INTRODUCTION — Methicillin-resistant Staphylococcus aureus (MRSA) was described shortly after the introduction of methicillin in 1961; subsequently, several outbreaks of MRSA were reported in the early 1960s [1,2]. MRSA has spread worldwide over the past decades and is now known to be prevalent in both humans and in various animal species.
Methicillin resistance is mediated by PBP-2a, a penicillin-binding protein encoded by the mecA gene that permits the organism to grow and divide in the presence of methicillin and other beta-lactam antibiotics. The mecA gene is located on a mobile genetic element called staphylococcal chromosome cassette (SCCmec). (See "Methicillin-resistant Staphylococcus aureus (MRSA): Microbiology".)
A single clone probably accounted for most MRSA isolates recovered during the 1960s; by 2004, six major MRSA clones emerged worldwide, labeled as SCCmec I to VI [3-7]. Dissemination of resistance was mediated by horizontal transfer of the mecA gene and related regulatory sequences .
The epidemiology and clinical manifestations of MRSA infection in adults will be reviewed here. Prevention, control, and treatment of MRSA infections in adults are discussed separately. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control" and "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia" and "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of skin and soft tissue infections" and "Epidemiology of Staphylococcus aureus bacteremia in adults".)
EPIDEMIOLOGY — Health care-associated methicillin-resistant S. aureus (HA-MRSA) and community-associated methicillin-resistant S. aureus (CA-MRSA) differ with respect to their clinical and molecular epidemiology.
Health care-associated MRSA infection — HA-MRSA is defined as MRSA infection that occurs >48 hours following hospitalization (hospital-onset, HA-MRSA, formerly "nosocomial") or MRSA infection that occurs outside of the hospital within 12 months of exposure to health care (eg, history of surgery, hospitalization, dialysis, or residence in a long-term care facility; community-onset, HA-MRSA) . HA-MRSA is associated with severe, invasive disease, including skin and soft tissue infection, bloodstream infection (BSI), and pneumonia [9-13]. In fact, MRSA is the leading cause of surgical site infection in both tertiary and community hospitals [14,15]. HA-MRSA strains tend to have multidrug resistance and carry staphylococcal cassette chromosome (SCCmec) type II . They are typified by a USA100 or USA200 pulse-field electrophoresis (PFGE) pattern . (See "Methicillin-resistant Staphylococcus aureus (MRSA): Microbiology".)
HA-MRSA has been a problem in hospital settings since the 1960s; there has since been a progressive increase in the prevalence of antimicrobial resistance in hospital-acquired S. aureus infections [10,18,19]. In a United States surveillance report of over 24,000 cases of hospital-acquired S. aureus BSIs, isolates with methicillin resistance increased from 22 to 57 percent between 1995 and 2001 . In the United States between 2005 and 2012, rates of hospital-onset MRSA bloodstream infection decreased by 17 percent annually . Between 2005 and 2017, United States Department of Veterans Affairs medical centers experienced a 43 percent decline in S. aureus infections following introduction of a multifaceted infection control intervention; most reductions were explained by a 55 percent decrease in MRSA .
Worldwide, HA-MRSA prevalence varies considerably, from <1 percent in Scandinavia to up to 40 percent in Japan, Israel, and elsewhere in Europe [22,23].
MRSA is one of the few pathogens routinely implicated in nearly every type of hospital-acquired infection. This is related in part to the organism's capacity for biofilm formation on invasive, foreign devices such as endotracheal tubes and urinary and endovascular catheters . Biofilm facilitates MRSA survival and multiplication on these surfaces, prolonging the duration of organism exposure to antibiotics as well as promoting the potential opportunity for transfer of antibiotic resistance genes between organisms .
Risk factors for HA-MRSA infection include antibiotic use, prolonged hospitalization, intensive care, hemodialysis, MRSA colonization, and proximity to others with MRSA colonization or infection [26-28]. Risk of MRSA infection related to antibiotic use, hemodialysis, and colonization are discussed in further detail below. (See 'Risk factors' below and 'Colonization' below.)
Risk factors associated with postdischarge MRSA infection include MRSA colonization, discharge to a nursing home, presence of a chronic wound, and discharge with a central venous catheter or other invasive device . (See "Epidemiology of Staphylococcus aureus bacteremia in adults".)
