Version July 2025
INTRODUCTION —
Staphylococcus aureus is among the most common human pathogens. It is responsible for a broad range of clinical manifestations including skin and soft tissue infection, bone and joint infection, bacteremia, and pneumonia [1,2]. (See "Clinical manifestations of Staphylococcus aureus infection in adults".)
Issues related to the epidemiology of SAB in adults will be reviewed here. Issues related to the management of SAB are discussed separately. (See "Clinical approach to Staphylococcus aureus bacteremia in adults".)
INCIDENCE —
The annual incidence of S. aureus bacteremia (SAB) ranges from 9.3 to 65 cases per 100,000 person-years, depending on the region and population [3]. Rates of SAB over time have remained largely stable. In a systematic review of population-based studies (including high-quality data from 11 resource-abundant countries), there was no change in the incidence trend over two decades [3].
DEFINITIONS —
Bacteremia due to S. aureus may be classified into three categories [4]:
●Health care associated, hospital onset (ie, nosocomial)
●Health care associated, community onset
●Community acquired
Health care associated bacteremia
Hospital onset — Health care-associated, hospital-onset infection refers to nosocomially acquired infection [5].
S. aureus is a leading cause of nosocomial bloodstream infection. Among >400,000 pathogens reported to >4500 hospitals in the National Healthcare Safety Network between 2011 and 2014, S. aureus was the second most common cause of central line-associated bloodstream infections [6]. Peripheral intravenous catheters are also an important source of SAB [7].
In a multicenter cohort including 847 cases of SAB, most patients had predisposing conditions including diabetes (33 percent), malignancy (26 percent), chronic kidney disease (22 percent), and immunosuppressive therapy (21 percent) [8].
Among patients who acquire health care-associated, hospital-onset SAB, approximately 20 percent develop metastatic complications, including endocarditis. The mortality rate is 20 to 30 percent [9,10].
Hospital-acquired S. aureus infections are more likely to be methicillin resistant than community-acquired infections [5]. [11]. (See 'Methicillin resistance' below.)
Community onset — Health care-associated, community-onset infection refers to infection in an outpatient who has had recent extensive contact with the health care system. The infection must be diagnosed as an outpatient or within 48 hours of hospital admission. Examples of health care contact include [4]:
●Hospitalization in an acute care hospital for ≥2 days within the prior 90 days
●Receipt of dialysis or intravenous therapy (including chemotherapy) within the prior 30 days
●Receipt of intravenous therapy, wound care, or specialized nursing care at home
●Residence in a nursing home or other long-term care facility
In a multicenter cohort of six sites and the electronic health records of >400 United States acute care hospitals, [4,12-14] community-onset rates of MRSA bacteremia were stable from 2012 to 2017, whereas rates of MSSA bacteremia increased by 3.9 percent per year [10].
SAB acquired in long-term care facilities typically affects older adults and chronically ill patients. Skin or soft tissue lesions such as decubitus ulcers, diabetic foot ulcers, and wounds are common risk factors for bacteremia among these individuals. (See "Clinical manifestations of Staphylococcus aureus infection in adults".)
Community acquired bacteremia — Community-acquired infection refers to infection in a patient who has had no recent contact with the health care system [15,16]. Patients with community-acquired SAB include patients who inject drugs and patients with a clinically inapparent source of bacteremia (such as vertebral osteomyelitis or epidural abscess). In a systematic review of population-based studies, most cases of SAB in Australia and New Zealand were community-acquired, whereas in other regions, community-acquired infections were the minority [3].
Patients with onset of SAB acquired in the community are likely to present with complicated infection. In one study, more than 40 percent of patients with community-acquired SAB had metastatic infection, including infective endocarditis (IE) [17]; another study noted as many as 90 percent of patients with community-acquired SAB had one or more complications [18]. In a study including more than 500 patients with SAB, IE was present in 21 percent of patients with community-acquired infection, a rate that was almost three times that seen among patients with hospital-acquired SAB [19].
Invasive MRSA infections disproportionately affect people who inject drugs (PWID). In surveillance data from the CDC Emerging Infections Program from 2005 to 2016, PWID were 16.3 times more likely to develop invasive MRSA infections than others, and the overall proportion of invasive MRSA cases that occurred in PWID increased to 9.2 percent [20]. Similarly, in a retrospective cohort in Denmark, almost one-quarter of hospitalized PWID had bacteremia, and S. aureus was the most common pathogen [21].
