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Clinical approach to Staphylococcus aureus bacteremia in adults

Clinical approach to Staphylococcus aureus bacteremia in adults
Authors:
Vance G Fowler, Jr, MD
Thomas L Holland, MD
Section Editor:
Steven Tong, MBBS, Hons, FRACP, PhD
Deputy Editor:
Elinor L Baron, MD, DTMH
Literature review current through: Jan 2024.
This topic last updated: Dec 14, 2023.

INTRODUCTION — Staphylococcus aureus is a leading cause of community-acquired and hospital-acquired bacteremia. Issues related to clinical manifestations of S. aureus infection are discussed separately. (See "Clinical manifestations of Staphylococcus aureus infection in adults".)

Issues related to the clinical approach to S. aureus bacteremia in adults with no cardiac device or prosthetic valve will be reviewed here. Issues related to evaluation of patients with a cardiac device or prosthetic valve are discussed separately. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis" and "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis".)

CLINICAL APPROACH — The clinical approach to S. aureus bacteremia consists of careful history and physical examination, infectious disease consultation, and diagnostic evaluation including echocardiography and additional imaging as needed.

History and physical examination

●History – A careful history and physical examination is essential. For circumstances in which the source of bacteremia is uncertain, patients should be questioned carefully regarding potential portals of entry including recent skin or soft tissue infection and presence of indwelling prosthetic devices (including intravascular catheters, orthopedic hardware, and cardiac devices).

Patients should also be questioned regarding symptoms that may reflect metastatic infection, which can occur in up to 40 percent of cases [1]. These include bone or joint pain (particularly back pain, suggesting vertebral osteomyelitis, discitis, and/or epidural abscess), protracted fever and/or sweats (suggestive of endocarditis), abdominal pain (particularly left upper quadrant pain, which may reflect splenic infarction), costovertebral angle tenderness (which may reflect renal infarction or psoas abscess), and headache (which may reflect septic emboli).

●Physical examination – The physical examination should include careful cardiac examination for signs of new murmurs or heart failure. A vigorous search should be undertaken for the clinical stigmata of endocarditis, including evidence of small and large emboli with special attention to the fundi, conjunctivae, skin, and digits. A neurologic evaluation should be undertaken for evidence of focal neurologic impairment; it is also important as a baseline examination should neurologic deficits develop later. These issues are discussed further separately. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Clinical manifestations'.)

Serial bedside examinations are critical for detection of complications that may develop after initial evaluation and during the course of treatment. Metastatic seeding may occur within the first few days of hospitalization, although in some cases it may not come to clinical attention for several weeks. In several case series, only 39 percent of 133 patients with bacteremic S. aureus vertebral osteomyelitis [2] and 57 percent of 35 patients with epidural abscess [3] had a diagnosis on admission related to the spine. Failure to identify such complications of S. aureus bacteremia may lead to catastrophic complications (eg, death, paralysis) [4] or relapsing bacteremia due to inadequate treatment [5].

Infectious disease consultation — Bedside infectious disease consultation is an important component of management for patients with S. aureus bacteremia and should occur whenever feasible, given the importance of serial examination to evaluate for metastatic infection and/or clues to the source of bacteremia.

Several studies have demonstrated bedside infectious disease consultation is associated with better outcomes including fewer deaths, fewer relapses, and lower readmission rates than telephone consultation or no consultation [6-11]:

●In a retrospective study comparing bedside consultation with telephone consultation for management of 342 patients with S. aureus bacteremia, bedside consultation was associated with a lower 90-day mortality (9 versus 29 percent; odds ratio [OR] 0.25, 95% CI 0.13-0.51) [8].

●In another study including 244 patients with S. aureus bacteremia, fewer relapses were observed among those who received bedside consultation (6 versus 18 percent), even among patients treated with an appropriate duration of therapy [7].

●In a randomized crossover clinical trial in Germany, unsolicited telephone consultations for S. aureus bacteremia did not improve 30-day mortality [12]. However, the study was underpowered given low overall mortality (approximately 5 percent).

Diagnostic evaluation — The diagnostic evaluation should include blood cultures, echocardiography, and additional imaging tailored to individual circumstances, as outlined below. Other studies include routine laboratory tests and electrocardiography.

Blood cultures

Interpreting results — Blood culture detection of Staphylococcus aureus should always be regarded as clinically significant, even if only a single positive blood culture bottle is observed [13]. Identification of positive blood cultures should prompt initiation of empiric therapy as well as further clinical evaluation.

Follow-up blood cultures — Blood cultures should be drawn every 24 to 48 hours until clearance is demonstrated.

Persistent S. aureus bacteremia despite appropriate antibiotic therapy is prognostically important. In a large European cohort including more than 900 patients, duration of bacteremia at least one additional day after starting appropriate antibiotic therapy was observed in 32 percent of cases; among such patients, the 30-day mortality was double that of the patients whose blood cultures cleared immediately (28 versus 13 percent) [14].

