Each key question was addressed by searching PubMed (July, 1965, to September, 2009) using the following MeSH search terms: “Staphylococcus aureus and (bacteraemia or blood stream infection)”. Further specific search terms, for example “echocardiography or cephalosporin”, were added, depending on the question. The search was limited to studies published in the English language. Bibliographies were hand-searched for secondary references. Studies were categorised by study design and the
ReviewClinical management of Staphylococcus aureus bacteraemia
Introduction
Staphylococcus aureus is an important cause of serious community and health-care-associated infections worldwide. In a study of 6697 bloodstream infections from 59 hospitals in the USA, S aureus was the most common bacterial isolate, accounting for 23% of all episodes, and was more strongly associated with death than any other bacterial pathogen.1 In the UK, around 12 500 cases of S aureus bacteraemia (SAB) are voluntarily reported each year,2 associated with a mortality of about 30%.3
Surprisingly little evidence is available to guide the management of SAB. Current UK and US treatment guidelines suggest that uncomplicated SAB should be treated for a minimum of 14 days, and for 4–6 weeks if there is a deep infection focus.4, 5, 6, 7, 8 To date, fewer than 1500 patients have been enrolled in 16 randomised controlled trials (RCTs) investigating SAB antimicrobial therapy. Much of our current practice is therefore based on clinical experience and observational studies; consequently, discrepant views of how to manage SAB abound.9 We review the evidence behind the key clinical decisions in the management of SAB and define the agenda for future clinical research.
Section snippets
How should SAB be defined?
A clinically significant bacteraemia, or bloodstream infection, is usually defined as the isolation of bacteria from one or more peripheral venous blood-culture samples collected from a patient with associated relevant symptoms and signs of systemic infection. Prospective studies including 1809 SAB episodes considered only 27 (1·5%) to be due to contamination.10, 11, 12, 13 Given the severity of disease associated with SAB, particularly the risk of metastatic complications, the isolation of S
Is identification and removal of the focus of infection important?
Expert opinion has long been that optimum management of SAB requires adequate antimicrobial therapy and, where possible, the removal or drainage of potential foci of infection.24 Three prospective studies have shown that not removing an infected intravenous catheter is the strongest independent risk factor for SAB relapse.10, 13, 22 Early surgical intervention in S aureus endocarditis (SAE), particularly the early removal of infected prosthetic heart valves, improves outcome,25, 26 and not
Should all patients with SAB have echocardiography?
SAB is a major risk factor for endocarditis, particularly in those with abnormal or prosthetic valves.16 Studies published before the advent of echocardiography suggested that around 60% of patients with SAB had endocarditis,24 and long-term antimicrobial therapy (4–6 weeks) was given to most patients with SAB in that era.
Transthoracic echocardiography has been extensively compared with transoesophageal echocardiography for infective endocarditis of any cause.33 These investigations confirmed
Are glycopeptides equivalent to β-lactams for the treatment of SAB?
Two trials, involving 47 intravenous drug users with right-sided S aureus endocarditis, showed poorer outcomes in those given either teicoplanin or vancomycin (19 [68%] of 28 failed therapy) versus cloxacillin (one [5%] of 19 failed therapy).42, 43 A third trial compared teicoplanin with flucloxacillin for the treatment of SAB and other sterile-site infections and was stopped early after six (67%) of nine patients given teicoplanin failed treatment compared with one (11%) of nine given
Are cephalosporins as effective as penicillins for the treatment of SAB?
Cephalosporins are often considered for the treatment of SAB in patients who are intolerant of penicillins and when longer-acting antimicrobials are needed for ease of administration. Despite substantial anecdotal experience of their use in the treatment of SAB, little published evidence exists to confirm their efficacy. No comparative RCTs have been done, but prospective observational studies suggest that most of the commonly used cephalosporins may be as effective as penicillins for the
Is teicoplanin as effective as vancomycin?
Vancomycin and teicoplanin are the first-line therapy for MRSA bacteraemia and for those with serious penicillin allergy. Teicoplanin is not licensed for use in the USA, and comparisons are complicated by the suboptimum dosing of teicoplanin in early studies. An RCT of 21 patients with serious S aureus infections (13 SAB; six with a deep focus) compared teicoplanin (400 mg daily) with vancomycin (1 g twice daily) and reported similar proportions cured for each drug.76 An RCT compared
What is the optimum duration of therapy for SAB?
