylococcus aureus and Escherichia coli) in Europe.
Background
The relative importance of human diseases is conventionally assessed by cause-specific mortality, morbidity, and economic impact. Current estimates for infections caused by antibiotic-resistant bacteria are not sufficiently supported by quantitative empirical data. This study determined the excess number of deaths, bed-days, and hospital costs associated with blood stream infections (BSIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) and third-generation cephalosporin-resistant Escherichia coli (G3CREC) in 31 countries that participated in the European Antimicrobial Resistance Surveillance System (EARSS).
Methods and Findings
The number of BSIs caused by MRSA and G3CREC was extrapolated from EARSS prevalence data and national health care statistics. Prospective cohort studies, carried out in hospitals participating in EARSS in 2007, provided the parameters for estimating the excess 30-d mortality and hospital stay associated with BSIs caused by either MRSA or G3CREC. Hospital expenditure was derived from a publicly available cost model. Trends established by EARSS were used to determine the trajectories for MRSA and G3CREC prevalence until 2015. In 2007, 27,711 episodes of MRSA BSIs were associated with 5,503 excess deaths and 255,683 excess hospital days in the participating countries, whereas 15,183 episodes of G3CREC BSIs were associated with 2,712 excess deaths and 120,065 extra hospital days. The total costs attributable to excess hospital stays for MRSA and G3CREC BSIs were 44.0 and 18.1 million Euros (63.1 and 29.7 million international dollars), respectively. Based on prevailing trends, the number of BSIs caused by G3CREC is likely to rapidly increase, outnumbering the number of MRSA BSIs in the near future.
Conclusions
Excess mortality associated with BSIs caused by MRSA and G3CREC is significant, and the prolongation of hospital stay imposes a considerable burden on health care systems. A foreseeable shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections will exacerbate this situation and is reason for concern.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Antimicrobial resistance—a consequence of the use and misuse of antimicrobial medicines—occurs when a microorganism becomes resistant (usually by mutation or acquiring a resistance gene) to an antimicrobial drug to which it was previously sensitive. Then standard treatments become ineffective, leading to persistent infections, which may spread to other people. With some notable exceptions such as TB, HIV, malaria, and gonorrhea, most of the disease burden attributable to antimicrobial resistance is caused by hospital-associated infections due to opportunistic bacterial pathogens. These bacteria often cause life-threatening or difficult-to-manage conditions such as deep tissue, wound, or bone infections, or infections of the lower respiratory tract, central nervous system, or blood stream. The two most frequent causes of blood stream infections encountered worldwide are Staphylococcus aureus and Escherichia coli.
Why Was This Study Done?
Although hospital-associated infections have gained much attention over the past decade, the overall effect of this growing phenomenon on human health and medical services has still to be adequately quantified. The researchers proposed to fill this information gap by estimating the impact—morbidity, mortality, and demands on health care services—of antibiotic resistance in Europe for two types of resistant organisms that are typically associated with resistance to multiple classes of antibiotics and can be regarded as surrogate markers for multi-drug resistance—methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli.
What Did the Researchers Do and Find?
Recently, the Burden of Resistance and Disease in European Nations project collected representative data on the clinical impact of antimicrobial resistance throughout Europe. Using and combining this information with 2007 prevalence data from the European Antibiotic Resistance Surveillance System, the researchers calculated the burden of disease associated with methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli blood stream infections. This burden of disease was expressed as excess number of deaths, excess number of days in hospital, and excess costs. Using statistical models, the researchers predicted trend-based resistance trajectories up to 2015 for the 31 participating countries in the European region.
The researchers included 1,293 hospitals from the 31 countries, typically covering 47% of all available acute care hospital beds in most countries, in their analysis. For S. aureus, the estimated number of blood stream infections totaled 108,434, of which 27,711 (25.6%) were methicillin-resistant. E. coli caused 163,476 blood stream infections, of which 15,183 (9.3%) were resistant to third-generation cephalosporins. An estimated 5,503 excess deaths were associated with blood stream infections caused by methicillin-resistant S. aureus (with the UK and France predicted to experience the highest excess mortality), and 2,712 excess deaths with blood stream infections caused by third-generation cephalosporin-resistant E. coli (predicted to be the highest in Turkey and the UK). The researchers also found that blood stream infections caused by both methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli contributed respective excesses of 255,683 and 120,065 extra bed-days, accounting for an estimated extra cost of 62.0 million Euros (92.8 million international dollars). In their trend analysis, the researchers found that 97,000 resistant blood stream infections and 17,000 associated deaths could be expected in 2015, along with increases in the lengths of hospital stays and costs. Importantly, the researchers estimated that in the near future, the burden of disease associated with third-generation cephalosporin-resistant E. coli is likely to surpass that associated with methicillin-resistant S. aureus.
What Do These Findings Mean?
These findings show that even though the blood stream infections studied represent only a fraction of the total burden of disease associated with antibiotic resistance, excess mortality associated with these infections caused by methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli is high, and the associated prolonged length of stays in hospital imposes a considerable burden on health care systems in Europe. Importantly, a possible shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections is concerning. Such forecasts suggest that despite anticipated gains in the control of methicillin-resistant S. aureus, the increasing number of infections caused by third-generation cephalosporin-resistant Gram-negative pathogens, such as E. coli, is likely to outweigh this achievement soon. This increasing burden will have a big impact on already stretched health systems.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001104.
The World Health Organization has a fact sheet on general antimicrobial resistance
The US Centers for Disease Control and Prevention webpage on antibiotic/antimicrobial resistance includes information on educational campaigns and resources
The European Centre for Disease Control provides data about the prevalence of resistance in Europe through an interactive database
doi:10.1371/journal.pmed.1001104
PMCID: PMC3191157  PMID: 22022233
10.  Methicillin-Resistant Staphylococcus aureus CC398 in Humans and Pigs in Norway: A “One Health” Perspective on Introduction and Transmission 
This study provides strong, novel evidence that humans may introduce methicillin-resistant Staphylococcus aureus CC398 into closed pig populations; it also demonstrates that stringent control and eradication measures were effective and prevented dissemination from pig farms to the general human population.