Echocardiography — Patients with S. aureus bacteremia should undergo echocardiography to evaluate for presence of endocarditis [15,16]. The approach for patients with no cardiac device or prosthetic device is discussed below.

Issues related to evaluation of patients with a cardiac device or prosthetic valve are discussed separately. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis" and "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis".)

Initial evaluation with TTE — Transthoracic echocardiography (TTE) is usually performed first [16]; identification of a vegetation on TTE may obviate the need for transesophageal echocardiography (TEE), although TTE is not sufficient for ruling out infective endocarditis (IE) [17,18].

The results of echocardiography are useful even when the study is negative, as the absence of IE may impact decisions about the duration of antimicrobial therapy. In one series including 103 patients with S. aureus bacteremia, the diagnosis of endocarditis was established by TTE and TEE in 7 versus 25 percent of cases, respectively [19].

Indications for TEE — The indications for TEE in patients with S. aureus bacteremia and no evidence of vegetation on TTE are controversial [20,21]. TEE is substantially more sensitive than TTE for identification of valvular vegetation [18,22-24]; it is most sensitive when performed five to seven days after the onset of bacteremia [25,26]. In the setting of high clinical suspicion for IE and a negative echocardiogram, a repeat study is warranted. However, TEE has associated costs and risks; major complications such as esophageal perforation occur in approximately 1 in 5000 procedures [27].

Pursuit of TEE is important in the setting of risk factors for IE; these include [17,28]:

●Persistent S. aureus bacteremia despite appropriate antimicrobial therapy

●Short time to blood culture positivity (ie, within 24 to 48 hours rather than at later time points) [29,30]

●Unknown duration of bacteremia (ie, community-acquired infection)

●Presence of cardiac prosthetic material

●Presence of predisposing valvular abnormality

●Absence of evident removable source of bacteremia

●Hemodialysis dependency [31]

●Presence of peripheral stigmata for IE

●Intravenous drug use

A number of clinical prediction rules have been developed to quantify the risk of endocarditis among patients with S. aureus bacteremia; thus far, evidence supporting use of the VIRSTA score is most favorable (table 1) [29,32-35]:

●The VIRSTA score was derived from a prospective cohort study including more than 2000 patients with S. aureus bacteremia to assess variables independently associated with IE (table 1) [33]. The findings suggest that TEE it may be reasonable to forgo TEE for patients with VIRSTA score ≤2; this score had a negative predictive value (NPV) of 98.8 percent (95% CI 98.4-99.4). In a validation study including 922 patients, 62 were diagnosed with IE; the sensitivity and NPV of the VIRSTA score were 96.7 and 99.5 percent, respectively [36]. In a survey of more than 650 infectious disease experts, a majority of respondents favored TEE for VIRSTA score ≥3 [37].

●The PREDICT tool uses a combination of day 1 and day 5 variables (cardiac device, community- versus health care-associated versus nosocomial infection, and duration of bacteremia) to identify patients most likely to benefit from TEE [34,38]. In a validation study including 922 patients, 62 were diagnosed with IE; the sensitivity and NPV for the PREDICT scale on day 5 were 51.6 and 95.1 percent, respectively [36].

●In a prospective study including 477 patients with S. aureus bacteremia in the Netherlands, the accuracy of the POSITIVE, PREDICT, and VIRSTA scores were compared [39]. The VIRSTA score was the most accurate (NPV 99.3 percent); approximately 70 percent of patients with S. aureus bacteremia were classified as high risk for endocarditis, warranting TEE.

For patients with IE complications warranting an extended course of parenteral antibiotic therapy (such as osteomyelitis, discitis, or epidural abscess), in the absence of concern for cardiac complications based on clinical findings and TTE, it may be reasonable to forgo TEE.

Additional imaging — Imaging should be tailored to findings on history and physical examination.

●Back pain – Patients with back pain should be evaluated for vertebral osteomyelitis and discitis; this is discussed further separately. (See "Vertebral osteomyelitis and discitis in adults".)

●Headache or focal neurologic signs – Patients with headache or focal neurologic signs or symptoms in the setting of known or suspected IE should undergo magnetic resonance imaging of the head. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Additional evaluation for IE source or complications'.)

●Abdominal symptoms and subclinical sites of metastatic infection

•Computed tomography (CT) – CT of the torso should be pursued for patients with abdominal pain or costovertebral angle tenderness (to evaluate for presence of splenic infarct, renal infarct, psoas abscess, or other intra-abdominal sites of infection). Such imaging may also be appropriate for patients in whom an unrecognized focus of infection is suspected (such as persistent fever or bacteremia despite appropriate antimicrobial therapy).

•Positron emission tomography/computed tomography (PET/CT) – PET/CT is a promising modality to evaluate for metastatic infection. In a prospective cohort study including more than 300 patients with S. aureus bacteremia (of whom half underwent PET/CT one to two weeks after diagnosis), PET/CT demonstrated a new focus of infection in almost half of cases, most commonly at osteoarticular sites; 90-day mortality was lower in the PET/CT group (13.9 versus 28.5 percent) [40]. In a subsequent review including 7 observational studies and 1300 patients with S. aureus bacteremia, use of PET/CT frequently provided clinically meaningful results that influenced patient management; numbers needed to treat to prevent death, modify antimicrobial therapy, or pursue further source control were 4 to 8, 7 to 9, and 10 to 27, respectively [41]. However, subsequent authors have suggested that the observed impact of PET/CT on mortality may have been confounded by immortal time bias [42]; further randomized trial data are needed.

