Clinical management of Staphylococcus aureus bacteraemia

doi:10.1016/S1473-3099(10)70285-1

The Lancet Infectious Diseases

Volume 11, Issue 3, March 2011, Pages 208-222

https://doi.org/10.1016/S1473-3099(10)70285-1 Get rights and content

Summary

Staphylococcus aureus bacteraemia is one of the most common serious bacterial infections worldwide. In the UK alone, around 12 500 cases each year are reported, with an associated mortality of about 30%, yet the evidence guiding optimum management is poor. To date, fewer than 1500 patients with S aureus bacteraemia have been recruited to 16 controlled trials of antimicrobial therapy. Consequently, clinical practice is driven by the results of observational studies and anecdote. Here, we propose and review ten unanswered clinical questions commonly posed by those managing S aureus bacteraemia. Our findings define the major areas of uncertainty in the management of S aureus bacteraemia and highlight just two key principles. First, all infective foci must be identified and removed as soon as possible. Second, long-term antimicrobial therapy is required for those with persistent bacteraemia or a deep, irremovable focus. Beyond this, the best drugs, dose, mode of delivery, and duration of therapy are uncertain, a situation compounded by emerging S aureus strains that are resistant to old and new antibiotics. We discuss the consequences on clinical practice, and how these findings define the agenda for future clinical research.

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

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

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Early switching from intravenous to oral antibiotic therapy in bone and joint infections associated with methicillin-susceptible Staphylococcus aureus bacteremia
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We aimed to evaluate the clinical outcomes of patients with bone and joint infection (BJI) associated with methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) treated with early oral switch to oral antibiotics (before day 14) versus later or no switch.
We included all cases reported between January 2016 and December 2021 in the University Hospital of Reims.
Among 79 patients with BJI associated with MSSAB, 50.6% had an early switch to oral antibiotics, with median duration of intravenous antibiotics of 9 (IQR 6–11) days. The overall cure rate was 81% with follow-up of 6 months, and was 85.7% after excluding the 9 patients whose death was not related to BJI infection. Failure to control BJI did not differ between the two groups.
An early (before day 14) switch to oral antibiotics may be a safe therapeutic option in BJI associated with MSSAB.
Development of amoxicillin Trihydrate-Loaded lyotropic liquid crystal nanoparticles for skin infection
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Bacterial infections are growing rapidly and are considered as a key public health concern in recent years. Antibacterial agents are generally preferred for the treatment of bacterial infections. However, available treatment options need to be addressed for better therapeutic effectiveness. Lyotropic liquid crystal nanoparticles are one of the novel nanocarrier systems which can be used to load hydrophilic and hydrophobic drugs. In the current study, amoxicillin trihydrate-laden lyotropic liquid crystal nanoparticles were fabricated by the emulsification technique. The formulation showed particle size and PDI<200 nm and 0.3, respectively. The entrapment efficiency was found to be about 94.76 ± 0.27 %. The morphological characterization was studied by Cryo-SEM and it showed a smooth surface with a spherical shape. In addition, the in vitro release was performed in pH 6.8 phosphate buffer using a dialysis membrane. The drug-loaded lyotropic liquid crystal nanoparticle gel exhibited sustained release behavior and attained 90 % of release in 24 h. The zone of inhibition study was done against Staphylococcus aureus. The stability data showed promising results, and the nanoparticles were found to be stable over a period of two months. Moreover, MTT assay on human dermal fibroblast cells suggests that amoxicillin trihydrate-loaded lyotropic liquid crystal nanoparticles are as safe as amoxicillin trihydrate solution and are thus non-toxic and biocompatible. As a whole, it can be concluded that lyotropic liquid crystal nanoparticles might be one of the potential nanocarriers for the loading of amoxicillin trihydrate and could be used with to treat superficial bacterial skin infections.
The Golden Grapes of Wrath – Staphylococcus aureus Bacteremia: A Clinical Review
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Citation 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 is common and associated with fatality rates approximating 25%. We provide a brief overview of S. aureus bacteremia from a clinical and microbiological lens and review the relevant evidence and literature gaps in its management. Using a case-based approach, evidence and clinical judgement are meshed to highlight and justify the 5 core interventions that ought to be performed for all cases of S. aureus bacteremia: 1) appropriate anti-staphylococcal therapy, 2) screening echocardiography, 3) assessment for metastatic phenomena and source control, 4) decision on duration of antimicrobial therapy, and 5) Infectious Diseases consultation.
Staphylococcus aureus bacteremia mortality across country income groups: A secondary analysis of a systematic review
2022, International Journal of Infectious Diseases
Staphylococcus aureus bacteremia (SAB) is a common infection worldwide. We compared SAB mortality in low- and middle-income countries (LMIC) versus high-income countries (HIC) in a meta-analysis.
We searched MEDLINE, Embase, and Cochrane Database of Systematic Reviews from 1991-2021 and included observational, single-country studies on patients with positive blood cultures for S. aureus. The main outcome was the proportion of patients with SAB who died in the hospital. A generalized linear mixed random-effects model was used to pool estimates, and a meta-regression was used to adjust for study-level characteristics.
A total of 332 studies involving 517,671 patients in 39 countries were included. No study was conducted in a low-income country. Only 33 (10%) studies were performed in middle-income countries (MIC), which described 6,216 patients. The pooled in-hospital mortality was 32.4% (95% confidence interval [CI] 27.2%-38.2%, T² = 0.3063) in MIC and 22.3% (95% CI 20.1%-24.6%, T² = 0.3257) in HIC. In a meta-regression model, MIC had higher in-hospital mortality (adjusted odds ratio 1.37, 95% CI 1.11-1.71; P = 0.0042) than HIC.
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Staphylococcus aureus bacteraemia mortality: a systematic review and meta-analysis
2022, Clinical Microbiology and Infection
Precise estimates of mortality in Staphylococcus aureus bacteraemia (SAB) are important to convey prognosis and guide the design of interventional studies.
We performed a systematic review and meta-analysis to estimate all-cause mortality in SAB and explore mortality change over time.
The MEDLINE and Embase databases, as well as the Cochrane Database of Systematic Reviews, were searched from January 1, 1991 to May 7, 2021.
Human observational studies on patients with S. aureus bloodstream infection were included.
The study analyzed data of patients with a positive blood culture for S. aureus.
Two independent reviewers extracted study data and assessed risk of bias using the Newcastle–Ottawa Scale. A generalized, linear, mixed random effects model was used to pool estimates.
A total of 341 studies were included, describing a total of 536,791 patients. From 2011 onward, the estimated mortality was 10.4% (95% CI, 9.0%–12.1%) at 7 days, 13.3% (95% CI, 11.1%–15.8%) at 2 weeks, 18.1% (95% CI, 16.3%–20.0%) at 1 month, 27.0% (95% CI, 21.5%–33.3%) at 3 months, and 30.2% (95% CI, 22.4%–39.3%) at 1 year. In a meta-regression model of 1-month mortality, methicillin-resistant S. aureus had a higher mortality rate (adjusted OR (aOR): 1.04; 95% CI, 1.02–1.06 per 10% increase in methicillin-resistant S. aureus proportion). Compared with prior to 2001, more recent time periods had a lower mortality rate (aOR: 0.88; 95% CI, 0.75–1.03 for 2001–2010; aOR: 0.82; 95% CI, 0.69–0.97 for 2011 onward).
SAB mortality has decreased over the last 3 decades. However, more than one in four patients will die within 3 months, and continuous improvement in care remains necessary.