ANTIMICROBIAL RESISTANCE
Methicillin resistance — Methicillin resistance among bloodstream S. aureus isolates has fluctuated; overall, the rate of methicillin resistance increased until approximately 2005. This was largely due to the spread of epidemic community-associated clones such as USA300 in North America and health care-associated clones in the United Kingdom. As an example, among 24,000 nosocomial bloodstream infections in the United States between 1995 and 2002, the proportion of S. aureus isolates that were methicillin resistant increased from 22 to 57 percent [11].
In a global surveillance program in 45 countries from 1997 to 2016, 37.1 percent of SAB isolates were MRSA. Nosocomial isolates were more likely to be MRSA than community onset isolates, and isolates from North America (47.0 percent), the Asia-Pacific (39.6 percent), and Latin America (38.7 percent) were more likely to be MRSA than those from Europe (26.8 percent) [22].
Since 2005, reductions in rates of methicillin-resistant S. aureus (MRSA) bacteremia have been observed. In nine metropolitan areas in the United States, hospital-onset MRSA bacteremia decreased by 11 percent per year between 2005 and 2008, while cases of health care-associated, community-onset MRSA bacteremia declined by 7 percent annually [23]. Similar trends were evident in the United Kingdom, France, and Australia [2,24].
The incidence of MRSA catheter-associated bloodstream infections in United States intensive care units also appears to be decreasing [25]. This was illustrated in a review of over 33,500 episodes of central line–associated bloodstream infections between 2001 and 2007; declines in MRSA central line–associated bloodstream infection incidence ranged from 51 to 69 percent. These findings call into question the utility of performing active MRSA surveillance rather than focusing on reducing health care-acquired infections in general. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Epidemiology" and "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control".)
With respect to health care-associated, community-onset infection, a retrospective study in 1998 found that 15 percent of community-onset SAB were due to MRSA [14]. Most patients with MRSA bacteremia had had contact with the health care system, including 47 percent with an indwelling catheter. Similar findings were noted in a prospective cohort study that included 186 patients with health care-associated, community-onset bloodstream infections in 2000; 52 percent were due to MRSA, and 42 percent were receiving intravenous or intravascular therapy at home or in a clinic [4]. Subsequent studies have shown that community-associated MRSA infections, including bacteremia, have become increasingly common among individuals with no prior health contact [26].
In a review of data from more than 200 countries, estimates for MRSA burden in 2019 were generated using predictive statistical modeling. MRSA prevalence was highest in north Africa and the Middle East (60 to 80 percent); it was lowest in parts of Western Europe and Sub-Saharan Africa (<5 percent). Overall, bloodstream infections were the second most common syndrome causing death (after lower respiratory tract infections) and S. aureus was the second leading pathogen (after Escherichia coli) [27].
Resistance to other antimicrobial agents
●Penicillin resistance – Resistance to penicillin among S. aureus emerged quickly, mediated by a beta-lactamase encoded by blaZ. By the 1970s, the prevalence of penicillin resistance among both hospital and community isolates was >90 percent [28].
However, in the past decade there has been a relative resurgence of penicillin susceptibility among S. aureus isolates [22,29-39]. Phenotypic susceptibility testing methods may not reliably detect blaZ penicillinase production [40]; blaZ PCR testing appears most reliable [31].
●Vancomycin resistance – Issues related to epidemiology of vancomycin resistance are discussed separately. (See "Staphylococcus aureus bacteremia with reduced susceptibility to vancomycin", section on 'Epidemiology'.)
Risk factors for the emergence of vancomycin resistance include previous exposure to vancomycin, infection with a methicillin-resistant S. aureus strain with a minimum inhibitory concentration to vancomycin of 2 mcg/mL or greater, and treatment with insufficient doses of vancomycin [41-43].
●Daptomycin resistance – De novo daptomycin resistance is uncommon [44]. Emergence of resistance to daptomycin in patients who receive prolonged treatment with daptomycin has been observed, particularly if the underlying infection is not amenable to surgical drainage or if it involves a prosthetic device such as a vascular graft. Among 124 patients with SAB treated with daptomycin in one trial, emergence of isolates with resistance to daptomycin was observed in 5 percent of cases [41].