MANAGEMENT — Management of S. aureus bacteremia consists of prompt source control and antimicrobial therapy [43,44].

Source control — Source control refers to surgical or procedural management of an infected site with the intent of mitigating a potential source of a patient’s systemic infection; it may include incision and drainage, and/or removal of infected prosthetic devices. (See "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis".)

Early source control is a cornerstone of management for S. aureus bacteremia. In an observational study including more than 800 patients with S. aureus bacteremia (of whom 63 percent had short duration [1 to 2 days], 28 percent had intermediate duration [3 to 6 days], and 9 percent had prolonged duration [≥7 days]), the time to source-control procedure was delayed in the prolonged and intermediate groups compared with the short group (3.5 days, 3 days, and 1 day, respectively); each continued day of bacteremia was associated with a relative risk of death of 1.16 (95% CI 1.1-1.2) [44].

Empiric antibiotic therapy

●Clinical approach – The optimal approach to empiric therapy in the setting of S. aureus bacteremia prior to availability of culture and susceptibility data is uncertain. We favor empiric antimicrobial therapy with activity against methicillin-resistant S. aureus (MRSA), rather than empiric therapy with activity against both MRSA and methicillin-sensitive S. aureus (MSSA)

•Empiric treatment for MRSA – Empiric treatment for MRSA consists of vancomycin (table 2); daptomycin (8 to 10 mg/kg intravenously once daily) is an alternative agent. Ceftobiprole is also a potential alternative agent; thus far it is not available in the United States. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia", section on 'Monotherapy'.)

Once susceptibility results are available, if the isolate is methicillin-sensitive S. aureus (MSSA), antibiotic treatment should be de-escalated to a beta-lactam agent (such as nafcillin, oxacillin, flucloxacillin, or cefazolin) as discussed below. (See 'Methicillin-sensitive S. aureus' below.)

•Limited support for empiric inclusion of targeted treatment for MSSA – In addition to empiric treatment for MRSA, some favor inclusion of an antimicrobial agent with targeted activity against MSSA [45-47]. Among patients with the highest risk of morbidity and mortality from S. aureus infection (including patients with severe sepsis, probable endocarditis, or presence of a prosthetic or intravascular device), there are data suggesting that initial vancomycin monotherapy with subsequent de-escalation to a beta-lactam agent for patients with MSSA may result in worse outcomes than initial empiric therapy with two agents (targeting MRSA and MSSA, respectively) [45,48-50].

However, a retrospective study including more than 5000 patients with MSSA bacteremia who received empiric monotherapy with a beta-lactam or vancomycin noted no difference in all-cause 30-day mortality, even though there was a significantly better outcome for the same cohort of patients who received definitive therapy with a beta-lactam from day 4 to 14 of treatment [51].

Tailoring antibiotic therapy

Methicillin-sensitive S. aureus

Clinical approach

●Tailoring to beta-lactam therapy – Treatment of MSSA bacteremia generally consists of a beta-lactam agent such as nafcillin (2 g IV every four hours), oxacillin (2 g IV every four hours), flucloxacillin (2 g IV every six hours), or cefazolin (2g IV every eight hours) [52].

If the isolate is penicillin sensitive, benzylpenicillin (4 million units intravenously [IV] every four hours) may be used for treatment of S. aureus bacteremia [53]. Historically, penicillin-susceptible S. aureus isolates are relatively rare [54]; however, some studies have reported an increase in prevalence [55,56]. However, phenotypic susceptibility testing methods may not reliably detect penicillinase production [57].

•Outpatient treatment – For continuation of intravenous therapy in outpatient settings, cefazolin may be more practical and better tolerated than antistaphylococcal penicillins [58,59]. There are no adequately powered prospective clinical trials comparing the efficacy of various beta-lactam agents for treatment of MSSA bacteremia; retrospective data suggest that cefazolin and antistaphylococcal penicillins are equally effective [60-63]. One retrospective study suggested that patients who received cefazolin had a lower risk of mortality and similar risk of recurrent infection compared with those who received oxacillin or nafcillin [64]; however, interpretation of the findings is limited by potential confounding.

•Cefazolin inoculum effect of uncertain significance – Cefazolin has been observed to demonstrate an inoculum effect among a subset of isolates; this is defined as an increase in the cefazolin minimum inhibitory concentration (MIC) at high inoculum (107 colony-forming units [CFU]/mL) compared with standard inoculum (105 CFU/mL) [65,66]. The clinical significance of this phenomenon is uncertain; studies examining the impact of this effect have produced conflicting results [67,68]. In one study including 89 isolates from 77 patients (55 percent of which demonstrated the inoculum effect) treated with cefazolin, a higher 30-day mortality was observed among patients with strains demonstrating the inoculum effect than patients with strains demonstrating no inoculum effect (risk ratio 2.65, 95% CI 1.1-6.4) [65]. However, other studies have not observed a clinical difference in outcomes [69,70].