Patients with MRSA infection have higher mortality, longer hospital stays, and higher health care costs than patients with methicillin-susceptible S. aureus (MSSA) infection [13,30-33]. For example, two meta-analyses including data on approximately 4000 patients demonstrated that patients with BSI due to MRSA were 1.5- to 2.0-fold more likely to die than patients with BSI due to MSSA [13,34]. Patients with infection due to MRSA also have higher rates of acute renal failure, hemodynamic instability, and prolonged ventilator dependency than patients with infection due to MSSA .
Community-associated MRSA infection — CA-MRSA is defined as MRSA infection that occurs in the absence of health care exposure . CA-MRSA is most often associated with skin and soft tissue infections in young, otherwise healthy individuals . Most CA-MRSA strains are sensitive to non-beta-lactam antibiotics, although a multidrug-resistant isolate has been described among men who have sex with men [35,36]. This strain contains the pUSA03 plasmid and carries resistance genes for beta-lactams, fluoroquinolones, tetracycline, macrolides, clindamycin, and mupirocin .
Most CA-MRSA strains frequently carry SCCmec type IV or V and frequently carry genes for the cytotoxin Panton-Valentine leukocidin that confers enhanced virulence [36-41]. Most CA-MRSA are typified by a USA300 or USA400 pulse-field electrophoresis pattern. (See "Methicillin-resistant Staphylococcus aureus (MRSA): Microbiology".)
CA-MRSA was initially reported among injection drug users in the early 1980s  and has since become the most frequent cause of skin and soft tissue infections (SSTIs) presenting to United States emergency departments and ambulatory clinics [43,44]. This was illustrated by a prospective study of 422 patients with SSTIs seen in emergency departments in August 2004; S. aureus was implicated in 76 percent of cases, 97 percent of these isolates were the CA-MRSA USA300 strain, and 98 percent possessed the Panton-Valentine leukocidin toxin gene . USA300 appears to be more transmissible among household members than other S. aureus genetic backgrounds . SSTI due to USA300 is a risk factor for bloodstream infection due to USA300, as is use of an antimicrobial with activity against MRSA in the preceding 30 days .
Community outbreaks have been reported in multiple settings, including native and aboriginal communities, sports teams, childcare centers, military personnel, men who have sex with men, and prison inmates and guards [35,47-62]. These observations have led to identification of risk factors for CA-MRSA. These include skin trauma (eg, lacerations, abrasions, tattoos, injection drug use), cosmetic body shaving, incarceration, sharing equipment that is not cleaned or laundered between users, and close contact with others who have MRSA colonization or infection [25,47,49,51-58,63-65]. Animals can also carry MRSA and function as a source of transmission [66-70]. However, the preceding risk factors have poor predictive values as many patients with CA-MRSA have no risk factors .
Skin and soft tissue remain the predominant sites of CA-MRSA infection, although MRSA can also cause invasive, severe disease such as necrotizing pneumonia, osteomyelitis, urinary tract infection, infective endocarditis, and sepsis (with or without Waterhouse-Friderichsen syndrome) [25,59,72-77]. (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'S. aureus'.)
Evolving epidemiologic observations — Patients can develop MRSA colonization in the community and manifest infection in the hospital; however, patients can also develop MRSA colonization in the hospital and manifest infection in the community [71,78-83]. In one study including more than 400 patients with S. aureus bacteremia, hospital-onset bloodstream infections were caused by community-acquired USA300 strains that had colonized patients while they were residing in the community prior to hospitalization . In two other studies, the opposite phenomenon was observed. In one study including more than 200 patients who received hospital care and developed new MRSA infection within 18 months of their hospital discharge, 49 percent of cases occurred while in the community . Similarly, in another series of 102 patients with CA-MRSA infections, 29 percent had molecular typing consistent with HA-MRSA .
CA-MRSA strains may also cause hospital-onset, health care-associated infections, since patients who become colonized with CA-MRSA strains in the community may require hospitalization and transmit such strains to other hospitalized patients or develop infection while hospitalized (eg, following surgery or insertion of an invasive device) . In a review of 352 patients with HA-MRSA, the proportion of isolates with CA-MRSA molecular typing increased from 17 to 56 percent between 1999 and 2004 .
