Can β-lactams be re-engineered to beat MRSA?

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Can β-lactams be re-engineered to beat MRSA? D.M. Livermore Clinical Microbiology and Infection Volume 12, Pages 11-16 (January 2006) DOI: 10.1111/j.1469-0691.2006.01403.x Copyright © 2006 European Society of Clinical Infectious Diseases Terms and Conditions

Fig. 1 Proportion of Staphylococcus aureus bacteraemias caused by methicillin-resistant S. aureus (MRSA) in England and Wales from 1989 to 2004 (open bars) and MRSA bacteraemias as a proportion of all bacteraemias (solid bars). Data are based on voluntary reporting to the Health Protection Agency, now about 70% comprehensive [4,5]. Adapted from Johnson et al. [5] with permission. Clinical Microbiology and Infection 2006 12, 11-16DOI: (10.1111/j.1469-0691.2006.01403.x) Copyright © 2006 European Society of Clinical Infectious Diseases Terms and Conditions

Fig. 2 Hospitals in England and Wales referring isolates of epidemic methicillin-resistant Staphylococcus aureus (EMRSA) strains 3, 15 and 16 to the then Public Health Laboratory Service Staphylococcal Reference Unit [6,7]. Reprinted from British Society for Antimicrobial Chemotherapy [7] with permission. Clinical Microbiology and Infection 2006 12, 11-16DOI: (10.1111/j.1469-0691.2006.01403.x) Copyright © 2006 European Society of Clinical Infectious Diseases Terms and Conditions

Fig. 3 Data from the European Antibiotic Resistance Surveillance System (EARSS) showing methicillin-resistant Staphylococcus aureus as a percentage of all S. aureus bacteraemias in various European countries 1999–2004 [8]. Clinical Microbiology and Infection 2006 12, 11-16DOI: (10.1111/j.1469-0691.2006.01403.x) Copyright © 2006 European Society of Clinical Infectious Diseases Terms and Conditions

Fig. 4 Molecular model showing ceftobiprole in the active site of Staphylococcus aureus PBP2′ (M. Page, personal communication). Clinical Microbiology and Infection 2006 12, 11-16DOI: (10.1111/j.1469-0691.2006.01403.x) Copyright © 2006 European Society of Clinical Infectious Diseases Terms and Conditions

Fig. 5 Activity of ceftobiprole against Staphylococcus aureus isolates from 25 UK hospitals tested on two different culture media conditions, one (Columbia) more inducing for expression of methicillin resistance [35]. MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus. Clinical Microbiology and Infection 2006 12, 11-16DOI: (10.1111/j.1469-0691.2006.01403.x) Copyright © 2006 European Society of Clinical Infectious Diseases Terms and Conditions

Fig. 6 Rapid, time-dependent bactericidal activity of ceftobiprole (at five times MIC) against methicillin-resistant Staphylococcus aureus (MRSA) (S. aureus 42080) and methicillin-susceptible S. aureus (MSSA) (S. aureus ATCC 25923) in contrast with vancomycin (at five times MIC) [34]. Adapted from Hebeisen et al. [34] with permission. Clinical Microbiology and Infection 2006 12, 11-16DOI: (10.1111/j.1469-0691.2006.01403.x) Copyright © 2006 European Society of Clinical Infectious Diseases Terms and Conditions