Evaluation of Antibiotics Active against Methicillin-Resistant Staphylococcus aureus Based on Activity in an Established Biofilm

• Published in: Antimicrobial agents and chemotherapy Vol. 60; no. 10; pp. 5688 - 5694
• Main Authors: Meeker, Daniel G, Beenken, Karen E, Mills, Weston B, Loughran, Allister J, Spencer, Horace J, Lynn, William B, Smeltzer, Mark S
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01-10-2016
• Subjects: Aminoglycosides - pharmacology; Animals; Anti-Bacterial Agents; Anti-Bacterial Agents - pharmacology; Biofilms - drug effects; Catheter-Related Infections - drug therapy; Catheter-Related Infections - microbiology; Clinical Therapeutics; Drug Evaluation, Preclinical - methods; Drug Resistance, Multiple, Bacterial - drug effects; Glycopeptides - pharmacology; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - pathogenicity; Mice; Microbial Sensitivity Tests; Staphylococcus aureus; Teicoplanin - analogs & derivatives; Teicoplanin - pharmacology
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.01251-16

We used in vitro and in vivo models of catheter-associated biofilm formation to compare the relative activity of antibiotics effective against methicillin-resistant Staphylococcus aureus (MRSA) in the specific context of an established biofilm. The results demonstrated that, under in vitro conditions, daptomycin and ceftaroline exhibited comparable activity relative to each other and greater activity than vancomycin, telavancin, oritavancin, dalbavancin, or tigecycline. This was true when assessed using established biofilms formed by the USA300 methicillin-resistant strain LAC and the USA200 methicillin-sensitive strain UAMS-1. Oxacillin exhibited greater activity against UAMS-1 than LAC, as would be expected, since LAC is an MRSA strain. However, the activity of oxacillin was less than that of daptomycin and ceftaroline even against UAMS-1. Among the lipoglycopeptides, telavancin exhibited the greatest overall activity. Specifically, telavancin exhibited greater activity than oritavancin or dalbavancin when tested against biofilms formed by LAC and was the only lipoglycopeptide capable of reducing the number of viable bacteria below the limit of detection. With biofilms formed by UAMS-1, telavancin and dalbavancin exhibited comparable activity relative to each other and greater activity than oritavancin. Importantly, ceftaroline was the only antibiotic that exhibited greater activity than vancomycin when tested in vivo in a murine model of catheter-associated biofilm formation. These results emphasize the need to consider antibiotics other than vancomycin, most notably, ceftaroline, for the treatment of biofilm-associated S. aureus infections, including by the matrix-based antibiotic delivery methods often employed for local antibiotic delivery in the treatment of these infections.