Background. Emerging livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) persist in livestock populations and represent a reservoir for transmission to humans. Understanding the routes of introduction and further transmission is crucial to control this threat to human health.
Methods. All reported cases of livestock-associated MRSA (CC398) in humans and pigs in Norway between 2008 and 2014 were included. Data were collected during an extensive outbreak investigation, including contact tracing and stringent surveillance. Whole-genome sequencing of isolates from all human cases and pig farms was performed to support and expand the epidemiological findings. The national strategy furthermore included a “search-and-destroy” policy at the pig farm level.
Results. Three outbreak clusters were identified, including 26 pig farms, 2 slaughterhouses, and 36 humans. Primary introductions likely occurred by human transmission to 3 sow farms with secondary transmission to other pig farms, mainly through animal trade and to a lesser extent via humans or livestock trucks. All MRSA CC398 isolated from humans without an epidemiological link to the outbreaks were genetically distinct from isolates within the outbreak clusters indicating limited dissemination to the general population.
Conclusions. This study identified preventable routes of MRSA CC398 introduction and transmission: human occupational exposure, trade of pigs and livestock transport vehicles. These findings are essential for keeping pig populations MRSA free and, from a “One Health” perspective, preventing pig farms from becoming reservoirs for MRSA transmission to humans.
doi:10.1093/cid/ciw552
PMCID: PMC5106606  PMID: 27516381
LA-MRSA; humans; pigs; epidemiology; control
11.  Evolutionary Dynamics of Pandemic Methicillin-Sensitive Staphylococcus aureus ST398 and Its International Spread via Routes of Human Migration 
mBio  2017;8(1):e01375-16.
ABSTRACT
Methicillin-susceptible Staphylococcus aureus (MSSA) accounts for the majority of S. aureus infections globally, and yet surprisingly little is known about its clonal evolution. We applied comparative whole-genome sequencing (WGS) analyses to epidemiologically and geographically diverse ST398-MSSA, a pandemic lineage affecting both humans and livestock. Bayesian phylogenetic analysis predicted divergence of human-associated ST398-MSSA ~40 years ago. Isolates from Midwestern pigs and veterinarians differed substantially from those in New York City (NYC). Pig ST398 strains contained a large region of recombination representing imports from multiple sequence types (STs). Phylogeographic analyses supported the spread of ST398-MSSA along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. Applying pairwise single-nucleotide polymorphism (SNP) distances as a measure of genetic relatedness between isolates, we observed that ST398 not only clustered in households but also frequently extended across local social networks. Isolates collected from environmental surfaces reflected the full diversity of colonizing individuals, highlighting their potentially critical role as reservoirs for transmission and diversification. Strikingly, we observed high within-host SNP variability compared to our previous studies on the dominant methicillin-resistant Staphylococcus aureus (MRSA) clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300-MRSA and ST398-MSSA. Taken together, our study reveals local and international routes of transmission for a major MSSA clone, indicating key impacts of recombination and mutation on genetic diversification and highlighting important ecological differences from epidemic USA300. Our study demonstrates extensive local and international routes of transmission for a major MSSA clone despite the lack of substantial antibiotic resistance.
IMPORTANCE
Unlike methicillin-resistant Staphylococcus aureus (MRSA), surprisingly little is known about the clonal evolution of methicillin-susceptible S. aureus (MSSA), although these strains account for the majority of S. aureus infections. To better understand how MSSA spreads and becomes established in communities, we applied comparative bacterial whole-genome sequencing to pandemic ST398-MSSA, a clone of clinical importance affecting humans and livestock in different geographic regions. Phylogeographic analyses identified that ST398-MSSA spread along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. We observed high within-host SNP variability compared to our previous studies on the dominant MRSA clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300 MRSA and ST398 MSSA.
doi:10.1128/mBio.01375-16
PMCID: PMC5241395  PMID: 28096484
12.  Molecular epidemiology and characteristic of virulence gene of community-acquired and hospital-acquired methicillin-resistant Staphylococcus aureus isolates in Sun Yat-sen Memorial hospital, Guangzhou, Southern China 
BMC Infectious Diseases  2016;16:339.
Background
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of both hospital and community infections globally. It’s important to illuminate the differences between community-acquired MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA), but there have been confusions on the definition, especially for the MRSA isolates identified within 48 h of admission. This study aimed to determine the molecular characteristics and virulence genes profile of CA and HA-MRSA isolates identified less than 48 h after hospital admission in our region.
Methods
A total 62 MRSA isolates identified within 48 h after admission and the clinical data were collected. Antimicrobial susceptibility test (AST) of collected isolates were performed according to the guidelines of Clinical and Laboratory Standards Institute (CLSI) 2015, and staphylococcal cassette chromosome mec (SCCmec) typing, multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and virulence gene profiling were performed to explore the molecular diversity.
Results
SCCmec III and sequence type (ST) 239 were the most prevalent SCCmec type and ST in both CA and HA-MRSA groups. HA-MRSA group had higher prevalence of SCCmec III (87.2 %) and ST239 (79.5 %) compared with CA-MRSA (60.9 and 43.4 %, both P < 0.001), while the frequency of SCCmec IV (26.0 %) and ST59 (21.7 %) were higher in CA-MRSA than its counterpart (P < 0.001 and P = 0.003). MRSA-ST239-III was the predominant type in this study (61.3 %, 38/62), especially in HA-MRSA group (76.9 %, 30/39). However, CA-MRSA strains exhibited more diversity in genotypes in this study. Meanwhile, CA-MRSA tended to have lower resistant percentage to non-β-lactams antibiotics but more virulence genes carriage, especially the staphylococcal enterotoxins (SE) genes. Notably, seb gene was only detected in CA-MRSA isolates (52.2 %), likely a significant marker for CA-MRSA isolates. Panton-Valentine leukocidin gene (PVL) was highly detected in both groups, while appeared no significantly different between CA-MRSA (47.8 %) and HA-MRSA (43.6 %).