There is evidence that CA-MRSA may be replacing traditional hospital-acquired strains in some regions. In one study that included molecular typing of 208 isolates from hospital-onset HA-MRSA BSIs between 2000 and 2006, community-acquired strains were responsible for an increasing proportion of cases (24 to 49 percent), even though the total number of MRSA BSIs was stable . A subsequent analysis of 60 hospital-onset MRSA bloodstream infections suggests that the majority of "hospital-onset" infections caused by USA 300 MRSA strains were due to colonizing strains acquired in the community before hospitalization .
Rates of invasive HA-MRSA infections declined steadily between 2005 and 2017. The incidence of MRSA infection in hospitalized patients declined from 114 to 94 cases per 10,000 hospitalizations . Rates of decline in HA-MRSA infections began to slow in 2017  and subsequently increased again during the coronavirus disease 2019 (COVID-19) pandemic .
Hospital admissions related to MRSA skin and soft tissue infections have also declined since 2010, while the proportion of cases due to methicillin- and penicillin-sensitive S. aureus strains has increased [90-92].
MRSA colonization — Colonization with S. aureus increases risk for staphylococcal infection following invasive medical or surgical procedures. Screening of hospital patients has focused on the nares, which are the primary colonization site for this pathogen. However, some individuals have MRSA colonization of the throat only, so routine nasal screening can miss colonization in some patients. For example, one study found that 12 percent of S. aureus carriers had throat carriage of S. aureus without concurrent positive nasal cultures .
Approximately 7 percent of patients in United States hospitals are colonized with MRSA . In a study by National Health and Nutrition Examination Survey (NHANES) in the early 2000s, the percent of MRSA-colonized individuals carried a PFGE type associated with community transmission was relatively low (19 percent), suggesting that CA-MRSA may cause disease in the absence of prior nasal colonization and/or that CA-MRSA favors other sites of colonization (such as the skin, throat, or gastrointestinal tract) . Among health care workers, the prevalence of MRSA nasal colonization is 4 to 15 percent [96,97].
Issues related to decolonization are discussed further separately. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control", section on 'Targeted decolonization'.)
RISK FACTORS — Risk factors for health care-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) are described above (table 1). More detailed discussions related to antibiotic use, HIV-infected individuals, hemodialysis, long-term care facilities, and injection drug users will be reviewed in this section.
Antibiotic use — MRSA probably arose due to antibiotic selective pressure [1,24]. Antibiotic use (particularly cephalosporin and fluoroquinolone use) strongly correlates with the risk for MRSA colonization and infection [5,11,16,103-107].
In a case-control study including 1981 cases of MRSA, the risk for MRSA increased with the number of antimicrobial agents; the odds ratios (OR) for MRSA diagnosis in patients who were prescribed 1, 2 to 3, or ≥4 antimicrobial drugs were 1.57, 2.46, and 6.24, respectively. The highest risk was for fluoroquinolones (OR 3.37) .
Cephalosporins were implicated in a case-control study of 387 patients with S. aureus infection (half with MRSA and half with methicillin-susceptible S. aureus [MSSA]); patients who had received cephalosporins for ≥5 days were three times more likely to acquire MRSA than those who had not received cephalosporins [104,105].
HIV infection — HIV-infected individuals are at increased risk for MRSA colonization and infection [108-113]. In a case-control surveillance study of MRSA colonization among 726 patients, HIV was an important risk factor for colonization (OR 3.3) . HIV is also a risk factor for MRSA infection; in a retrospective study of 3455 HIV patients, the incidence of MRSA infection was nearly 5 per 100 patient-years; the incidence of MRSA infection had increased sixfold between 2000 and 2003 . The primary sites of these infections were skin and soft tissue (83 percent). Risk factors included advanced immunosuppression (CD4 count <50 cells/microL), high plasma HIV RNA (>100,000 copies/microL), and lack of antiretroviral therapy.