50 years ago, two-thirds of SAB were associated with endocarditis, and long-term (≥4 weeks) intravenous therapy was thought mandatory.24 Intravascular catheters are now the most common source of SAB,81 and the risks of endocarditis and disease recurrence are low, provided the source is removed.82 This has prompted use of much shorter courses of antibiotics, particularly for catheter-associated SAB.83
Only one published RCT has examined the duration of intravenous therapy for any form of SAB: 11
Is oral therapy as effective as intravenous therapy?
Two RCTs indicate some oral antibiotics are as effective as those given intravenously.98, 99 The first compared oral fleroxacin plus rifampicin against conventional intravenous therapy with a β-lactam or glycopeptide in 104 adults with SAB (55 with catheter-associated infection, 35 with bone or joint infection).98 Patients with left-sided endocarditis were excluded. The second trial compared oral ciprofloxacin plus rifampicin versus standard intravenous therapy in 85 intravenous drug users with
Is combination antimicrobial therapy better than monotherapy?
Combining antimicrobials to enhance bacterial killing has long been used for the treatment of SAB, particularly SAE, but has never been shown to improve outcome (table 6). Synergy between β-lactams and gentamicin has been shown experimentally,110, 111 but the evidence for clinical effectiveness in human beings is limited to one report of 78 patients with SAE in whom the addition of gentamicin to the first 2 weeks of nafcillin treatment reduced the time to defervescence and duration of
What is the role of the newer antimicrobials in the treatment of SAB?
Several new antimicrobials may have important future roles in the management of SAB (table 7), although only linezolid and daptomycin have entered mainstream clinical practice.
Discussion
SAB is a common and serious infection worldwide, yet the evidence base for almost all aspects of its management is poor. We first examined the evidence on the definition of SAB and the need to identify the infection source and focus (panel). A single positive blood culture for S aureus should always be defined as clinically significant, given the intrinsic pathogenicity of S aureus, the high number and frequency of complications following SAB, and the rarity of S aureus contamination of blood
Search strategy and selection criteria
References (157)
- et al.
Healthcare-associated bloodstream infection: a distinct entity? Insights from a large U.S. database
Crit Care Med
(2006) Voluntary reporting of Staphylococcus aureus bacteraemia in England, Wales, and Northern Ireland January–December
- et al.
Mortality after Staphylococcus aureus bacteraemia in two hospitals in Oxfordshire, 1997–2003: cohort study
BMJ
(2006) - et al.
Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America
Circulation
(2005) - et al.
Guidelines for the antibiotic treatment of endocarditis in adults: report of the Working Party of the British Society for Antimicrobial Chemotherapy
J Antimicrob Chemother
(2004) - et al.
Guidelines for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK
J Antimicrob Chemother
(2006) - et al.
Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America
Clin Infect Dis
(2009) - et al.
Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC)
Eur Heart J
(2009) - et al.
Clinical consensus conference: survey on Gram-positive bloodstream infections with a focus on Staphylococcus aureus
Clin Infect Dis
(2009) - et al.
Treatment and outcome of Staphylococcus aureus bacteremia: a prospective study of 278 cases
Arch Intern Med
(2002)
Clinical identifiers of complicated Staphylococcus aureus bacteremia
Arch Intern Med
Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study
Medicine (Baltimore)
Staphylococcus aureus bacteremia: compliance with standard treatment, long-term outcome and predictors of relapse
Scand J Infect Dis
Risk factors for metastatic infection in patients with Staphylococcus aureus bacteremia with and without endocarditis
Eur J Intern Med
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation
J Chronic Dis
A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance
Medicine (Baltimore)
New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service
Am J Med
Staphylococcus aureus bacteraemia: a major cause of mortality in Australia and New Zealand
Med J Aust
Optimal duration of therapy for catheter-related Staphylococcus aureus bacteremia: a study of 55 cases and review
Clin Infect Dis
The role of vancomycin in the persistence or recurrence of Staphylococcus aureus bacteraemia
Scand J Infect Dis
Persistence in Staphylococcus aureus bacteremia: incidence, characteristics of patients and outcome
Scand J Infect Dis
Outcome of Staphylococcus aureus bacteremia according to compliance with recommendations of infectious diseases specialists: experience with 244 patients
Clin Infect Dis
Impact of routine infectious diseases service consultation on the evaluation, management, and outcomes of Staphylococcus aureus bacteremia
Clin Infect Dis
Fifteen years' experience with staphylococcus septicemia in a large city hospital; analysis of fifty-five cases in the Cincinnati General Hospital 1940 to 1954
Am J Med
Endocarditis caused by Staphylococcus aureus: a reappraisal of the epidemiologic, clinical, and pathologic manifestations with analysis of factors determining outcome
Medicine (Baltimore)
Staphylococcus aureus infective endocarditis: diagnosis and management guidelines
Intern Med J
The fate of acute methicillin-resistant Staphylococcus aureus periprosthetic knee infections treated by open debridement and retention of components
J Arthroplasty
Management of bone and joint infections due to Staphylococcus aureus
Intern Med J
Staphylococcus aureus bacteremia: predictors of 30-day mortality in a large cohort
Clin Infect Dis
The role of transthoracic echocardiography in excluding left sided infective endocarditis in Staphylococcus aureus bacteraemia
J Infect
Staphylococcus aureus bacteremia. Clinical, serologic, and echocardiographic findings in patients with and without endocarditis
Arch Intern Med
Management of catheter-related Staphylococcus aureus bacteremia: when may sonographic study be unnecessary?