Conclusions
Our findings support a difference in the molecular epidemiology and virulence genes profile of CA-MRSA and HA-MRSA. Furthermore, this study indicates a possible transmission from HA-MRSA to CA-MRSA, which may cause the overlap of the definition.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-016-1684-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-016-1684-y
PMCID: PMC4957337  PMID: 27450316
Methicillin-resistant Staphylococcus aureus; Antimicrobial susceptibility; Molecular characteristics; Virulence gene
13.  Carriage of Methicillin-Resistant Staphylococcus aureus by Wild Urban Norway Rats (Rattus norvegicus) 
PLoS ONE  2014;9(2):e87983.
Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of multi-drug-resistant infections in people, particularly indigent populations. MRSA can be transmitted between people and domestic animals, but the potential for transmission between people and commensal pests, particularly rodents, had not been investigated. The objective of this study was to identify the presence and characterize the ecology of MRSA in rats (Rattus spp.) from in an impoverished, inner-city neighborhood. Oropharyngeal swabs were collected from rats trapped in 33 city blocks and one location within the adjacent port. Bacterial culture was performed and MRSA isolates were characterized using a variety of methods, including whole-genome sequencing (WGS). The ecology of MRSA in rats was described using phylogenetic analysis, geospatial analysis, and generalized linear mixed models. MRSA was identified 22 of 637 (3.5%) rats tested, although prevalence varied from 0 – 50% among blocks. Isolates belonged to 4 clusters according to WGS, with the largest cluster (n = 10) containing isolates that were genetically indistinguishable from community-acquired USA300 MRSA strains isolated from people within the study area. MRSA strains demonstrated both geographic clustering and dispersion. The odds of an individual rat carrying MRSA increased with increased body fat (OR = 2.53, 95% CI = 1.33 – 4.82), and in the winter (OR = 5.29, 95% CI = 1.04 – 26.85) and spring (OR = 5.50, 95% CI = 1.10 – 27.58) compared to the fall. The results show that urban rats carried the same MRSA lineages occurring in local human and/or animal populations, supporting recent transmission from external sources. MRSA carriage was influenced by season, most likely as a result of temporal variation in rat behavior and rat-human interactions.
doi:10.1371/journal.pone.0087983
PMCID: PMC3912160  PMID: 24498421
14.  Characterization of Methicillin-Resistant and -Susceptible Staphylococcal Isolates from Bovine Milk in Northwestern China 
PLoS ONE  2015;10(3):e0116699.
Emergence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) in bovine milk is a major public health concern. The primary purpose of this research was to determine molecular genetic characteristics and antibiotic resistance of staphylococcal isolates recovered from milk of mastitic cows in the Shaanxi Province in Northwestern China. One hundred and thirteen methicillin-susceptible Staphylococcus aureus (MSSA), one mecA-positive and phenotype-positive MRSA, seven mecA- and mecC- negative but phenotype-positive MRSA and two MR-CoNS including one oxacillin-susceptible mecA-positive Staphylococcus haemolyticus (OS-MRSH) and one mecA-positive and methicillin-resistant Staphylococcus epidermidis (MRSE) isolates were recovered from 214 quarter milk samples on 4 dairy farms. All above 123 isolates were subjected to antibiotic resistance profiling. S. aureus isolates were also genotyped using the spa typing and the multilocus sequence typing (MLST). Eight MRSA and 2 MR-CoNS isolates were additionally tested for SCCmec types. Resistance was common among isolates against ampicillin or penicillin (80.5%), kanamycin (68.3%), gentamicin (67.5%), tetracycline (43.9%) and chloramphenicol (30.1%). However, no isolate was resistant to vancomycin or teicoplanin. Twenty, 29 and 58 isolates showed resistance to 1, 2 or more than 2 antibiotics, respectively. The predominant multidrug resistance profile was penicillin/ampicillin/kanamycin/gentamicin/tetracycline (46 isolates). Most S. aureus isolates belonged to spa types t524 (n = 63), t11772 (a new type, n = 31) and t4207 (n = 15). At the same time, MLST types ST71 (n = 67) and ST2738 (a new type, n = 45) were identified as dominant sequence types. The mecA-positive and phenotype-positive MRSA isolate had a composite genotype t524-ST71-SCCmecIVa, while 7 mecA-negative but phenotype-positive MRSA isolates were all t524-ST71. The OS-MRSH isolate contained a type V SCCmec cassette, while the MRSE isolate possessed a non-typeable SCCmec. The spa-MLST types t11772-ST2738 (n = 27), t11807-ST2683 (n = 4) and t11771-ST2738 (n = 3) were newly identified genotypes of S. aureus. These new genotypes and multidrug-resistant staphylococci could pose additional threat to animal and human health.
doi:10.1371/journal.pone.0116699
PMCID: PMC4355487  PMID: 25756992
15.  Transmission of Methicillin-Resistant Staphylococcus aureus to Household Contacts▿  
Journal of Clinical Microbiology  2009;48(1):202-207.
