Appropriately designed antibiotic regimens are critical to the management of all stages of osteomyelitis, although goals of therapy may vary in different stages of infection. The most important consideration for antibiotic selection is spectrum of action. Route of administration by intravenous or oral route is less important than drug levels that are achievable at the site of infection. Outpatient parenteral therapy and use of oral agents has simplified delivery of long-term treatment regimens. There are few high-quality studies that compare specific treatment regimens or durations of therapy, and recommendations for drugs and duration of antibiotic therapy are based on expert opinion, case series, and extrapolations from animal models. Intravenous beta-lactams are the treatment of choice for methicillin-susceptible Staphylococcus aureus, but there are also oral options available. Vancomycin has been the treatment of choice for methicillin-resistant Staphylococcus aureus osteomyelitis, but there are several newer parenteral and oral agents for treatment of methicillin-resistant Staphylococcus aureus including linezolid and daptomycin. Rifampin combined with other staphylococcal agents may increase cure rates, especially for device-associated infections. Oral fluoroquinolones and parenteral beta-lactam agents can be used for treatment of gram-negative osteomyelitis, but increasing resistance has complicated management of these infections.

h Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have emerged as major nosocomial pathogens. bla KPC , commonly located on Tn4401, is found in Gram-negative bacterial strains, with the two most common variants, bla KPC-2 and bla KPC-3 , identified in plasmids with diverse genetic backgrounds. In this study, we examined bla KPC-4 -and bla KPC-5 -bearing plasmids recovered from two K. pneumoniae strains, which were isolated from a single New Jersey hospital in 2005 and 2006, respectively. IncN plasmid pBK31551 is 84 kb in length and harbors bla KPC-4 , bla TEM-1 , qnrB2, aac(3)-Ib, aph(3=)-I, qacF, qacE⌬1, sul1, and dfrA14, which confer resistance to ␤-lactams, quinolones, aminoglycosides, quaternary ammonium compounds, and co-trimoxazole. The conserved regions within pBK31551 are similar to those of other IncN plasmids. Surprisingly, analysis of the Tn4401 sequence revealed a large IS110-and Tn6901-carrying element (8.3 kb) inserted into the istA gene, encoding glyoxalase/bleomycin resistance, alcohol dehydrogenase, and S-formylglutathione hydrolase. Plasmid pBK31567 is 47 kb in length and harbors bla KPC-5 , dfrA5, qacE⌬1, and sul1. pBK31567 belongs to a novel IncX subgroup (IncX5) and possesses a highly syntenic plasmid backbone like other IncX plasmids; however, sequence similarity at the nucleotide level is divergent. The bla KPC-5 gene is carried on a Tn4401 element and differs from the genetic environment of bla KPC-5 described in Pseudomonas aeruginosa strain P28 from Puerto Rico. This study underscores the genetic diversity of multidrug-resistant plasmids involved in the spread of bla KPC genes and highlights the mobility and plasticity of Tn4401. Comparative genomic analysis provides new insights into the evolution and dissemination of KPC plasmids belonging to different incompatibility groups.

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This is the first reported example of a clinical bacterial isolate that requires an antimicrobial agent to grow.