Impact of neutropenia on clinical manifestations and outcome of Staphylococcus aureus bloodstream infection: a propensity score-based overlap weight analysis in two large,prospectively evaluated cohorts

ObjectivesThis study aimed to investigate whether neutropenia influenced mortality and long-term outcomes of Staphylococcus aureus bloodstream (SAB) infection.MethodsData from two prospective, multicentre cohort studies (INSTINCT and ISAC) conducted at 20 tertiary care hospitals in six countries between 2006 and 2015 were analyzed. Neutropenic and severely neutropenic patients (defined by proxy of total white blood cell count <1000/μl and <500/μl, respectively, at onset of SAB infection) were compared with a control group using a propensity score model and overlapping weights to adjust for baseline characteristics. Overall survival and time to SAB infection-related late complications (SAB infection recurrence, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed with Cox regression and competing risk analyses, respectively.ResultsOf the 3187 included patients, 102 were neutropenic and 70 severely neutropenic at the time of SAB infection onset. Applying overlap weights yielded two groups of 83 neutropenic and 220 nonneutropenic patients, respectively. The baseline characteristics of these groups were exactly balanced. In the Cox regression analysis, we observed no significant difference in survival between the two groups (death during follow up: 36.1% in neutropenic vs. 30.6% in nonneutropenic patients; hazard ratio (HR): 1.21; 95% CI, 0.79–1.83). This finding remained unchanged when we considered severely neutropenic patients (HR: 1.08; 95% CI, 0.60–1.94). A competing risk analysis showed a cause-specific HR of 0.39 (95% CI, 0.11–1.39) for SAB infection-related late complications in neutropenic patients.DiscussionNeutropenia was not associated with a higher survival rate during follow up. The lower rate of SAB infection-related late complications in neutropenic patients should be validated in other cohorts.     

Bacterial and fungal bloodstream infections in solid organ transplant recipients: results from a Danish cohort with nationwide follow-up

ObjectivesBloodstream infections (BSI) are prevalent after solid organ transplantation (SOT). In this study, we aimed to investigate the incidence and risk factors for BSI in the first 5 years post-transplantation.MethodsThe study included 1322 SOT (kidney, liver, lung and heart) recipients transplanted from 2010 to 2017 with a total of 5616 years of follow-up. Clinical characteristics and microbiology were obtained from the Centre of Excellence for Personalized Medicine of Infectious Complications in Immune Deficiency (PERSIMUNE) data repository with nationwide follow-up. Incidence was investigated in the different SOT groups. Risk factors associated with BSI were assed in the combined group in time-updated multivariable Cox regressions.ResultsThe cumulative incidence of first BSI in the first 5 years post-transplantation differed in the SOT groups with a lower incidence in heart transplant recipients than in the other SOT groups (heart: 4.4%, CI 0.0–9.7%, vs. kidney: 24.6%, CI 20.9–28.2%, liver: 24.7%, CI 19.4–29.9%, and lung: 19.6%, CI 14.5–24.8%, p <0.001). Age above 55 years (HR 1.71, CI 1.2–2.4, p=0.002) and higher Charlson comorbidity index score (HR per unit increase: 1.25, CI 1.1–1.4, p<0.001) at transplantation, current cytomegalovirus (CMV) infection (HR 4.5, CI 2.6–7.9, p<0.001) and current leucopenia (HR 13.3, CI 3.7–47.9, p<0.001) were all associated with an increased risk of BSI.ConclusionIn SOT recipients, the incidence of BSI differed with the type of transplanted organ. Risk of BSI was higher in older recipients and in recipients with comorbidity, current CMV infection or leucopenia. Thus, increased attention towards BSI in recipients with these characteristics is warranted.     

Extensively drug-resistant Pseudomonas aeruginosa: risk of bloodstream infection in hospitalized patients

Several studies have suggested that resistance determinants usually reduce virulence. However, their contribution to decrease bloodstream infections is unclear. Our aim was to identify risk factors of extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) bacteremia and to assess the prevalence of XDR-PA bacteremia. A retrospective study of PA bloodstream infections in our patient population with at least one clinical sample isolate due to PA (2006-2007) was carried out. A total of 2,131 patients with PA clinical samples were detected. Among 1,657 patients with susceptible-PA isolates, 95 developed PA-susceptible bacteremia. Concomitantly, among 474 patients with multidrug-resistant (MDR)-PA isolates, 265 with XDR-PA, and 209 with non-XDR MDR-PA, 43 developed XDR-PA bacteremia and 13 non-XDR MDR-PA bacteremia, respectively. Pulsed-field gel electrophoresis (PFGE) revealed the clonal nature of the two predominant XDR-PA phenotypes and genetic heterogeneity in non-XDR MDR-PA phenotypes. The proportion of XDR-PA bacteremia was higher than the proportion of bacteremia in the susceptible-PA population (16?% vs. 6?%; p?相似文献   