The frequency of and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) transmission from a MRSA index person to household contacts were assessed in this prospective study. Between January 2005 and December 2007, 62 newly diagnosed MRSA index persons (46 patients and 16 health care workers) and their 160 household contacts were included in the study analysis. Transmission of MRSA from an index person to household contacts occurred in nearly half of the cases (47%; n = 29). These 29 index persons together had 84 household contacts, of which two-thirds (67%; n = 56) became MRSA positive. Prolonged exposure time to MRSA at home was a significant risk factor for MRSA transmission to household contacts. In addition, MRSA colonization at least in the throat, younger age, and eczema in index persons were significantly associated with MRSA transmission; the presence of wounds was negatively associated with MRSA transmission. Furthermore, an increased number of household contacts and being the partner of a MRSA index person were household-related risk factors for MRSA acquisition from the index person. No predominant pulsed-field gel electrophoresis (PFGE) type was observed to be transmitted more frequently than other PFGE types. To date, screening household contacts and providing MRSA eradication therapy to those found positive simultaneously with the index person is not included in the “search-and-destroy” policy. We suggest including both in MRSA prevention guidelines, as this may reduce further spread of MRSA.
doi:10.1128/JCM.01499-09
PMCID: PMC2812253  PMID: 19923490
16.  Usefulness of previous methicillin-resistant Staphylococcus aureus screening results in guiding empirical therapy for S aureus bacteremia 
Staphylococcus aureus bacteremia (SAB), which may be caused by methicillin-resistant S aureus (MRSA), is a leading cause of bloodstream infections. SAB and MRSA can cause an increase in mortality, result in longer hospital stays and increase medical costs. However, it is possible that MRSA colonization may predict infection. Using a retrospective cohort investigation, this study evaluated the clinical utility of past MRSA screening swabs for predicting methicillin resistance and its use in guiding empirical antibiotic therapy for SAB.
BACKGROUND:
Staphylococcus aureus bacteremia (SAB) is an important infection. Methicillin-resistant S aureus (MRSA) screening is performed on hospitalized patients for infection control purposes.
OBJECTIVE:
To assess the usefulness of past MRSA screening for guiding empirical antibiotic therapy for SAB.
METHODS:
A retrospective cohort study examined consecutive patients with confirmed SAB and previous MRSA screening swab from six academic and community hospitals between 2007 and 2010. Diagnostic test properties were calculated for MRSA screening swab for predicting methicillin resistance of SAB.
RESULTS:
A total of 799 patients underwent MRSA screening swabs before SAB. Of the 799 patients, 95 (12%) had a positive and 704 (88%) had a negative previous MRSA screening swab. There were 150 (19%) patients with MRSA bacteremia. Overall, previous MRSA screening swabs had a positive likelihood ratio of 33 (95% CI 18 to 60) and a negative likelihood ratio of 0.45 (95% CI 0.37 to 0.54). Diagnostic accuracy differed depending on mode of acquisition (ie, community-acquired, nosocomial or health care-associated infection) (P<0.0001) and hospital (P=0.0002). At best, for health care-associated infection, prior MRSA screening swab had a positive likelihood ratio of 16 (95% CI 9 to 28) and a negative likelihood ratio of 0.27 (95% CI 0.17 to 0.41).
CONCLUSIONS:
A negative prior MRSA screening swab cannot reliably rule out MRSA bacteremia and should not be used to guide empirical antibiotic therapy for SAB. A positive prior MRSA screening swab greatly increases likelihood of MRSA, necessitating MRSA coverage in empirical antibiotic therapy for SAB.
PMCID: PMC4556181  PMID: 26361488
Antimicrobial stewardship; Empirical antimicrobial therapy; MRSA screening; Sensitivity; Specificity; Staphylococcus aureus bacteremia
17.  Environmental Methicillin-Resistant Staphylococcus aureus in a Veterinary Teaching Hospital During a Nonoutbreak Period 
Abstract
Concurrent to reports of zoonotic and nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) in veterinary settings, recent evidence indicates that the environment in veterinary hospitals may be a potential source of MRSA. The present report is a cross-sectional study to determine the prevalence of MRSA on specific human and animal contact surfaces at a large veterinary hospital during a nonoutbreak period. A total of 156 samples were collected using Swiffers® or premoistened swabs from the small animal, equine, and food animal sections. MRSA was isolated and identified by pre-enrichment culture and standard microbiology procedures, including growth on Mueller-Hinton agar supplemented with NaCl and oxacillin, and by detection of the mecA gene. Staphylococcal chromosome cassette mec (SCCmec) typing and pulsed-field gel electrophoresis profile were also determined. MRSA was detected in 12% (19/157) of the hospital environments sampled. The prevalence of MRSA in the small animal, equine, and food animal areas were 16%, 4%, and 0%, respectively. Sixteen of the MRSA isolates from the small animal section were classified as USA100, SCCmec type II, two of which had pulsed-field gel electrophoresis pattern that does not conform to any known type. The one isolate obtained from the equine section was classified as USA500, SCCmec type IV. The molecular epidemiological analysis revealed a very diverse population of MRSA isolates circulating in the hospital; however, in some instances, multiple locations/surfaces, not directly associated, had the same MRSA clone. No significant difference was observed between animal and human contact surfaces in regard to prevalence and type of isolates. Surfaces touched by multiple people (doors) and patients (carts) were frequently contaminated with MRSA. The results from this study indicate that MRSA is present in the environment even during nonoutbreak periods. This study also identified specific surfaces in a veterinary environment that need to be targeted when designing and executing infection control programs.
doi:10.1089/vbz.2010.0181
PMCID: PMC3391706  PMID: 21417926
environment; MRSA; nosocomial; veterinary hospital
18.  Epidemiology and molecular characterization of methicillin-resistant Staphylococcus aureus nasal carriage isolates from bovines 
BMC Veterinary Research  2014;10:153.
Background
Staphylococcus aureus is a common bacterium usually found on skin and mucous membranes of warm blooded animals. Resistance in S. aureus has been increasingly reported though depending on the clonal lineage. Indeed, while hospital acquired (HA)-methicillin resistant S. aureus (MRSA) are typically multi-resistant, community associated (CA)-MRSA are by large more susceptible to many antibiotics. Although S. aureus isolated from animals are often susceptible to most antibiotics, multi-resistant livestock associated (LA)-MRSA have been recovered from bovine mastitis.
