Glycopeptide and daptomycin resistance in community-associated MRSA in the UK

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infections are commonly treated with glycopeptides. When glycopeptide resistance occurs, one of the few remaining therapeutic options is daptomycin. We describe the in vivo development of both glycopeptide and daptomycin resistance in a patient from the UK with community-associated (CA) MRSA infective endocarditis. A 35-year-old man presented to our hospital in Liverpool, UK, in 2008. A diagnosis of tricuspid valve infective endocarditis was made, secondary to intravenous drug use. Both MRSA and group G haemolytic streptococcus grew from the blood cultures. Antimicrobial therapy was initiated with teicoplanin and rifampicin, but after 3 weeks of treatment MRSA was cultured again from the patient’s blood, suggesting that resistance may have developed. Glycopeptide minimum inhibitory concentration (MIC) testing was therefore performed. The MIC to teicoplanin was determined to be 8 mg/L, identifying the MRSA isolate as glycopeptide-resistant S. aureus (GRSA). Daptomycin therapy was prescribed, but 1 week later, after an initial clinical improvement, the patient suffered cerebral emboli. Blood cultures again recovered MRSA, leading to daptomycin MIC testing. Daptomycin resistance was confirmed with an MIC to daptomycin of 4 mg/L. Linezolid, ciprofloxacin and gentamicin were then administered to the patient (Fig. 1). The patient clinically responded to this treatment, and mitral valve replacement was subsequently completed. A total of 6 weeks of oral ciprofloxacin and linezolid were prescribed post-operatively, and the patient was well upon review in January 2010. This patient was initially infected with a glycopeptidesusceptible MRSA, with initial teicoplanin and vancomycin MICs of B2 mg/L [MICs by Etest method (bioMerieux, Marcy l’Etoile, France)]. However, following treatment with teicoplanin, the isolate became glycopeptide resistant, with teicoplanin and vancomycin MICs of 8 and 3 mg/L, respectively. The MIC breakpoint for glycopeptide resistance is[2 mg/L according to the European Committee on Antimicrobial Susceptibility testing (EUCAST 2010: http://www.eucast.org). The development of glycopeptide resistance was associated with that of daptomycin resistance. The daptomycin MIC increased from a range of 0.19–0.25 to 1.5–3 mg/L, and this occurred prior to in vivo exposure to daptomycin (EUCAST MIC breakpoint for daptomycin resistance is [1 mg/L). Daptomycin therapy was associated with a further rise in the daptomycin MIC to 4 mg/L (Table 1). The MRSA isolate was confirmed as CA-MRSA [1] based on its susceptibility to ciprofloxacin [2], positivity for the Panton–Valentine Leukocidin (PVL) gene [3] and spa type t127 [4]. SCCmec typing, which is also used to differentiate CA-MRSA and health care-associated MRSA (HA-MRSA) is not valid in the UK as HA-MRSA and CA-MRSA are both commonly SCCmec type IV [5]. Pulsed field gel electrophoresis (PFGE) confirmed the A. Kirby (&) C. M. Broughton Institute of Infection and Global Health, Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, 8th Floor Duncan Building, Daulby Street, Liverpool L69 3GA, UK e-mail: amk@liv.ac.uk