Predictive scoring model of mortality in Gram-negative bloodstream infection

Mortality is a well-recognized complication of Gram-negative bloodstream infection (BSI). The aim of this study was to develop a model to predict mortality in patients with Gram-negative BSI by using the Pitt bacteraemia score (PBS) and other clinical and laboratory variables. A cohort of 683 unique adult patients who were followed for at least 28 days after admission to Mayo Clinic Hospitals with Gram-negative BSI from 1 January 2001 to 31 October 2006 and who received clinically predefined appropriate empirical antimicrobial therapy was retrospectively identified. Multivariable logistic regression was used to identify independent risk factors for 28-day all-cause mortality. Regression coefficients from a multivariable model were used to develop a risk score to predict mortality following Gram-negative BSI. Malignancy (OR 3.48, 95% CI 1.94–6.22), liver cirrhosis (OR 5.42, 95% CI 2.52–11.65), source of BSI other than urinary tract or central venous catheter infection (OR 5.54, 95% CI 2.42–12.69), and PBS (OR 1.98, 95% CI 0.92–4.25 for PBS of 2–3 and OR 6.42, 95% CI 3.11–13.24 for PBS ≥ 4) were identified as independent risk factors for 28-day mortality in patients with Gram-negative BSI. A risk-score model was created by adding points for each independent risk factor, and had a c-statistic of 0.84. Patients with risk scores of 0, 4, 8, 12 and 16 had estimated 28-day mortality rates of approximately 0%, 3%, 14%, 45%, and 81%, respectively. The Gram-negative BSI risk score described herein estimated mortality risk with high discrimination in patients with Gram-negative BSI who received clinically adequate empirical antimicrobial therapy.     

Predictors and microbiology of respiratory and bloodstream bacterial infection in patients with COVID-19: living rapid review update and meta-regression

BackgroundThe prevalence of bacterial infection in patients with COVID-19 is low, however, empiric antibiotic use is high. Risk stratification may be needed to minimize unnecessary empiric antibiotic use.ObjectiveTo identify risk factors and microbiology associated with respiratory and bloodstream bacterial infection in patients with COVID-19.Data sourcesWe searched MEDLINE, OVID Epub and EMBASE for published literature up to 5 February 2021.Study eligibility criteriaStudies including at least 50 patients with COVID-19 in any healthcare setting.MethodsWe used a validated ten-item risk of bias tool for disease prevalence. The main outcome of interest was the proportion of COVID-19 patients with bloodstream and/or respiratory bacterial co-infection and secondary infection. We performed meta-regression to identify study population factors associated with bacterial infection including healthcare setting, age, comorbidities and COVID-19 medication.ResultsOut of 33 345 studies screened, 171 were included in the final analysis. Bacterial infection data were available from 171 262 patients. The prevalence of co-infection was 5.1% (95% CI 3.6–7.1%) and secondary infection was 13.1% (95% CI 9.8–17.2%). There was a higher odds of bacterial infection in studies with a higher proportion of patients in the intensive care unit (ICU) (adjusted OR 18.8, 95% CI 6.5–54.8). Female sex was associated with a lower odds of secondary infection (adjusted OR 0.73, 95% CI 0.55–0.97) but not co-infection (adjusted OR 1.05, 95% CI 0.80–1.37). The most common organisms isolated included Staphylococcus aureus, coagulase-negative staphylococci and Klebsiella species.ConclusionsWhile the odds of respiratory and bloodstream bacterial infection are low in patients with COVID-19, meta-regression revealed potential risk factors for infection, including ICU setting and mechanical ventilation. The risk for secondary infection is substantially greater than the risk for co-infection in patients with COVID-19. Understanding predictors of co-infection and secondary infection may help to support improved antibiotic stewardship in patients with COVID-19.     