In this study, we investigated the prevalence and types of MRSA present in the nose of healthy bovines of different age groups and rearing practices. Since no validated methods for MRSA isolation from nasal swabs were available, we compared two isolation methods. Molecular characterization was performed by means of spa-typing, MLST, SCCmec typing and microarray analysis for the detection of antimicrobial resistance and virulence genes.
Results
MRSA between herd prevalence in bovines was estimated at 19.8%. There was a marked difference between rearing practices with 9.9%, 10.2% and 46.1% of the dairy, beef and veal calve farms respectively being MRSA positive. No significant difference was observed between both isolation methods tested. Most isolates were ST398 spa type t011 or closely related spa types. Few ST239 spa type t037 and t388 and ST8 spa type t121 were also found. SCCmec types carried by these strains were mainly type IV(2B), IV(2B&5) and type V. Type III and non-typeable SCCmec were recovered to a lesser extent. All isolates were multi-resistant to at least two antimicrobials in addition to the expected cefoxitin and penicillin resistance, with an average of resistance to 9.5 different antimicrobials. Isolates selected for microarray analysis carried a broad range of antimicrobial resistance and virulence genes.
Conclusion
MRSA were mainly present in veal farms, compared to the lower prevalence in dairy or beef farms. Multi-resistance in these strains was high. Though mainly CC398 spa t011 was found, the genetic diversity was higher than what was found for pigs in Belgium. CC8 strains, a typically human lineage but also recently found also in association with bovines, has been retrieved here also.
doi:10.1186/1746-6148-10-153
PMCID: PMC4103977  PMID: 25011427
Nasal carriage; Bovine; Epidemiology; Molecular characterization; Antimicrobial resistance
19.  Prevalence of colonization by methicillin-resistant Staphylococcus aureus ST398 in pigs and pig farm workers in an area of Catalonia, Spain 
BMC Infectious Diseases  2016;16:716.
Background
A livestock-associated clonal lineage (ST398) of methicillin-resistant Staphylococcus aureus (MRSA) has been identified causing colonization or infection in farm workers. The aim of the study was to analyze the prevalence of MRSA-ST398 colonization in pigs and in pig farmers in an area with a high pig population (Osona, Barcelona province, Catalonia, Spain).
Methods
We performed a cross-sectional prevalence study in Osona (Catalonia, Spain), from June 2014 to June 2015. All pig farm workers from 83 farms were studied. Twenty of these farms were randomly selected for the study of both pigs and farmers: 9 fattening and 11 farrow-to-finish farms. All workers over the age of 18 who agreed to participate were included. Samples were analyzed to identify MRSA-ST398 and their spa type.
Results
Eighty-one of the 140 pig farm workers analyzed (57.9% (95% IC: 50.0–66.4%)) were MRSA-positive, all of them ST398. The mean number of years worked on farms was 17.5 ± 12.6 (range:1–50), without significant differences between positive and negative MRSA results (p = 0.763). Over 75% of MRSA-ST398 carriers worked on farms with more than 1250 pigs (p < 0.001). At least one worker tested positive for MRSA-ST398 on all 20 selected pig farms. Ninety-two (46.0% (95% IC: 39.0–53.0%)) of the nasal swabs from 200 pigs from these 20 farms were MRSA-positive, with 50.5% of sows and 41.4% of fattening pigs (p = 0.198) giving MRSA-positive results. All the isolates were tetracycline-resistant, and were identified as MRSA-ST398. The spa type identified most frequently was t011 (62%). Similar spa types and phenotypes of antibiotic resistance were identified in pigs and farmers of 19/20 tested farms.
Conclusions
The prevalence of MRSA-ST398 among pig farm workers and pigs on farms in the studied region is very high, and the size of the farm seems to correlate with the frequency of colonization of farmers. The similar spa-types and phenotypes of resistance detected in pigs and workers in most of the farms studied suggest animal-to-human transmission.
doi:10.1186/s12879-016-2050-9
PMCID: PMC5127002  PMID: 27894267
MRSA ST398; ST398; Pig farmer; Pig; Livestock associated MRSA
20.  Methicillin-Resistant Staphylococcus aureus Colonization and Risk of Subsequent Infection in Critically Ill Children: Importance of Preventing Nosocomial Methicillin-Resistant Staphylococcus aureus Transmission 
Methicillin-resistant Staphylococcus aureus (MRSA) colonization is a risk factor for infection in critically ill children. Almost half of children who acquired MRSA colonization in our ICU developed an MRSA infection during their hospitalization or after discharge, highlighting the importance of preventing nosocomial MRSA transmission.
Background. Methicillin-resistant Staphylococcus aureus (MRSA) colonization is a predictor of subsequent infection in hospitalized adults. The risk of subsequent MRSA infections in hospitalized children colonized with MRSA is unknown.
Methods. Children admitted to an academic medical center’s pediatric intensive care unit between March 2007 and March 2010 were included in the study. Anterior naris swabs were cultured to identify children with MRSA colonization at admission. Laboratory databases were queried and National Healthcare Safety Network definitions applied to identify patients with MRSA infections during their hospitalization or after discharge.
Results. The MRSA admission prevalence among 3140 children was 4.9%. Overall, 56 children (1.8%) developed an MRSA infection, including 13 (8.5%) colonized on admission and 43 (1.4%) not colonized on admission (relative risk [RR], 5.9; 95% confidence interval [CI], 3.4–10.1). Of those, 10 children (0.3%) developed an MRSA infection during their hospitalization, including 3 of 153 children (1.9%) colonized on admission and 7 of 2987 children (0.2%) not colonized on admission (RR, 8.4; 95% CI, 2.7–25.8). African-Americans and those with public health insurance were more likely to get a subsequent infection (P < .01 and P = .03, respectively). We found that 15 children acquired MRSA colonization in the pediatric intensive care unit, and 7 (47%) developed a subsequent MRSA infection.
