New and emerging treatment of Staphylococcus aureus infections in the hospital setting

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA), both hospital-acquired and community-acquired, is a dangerous pathogen that is involved in an increasing number of serious infections with high risk for morbidity and mortality. Community-acquired MRSA strains have epidemic potential and can be particularly virulent. Vancomycin has been the standard hospital treatment for the past 40 years, but vancomycin-resistant isolates of S. aureus have emerged in the USA, and vancomycin-intermediate isolates are increasingly being reported worldwide. New antimicrobial agents with activity against multidrug-resistant S. aureus and other resistant pathogens are urgently needed. Despite great strides, further advances in our understanding of the molecular and biochemical mechanisms responsible for antimicrobial resistance are still required. Several agents have been recently approved for the treatment of serious Gram-positive infections, including linezolid, daptomycin, and tigecycline. The novel investigational cephalosporin, ceftobiprole, is one of the first penicillinase-resistant agents to target penicillin-binding protein 2a (or PBP2a), an acquired PBP with low beta-lactam-affinity that confers intrinsic beta-lactam resistance to S. aureus and other staphylococci. This mechanism of PBP binding, including inhibition of PBP2a, confers broad-spectrum activity against clinically important Gram-negative and Gram-positive pathogens, including MRSA. Phase III clinical trials comparing ceftobiprole with vancomycin alone and in combination with ceftazidime for the treatment of complicated skin and skin structure infections showed ceftobiprole to have efficacy similar to the efficacy of these comparators as evidenced by non-inferior clinical cure and microbiological eradication rates.