Clinical features and outcome of patients with community-acquired Pseudomonas aeruginosa bacteraemia

Cases of community-acquired Pseudomonas aeruginosa bacteraemia (n = 39) that occurred at a tertiary-care hospital during a 5-year period were analysed retrospectively. The commonest underlying diseases were solid tumour (41%) and haematological malignancy (18%). Most (44%) of the patients were neutropenic, and 39% had septic shock at initial presentation. The 30-day attributable mortality rate was 39%. Two previously healthy patients were identified with fatal P. aeruginosa pneumonia with bacteraemia. P. aeruginosa bacteraemia is a fatal infection that should be considered in the differential diagnosis of patients presenting from the community with rapidly progressive sepsis.     

Overall burden of bloodstream infection and nosocomial bloodstream infection in North America and Europe

In this systematic review, we estimated the total number of episodes of bloodstream infection (BSI) and deaths from BSI per year in North America and Europe, using data from population-based settings. Then, we estimated the number of episodes and deaths from nosocomial BSI from population-based studies and nosocomial infection surveillance systems. We estimated 575 000–677 000 episodes of BSI per year in North America (536 000–628 000 in the USA and 40 000–49 000 in Canada) and 79 000–94 000 deaths (72 000–85 000 in the USA and 7000–9000 in Canada), using estimates from three population-based studies. We estimated over 1 200 000 episodes of BSI and 157 000 deaths per year in Europe, using estimates from one population-based study in each of the following countries: Denmark (9100 episodes and 1900 deaths), Finland (8700 episodes and 1100 deaths) and England (96 000 episodes and 12 000–19 000 deaths). There were substantial differences in estimates of nosocomial BSI between population-based and nosocomial infection surveillance data. BSI has a major impact on the morbidity and mortality of the general population, as it ranks among the top seven causes of death in all included countries in North America and Europe. However, it is difficult to obtain precise estimates of nosocomial BSI, owing to the limited number of studies. This review highlights the need for a greater focus on BSI research in order to reduce the overall burden of disease by improving the outcome of patients with BSI. It also emphasizes the role of infection control and prevention methods in reducing the burden of nosocomial BSI.     

External validation of bloodstream infection mortality risk score in a population-based cohort

A risk score was recently derived to predict mortality in adult patients with Gram-negative bloodstream infection (BSI). The aim of this study was to provide external validation of the BSI mortality risk score (BSIMRS) in a population-based cohort. All residents of Olmsted County, Minnesota, with Escherichia coli and Pseudomonas aeruginosa BSI from 1 January 1998 to 31 December 2007 were identified. Logistic regression was used to examine the association between BSIMRS and mortality. Area under receiver operating characteristic curve (AUC) was calculated to quantify the discriminative ability of the BSIMRS to predict a variety of short-term and long-term outcomes. Overall, 424 unique Olmsted County residents with first episodes of E. coli and P. aeruginosa BSI were included in the study. Median age was 68 (range 0–99) years, 280 (66%) were women, 61 (14%) had cancer and 9 (2%) had liver cirrhosis. The BSIMRS was associated with 28-day mortality (p <0.001) with an AUC of 0.86. There was an almost 56% increase in 28-day mortality for each point increase in BSIMRS (OR 1.56, 95% CI 1.40–1.78). A BSIMRS ≥5 had a sensitivity of 74% and a specificity of 87% to predict 28-day mortality with a negative predictive value of 97%. The BSIMRS had AUC of 0.85, 0.85 and 0.81 for 7-, 14- and 365-day mortality, respectively. BSIMRS stratified mortality with high discrimination in a population-based cohort that included patients of all age groups who had a relatively low prevalence of cancer and liver cirrhosis.     

Long-term mortality following bloodstream infection

Bloodstream infection is associated with significant short-term mortality, but less is known about long-term outcome. We describe factors affecting mortality up to 3 years after bloodstream infection in a cohort of patients reviewed at the bedside by an infection specialist. Patients seen by the bacteraemia service of our infectious diseases department between June 2005 and November 2008 were included in analyses. Routine clinical data collected at the time of consultation, together with laboratory, demographic and outcome data were analysed to identify factors predicting death at 30 days and 3 years after bloodstream infection. Cox regression models for both time-points were constructed, together with Kaplan–Meier survival curves. In all, 322 bloodstream infections were recorded in 304 patients. The 30-day mortality was 15%, with a 3-year mortality of 49%. At 30 days after bacteraemia, in the Cox regression model, increasing age (p 0.003) and lower serum albumin (p 0.014) were predictive of death. At 3 years, age (p <0.0001) and albumin (p 0.004) remained significant predictors of death, with the presence of vascular disease (p 0.05) also significantly associated with mortality. If temperature was treated as a continuous variable then urea was significant (p 0.044); however, if temperature was categorized into hypothermia and non-hypothermia, then the presence of hypothermia (p 0.008) and chronic renal disease (p 0.034) became significant. There is an appreciable and gradual increase in mortality after an episode of bloodstream infection. Although many factors may not be amenable to intervention, patients at high risk of long-term mortality might require further follow up and assessment for potentially modifiable factors.     