●Beta-lactam allergy

•Vancomycin – Vancomycin is less effective for treatment of S. aureus bacteremia than beta-lactam agents and should not be administered as primary therapy for methicillin-sensitive strains unless the use of a beta-lactam agent is precluded by drug intolerance [71-80]. Patients with MSSA bacteremia and a reported penicillin allergy should have treatment guided by allergy history (cefazolin may be given if history excludes anaphylactic features) or, if available, full allergy evaluation with skin testing or oral challenge [81,82].

In an observational study of 505 patients with S. aureus bacteremia, nafcillin was superior to vancomycin for preventing relapse or persistent MSSA bacteremia; the failure rate was 4 versus 20 percent [77]. In another study of 294 patients with S. aureus bacteremia, vancomycin therapy was associated with a higher risk of relapse (odds ratio 4.1, 95% CI 1.5-11.6) [72].

•Alternative agents – Alternative agents for the treatment of S. aureus bacteremia should be reserved for patients who are intolerant to beta-lactams and vancomycin, and should be guided by the results of susceptibility testing. The use of these agents is discussed further separately. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia", section on 'Antimicrobial therapy'.)

Patients who require treatment with an alternative agent should be managed by clinicians who are experts in the treatment of infectious diseases and who are familiar with the available (and limited) literature on the efficacy, dosing, and side effects of such therapy. The use of all alternative agents is limited because of the development of resistance or an increased rate of adverse effects during therapy.

No role for routine combination therapy — There is no role for routine combination therapy of antistaphylococcal penicillins or vancomycin with aminoglycosides, rifampin, or daptomycin for treatment of staphylococcal bacteremia:

●Routine combination of antistaphylococcal penicillins or vancomycin with aminoglycosides is not warranted. While in vitro and experimental models of endocarditis have demonstrated that combination therapy facilitates more rapid killing of MSSA than monotherapy, the evidence for clinically significant benefit is minimal.

This was illustrated by a randomized trial of 48 patients with MSSA native valve endocarditis [83]. While patients who received nafcillin plus gentamicin for the first two weeks of therapy had more rapid clearance of bacteremia than those who received nafcillin alone, cure rates were comparable and combination therapy was associated with a higher incidence of renal dysfunction. (See "Antimicrobial therapy of left-sided native valve endocarditis", section on 'Staphylococci'.)

Subsequently, a randomized trial including 236 patients with S. aureus bacteremia and endocarditis demonstrated that daptomycin monotherapy is not inferior to low-dose gentamicin plus an antistaphylococcal penicillin or vancomycin; those in the standard therapy arm experienced significantly more renal impairment than those in the daptomycin arm [84]. An investigation of safety data from the trial noted significantly greater reduction in creatinine clearance among those who received initial low-dose gentamicin than those who did not (22 versus 8 percent, respectively) [85].

●There is no role for adjunctive rifampin for treatment of S. aureus bacteremia in the absence of prosthetic valve endocarditis or orthopedic hardware. In a randomized trial including more than 700 adults with S. aureus bacteremia (only 14 of whom had a prosthetic valve or prosthetic joint) randomly assigned to treatment with standard therapy plus rifampin (600 or 900 mg per day, orally or intravenously) or placebo, no significant difference in mortality or bacteriologic failure was observed after 12 weeks (17 versus 18 percent; hazard ratio 0.96, CI 0.68-1.35) [86]. In addition, patients treated with rifampin were more likely to have adverse drug interactions than those who received placebo.

Issues related to use of adjunctive rifampin for treatment of staphylococcal infection in the context of prosthetic valve endocarditis or orthopedic hardware are discussed separately. (See "Antimicrobial therapy of prosthetic valve endocarditis" and "Prosthetic joint infection: Treatment", section on 'Use of adjunctive rifampin'.)

●There is no role for adjunctive daptomycin for the treatment of MSSA bacteremia. In a randomized trial including more than 100 patients with MSSA bacteremia treated with an anti-staphylococcal beta-lactam in combination with daptomycin or placebo, addition of daptomycin did not shorten duration of bacteremia or improve clinical outcomes [87].

Methicillin-resistant S. aureus — The treatment of patients with bacteremia due to MRSA is discussed separately. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia", section on 'Antimicrobial therapy'.)

Follow-up cultures — Once the diagnosis of S. aureus bacteremia has been established and treatment has been initiated, blood cultures should be repeated to document clearance of bacteremia. At least one blood culture set with an adequate volume of 8 to 10 mL per bottle should be collected; a single blood culture bottle may not be sufficient to demonstrate resolution of bacteremia [88,89].

Failure to clear bacteremia within 48 hours after initiation of therapy should prompt further evaluation, including evaluation of susceptibility data to ensure appropriate antibiotic selection and dosing, as well as clinical evaluation for occult focus of infection that may require drainage or other intervention beyond antimicrobial therapy alone.