Conclusions. MRSA colonization is a risk factor for subsequent MRSA infection in children. Although MRSA colonized children may have lower risks of subsequent infection than adults, children who acquire MRSA in the hospital have similarly high rates of infection. Preventing transmission of MRSA in hospitalized children should remain a priority.
doi:10.1093/cid/cir547
PMCID: PMC3189167  PMID: 21878424
21.  Mupirocin-Resistant, Methicillin-Resistant Staphylococcus aureus Strains in Canadian Hospitals▿  
Antimicrobial Agents and Chemotherapy  2007;51(11):3880-3886.
Mupirocin resistance in Staphylococcus aureus is increasingly being reported in many parts of the world. This study describes the epidemiology and laboratory characterization of mupirocin-resistant methicillin-resistant S. aureus (MRSA) strains in Canadian hospitals. Broth microdilution susceptibility testing of 4,980 MRSA isolates obtained between 1995 and 2004 from 32 Canadian hospitals was done in accordance with CLSI guidelines. The clinical and epidemiologic characteristics of strains with high-level mupirocin resistance (HLMupr) were compared with those of mupirocin-susceptible (Mups) strains. MRSA strains were characterized by pulsed-field gel electrophoresis (PFGE) and typing of the staphylococcal chromosomal cassette mec. PCR was done to detect the presence of the mupA gene. For strains with mupA, plasmid DNA was extracted and subjected to Southern blot hybridization. A total of 198 (4.0%) HLMupr MRSA isolates were identified. The proportion of MRSA strains with HLMupr increased from 1.6% in the first 5 years of surveillance (1995 to 1999) to 7.0% from 2000 to 2004 (P < 0.001). Patients with HLMupr MRSA strains were more likely to have been aboriginal (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5 to 9.4; P = 0.006), to have had community-associated MRSA (OR, 2.2; 95% CI, 1.0 to 5.0; P = 0.05), and to have been colonized with MRSA (OR, 1.7; 95% CI, 1.0 to 3.0; P = 0.04). HLMupr MRSA strains were also more likely to be resistant to fusidic acid (21% versus 4% for mupirocin-susceptible strains; P < 0.001). All HLMupr MRSA strains had a plasmid-associated mupA gene, most often associated with a 9-kb HindIII fragment. PFGE typing and analysis of the plasmid profiles indicate that both plasmid transmission and the clonal spread of HLMupr MRSA have occurred in Canadian hospitals. These results indicate that the incidence of HLMupr is increasing among Canadian strains of MRSA and that HLMupr MRSA is recovered from patients with distinct clinical and epidemiologic characteristics compared to the characteristics of patents with Mups MRSA strains.
doi:10.1128/AAC.00846-07
PMCID: PMC2151460  PMID: 17724154
22.  Frequency of resistance to methicillin and other antimicrobial agents among Staphylococcus aureus strains isolated from pigs and their human handlers in Trinidad 
Infection Ecology & Epidemiology  2014;4:10.3402/iee.v4.22736.
Background
Methicillin-resistant Staphylococcus aureus (MRSA) has emerged recently worldwide in production animals, particularly pigs and veal calves, which act as reservoirs for MRSA strains for human infection. The study determined the prevalence of MRSA and other resistant strains of S. aureus isolated from the anterior nares of pigs and human handlers on pig farms in Trinidad.
Methods
Isolation of S. aureus was done by concurrently inoculating Baird-Parker agar (BPA) and Chromagar MRSA (CHROM) with swab samples and isolates were identified using standard methods. Suspect MRSA isolates from Chromagar and BPA were subjected to confirmatory test using Oxoid PBP2 latex agglutination test. The disc diffusion method was used to determine resistance to antimicrobial agents.
Results
The frequency of isolation of MRSA was 2.1% (15 of 723) for pigs but 0.0% (0 of 72) for humans. Generally, for isolates of S. aureus from humans there was a high frequency of resistance compared with those from pigs, which had moderate resistance to the following antimicrobials: penicillin G (54.5%, 51.5%), ampicillin (59.1%, 49.5%), and streptomycin (59.1%, 37.1%), respectively. There was moderate resistance to tetracycline (36.4%, 41.2%) and gentamycin (27.2%, 23.7%) for human and pig S. aureus isolates, respectively, and low resistance to sulfamethoxazole-trimethoprim (4.5%, 6.2%) and norfloxacin (9.1%, 12.4%), respectively. The frequency of resistance to oxacillin by the disc method was 36.4 and 34.0% from S. aureus isolates from humans and pigs, respectively. Out of a total of 78 isolates of S. aureus from both human and pig sources that were resistant to oxacillin by the disc diffusion method, only 15 (19.2%) were confirmed as MRSA by the PBP'2 latex test kit.
Conclusions
The detection of MRSA strains in pigs, albeit at a low frequency, coupled with a high frequency of resistance to commonly used antimicrobial agents in pig and humans could have zoonotic and therapeutic implications. Finally, the diagnostic limitation of using CHROMagar and testing for oxacillin resistance by the disc diffusion method alone to determine MRSA strains without performing confirmatory tests cannot be overemphasized because the possibility of overdiagnosis of MRSA infections cannot be ignored.
doi:10.3402/iee.v4.22736
PMCID: PMC3974178  PMID: 24765251
Staphylococcus aureus; MRSA; methicillin; pigs; resistance; Trinidad
23.  Genotypic and Phenotypic Markers of Livestock-Associated Methicillin-Resistant Staphylococcus aureus CC9 in Humans 
Applied and Environmental Microbiology  2016;82(13):3892-3899.
