MRSA: treating people with infection
Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are common worldwide. These include skin and soft tissue infections, bone and joint infections, pneumonia, bacteraemia, and endocarditis. Due to resistance to beta-lactam-based agents used to treat methicillin-susceptible strains, other antimicrobial agents are used in the treatment of MRSA infections. These agents have increased toxicity or adverse effects and appear less efficacious when compared to beta-lactam-based therapy for methicillin-sensitive S aureus (MSSA). Despite the widespread distribution of MRSA and the negative impact that serious bloodstream and other infections have on mortality and length of hospital stay, there is surprisingly little robust evidence to aid clinicians in the most effective choice of antimicrobial therapy.
Focus of the review
This updated overview largely focuses on newer anti-MRSA antimicrobials or those with an expanding role as an anti-MRSA agent. While many other agents possess activity against MRSA, susceptibility is variable and robust evidence for their use is lacking. The aim of this overview is to appraise evidence for agents indicated specifically for use in treatment of infections caused by MRSA, compared with standard therapy with glycopeptides (vancomycin or teicoplanin). This update is particularly important, as existing good-quality guidelines on this subject are already out of date. This overview will help to inform any forthcoming guidance on this subject.
Comments on evidence
While there are RCTs evaluating glycopeptides against other agents in the treatment of MRSA infection, there remains insufficient evidence to strongly recommend other agents over glycopeptide therapy. The RCTs evaluated were generally heterogeneous, consisted of small numbers of patients with MRSA infection, and were prone to bias, as well as being powered to detect non-inferiority rather than superiority, making it difficult to draw firm conclusions. The challenge of incorporating patients in clinical trials that reflect 'real world practice' remains. These people include patients with multiple comorbidity, obesity and severe disease. The limited available evidence suggests that linezolid appears to be similar in efficacy to glycopeptides and could be used as an alternative, with the strongest evidence in microbiologically-proven MRSA nosocomial pneumonia. There is some tentative evidence to support its use in skin and soft tissue infections (SSTI), bacteraemia, and endocarditis, but no convincing evidence of superior effectiveness. New agents, including the anti-MRSA cephalosporins, are promising additional options, although there is insufficient evidence to support their use presently. The exclusion criteria used in many studies, including comorbidities and severe illness, potentially impacts on the applicability of evidence derived from trials to patients encountered in clinical practice.
Search and appraisal summary
The update literature search for this overview was carried out from the date of the last search, November 2009, to June 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 312 studies. After deduplication and removal of conference abstracts, 133 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 55 studies and the further review of 78 full publications. Of the 78 full articles evaluated, 15 systematic reviews and one RCTs were added at this update. In addition, six studies were added to the Comment sections.
Substantive changes at this update
Ceftobiprole, ceftaroline (cephalosporins) New option. Seven systematic reviews added, none of which identified any RCTs meeting BMJ Clinical Evidence reporting criteria. Categorised as 'unknown effectiveness'.
Quinupristin-dalfopristin, pristinamycin (streptogramins) Two systematic reviews added, both of which identified one RCT that was already reported in the overview. Categorised as 'unknown effectiveness'.
INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) has a gene that makes it resistant to methicillin, as well as to other beta-lactam antibiotics, including flucloxacillin, beta-lactam/beta-lactamase inhibitor combinations, cephalosporins, and carbapenems. MRSA can be part of the normal body flora (colonisation), especially in the nose, but it can cause infection, particularly in people with prolonged hospital admissions, with underlying disease, or after antibiotic use. About 8% of S aureus in blood cultures in England, Wales, and Northern Ireland is resistant to methicillin. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of selected treatments for MRSA infections at any body site? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 312 studies. After deduplication and removal of conference abstracts, 133 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 55 studies and the further review of 78 full publications. Of the 78 full articles evaluated, 15 systematic reviews and one subsequent RCT were added at this update. In addition, six studies were added to the Comment sections. We performed a GRADE evaluation for 12 PICO combinations. CONCLUSIONS: In this systematic overview we categorised the efficacy for five interventions, based on information about the effectiveness and safety of cephalosporins (ceftobiprole, ceftaroline), daptomycin, linezolid, quinupristin-dalfopristin, pristinamycin (streptogramins), and tigecycline.
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