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ReviewClinical management of Staphylococcus aureus bacteraemia

Summary

Introduction

Section snippets

How should SAB be defined?

Is identification and removal of the focus of infection important?

Should all patients with SAB have echocardiography?

Are glycopeptides equivalent to β-lactams for the treatment of SAB?

Are cephalosporins as effective as penicillins for the treatment of SAB?

Is teicoplanin as effective as vancomycin?

What is the optimum duration of therapy for SAB?

Is oral therapy as effective as intravenous therapy?

Is combination antimicrobial therapy better than monotherapy?

What is the role of the newer antimicrobials in the treatment of SAB?

Discussion

Search strategy and selection criteria

Healthcare-associated bloodstream infection: a distinct entity? Insights from a large U.S. database

Crit Care Med

Voluntary reporting of Staphylococcus aureus bacteraemia in England, Wales, and Northern Ireland January–December

Mortality after Staphylococcus aureus bacteraemia in two hospitals in Oxfordshire, 1997–2003: cohort study

BMJ

Circulation

Guidelines for the antibiotic treatment of endocarditis in adults: report of the Working Party of the British Society for Antimicrobial Chemotherapy

J Antimicrob Chemother

Guidelines for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK

J Antimicrob Chemother

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

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

Clinical consensus conference: survey on Gram-positive bloodstream infections with a focus on Staphylococcus aureus

Clin Infect Dis

Treatment and outcome of Staphylococcus aureus bacteremia: a prospective study of 278 cases

Arch Intern Med

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

Review
Clinical management of Staphylococcus aureus bacteraemia