ABSTRACT
Use of antimicrobials in industrial food animal production is associated with the presence of multidrug-resistant Staphylococcus aureus among animals and humans. The livestock-associated (LA) methicillin-resistant S. aureus (MRSA) clonal complex 9 (CC9) is associated with animals and related workers in Asia. This study aimed to explore the genotypic and phenotypic markers of LA-MRSA CC9 in humans. We conducted a cross-sectional study of livestock workers and controls in Guangdong, China. The study participants responded to a questionnaire and provided a nasal swab for S. aureus analysis. The resulting isolates were assessed for antibiotic susceptibility, multilocus sequence type, and immune evasion cluster (IEC) genes. Livestock workers had significantly higher rates of S. aureus CC9 (odds ratio [OR] = 30.98; 95% confidence interval [CI], 4.06 to 236.39) and tetracycline-resistant S. aureus (OR = 3.26; 95% CI, 2.12 to 5.00) carriage than controls. All 19 S. aureus CC9 isolates from livestock workers were MRSA isolates and also exhibited the characteristics of resistance to several classes of antibiotics and absence of the IEC genes. Notably, the interaction analyses indicated phenotype-phenotype (OR = 525.7; 95% CI, 60.0 to 4,602.1) and gene-environment (OR = 232.3; 95% CI, 28.7 to 1,876.7) interactions associated with increased risk for livestock-associated S. aureus CC9 carriage. These findings suggest that livestock-associated S. aureus and MRSA (CC9, IEC negative, and tetracycline resistant) in humans are associated with occupational livestock contact, raising questions about the potential for occupational exposure to opportunistic S. aureus.
IMPORTANCE This study adds to existing knowledge by giving insight into the genotypic and phenotypic markers of LA-MRSA. Our findings suggest that livestock-associated S. aureus and MRSA (CC9, IEC negative, and tetracycline resistant) in humans are associated with occupational livestock contact. Future studies should direct more attention to exploring the exact transmission routes and establishing measures to prevent the spread of LA-MRSA.
doi:10.1128/AEM.00091-16
PMCID: PMC4907189  PMID: 27107114
24.  Factors Associated with Nasal Colonization of Methicillin-Resistant Staphylococcus aureus among Healthy Children in Taiwan▿  
Journal of Clinical Microbiology  2010;49(1):131-137.
Methicillin-resistant Staphylococcus aureus (MRSA) has been identified as a major cause of community-associated (CA) S. aureus infections in the past decade. The main reservoir in the community for MRSA and the factors contributing to its worldwide spread remain poorly defined. Between July 2005 and June 2008, a total of 6,057 healthy children 2 to 60 months of age were screened for carriage of S. aureus and Streptococcus pneumoniae in Taiwan. The prevalence and epidemiological factors influencing MRSA carriage were determined. MRSA strains were tested for antimicrobial susceptibility and underwent molecular characterization. The overall prevalences of MRSA and S. aureus carriage were 7.8% and 23.2%, respectively. A majority (88%) of MRSA isolates belonged to a common Asian-Pacific CA-MRSA lineage, multilocus sequence type 59, and were resistant to multiple non-beta-lactam antibiotics. The carriage rate of MRSA was higher among subjects 2 to 6 months old (P < 0.0001), residing in northern Taiwan (P = 0.0003), and enrolled later in the study (P < 0.0001). MRSA colonization was associated with the number of children in the family (adjusted odds ratio [aOR], 1.114; 95% confidence interval [CI], 1.002 to 1.240; P = 0.0463) and day care attendance (aOR, 1.530; 95% CI, 1.201 to 1.949; P = 0.0006). Breast feeding (P < 0.0001) and colonization with S. pneumoniae (P = 0.0170) were protective against MRSA colonization. We concluded that epidemic CA-MRSA strains increasingly colonized Taiwanese children between 2005 and 2008. The carriage rate varied significantly across different demographical features. Crowding was an independent environmental risk factor that might accelerate CA-MRSA transmission in the community.
doi:10.1128/JCM.01774-10
PMCID: PMC3020448  PMID: 21084507
25.  Community-Acquired Methicillin-Resistant Staphylococcus aureus: Prevalence and Risk Factors  
Journal of Athletic Training  2006;41(3):337-340.
Reference/Citation: Salgado CD, Farr BM, Calfee DP. Community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis of prevalence and risk factors. Clin Infect Dis.20033613113912522744.
Clinical Question: What are the prevalence rates and risk factors associated with community-acquired methicillin-resistant Staphylococcus aureus (MRSA)?
Data Sources: Studies were identified by searching MEDLINE (January 1966–February 2002) and abstracts from scientific meetings (1996–2001). Reviews of citations and reference lists were performed to identify additional eligible studies. The search terms included Staphylococcus aureus , infection, colonization, methicillin resistance, community-acquired, community-onset, prevalence, frequency, and risk factors.
Study Selection: The search was limited to English-language investigations identified from the electronic and manual searches. Studies were divided into 2 groups, as follows: group 1, retrospective or prospective studies that reported the prevalence of community-acquired MRSA (CA-MRSA) among hospital patients who were colonized (presence of bacteria without infection) or infected with MRSA; and group 2, studies that reported the prevalence of MRSA colonization in the community. The studies were evaluated independently by 2 authors, and case reports were excluded.
Data Extraction: Data extraction and study quality assessment procedures were not fully explained. The outcome measures for hospital patients were definitions of CA-MRSA used in the study, prevalence of CA-MRSA, sample size, number and type of risk factors assessed, and number of patients with ≥1 health care–associated risk factor. The studies were grouped based on type, retrospective or prospective. The pooled prevalence of CA-MRSA was calculated for each group (retrospective or prospective) and was limited to the prevalence among patients with MRSA. The proportion of patients who reported ≥1 health care–associated risk factor was also calculated. The outcome measures among community members were prevalence of MRSA, sample size, number and type of risk factors assessed, number of members with ≥1 risk factor, and MRSA strain type, when available. The studies were grouped based on the population surveyed (surveillance cultures, contacts with MRSA-colonized individuals, or sport team members or day care contacts). The pooled prevalence of MRSA colonization and the proportion of members with ≥1 reported risk factor were calculated for each of the study populations listed above. The proportion of CA-MRSA strains that represented typical nosocomial (infection that develops in the hospital) strains was also determined. Chi-square analysis was performed to compare proportions and to determine heterogeneity among the studies.
