SUMMARY Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.

Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed. We randomly assigned 124 patients with S. aureus bacteremia with or without endocarditis to receive 6 mg of daptomycin intravenously per kilogram of body weight daily and 122 to receive initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success 42 days after the end of therapy. Forty-two days after the end of therapy in the modified intention-to-treat analysis, a successful outcome was documented for 53 of 120 patients who received daptomycin as compared with 48 of 115 patients who received standard therapy (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval, −10.2 to 15.1 percent). Our results met prespecified criteria for the noninferiority of daptomycin. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and methicillin-resistant S. aureus. Daptomycin therapy was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). In 6 of the 19 patients with microbiologic failure in the daptomycin group, isolates with reduced susceptibility to daptomycin emerged; similarly, a reduced susceptibility to vancomycin was noted in isolates from patients treated with vancomycin. As compared with daptomycin therapy, standard therapy was associated with a nonsignificantly higher rate of adverse events that led to treatment failure due to the discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11.0 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004). Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis. (ClinicalTrials.gov number, NCT00093067.)

For decades, infective endocarditis (IE) caused by Staphylococcus aureus has been viewed primarily as a community-acquired disease, especially associated with injection drug use.^1-7 In contrast, patients with nosocomial or intravascular catheter–associated S aureus bacteremia were considered to be at low risk for IE.^5,6,8-11S aureus IE is relatively infrequent at any individual institution, and observations of its characteristics were based primarily upon relatively small samples,^{1,3,6,9,12-14} single-center experiences,^{5,6,8,9,13-16} or retrospectively identified patients.^2,7,8,15,16 Patient characteristics, treatment practices, and outcomes in these single-center studies often differed considerably. Moreover, because no large, prospectively collected, and geographically diverse cohort of patients with IE existed before now, the impact of regional variations on the characteristics, treatment, and outcome of S aureus IE was unknown.

The microbiology, epidemiology, diagnostics, and treatment of infective endocarditis (IE) have changed significantly since the Duke Criteria were published in 1994 and modified in 2000. The International Society for Cardiovascular Infectious Diseases (ISCVID) convened a multidisciplinary Working Group to update the diagnostic criteria for IE. The resulting 2023 Duke-ISCVID IE Criteria propose significant changes, including new microbiology diagnostics (enzyme immunoassay for Bartonella species, PCR, amplicon/metagenomic sequencing, in situ hybridization), imaging ([18F]FDG PET/CT, Cardiac Computed Tomography), and inclusion of intraoperative inspection as a new Major Clinical Criterion. The list of “typical” microorganisms causing IE was expanded and includes pathogens to be considered as typical only in the presence of intracardiac prostheses. The requirements for timing and separate venipunctures for blood cultures were removed. Last, additional predisposing conditions (transcatheter valve implants, endovascular cardiac implantable electronic devices, prior IE) were clarified. These diagnostic criteria should be updated periodically by making the ISCVID-Duke Criteria available online as a “Living Document”.

STAPHYLOCOCCUS AUREUS bacteremia (SAB) is a serious, common infection.^1,2 Complications of SAB such as infective endocarditis^3-6 and vertebral osteomyelitis⁷ are also common but are often difficult to identify at the time of the initial positive blood culture result.^8-16 For example, in a recent report of 260 patients with SAB due to infective endocarditis, the diagnosis of endocarditis was not clinically suspected and was first detected at autopsy in 32% of patients.¹³ Failure to identify such complications of SAB may lead to relapsing bacteremia¹⁷ or catastrophic outcomes.¹⁸ Thus, predicting the likelihood of these complications may greatly impact patient management.