RISK FACTORS —
Risk factors for development of SAB include presence of a prosthetic device, injection drug use, and underlying host factors.
Indwelling prosthetic device — Any implanted foreign body that becomes infected is a potential source for SAB. Implanted devices include vascular catheters, surgically implanted materials, and orthopedic prostheses. In a longitudinal study between 1995 and 2015 including more than 2300 patients with SAB, more than half of patients had at least one indwelling prosthetic device [45].
Intravascular catheters are the most common cause of SAB in hospitalized patients [46] and are an increasingly important cause of community-acquired infection [4,13,14]. These devices serve as a direct conduit into the intravascular space, allowing easy access for S. aureus to enter the bloodstream. In a pooled analysis of five observational studies including more than 3000 patients with SAB, intravenous catheters were identified as the probable focus in 28 percent of cases [47]. (See "Intravascular catheter-related infection: Epidemiology, pathogenesis, and microbiology".)
SAB in patients with cardiac implantable electronic devices can be due to primary device infection or a separate source. Rates of device infection in the presence of SAB are approximately 30 to 50 percent [48,49]. Leadless pacemakers have emerged as an option with a significantly lower risk of infection, compared to traditional pacemakers [50]
Injection drug use — PWID who develop SAB are usually young and otherwise healthy [51-53]. PWID have a high rate of nasal colonization with S. aureus, and the phage type of the colonizing organism typically matches that of the isolate recovered from the blood [54,55]. The combination of high S. aureus nasal colonization rate and repeated parenteral injection of nonsterile material makes IDUs prone to SAB [56,57]. (See 'Nasal colonization' below.)
Host factors
General principles — SAB incidence varies by age, gender, and ethnicity. Rates are highest at extremes of age [58]. Male-to-female ratios of approximately 1.5 have been reported consistently. In Australia and New Zealand, indigenous populations have markedly higher SAB incidence, of which socioeconomic factors likely play a large role [2,59].
Diabetes mellitus is an independent risk factor for community-acquired SAB, with greatest risk in patients with type 1 diabetes, ≥10 years of diabetes, history of poor glycemic control, and individuals with other complications of diabetes [60]. (See "Susceptibility to infections in persons with diabetes mellitus".)
In a longitudinal study between 1995 and 2015 including more than 2300 patients with SAB, the most common comorbid conditions were diabetes, dialysis dependence, cancer, and corticosteroid use [45]. Of these, diabetes, cancer, and steroid use increased over time; the proportion of SAB patients with dialysis dependence decreased, possibly due to advances in vascular access methods or improvement in infection control practices [45].
Surveillance data among patients receiving hemodialysis in the United States between 2017 and 2020 demonstrated that SAB incidence was 100 times higher in adults on hemodialysis than in adults not on hemodialysis; using a central venous catheter for dialysis access was the strongest risk factor for SAB. Race, ethnicity, and social determinants of health also impacted infection rates, with Hispanic ethnicity independently associated with higher risk [61].
Genetic susceptibility — A substantial body of evidence supports a host genetic basis for susceptibility to SAB including higher rates of S. aureus infections in distinct populations [23,62-65], familial clusters of S. aureus infection [66-69], and rare genetic conditions causing susceptibility to S. aureus [70-74]. As an example, a nationwide Danish cohort study identified a higher rate of SAB in the first-degree relatives of patients who had experienced SAB (Standardized Incidence Ratio [SIR], 2.49 [95% CI, 1.95 to 3.19]) than in the background population [66].
HLA class II haplotypes may influence susceptibility to S. aureus infection. First, specific HLA alleles are associated with severe infections caused by Streptococcus pyogenes, a bacterium closely related to S. aureus [75]. In addition, specific HLA alleles determine severity of response to bacterial superantigens from both S. pyogenes [76] and S. aureus [77]. Third, S. aureus superantigens that bind preferentially to specific HLA Class II isotypes [78] are critical in the development of SAB and endocarditis [79], and elicit a distinct profile of T-cell receptor activation [80].
Some studies suggest HLA genomic variation may influence susceptibility to complicated SAB:
●A genome-wide association study [81] of >50,000 individuals (4701 cases with S. aureus infection and 45,344 controls) identified two imputed single nucleotide variants (SNV) near the HLA-DRA and HLA-DRB1 genes that were associated with infection and one genotyped SNV near genome-wide significance.
