New antibiotics for treatment of serious infections due to antibiotic-resistant Gram-positive cocci

Gram-positive infections pose enormous challenges for clinicians, particularly those pathogens that show increasing antimicrobial resistance. These pathogens cause both nosocomial and community blood, respiratory and urinary tract, skin and soft tissue infections. Recent pooled data have demonstrated high rates of methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci isolates. Until recently, the only available agents against these bacteria were vancomycin and teicoplanin. As a result of increased resistance to methicillin, vancomycin and teicoplanin use increased exponentially over the past 15 years and because of this Enterococcus spp. has become vancomycin resistant. Recently, vancomycin- intermediate and vancomycin-resistant S. aureus have also been reported. Consequently, the traditional empirical options have lost their predictable activity in many countries and this emergence of resistance to glycopeptide antibiotics has caused therapy failures, use of more antimicrobials and extended hospitalization, and increased morbidity and mortality. Traditional therapeutic options include anti-staphylococcal penicillins or first-generation cephalosporins, clindamycin, vancomycin, teicoplanin, beta-lactam/beta-lactam inhibitor combinations, macrolides, fluoroquinolones and trimethoprim–sulphamethoxazole. These resistance problems have lead to the development of several new compounds; two of them, quinupristin/dalfopristin and linezolid (and more recently daptomycin) have been approved while at least five other compounds are in various stages of development: oritavancin, dalbavancin, glycyclyclines, ramoplanin and novel broad spectrum cephalosporins. This review examines the new treatment options for Gram-positive infections that have either been developed or are presently in development.