This review assessed the effectiveness of linezolid for the treatment of patients with infective endocarditis. The authors concluded that limited data suggest that linezolid should be considered in patients with infective endocarditis with limited treatment options but randomised controlled trials are required. These conclusions reflect the evidence presented, but their reliability is limited by methodological weaknesses of the review.

To assess the effectiveness and safety of linezolid for the treatment of patients with infective endocarditis.

Two reviewers independently searched PubMed from January 1995 to March 2006. Search terms were reported. The authors also searched the reference lists of retrieved articles for other potentially relevant studies. The authors did not state whether any language restrictions were applied.

Case series and case reports that assessed the effectiveness and safety of linezolid for the treatment of patients with infective endocarditis (according to Duke's criteria) were eligible for inclusion in the review, if data could be extracted individually for each patient. The main outcomes were cure of infection, improvement and treatment failure.

Most of the patients included in the studies were male and adults (median age 66 years), although one study included a paediatric patient. In some of the included studies patients had prosthetic valve infective endocarditis. The most commonly isolated infective pathogens were vancomycin-intermediate Staphylococcus aureus (VISA) and methicillin-resistant Staphylococcus aureus (MRSA). In most cases linezolid was used when previously administered treatment had failed or caused adverse effects. The dosage of linezolid in adults was 600mg twice daily and the median duration of treatment with linezolid was 42 days. Two thirds of patients received linezolid alone, while others received linezolid in combination with rifampicin, gentamicin, fusidic acid or amikacin.

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

The authors did not state that they assessed validity.

The authors extracted data on cure of infection, improvement, and treatment failure (according to definitions specified in the review) for individual patients included in the studies.

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction.

Studies were combined in a narrative synthesis. Study details were presented in tables, allowing the reader to assess differences between studies.

Twenty four studies were included in the review (n=33); 1 case series and 23 case reports. The median duration of follow-up was six months.

Linezolid was associated with cure or clinical improvement of infection in 21/33 (63.6%) patients. Failure of linezolid treatment was seen in seven (21.2%) patients. The results were considered indeterminate for five patients, even though their laboratory and/or imaging findings improved after the administration of linezolid. Overall mortality was 33.3% (11/33 patients) and endocarditis-related mortality was 12.1% (4/33 patients).

Twenty six case reports reported data regarding adverse effects associated with linezolid. Adverse effects developed in nine patients (34.6%). Eight patients developed thrombocytopenia. As a result, two patients discontinued treatment with linezolid, one also required platelet transfusion. The following adverse effects were reported for one patient each: anaemia, decrease of white blood cells, nausea, vomiting and mild alopecia.

In addition, the authors identified another two case series (n=23) for which data could not be extracted for individual patients. These were not included in the review but results were reported.

The limited data suggest that linezolid should be considered for the treatment of patients with infective endocarditis for whom limited treatment options are available. However, randomised controlled trials are needed to evaluate whether a bacteriostatic antibiotic could be proven beneficial for an infection for which bactericidal antibiotics have been traditionally used.

The review addressed a clear question and was supported by appropriate inclusion criteria. Only one electronic database was searched, along with reference lists, to identify relevant studies, so relevant studies may have been missed and publication bias may be present. Also, the authors did not state whether any language restrictions were applied, so there is the possibility of language bias. The authors did not report the methods used for study selection or data extraction, so the possibility of reviewer bias and error cannot be excluded. The validity of the included studies was not formally assessed. Study details were tabulated with adequate information on participant characteristics and treatment regimen. The details of study results were limited. In view of the nature of the included studies and differences between studies, a narrative synthesis was appropriate. The authors' cautious conclusions reflect the evidence presented. but owing to the lack of reporting of review methods and the potential for publication and language bias, these conclusions may not be reliable.

Practice: The authors stated that linezolid should be considered for the treatment of patients with infective endocarditis for whom limited treatment options are available.

Research: The authors stated that randomised controlled trials are needed to provide a definitive answer to the question of which antibiotic (vancomycin or linezolid) is more effective for the treatment of patients with infective endocarditis due to multidrug-resistant Gram-positive cocci.

No funding received.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.