Injection drug use — In one report summarizing data from six Emerging Infections Program sites in the United States between 2005 and 2016; injection drug users were 16 times more likely to develop an invasive MRSA infection than noninjection users; infections included bacteremia, endocarditis, and osteomyelitis . The proportion of invasive MRSA cases that occurred among injection drug users increased from 4 to 9 percent over the last five years of the study.
Presence of an indwelling hemodialysis catheter — Patients with long-term catheters for hemodialysis access are at significantly higher risk for invasive catheter-related infections due to MRSA and other pathogens. For example, in a review of 5287 cases of invasive MRSA infection during 2005, 15 percent occurred in dialysis patients; in fact, the incidence of invasive MRSA infection was 100 times higher among dialysis patients than in the general population (45 versus 0.4 per 1000 patients) . Between 2005 and 2011, however, there was a significant decrease in incidence of invasive MRSA among dialysis patients (from 6.5 to 4.2 cases per 100 dialysis patients) .
Residence in a long-term care facility — HA-MRSA is prevalent among residents of long-term care facilities . For example, S. aureus accounted for about 15 percent of acquired infections in a five-year observational study of a 120-bed nursing facility; roughly half were due to MRSA. In addition, MRSA-colonized residents are frequently transferred between hospitals and long-term care facilities, creating an ongoing circuit of MRSA transmission in areas where these organisms are prevalent.
TRANSMISSION — Health care-associated MRSA (HA-MRSA) strains are most commonly transmitted to patients via the transiently contaminated hands of health care workers. Hospitalized patients may also acquire HA-MRSA from contaminated environmental surfaces. In contrast, community-associated MRSA (CA-MRSA) strains are most often transmitted by direct contact with a colonized or infected individual.
However, individuals in the community may also acquire CA-MRSA by contact with contaminated fomites used by an affected individual. Among 188 household contacts of 148 patients known to be colonized with MRSA prior to hospital discharge, 19 percent acquired MRSA colonization, though none developed MRSA infection . Household environmental contamination is also associated with a risk of recurrent infection . Older age and providing health care to the discharged patient were associated with MRSA acquisition. Adherence to infection control measures is critical for interrupting MRSA transmission. (See "Infection prevention: Precautions for preventing transmission of infection" and "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control".)
MRSA transmission from pets such as dogs and cats to humans may also occur as can transmission from food animals to farm workers [118,119].
Whole genome sequencing (WGS) has shed significant light on the transmission dynamics of MRSA [120-125]. In fact, real-time application of whole genome sequencing is increasingly used as a tool to identify transmission within hospitals .
●An analysis of 37 MRSA acquisitions among patients admitted to the ICU used WGS to conclude that only 7 (19 percent) were transmissions from other colonized patients .
●Investigation of 685 MRSA isolates from 610 patients in London demonstrated that sequence-type clusters could be identified across hospital and outpatient settings .
●An evaluation of more than 2200 MRSA isolates from more than 1400 patients in the east of England suggested that confirmed transmission of MRSA is still more likely to occur in the hospital setting; of 173 clusters of acquisition, 68 percent occurred among patients with hospitals contact alone and 16 percent occurred among patients with both hospital and community contact .
●In a study of 413 MRSA isolates from 66 intensive care unit (ICU) patients in a single hospital, multiple separate MRSA infection clusters due to identical strains occurred between and within ICUs, illustrating that MRSA transmission occurs among patients, health care workers, and the environment .
Colonization — Individuals colonized with MRSA serve as a reservoir for transmission. MRSA can colonize the skin and nares of hospitalized patients, health care workers, and healthy individuals (up to 7 percent) [28,108,127-129].
Colonization increases the risk for MRSA infection [18,130]. In a study of 758 patients for whom nares cultures were obtained on hospital admission , the rate of MRSA infection in the year following admission was substantially higher among those with baseline MRSA colonization than those without colonization (19 versus 2 percent, respectively).
Colonization can occur in the following ways [1,131]:
●Contact with contaminated wounds or dressings of infected patients
●Contact with another individual's colonized intact skin
●Contact with contaminated inanimate objects
●Inhalation of aerosolized droplets from chronic nasal carriers
The anterior nares is the most common site of MRSA colonization [131-134]. Individuals with nasal MRSA carriage transmit MRSA more readily in the setting of concomitant sinus infection or upper respiratory infection [135,136]. A majority of individuals with nasal colonization are also colonized on other areas of intact skin including the hands, axillae, perineum, and umbilicus (in infants) [131,133,137-139].