Completing antibiotic therapy

Parenteral versus oral therapy — For patients with uncomplicated S. aureus bacteremia, parenteral therapy remains standard treatment. In carefully selected patients, it is possible that treatment may be completed successfully with an oral antibiotic regimen; however, this approach requires further evaluation in well-designed clinical trials before it can be considered standard of care [90].

Some data supporting the potential utility of oral stepdown therapy for patients with S. aureus bacteremia were provided by the trial of partial oral treatment of endocarditis (POET trial) for carefully selected patients with left-sided endocarditis [91]. In the full cohort study, partial oral treatment was noninferior to full parenteral therapy; however, generalizability to patients with S. aureus bacteremia is limited since only 22 percent of the cohort had S. aureus infective endocarditis and none were infected with MRSA.

Duration of therapy — The duration of therapy for S. aureus bacteremia depends on the etiology of infection [7]. Determination of treatment duration requires differentiation of patients with uncomplicated S aureus bacteremia (who may be treated with 14 days of intravenous therapy) from patients with complicated S. aureus bacteremia (who require longer duration of intravenous treatment) [15].

In general, a patient may be presumed to have uncomplicated S. aureus bacteremia if all of the following criteria are met [16,92,93]:

●Infective endocarditis has been excluded via echocardiography. (See 'Echocardiography' above.)

●No indwelling devices (such as prosthetic heart valves or vascular grafts) are present.

●Follow-up blood cultures drawn two to four days after initiating intravenous antistaphylococcal therapy and removing the presumed focus of infection (if present) are negative.

●The patient defervesced within 48 to 72 hours after initiating intravenous antistaphylococcal therapy and removal of the presumed focus of infection (such as debridement of soft tissue infection or intravascular catheter removal).

●There is no evidence of metastatic staphylococcal infection on physical examination.

Patients meeting all of these criteria may be treated with 14 days of effective antimicrobial therapy from the first negative blood culture. These patients should have negative surveillance blood cultures within 72 hours after initiation of appropriate antimicrobial therapy and no signs of ongoing systemic staphylococcal infection. Use of an algorithm to guide management of staphylococcal bacteremia may be useful to optimize duration of antibiotic therapy [94].

It is uncertain whether a shorter treatment duration (<14 days) may be appropriate for some patients with uncomplicated methicillin-sensitive S. aureus bacteremia. In one retrospective cohort of carefully selected low-risk patients in Denmark, outcomes were similar for shorter (6 to 10 days) and longer (13 to 15 days) treatment duration; however, mortality even among the low-risk patients was high (17 to 23 percent); further study of treatment duration is needed [95,96].

Patients with S. aureus bacteremia who do not meet all of the above criteria should be presumed to have a deep focus of infection, warranting intravenous treatment for longer than two weeks. The duration of therapy for such patients depends on the nature of the underlying infection, as discussed in the following sections:

●Infective endocarditis (see "Antimicrobial therapy of left-sided native valve endocarditis")

●Cardiac device infection (see "Infections involving cardiac implantable electronic devices: Treatment and prevention")

●Osteomyelitis (see "Nonvertebral osteomyelitis in adults: Treatment" and "Vertebral osteomyelitis and discitis in adults")

●Prosthetic joint infection (see "Prosthetic joint infection: Treatment")

●Septic arthritis (see "Septic arthritis in adults")

●Meningitis (see "Treatment of bacterial meningitis caused by specific pathogens in adults")

●Pneumonia (see "Treatment of hospital-acquired and ventilator-associated pneumonia in adults" and "Treatment of community-acquired pneumonia in adults who require hospitalization")

Issues related to the likelihood of hardware seeding during S. aureus bacteremia are discussed further separately. (See "Clinical manifestations of Staphylococcus aureus infection in adults", section on 'Prosthetic joint infection'.)

PROGNOSIS — A systematic review including 341 studies noted mortality rates are >25 percent at three months [97]. Mortality is higher among patients with underlying comorbidities, methicillin-resistant S. aureus (MRSA) infection (odds ratio [OR] 9.3, 95% CI 1.5-59.2), and/or time to positivity of blood cultures ≤12 hours (OR 6.9, 95% CI 1.1-44.7) [97-101].

Treatment failure (ie, death within 30 days following treatment, persistent bacteremia >10 days after initiation of appropriate therapy, or recurrence of bacteremia within 60 days of discontinuing therapy) and hospital readmission are common in patients with S. aureus bacteremia, particularly in the setting of infection due to MRSA [102].

The presence of prosthetic material or devices in a patient with S. aureus increases the risk of relapsed infection. This was illustrated in a series of 294 patients with S. aureus bacteremia; relapses occur more frequently among patients with an indwelling foreign body (83 versus 21 percent) [72]. The median time to relapse after the first detected bacteremic episode in patients with retained foreign bodies was 69 days (range 35 to 89 days). The proportion of patients with S. aureus bacteremia who have a permanent prosthetic device has increased over time. In one cohort including more than 2300 patients with S. aureus bacteremia enrolled between 1995 and 2015, more than half had an indwelling prosthetic device [1].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Management of Staphylococcus aureus infection".)

