Activity of daptomycin against multi-resistant Gram-positive bacteria including enterococci and Staphylococcus aureus resistant to linezolid

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Abstract

The activity of daptomycin was assessed against 545 isolates of Gram-positive bacteria including enterococci, coagulase-positive and -negative staphylococci, β-haemolytic streptococci, viridans streptococci and coryneforms. The panel of isolates was biased towards those with resistance to first-line antimicrobial agents and included linezolid-resistant enterococci and Staphylococcus aureus. MICs of daptomycin were ≤1 mg/l for all the staphylococci, streptococci, and coryneforms, except for two isolates of Corynebacterium aquaticum, for which MICs were 8 mg/l. Daptomycin MICs were ≤2 and ≤4 mg/l for Enterococcus faecalis and Enterococcus faecium, respectively.

Introduction

The increasing prevalence of Gram-positive pathogens with resistance to first-line agents, particularly methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci and β-lactam- and macrolide-resistant pneumococci [1], is causing mounting concern. This concern has been exacerbated by reports of MRSA and enterococci resistant to linezolid, a drug with generally useful activity against multi-resistant Gram-positive pathogens [2], [3], [4], [5]. In response, the pharmaceutical industry continues to develop new antibacterial agents with activity against such strains. One such drug is daptomycin, a cyclic lipopeptide produced by Streptomyces roseosporus, which shows potent bactericidal activity against a wide range of Gram-positive bacteria [6]. Following successful clinical trials, daptomycin received approval by the US Food and Drug Administration in late 2003, for the treatment of complicated skin and skin structure infections [7].

We report here on the activity of daptomycin against a panel of staphylococci, pneumococci, streptococci, enterococci and corynebacteria selected for epidemiological diversity and enriched for resistance to first-line agents. Isolates of enterococci and S. aureus resistant to linezolid were included.

Section snippets

Bacteria

Isolates for study were selected from those referred to the Antibiotic Resistance Monitoring and Reference Laboratory, and were chosen to over-represent resistance to relevant first-line antibiotics including linezolid, and for geographical diversity. In the case of pneumococci and S. aureus, isolates were also chosen for diversity of serotypes and phage types, respectively. Five hundred and forty-five isolates from 132 source laboratories were tested, comprising 46 Enterococcus faecalis, 43 E.

Results and discussion

Five hundred and forty-five isolates, selected to over-represent resistance to first-line agents, were tested (Table 1). The panel of test organisms included 15 enterococci (nine E. faecalis and six E. faecium) and one MRSA that were resistant to linezolid (MICs 8–64 mg/l), and six isolates of E. faecium resistant to quinupristin/dalfopristin (MICs 4–32 mg/l). The enterococcal panel was also biased towards inclusion of isolates resistant to glycopeptides and to high-levels of gentamicin, while

Acknowledgements

This work was supported by Cubist Pharmaceuticals, Lexington, MA, USA.

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