Catheter-related bloodstream infection caused by Enterococcus spp.

The role of Enterococcus spp. as a cause of catheter-related bloodstream infections (CR-BSI) is almost unexplored. We assessed the incidence and clinical characteristics of enterococcal CR-BSI (ECR-BSI) over an 8-year period in our hospital. We performed a retrospective study (January 2003 to December 2010) in a large teaching institution. We recorded the incidence, and the microbiological and clinical data from patients with ECR-BSI. The incidence per 10 000 admissions for enterococcal BSI and ECR-BSI was 25 and 1.7, respectively. ECR-BSI was the fourth leading cause of CR-BSI in our institution (6%). A total of 75 episodes of ECR-BSI were detected in 73 patients (6% of all enterococcal BSI). The incidence of ECR-BSI increased by 17% annually (95% CI 19.0–21.0%) during the study period. Nineteen percent of ECR-BSI episodes were polymicrobial. Overall mortality was 33%. ECR-BSI is an emerging and increasingly common entity with a high mortality. This finding should be taken into account when selecting empirical treatment for presumptive CR-BSI.     

Serial granulocyte transfusions as a treatment for sepsis due to multidrug-resistant Pseudomonas aeruginosa in a neutropenic patient

The emergence of multidrug-resistant Pseudomonas aeruginosa (MRPA) has become a major clinical problem. We successfully treated MRPA sepsis in a neutropenic patient undergoing peripheral blood stem cell transplantation with serial granulocyte transfusions. Granulocyte transfusion should be considered as a treatment for severe infection in patients with neutropenia.     

Risk factors for antimicrobial resistance and influence of resistance on mortality in patients with bloodstream infection caused by Pseudomonas aeruginosa

This study was conducted to evaluate risk factors for antimicrobial resistance and influence of resistance on mortality in Pseudomonas aeruginosa bacteremia. Data on 190 patients with P. aeruginosa bacteremia were analyzed retrospectively. Antimicrobial resistance to antipseudomonal antibiotics was evaluated. The main outcome measure was 30-day mortality. In P. aeruginosa bacteremia, resistance rates to piperacillin (PIP), ceftazidime (CAZ), ciprofloxacin (CIP), and imipenem (IPM) were 29 (56/190), 19 (36/190), 17 (32/190) and 15% (28/190), respectively. Prior uses of fluoroquinolones or carbapenems were independent risk factors for resistance to CIP and IPM, and prior use of extended-spectrum cephalosporins was a risk factor for PIP-R. An indwelling urinary catheter was a risk factor for PIP-R, CAZ-R, and CIP-R. An invasive procedure was a risk factor for CIP-R and IPM-R. The 30-day mortality rate was 44% (33/75) in patients infected by strains resistant to any of the antipseudomonal antibiotics, but 33.9% (39/115) in those by strains susceptible to all antipseudomonal antibiotics (p = 0.161). Among patients with bloodstream infection due to antimicrobial-resistant P. aeruginosa, those infected by IPM-R strains had the highest mortality (IPM-R, 53.6% vs. CAZ-R, 47.2% vs. CIP-R 46.9%, PIP-R, 39.3%). In this study regarding P. aeruginosa bacteremia, prior uses of fluoroquinolones, carbapenems, or extended-spectrum cephalosporins, a prior invasive procedure, and an indwelling urinary catheter were found to be associated with antimicrobial resistance. The patients with bloodstream infection caused by antimicrobial-resistant P. aeruginosa, especially to imipenem, had a tendency toward higher mortality than those infected by susceptible strains.     