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.)

●Basics topic (see "Patient education: Sepsis in adults (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Clinical approach − The clinical approach to Staphylococcus aureus bacteremia consists of careful history and physical examination, infectious disease consultation, and diagnostic evaluation including echocardiography and additional imaging as needed. (See 'Clinical approach' above.)

●History and physical examination

•Clinical history − Patients should be questioned regarding potential portals of entry, presence of indwelling prosthetic devices, and symptoms that may reflect metastatic infection. These include bone or joint pain (particularly back pain, suggesting vertebral osteomyelitis, discitis, and/or epidural abscess) and protracted fever and/or sweats (suggestive of endocarditis). (See 'History and physical examination' above.)

•Physical examination − The physical examination should include cardiac examination for signs of new murmurs or heart failure. A search should be undertaken for clinical stigmata of endocarditis, including evidence of small and large emboli. Serial bedside examinations are critical for detection of complications that may develop after initial evaluation and during the course of treatment. (See 'History and physical examination' above.)

●Infectious disease consultation − We recommend bedside infectious disease consultation for management of patients with S. aureus bacteremia (Grade 1B); this is a critical component of management for patients with S. aureus bacteremia and is associated with better outcomes including fewer deaths, fewer relapses, and lower readmission rates. (See 'Infectious disease consultation' above.)

●Diagnostic evaluation − In general, blood cultures positive for S. aureus should be respected as a clinically significant finding that should prompt clinical evaluation and initiation of empiric therapy. All patients with S. aureus bacteremia should undergo echocardiography to evaluate for presence of endocarditis. Additional diagnostic imaging should be tailored to findings on history and physical examination. (See 'Diagnostic evaluation' above.)

●Empiric treatment − In the setting of blood cultures with gram-positive cocci prior to availability of culture and susceptibility data, we suggest administration of empiric antimicrobial therapy with activity against methicillin resistant S. aureus (MRSA), rather than empiric therapy with activity against both MRSA and methicillin-sensitive S. aureus (MSSA) (Grade 2B). Empiric treatment consists of vancomycin (table 2); daptomycin is an acceptable alternative agent. (See 'Empiric antibiotic therapy' above.)

●Tailored treatment

•MSSA − (see 'Methicillin-sensitive S. aureus' above):

-We recommend treating MSSA bacteremia with a beta-lactam antibiotic (in preference to vancomycin or daptomycin) (Grade 1B). Regimens include penicillin, nafcillin, oxacillin, flucloxacillin, or cefazolin.

-Vancomycin is less effective for treatment of S. aureus bacteremia than beta-lactam agents and should not be administered as primary therapy for methicillin-sensitive strains unless the use of a beta-lactam agent is precluded by drug intolerance.

-There is no role for routine combination therapy of antistaphylococcal penicillins or vancomycin with aminoglycosides, rifampin, or daptomycin for treatment of S. aureus bacteremia.

•MRSA − The treatment of patients with bacteremia due to MRSA is discussed separately. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia", section on 'Antimicrobial therapy'.)

●Parenteral versus oral therapy – For patients with uncomplicated S. aureus bacteremia, standard treatment consists of parenteral therapy. It is uncertain whether treatment may be completed with an oral antibiotic regimen in some circumstances; further well-designed clinical trials are needed. (See 'Parenteral versus oral therapy' above.)

●Duration of therapy − The duration of therapy depends on the etiology of infection. In general, patients with bacteremia with a removable focus of infection may be treated with 14 days of therapy. (See 'Duration of therapy' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff at acknowledges Daniel Sexton, MD, who contributed to earlier versions of this topic review.

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Topic 2134 Version 72.0

References

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2 : Bacteremic Staphylococcus aureus spondylitis.

3 : Update on spinal epidural abscess: 35 cases and review of the literature.

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5 : Short-course therapy of catheter-related Staphylococcus aureus bacteremia: a meta-analysis.

6 : Mortality of S. aureus bacteremia and infectious diseases specialist consultation--a study of 521 patients in Germany.

7 : Outcome of Staphylococcus aureus bacteremia according to compliance with recommendations of infectious diseases specialists: experience with 244 patients.

8 : Telephone consultation cannot replace bedside infectious disease consultation in the management of Staphylococcus aureus Bacteremia.

9 : Impact of Infectious Disease Consultation on Quality of Care, Mortality, and Length of Stay in Staphylococcus aureus Bacteremia: Results From a Large Multicenter Cohort Study.

10 : Infectious disease consultation for Staphylococcus aureus bacteremia - A systematic review and meta-analysis.

11 : Association of Evidence-Based Care Processes With Mortality in Staphylococcus aureus Bacteremia at Veterans Health Administration Hospitals, 2003-2014.

12 : Effect of Automated Telephone Infectious Disease Consultations to Nonacademic Hospitals on 30-Day Mortality Among Patients With Staphylococcus aureus Bacteremia: The SUPPORT Cluster Randomized Clinical Trial.

