Tedizolid: A Novel Oxazolidinone for Gram-Positive Infections

Despite the concerted efforts of modern medicine, infections due to gram-positive bacteria, such as skin and soft tissue infections, pneumonia, bacteremia, and endocarditis, continue to pose many challenges to achieving successful treatment outcomes. A good case in point is found in the emergence and spread of methicillin resistance in Staphylococcus aureus. The first strains of methicillin-resistant S. aureus (MRSA) were discovered a half-century ago in a hospital in London, just 2 years after the first clinical use of methicillin [1]. During the ensuing 50 years, these organisms have spread worldwide despite extensive attempts to control them. In some of the Scandinavian countries and the Netherlands, “search and destroy” efforts in hospitals have been successful in controlling infections caused by MRSA. This was aided by the fact that most MRSA infections were hospital acquired. That situation, however, began to change in the early 1990s, when infections due to MRSA were noted in patients without previous inpatient healthcare exposure across 6 different continents, including Australia, where several outbreaks were detected in Western Australia and the Northern Territory [2, 3]. Community-acquired (or community-associated) MRSA (CA-MRSA) subsequently spread throughout North America, where one particular clone (USA-300) quickly established dominance. Not surprisingly, these strains have also spread to Europe, where they have caused significant problems due to the fact that European guidelines for infection control have been geared to inpatient rather than outpatient acquisition of methicillin-resistant strains [4]. However, MRSA is not the only gram-positive organism causing major problems because of the development of antibiotic resistance. Macrolide-resistant group A streptococci and pneumococci as well as multiresistant enterococci (including strains of Enterococcus faecium resistant to virtually all currently available antimicrobial agents) are becoming greater and greater problems throughout the world. The development of resistance in these organisms is not surprising. Most antimicrobial agents in clinical use are antibiotics, which are antimicrobial substances produced by a variety of microorganisms in nature, presumably to secure their ecologic niches. Resistance genes are, of course, found in antibiotic producers to prevent them from essentially committing suicide due to the toxic substances they themselves emit. Such genes have thus been present in nature for millions, if not billions, of years before the clinical use of antibiotics. A number of studies have demonstrated the presence of this type of genetic material among bacteria found in isolated human populations who had never received therapeutic antibiotics [5]. Recently, D’Costa and coworkers reported on finding resistance genes among core samples obtained from Late Pleistocene permafrost sediments collected east of Dawson City, Yukon. Those were estimated to be 25 000 to 30 000 calendar years old by radiocarbon dating and contained genes coding for βlactamases related to TEM enzymes, tetracycline resistance genes (tetM), and even more strikingly, vancomycin resistance genes (vanA) [6]. Given these findings, it is not surprising that the clinical and nonclinical (such as inclusion in livestock feed) use of antimicrobial agents has rapidly selected resistant bacterial isolates. In this Correspondence: Robert C. Moellering Jr, MD, Department of Medicine, Beth Israel Deaconess Medical Center, 110 Francis St, Ste 6A, Boston, MA 02215 (rmoeller@bidmc.harvard.edu). Clinical Infectious Diseases 2014;58(S1):S1–3 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. DOI: 10.1093/cid/cit658