Short-course aminoglycosides as adjunctive empirical therapy in patients with Gram-negative bloodstream infection,a cohort study

ObjectiveShort-course aminoglycosides as adjunctive empirical therapy to β-lactams in patients with a clinical suspicion of sepsis are used to broaden antibiotic susceptibility coverage and to enhance bacterial killing. We quantified the impact of this approach on 30-day mortality in a subset of sepsis patients with a Gram-negative bloodstream infection.MethodsFrom a prospective cohort study conducted in seven hospitals in the Netherlands between June 2013 and November 2015, we selected all patients with Gram-negative bloodstream infection (GN-BSI). Short-course aminoglycoside therapy was defined as tobramycin, gentamicin or amikacin initiated within a 48-hour time window around blood-culture obtainment, and prescribed for a maximum of 2 days. The outcome of interest was 30-day all-cause mortality. Confounders were selected a priori for adjustment using a propensity score analysis with inverse probability weighting.ResultsA total of 626 individuals with GN-BSI who received β-lactams were included; 156 (24.9%) also received aminoglycosides for a median of 1 day. Patients receiving aminoglycosides more often had septic shock (31/156, 19.9% versus 34/470, 7.2%) and had an eight-fold lower risk of inappropriate treatment (3/156, 1.9% versus 69/470, 14.7%). Thirty-day mortality was 17.3% (27/156) and 13.6% (64/470) for patients receiving and not receiving aminoglycosides, respectively; yielding crude and adjusted odds ratios for 30-day mortality for patients treated with aminoglycosides of 1.33 (95% CI 0.80–2.15) and 1.57 (0.84–2.93), respectively.ConclusionsShort-course adjunctive aminoglycoside treatment as part of empirical therapy with β-lactam antibiotics in patients with GN-BSI did not result in improved outcomes, despite better antibiotic coverage of pathogens.     

Clinical outcome and costs of nosocomial and community-acquired Staphylococcus aureus bloodstream infection in haemodialysis patients

The main aim of this study was to evaluate the clinical outcome and costs of nosocomial and community-acquired methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant S. aureus (MRSA) bloodstream infection (BSI) in patients undergoing haemodialysis. A multicentre retrospective study was conducted that included 109 patients with end-stage renal disease and S. aureus BSI who were hospitalised in three German centres between 1999 and 2005. Nosocomial and community-acquired infections were analysed separately with regard to costs and outcome. Forty-nine (45%) patients had nosocomial infection. Compared to patients with community-acquired infection, these patients were more likely to have had BSI caused by MRSA (40.8% vs. 13.3%, p <0.05). BSI was the initial reason for admission for 33 (55%) patients who had community-acquired infection. The mean length of hospitalisation was 24 days for patients with community-acquired infection and 51 days for patients with nosocomial infection (p <0.05). Costs per treatment episode were 20,024 Euros for nosocomial infection vs. 9554 Euros for community-acquired infection (p <0.05). The average treatment costs for patients with MSSA BSI were <50% of those for patients with MRSA BSI (10,573 vs. 24,931 Euros, p <0.05). S. aureus BSI is an underlying cause of substantial health risk and high morbidity among the haemodialysis-dependent population, who are already at high-risk for other reasons. This study also highlighted differences according to the source of BSI, including costs arising from hospitalisation and treatment.     

Seasonal variation in Escherichia coli bloodstream infection: a population-based study

Seasonal variation in the rates of infection with certain Gram-negative organisms has been previously examined in tertiary-care centres. We performed a population-based investigation to evaluate the seasonal variation in Escherichia coli bloodstream infection (BSI). We identified 461 unique patients in Olmsted County, Minnesota, from 1 January 1998 to 31 December 2007, with E. coli BSI. Incidence rates (IR) and IR ratios were calculated using Rochester Epidemiology Project tools. Multivariable Poisson regression was used to examine the association between the IR of E. coli BSI and average temperature. The age- and gender-adjusted IR of E. coli BSI per 100 000 person-years was 50.2 (95% CI 42.9–57.5) during the warmest 4 months (June through September) compared with 37.1 (95% CI 32.7–41.5) during the remainder of the year, resulting in a 35% (95% CI 12–66%) increase in IR during the warmest 4 months. The average temperature was predictive of increasing IR of E. coli BSI (p 0.004); there was a 7% (95% CI 2–12%) increase in the IR for each 10-degree Fahrenheit ( c. 5.5°C) increase in average temperature. To our knowledge, this is the first study to demonstrate seasonal variation in E. coli BSI, with a higher IR during the warmest 4 months than during the remainder of the year.     