13 : Clinical Significance of Staphylococcus aureus in a Single Positive Blood Culture Bottle.

14 : Defining persistent Staphylococcus aureus bacteraemia: secondary analysis of a prospective cohort study.

15 : Clinical management of Staphylococcus aureus bacteremia: a review.

16 : Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.

17 : Use of a simple criteria set for guiding echocardiography in nosocomial Staphylococcus aureus bacteremia.

18 : Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography.

19 : Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients.

20 : Echocardiography is dispensable in uncomplicated Staphylococcus aureus bacteremia.

21 : Low rates of endocarditis in healthcare-associated Staphylococcus aureus bacteremia suggest that echocardiography might not always be required.

22 : Staphylococcus aureus bacteremia and endocarditis: the Grady Memorial Hospital experience with methicillin-sensitive S aureus and methicillin-resistant S aureus bacteremia.

23 : Importance of transesophageal echocardiography in the evaluation of Staphylococcus aureus bacteremia.

24 : Staphylococcus aureus bacteraemia: evaluation of the role of transoesophageal echocardiography in identifying clinically unsuspected endocarditis.

25 : Cost-effectiveness of transesophageal echocardiography to determine the duration of therapy for intravascular catheter-associated Staphylococcus aureus bacteremia.

26 : Implication of negative results on a monoplane transesophageal echocardiographic study in patients with suspected infective endocarditis.

27 : Transesophageal echocardiography.

28 : Use of Transthoracic Echocardiography in the Management of Low-Risk Staphylococcus aureus Bacteremia: Results From a Retrospective Multicenter Cohort Study.

29 : Time to blood culture positivity in Staphylococcus aureus bacteraemia to determine risk of infective endocarditis.

30 : Clinical prediction scores and the utility of time to blood culture positivity in stratifying the risk of infective endocarditis in Staphylococcus aureus bacteraemia.

31 : Staphylococcus aureus Bacteremia Among Patients Receiving Maintenance Hemodialysis: Trends in Clinical Characteristics and Outcomes.

32 : Clinical predictors and clinical prediction rules to estimate initial patient risk for infective endocarditis in Staphylococcus aureus bacteraemia: a systematic review and meta-analysis.

33 : The VIRSTA score, a prediction score to estimate risk of infective endocarditis and determine priority for echocardiography in patients with Staphylococcus aureus bacteremia.

34 : Prospective Validation of PREDICT and Its Impact on the Transesophageal Echocardiography Use in Management of Staphylococcus aureus Bacteremia.

35 : Time to blood culture positivity: An independent predictor of infective endocarditis and mortality in patients with Staphylococcus aureus bacteraemia.

36 : Validation of VIRSTA and PREDICT scores to determine the priority of echocardiography in patients with Staphylococcus aureus bacteremia.

37 : A Scenario-Based Survey of Expert Echocardiography Recommendations for Patients With Staphylococcus aureus Bacteremia at Varying Risk for Endocarditis.

38 : Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT): Scoring System to Guide Use of Echocardiography in the Management of Staphylococcus aureus Bacteremia.

39 : Prediction Rules for Ruling Out Endocarditis in Patients With Staphylococcus aureus Bacteremia.

40 : Integration of FDG-PET/CT in the Diagnostic Workup for Staphylococcus aureus Bacteremia: A Prospective Interventional Matched-cohort Study.

41 : Evidence of Clinical Impact Supports a New Petition for Medicare Coverage of 2-[18F]Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography in the Evaluation of Staphylococcus aureus Bacteremia: A Focused Literature Review and Call to Action.

42 : Positive Impact of [18F]FDG-PET/CT on Mortality in Patients With Staphylococcus aureus Bacteremia Explained by Immortal Time Bias.

43 : Impact of an evidence-based bundle intervention in the quality-of-care management and outcome of Staphylococcus aureus bacteremia.

44 : Defining the Breakpoint Duration of Staphylococcus aureus Bacteremia Predictive of Poor Outcomes.

45 : The empirical combination of vancomycin and aβ-lactam for Staphylococcal bacteremia.

46 : Outcome of vancomycin treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia.

47 : Combination of Vancomycin andβ-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial.

48 : Impact of initial antibiotic choice and delayed appropriate treatment on the outcome of Staphylococcus aureus bacteremia.

49 : Impact of empirical-therapy selection on outcomes of intravenous drug users with infective endocarditis caused by methicillin-susceptible Staphylococcus aureus.

50 : Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible Staphylococcus aureus bacteremia.

51 : Comparative effectiveness of beta-lactams versus vancomycin for treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections among 122 hospitals.

52 : Flucloxacillin, a new isoxazolyl penicillin, compared with oxacillin, cloxacillin, and dicloxacillin.

53 : Effectiveness of penicillin, dicloxacillin and cefuroxime for penicillin-susceptible Staphylococcus aureus bacteraemia: a retrospective, propensity-score-adjusted case-control and cohort analysis.