Other potential sites of MRSA colonization include surgical wounds, decubitus ulcers, intravascular catheter sites and other invasive devices, throat, sputum, stool, and the genitourinary tract. In one study of 71 hospitalized patients with S. aureus colonization, 67 percent had colonization of the gastrointestinal tract, which was associated with increased frequency of S. aureus skin colonization . The durability of MRSA colonization can vary from a few days or weeks to up to several years [132,141]. In one prospective cohort study of 78 patients with MRSA colonization, the median duration of colonization was 8.5 months . Patients with breaks in skin were more likely to have longer duration of MRSA colonization than patients with intact skin (odds ratio 4.3, p = 0.004).
The natural history of MRSA and methicillin-susceptible S. aureus (MSSA) colonization was evaluated in a 10-week prospective observational study of 812 soldiers . Baseline colonization rates with MRSA were lower than MSSA (3 versus 28 percent), but subsequent development of infection was higher among those with MRSA than MSSA colonization (38 versus 3 percent). The rate of CA-MRSA colonization fell to under 2 percent at 10-week follow-up.
Individual MRSA colonization is an important risk factor for subsequent development of MRSA infection . In a review of 758 hospitalized patients, MRSA colonization was observed in 3.4 percent of admissions and acquired in an additional 3 percent; the rates of MRSA infection within one year in these groups were 19 and 25 percent (relative risks 9.5 and 13 compared with patients with no colonization or MSSA colonization, respectively) . Previously colonized patients should be considered to be at risk of continued carriage for at least four years . Among 1564 MRSA carriers, the prevalence of colonization was observed to decrease rapidly to 48 percent at one year; thereafter, rates of colonization remained high for prolonged periods, as 21 percent remained colonized at four years.
Environmental contamination — MRSA-contaminated surfaces can serve as reservoirs for MRSA transmission [145-147]. In a prospective culture survey of a 200-bed hospital, cultures obtained from the hospital room inanimate surfaces of MRSA-infected patients were positive more frequently in the setting of wound infections or urinary tract infections than in the setting of MRSA infection at other sites (36 versus 6 percent) . In another study, environmental surfaces in the rooms of patients with heavy gastrointestinal MRSA colonization and diarrhea were contaminated in 59 percent of cases .
MRSA may also be transmissible between health care workers via medical equipment. In a study of cultures from 200 stethoscope ear tips, 80 percent were contaminated with microorganisms. Among the positive cultures, 58 percent were Staphylococcus species and 17 percent were MRSA .
Issues related to environmental cleaning are discussed further separately. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control", section on 'Environmental cleaning'.)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topic (see "Patient education: Methicillin-resistant Staphylococcus aureus (MRSA) (Beyond the Basics)")
●Health care-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) is associated with severe, invasive disease in hospitalized patients. (See 'Health care-associated MRSA infection' above.)
●Community-associated methicillin-resistant S. aureus (CA-MRSA) is most often associated with skin and soft tissue infections in young, healthy individuals with no recent health care exposure. (See 'Community-associated MRSA infection' above.)
●Though convenient epidemiologic terms, the line between "health care-associated" and "community-associated" MRSA is significantly blurred. Patients can develop MRSA colonization in one realm and develop manifestations of infection in another or simply introduce MRSA in the second realm. (See 'Evolving epidemiologic observations' above.)
●Risk factors for infection due to HA-MRSA include antibiotic use, prolonged hospitalization, intensive care, invasive devices, hemodialysis, MRSA colonization, and proximity to others with MRSA colonization or infection. (See 'Health care-associated MRSA infection' above.)
●Additional risk factors for CA-MRSA infection include skin trauma (eg, lacerations, abrasions, tattoos, injection drug use), cosmetic body shaving, incarceration, HIV infection, and sharing equipment that is not cleaned or laundered between users. (See 'Community-associated MRSA infection' above and 'Risk factors' above.)
●MRSA transmission occurs via contact with a colonized individual or a contaminated fomite. (See 'Transmission' above.)
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