Aminoglycosides in Combination Therapy with beta-Lactam Antibiotics for Staphylococcus aureus Endocarditis: A Systematic Review

Background: There is no consensus as to whether aminoglycosides have a role in combination with beta-lactams for the treatment of Staphylococcus aureus endocarditis. Objective: To review the literature pertaining to the use of aminoglycosides in combination with beta-lactams for S. aureus endocarditis. Methods: A literature search was conducted in PubMed, EMBASE, and the Cochrane Database of Systematic Reviews (with various time frames, depending on the database). The search terms were "aminoglycoside", "gentamicin", "tobramycin", "amikacin", "netilmicin", "streptomycin", "staphylococcal", and "endocarditis"; restrictions were set to identify only English-language articles describing research involving human subjects. The reference lists of all relevant articles identified in these searches were reviewed manually. All published reports of an aminoglycoside being given in combination with a beta- lactam for the treatment of S. aureus endocarditis were reviewed to assess whether the results favoured combination therapy. A survey of the use of therapeutic drug monitoring for aminoglycosides was also conducted. Results: Twelve relevant articles were identified. Seven of the articles were categorized as presenting the highest quality of evidence (levels I and II), and only 1 of these favoured combination therapy, the outcome being time to clinical improvement in the subpopulation of intravenous drug users. The 5 articles with lower-quality (level III) evidence favoured the combination regimens but did not make comparisons with beta-lactam monotherapy. Only 2 articles described therapeutic drug monitoring techniques with respect to aminoglycoside therapy. Conclusion: Current evidence does not support the use of aminoglycosides for the treatment of S. aureus endocarditis.