54 : Staphylococcus aureus infections.

55 : The prevalence, population structure and screening test specificity of penicillin-susceptible Staphylococcus aureus bacteremia isolates in Malmö, Sweden.

56 : Resurgence of penicillin-susceptible Staphylococcus aureus at a hospital in New York State, USA.

57 : A multi-site, international laboratory study to assess the performance of penicillin susceptibility testing of Staphylococcus aureus.

58 : Comparative evaluation of the tolerability of cefazolin and nafcillin for treatment of methicillin-susceptible Staphylococcus aureus infections in the outpatient setting.

59 : Comparison of cefazolin versus oxacillin for treatment of complicated bacteremia caused by methicillin-susceptible Staphylococcus aureus.

60 : Comparative effectiveness of cefazolin versus cloxacillin as definitive antibiotic therapy for MSSA bacteraemia: results from a large multicentre cohort study.

61 : Is cefazolin inferior to nafcillin for treatment of methicillin-susceptible Staphylococcus aureus bacteremia?

62 : Cefazolin versus anti-staphylococcal penicillins for the treatment of patients with Staphylococcus aureus bacteraemia.

63 : Optimal treatment of MSSA bacteraemias: a meta-analysis of cefazolin versus antistaphylococcal penicillins.

64 : Comparative Effectiveness of Cefazolin Versus Nafcillin or Oxacillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections Complicated by Bacteremia: A Nationwide Cohort Study.

65 : The Cefazolin Inoculum Effect Is Associated With Increased Mortality in Methicillin-Susceptible Staphylococcus aureus Bacteremia.

66 : Prevalence and Characterization of the Cefazolin Inoculum Effect in North American Methicillin-Susceptible Staphylococcus aureus Isolates.

67 : Cefazolin versus anti-staphylococcal penicillins for treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a narrative review.

68 : Inactivation of cefazolin, cephaloridine, and cephalothin by methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus.

69 : Inoculum effect with cefazolin among clinical isolates of methicillin-susceptible Staphylococcus aureus: frequency and possible cause of cefazolin treatment failure.

70 : Determination of an inoculum effect with various cephalosporins among clinical isolates of methicillin-susceptible Staphylococcus aureus.

71 : Recurrent Staphylococcus aureus bacteremia.

72 : Recurrent Staphylococcus aureus bacteremia: pulsed-field gel electrophoresis findings in 29 patients.

73 : Staphylococcus aureus and vancomycin: the sequel.

74 : Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis.

75 : Staphylococcus aureus bacteremia and endocarditis. New diagnostic and therapeutic concepts.

76 : Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users.

77 : Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study.

78 : The role of vancomycin in the treatment paradigm.

79 : Bacteremic pneumonia due to Staphylococcus aureus: A comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms.

80 : Retrospective evaluation of therapies for Staphylococcus aureus endocarditis.

81 : Improving Clinical Outcomes in Patients With Methicillin-Sensitive Staphylococcus aureus Bacteremia and Reported Penicillin Allergy.

82 : Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin Allergy: The PALACE Randomized Clinical Trial.

83 : Combination antimicrobial therapy for Staphylococcus aureus endocarditis in patients addicted to parenteral drugs and in nonaddicts: A prospective study.

84 : Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus.

85 : Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic.

86 : Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

87 : Adjunctive Daptomycin in the Treatment of Methicillin-susceptible Staphylococcus aureus Bacteremia: A Randomized, Controlled Trial.

88 : Using Data to Optimize Blood Bottle Fill Volumes and Pathogen Detection: Making Blood Cultures Great Again.

89 : Intermittent Negative Blood Cultures in Staphylococcus aureus Bacteremia; a Retrospective Study of 1071 Episodes.

90 : A Narrative Review of Early Oral Stepdown Therapy for the Treatment of Uncomplicated Staphylococcus aureus Bacteremia: Yay or Nay?

91 : Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis.

92 : Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America.

93 : Treatment duration for uncomplicated Staphylococcus aureus bacteremia to prevent relapse: analysis of a prospective observational cohort study.

94 : Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial.

95 : Comparable Outcomes of Short-Course and Prolonged-Course Therapy in Selected Cases of Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Pooled Cohort Study.

96 : Shortening the Duration of Therapy for Staphylococcus aureus Bacteremia: Opening the Overton Window.

97 : Staphylococcus aureus bacteraemia mortality: a systematic review and meta-analysis.

98 : Predictors of mortality in Staphylococcus aureus Bacteremia.

99 : Prospective analysis of Staphylococcus aureus bacteremia in nonneutropenic adults with malignancy.

100 : Role of comorbidity in mortality related to Staphylococcus aureus bacteremia: a prospective study using the Charlson weighted index of comorbidity.

101 : Time to blood culture positivity as a predictor of clinical outcome of Staphylococcus aureus bloodstream infection.

102 : Methicillin-susceptible and Methicillin-resistant Staphylococcus aureus Bacteremia: Nationwide Estimates of 30-Day Readmission, In-hospital Mortality, Length of Stay, and Cost in the United States.

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