Risk-adjusted comparisons of bloodstream infection rates in neonatal intensive-care units

Comparisons of bloodstream infection (BSI) rates between neonatal intensive-care units (NICUs) should take into account differences in babies' vulnerability and invasive procedures that can introduce infection. Our aim was to investigate which risk factors recorded in routine records should be adjusted for when NICUs are compared. This was a retrospective cohort study using routine records for two London NICUs. We analysed rates of BSI with Poisson regression models. The level of neonatal care used by the National Health Service was the strongest predictor of BSI incidence. The rate ratios for BSI, adjusted for birthweight, inborn/outborn status, and postnatal age, were 3.15 (95% CI 2.01–4.94) for intensive care and 6.58 (95% CI 4.18-10.36) for high-dependency care, relative to special care. Total parenteral nutrition was significantly associated with BSI incidence, but explained less of the variance among babies than level of care. A case—control study with the same dataset gave similar results. Further multicentre studies are required to confirm our predictive model. Until then, we recommend that comparisons of BSI rates between NICUs should include adjustments for level of care, birthweight, inborn/outborn status, and postnatal age, with the use of routinely recorded standardized measures in hospital administrative data.     

Prevention of Pseudomonas aeruginosa infection in cystic fibrosis patients

In patients with cystic fibrosis (CF) prevention of lung infections with Pseudomonas aeruginosa is of major importance. Principles to achieve this goal include vaccination, immediate use of antibiotics in patients newly colonized with the pathogen, and hygienic measures. The purpose of this review is to discuss recent developments in this context.     

Prevalence of AmpC over-expression in bloodstream isolates of Pseudomonas aeruginosa

This study examined the contribution of AmpC over-expression to beta-lactam resistance in clinical isolates of Pseudomonas aeruginosa obtained from a hospital in Houston, TX, USA. Seventy-six non-repeat bloodstream isolates obtained during 2003 were screened for ceftazidime resistance in the presence and absence of clavulanic acid 4 mg/L. AmpC was identified by isoelectric focusing (with and without cloxacillin inhibition); stable derepression was ascertained phenotypically by a spectrophotometric assay (with and without preceding induction by imipenem) using nitrocefin as the substrate, and was confirmed subsequently by quantitative RT-PCR of the ampC gene. The clonal relatedness of the AmpC-over-expressing isolates was assessed by pulsed-field gel electrophoresis. In addition, the ampC and ampR gene sequences were determined by PCR and sequencing. For comparison, two standard wild-type strains (PAO1 and ATCC 27853) and three multidrug-susceptible isolates were used as controls. AmpC over-expression was confirmed in 14 ceftazidime-resistant isolates (overall prevalence rate, 18.4%), belonging to seven distinct clones. The most prevalent point mutations in ampC were G27D, V205L and G391A. Point mutations in ampR were also detected in eight ceftazidime-resistant isolates. AmpC over-expression appears to be a significant mechanism of beta-lactam resistance in P. aeruginosa. Understanding the prevalence and mechanisms of beta-lactam resistance in P. aeruginosa may guide the choice of empirical therapy for nosocomial infections in hospitals.     

The changing epidemiology of Staphylococcus aureus bloodstream infection: a multinational population-based surveillance study

Although the epidemiology of Staphylococcus aureus bloodstream infection (BSI) has been changing, international comparisons are lacking. We sought to determine the incidence of S. aureus BSI and assess trends over time and by region. Population-based surveillance was conducted nationally in Finland and regionally in Canberra, Australia, western Sweden, and three areas in each of Canada and Denmark during 2000–2008. Incidence rates were age-standardized and gender-standardized to the EU 27-country 2007 population. During 83 million person-years of surveillance, 18 430 episodes of S. aureus BSI were identified. The overall annual incidence rate for S. aureus BSI was 26.1 per 100 000 population, and those for methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) were 24.2 and 1.9 per 100 000, respectively. Although the overall incidence of community-onset MSSA BSI (15.0 per 100 000) was relatively similar across regions, the incidence rates of hospital-onset MSSA (9.2 per 100 000), community-onset MRSA (1.0 per 100 000) and hospital-onset MRSA (0.8 per 100 000) BSI varied substantially. Whereas the overall incidence of S. aureus BSI did not increase over the study period, there was an increase in the incidence of MRSA BSI. Major changes in the occurrence of community-onset and hospital-onset MSSA and MRSA BSI occurred, but these varied significantly among regions, even within the same country. Although major changes in the epidemiology of community-onset and hospital-onset MSSA and MRSA BSIs are occurring, this multinational population-based study did not find that the overall incidence of S. aureus BSI is increasing.