Eur J Clin Microbiol Infect Dis
Echocardiography in infective endocarditis
Heart
Improved diagnostic value of echocardiography in patients with infective endocarditis by transoesophageal approach. A prospective study
Eur Heart J
Diagnostic value of transesophageal compared with transthoracic echocardiography in infective endocarditis
J Am Coll Cardiol
Transesophageal echocardiography in diagnosis of infective endocarditis
Chest
Mechanical prosthetic valve-associated strands: pathologic correlates to transesophageal echocardiography
J Am Soc Echocardiogr
Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients
J Am Coll Cardiol
Cost-effectiveness of transesophageal echocardiography to determine the duration of therapy for intravascular catheter-associated Staphylococcus aureus bacteremia
Ann Intern Med
Evaluation of clinical guidelines for the management of Staphylococcus aureus bacteraemia
Intern Med J
Importance of transesophageal echocardiography in the evaluation of Staphylococcus aureus bacteremia
J Heart Valve Dis
Right-sided endocarditis caused by Staphylococcus aureus in drug abusers
Antimicrob Agents Chemother
Short-course therapy for right-side endocarditis due to Staphylococcus aureus in drug abusers: cloxacillin versus glycopeptides in combination with gentamicin
Clin Infect Dis
Early termination of a prospective, randomized trial comparing teicoplanin and flucloxacillin for treating severe staphylococcal infections
J Infect Dis
The efficacy of the combination of teicoplanin or flucloxacillin with netilmicin in the treatment of Staphylococcus aureus bacteraemia
J Antimicrob Chemother
Persistent Staphylococcus aureus bacteremia: incidence and outcome trends over time
Scand J Infect Dis
Risk factors for recurrence in patients with Staphylococcus aureus infections complicated by bacteremia
Diagn Microbiol Infect Dis
Risk factors for recurrence after Staphylococcus aureus bacteraemia. A retrospective matched case-control study
J Infect
Impact of empirical-therapy selection on outcomes of intravenous drug users with infective endocarditis caused by methicillin-susceptible Staphylococcus aureus
Antimicrob Agents Chemother
Reduced glycopeptide susceptibility in methicillin-resistant Staphylococcus aureus (MRSA)
Int J Antimicrob Agents
Cited by (210)
Development of amoxicillin Trihydrate-Loaded lyotropic liquid crystal nanoparticles for skin infection
2023, Journal of Molecular LiquidsThe Golden Grapes of Wrath – Staphylococcus aureus Bacteremia: A Clinical Review
2023, American Journal of MedicineCitation Excerpt :Despite the lethality of S. aureus bacteremia, there remain no contemporary uniform guidelines to inform clinical practice. Rather, the evidence that guides the treatment of patients with S. aureus bacteremia focus on specific questions (eg, comparison of antibacterials, comparison of cardiac imaging modalities) rather than S. aureus bacteremia as an entity in itself.6,7 Regardless, a series of diagnostic and therapeutic investigations should be performed in all patients with S. aureus bacteremia.
Staphylococcus aureus bacteremia mortality across country income groups: A secondary analysis of a systematic review
2022, International Journal of Infectious DiseasesStaphylococcus aureus bacteraemia mortality: a systematic review and meta-analysis
2022, Clinical Microbiology and Infection
- ‡
Members listed at end of paper