●A study used admixture mapping to evaluate whether genetic variants with different frequencies in European and African ancestral populations influence susceptibility to SAB among 590 African Americans with and without SAB [82]. This study implicated the same region in HLA class II region identified in the study described above [81], with a genome-wide increase of European ancestry among African Americans with SAB. These data suggest SAB susceptibility is influenced by European-derived HLA class II alleles in both populations.
●Two studies have also shown that this same region of HLA-DR exhibited significantly lower expression in patients with complicated SAB than patients with uncomplicated SAB during the first week of bacteremia [83,84].
Nasal colonization — Patients with S. aureus nasal colonization are at increased risk for SAB [85-87]. In one study including 3420 patients with S. aureus nasal carriage on hospital admission, methicillin-susceptible SAB was observed more frequently among carriers than noncarriers (1.2 versus 0.4 percent) [88].
The association between nasal carriage and outcome of bacteremia is uncertain. In one study including 3420 patients with S. aureus nasal carriage, the likelihood of bacteremia-related death was lower among carriers than noncarriers (8 versus 32 percent) [88]. However, another study including more than 3000 MRSA-colonized patients noted no difference in all-cause mortality between colonized and non-colonized patients who developed MRSA bacteremia [89].
Lower mortality among nasal carriers may be explained by differences in the immune response between S. aureus carriers and noncarriers; among healthy S. aureus carriers, antibody response against the colonizing strain has been observed [90].
Patients with conditions conferring increased risk for nasal colonization (such as patients with diabetes and patients who are hemodialysis dependent) are at increased risk for SAB [85-87].
HIV infection — HIV infection is associated with an increased risk of SAB . Injection drug use accounts for some of this risk; however, even in the absence of IDU, rates of SAB are higher among HIV-infected patients than among HIV-uninfected patients [91]. A low CD4 count appears to be the strongest independent risk factor among HIV-infected patients [91,92].
REPEAT INFECTION —
Repeat infection with SAB is common [93,94]. In one cohort including more than 10,000 patients, approximately 7 percent of patients with SAB developed recurrent SAB; the risk of reinfection was defined as an episode of SAB >90 days after an initial episode of SAB [94]. The median time to recurrent infection was 15 months. Risk of recurrent SAB was associated with comorbidities including injection drug use, kidney disease, diabetes with associated complications, severe liver disease, and paraplegia.
SUMMARY
●Bacteremia due to Staphylococcus aureus can be classified into three categories: health care associated, hospital onset; health care associated, community onset; and community acquired. The incidence of S. aureus bacteremia (SAB) for each of these categories has increased over the last several decades. (See 'Definitions' above.)
●SAB is a leading cause of bloodstream infections. During the past decade, the proportion of SAB cases due to MRSA appears to be declining, possibly due to improved infection control practices. Concurrently, rates of penicillin susceptibility appear to be increasing. (See 'Hospital onset' above.)
●SAB acquired in long-term care facilities typically affects older adults and chronically ill patients. Skin or soft tissue lesions such as decubitus ulcers, diabetic foot ulcers, or wounds are common causes of SAB in individuals who reside in these facilities. (See 'Community onset' above.)
●The presence of community-acquired SAB, particularly in the absence of an identifiable focus of infection, is an important marker for complicated staphylococcal infection. (See 'Community acquired bacteremia' above.)
●Health care contact (eg, prior hospitalization) is an important risk factor for methicillin-resistant S. aureus infection, but there are numerous reports of patients with no identifiable health care contacts or other risk factors. (See 'Methicillin resistance' above.)
●An implanted foreign body that becomes infected is a potential source for SAB. Implanted devices include cardiac devices, vascular catheters, surgically implanted materials, and orthopedic prostheses. (See 'Indwelling prosthetic device' above.)
●Persons who inject drugs (PWID) who develop SAB are usually young and otherwise healthy. The combination of high skin colonization rate with S. aureus and repeated parenteral injection of nonsterile material makes IDUs prone to SAB. (See 'Injection drug use' above.)
●Inherited defects in white blood cell function or immune function predispose patients to recurrent staphylococcal infections. Patients with nasal colonization are more prone to S. aureus infection, including SAB. (See 'Host factors' above and 'Nasal colonization' above.)
