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Semin Respir Crit Care Med 2015; 36(01): 003-016
DOI: 10.1055/s-0034-1396906
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Combination Antibiotic Treatment of Serious Methicillin-Resistant Staphylococcus aureus Infections

J. S. Davis
1   Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia
2   Department of Infectious Diseases, John Hunter Hospital, Newcastle, New South Wales, Australia
,
S. van Hal
3   Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Sydney, Australia
4   Antibiotic Resistance and Mobile Elements Group, University of Western Sydney, Sydney, Australia
,
S. Y. C. Tong
1   Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia
5   Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory, Australia
› Author Affiliations
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Publication History

Publication Date:
02 February 2015 (online)

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Abstract

Outcomes from methicillin-resistant Staphylococcus aureus (MRSA) infections are relatively poor, at least in part due to the limitations of vancomycin (the current standard treatment for MRSA). Combination antibiotic treatment for MRSA infections is an attractive alternative as it could address most of vancomycin's shortcomings, including poor tissue penetration, slow bacterial killing, and emerging resistance in some strains of MRSA. However, the theoretical promise of combination therapy for MRSA infections has not been borne out in most in vitro and animal studies. Multiple combinations have been tested and have been either antagonistic, indifferent, or have had conflicting findings in various studies. This includes combinations of two primarily active agents (such as vancomycin plus daptomycin or linezolid), or the addition of gentamicin or rifampin to either vancomycin or daptomycin. However, hope on this front has come from an unexpected quarter. Although MRSA is by definition inherently resistant to nearly all β-lactam antibiotics, this class of drugs has consistently shown evidence of synergy with either daptomycin or vancomycin in over 25 separate in vitro studies, and a limited number of animal and human observational studies. However, there are currently insufficient data to recommend β-lactam combination therapy in routine clinical use. Results of current and planned randomized controlled trials of this strategy are awaited.

Keywords

methicillin-resistant Staphylococcus aureus - combination antibiotic therapy - vancomycin - daptomycin