Main Results: Specific search criteria identified 104 studies for review, of which 57 met inclusion and exclusion criteria. Thirty-nine studies focused on CA-MRSA among hospital patients who were colonized or infected with MRSA. Of these, 32 groups (27 retrospective, 5 prospective) reported the prevalence of CA-MRSA using clinical specimens. Seven groups identified risk factors of CA-MRSA among patients previously diagnosed with MRSA. Thirteen different definitions of CA-MRSA were used in 31 of these studies, and 8 groups did not report the definitions used. The isolation of MRSA within 48 hours of hospital admission, with or without recent admission to a hospital or long-term care facility, or previous history of MRSA colonization were the most common definitions in the studies.
The risk factors included recent hospitalization (range, 1–24 months before identification of MRSA infection or colonization), recent outpatient visit (usually within 12 months), recent nursing home admission (usually within 12 months), recent antibiotic exposure (range, 1–12 months), chronic illness (eg, end-stage renal disease, diabetes, or malignancy), injection drug use, and close contact with a person who had risk factor(s) for MRSA acquisition. The presence of health care–associated risk factors was examined in 17 of the retrospective studies, and the median number of factors studied was 2 (range, 1–6). Among 4121 patients in these studies, 86.1% were found to have ≥1 health care–associated risk factor. All authors of prospective studies (5) examined health care–associated risk factors, and the median number of factors studied was 4 (range, 2–4). Among the 636 patients, 86.9% had ≥1 health care–associated risk factor. In the 7 studies with 515 patients previously diagnosed with MRSA, 84.7% had ≥1 health care–associated risk factor. The most common risk factors assessed in the 17 retrospective studies were recent hospitalization and chronic illness requiring health care visits.
The pooled CA-MRSA prevalence was 30.2% (range, 1.9%– 96%) among 5932 patients from the 27 retrospective studies and 37.3% (range, 18.2%–51.2%) among 636 patients from the 5 prospective studies. Eighteen groups reported the prevalence of MRSA colonization in the community. Ten of these reported MRSA prevalence using surveillance cultures, 4 examined colonization status of household contacts with discharged hospital patients with nosocomial MRSA colonization, and 4 reported colonization status of sports team members or day care contacts of persons colonized with MRSA. In the 10 surveillance studies, the pooled MRSA colonization prevalence was 1.3% (95% confidence interval [CI], 1.04%–1.53%; range, 0.2%– 7.4%) among 8350 community members. Nine of these studies were stratified based on culture samples taken before the assessment of risk factors, and among 4825 people, the pooled MRSA colonization prevalence was 2.1%. When examining health care–associated risk factors, the median number of factors studied was 5 (range, 1–10), and 47.5% with MRSA had ≥1 health care–associated risk factor. The risk factors included those previously identified. In the remaining surveillance study, the MRSA colonization prevalence was 0.20% among 3525 people without prior health care contact. Compared with subjects in the 9 stratified studies with a health care contact, subjects in this study were 90% less likely to have MRSA (relative risk, 0.10; 95% CI, 0.05–0.21). Cultures for 3898 subjects in 7 of the 10 surveillance studies were obtained at the time of a hospital admission, an outpatient clinic visit, or an emergency department visit, and the pooled prevalence of MRSA colonization was 1.8%. In 3 studies in which cultures were obtained outside of a health care facility (schools, day care centers, homeless shelters, or military bases), the pooled MRSA colonization prevalence among 4452 subjects was reported to be 0.76%. Therefore, subjects in a health care facility were 2.35 times more likely to carry MRSA than were subjects outside of a health care facility (95% CI, 1.56–3.53). In one study examining 94 subjects in a semiclosed community, the prevalence of MRSA colonization was 7.4%. These subjects were 36 times more likely to carry MRSA than were subjects who were not in a semiclosed community (95% CI, 13.7–94.7).
The studies also identified 70 MRSA isolates (pure form of an organism in a microbial culture) from subjects who reported no health care–associated risk factors. Strain typing was performed with 32 isolates, and 29 (91%) isolates were similar to strains identified in hospitals. The colonization status of 191 household contacts of 93 patients with nosocomial MRSA colonization discharged from the hospital was examined in 4 studies. The results demonstrated that 17.8% of the contact subjects were colonized with a strain of MRSA having the same antibiogram (record of the susceptibility of bacteria to antibiotics) as the index case (initial individual with the strain). The authors reported that subjects who had household contacts with MRSA-colonized patients were 14 times more likely to be colonized than were community subjects without a known MRSA contact (95% CI, 9.8–20.1). In 4 studies examining 517 sports team members or day care contacts of persons known to be colonized with MRSA, 5.4% demonstrated colonization of MRSA with the same strain as the index case.
Conclusions: Based on the available data, the prevalence of MRSA among community members without health care–associated risk factors was relatively low. However, 85% of hospital patients diagnosed with CA-MRSA and 47.5% of healthy community members colonized with MRSA were found to have ≥1 health care–associated risk factor. The risk factors identified were recent hospitalization, outpatient visit, nursing home admission, antibiotic exposure, chronic illness, injection drug use, and close contact with a person with risk factor(s). Most MRSA colonization occurred among community members who had health care–associated risk factors or contact with persons with risk factors. The evidence indicated that control of MRSA in the community may require control of MRSA in the health care setting (hospital, health care office, and nursing home). The absence of a standardized definition for CA-MRSA and questions regarding the actual site of colonization versus acquisition should be considered in the interpretation of these findings.
PMCID: PMC1569547  PMID: 17043704
infectious diseases

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