Drug Topics - January 2009 - (Page 38) Continuing Education COMMUNITY-ACQUIRED MRSA discussion of therapeutic drug-monitoring and the appropriate therapeutic concentrations that need to be achieved for eradication of bacteria. Daptomycin Daptomycin demonstrates bactericidal activity against MRSA by binding to bacterial cell membranes and causing rapid depolarization resulting in cell death. The spectrum of activity of daptomycin is limited to gram-positive organisms; the drug cannot penetrate the cell walls of gram-negative organisms. Daptomycin has demonstrated efficacy against a variety of multiply drug-resistant gram-positive pathogens, including MRSA, VRE, VRSA, and VISA. Clinical data support the use of daptomycin in skin and soft-tissue infections. In two randomized trials, daptomycin demonstrated a 75 percent clinical success rate in patients who presented with MRSA infections. This was not significantly different from what is seen with penicillinase-resistant penicillins or in vancomycin treatment arms. In addition to the above trial, a retrospective chart review evaluating outcomes for CA-MRSA was conducted. Results demonstrated that daptomycin was as effective in CA-MRSA treatment as it was in treatment of HA-MRSA. It is important to note that daptomycin is not indicated for the treatment of pneumonia, owing to demonstrated lack of clinical efficacy in comparison with standard antibiotic therapy. The leading theory behind daptomycin’s lack of efficacy suggests that its antimicrobial effects appear to be inhibited by lung surfactant. Daptomycin may be an attractive treatment option for a few reasons: It does not require therapeutic drug-monitoring, dosing is once daily, and its mechanism of action is unique. However, the possibility of rhabdomyolysis does call for patients’ creatine phosphokinase to be monitored at least weekly. Resistance to daptomycin has been encountered both in vitro and in vivo after exposure, but it appears to be rare at the present time. Future surveillance to track potential resistance patterns is indicated. It should be noted, however, that 25 percent of the patients receiving tigecycline reported experiencing nausea. Tigecycline has FDA approval for the treatment of complicated skin and soft-tissue infections caused by MRSA. It is also approved for complicated intra-abdominal infections. Other indications are being studied. Data regarding the use of tigecyline for MRSA infections at other sites are forthcoming. Because of tigecycline‘s large volume of distribution and low plasma concentrations, its use for bloodstream infections is not currently recommended. In addition, owing to low concentrations in the urine, it is also not recommended for urinary tract infections. Quinupristin/dalfopristin Quinupristin/dalfopristin is a 30:70 mixture of streptogramins from groups B and A. It acts by binding to the 50S ribosomal subunit at two different sites, resulting in disruption of both early and late stages of protein synthesis. Quinupristin/dalfopristin demonstrates bactericidal activity against MRSA that lack the ermB gene. However, it is bacteriostatic against strains that express the ermB gene. In two randomized trials, patients were given quinupristin/ dalfopristin dosed at 7.5 mg/kg every 12 hours for 3 to 14 days. It was compared against cefazolin, oxacillin, or vancomycin in the treatment of skin or soft-tissue infections. In the MRSA subgroup, there was a 77.8 percent rate of eradication or presumed eradication in the quinupristin/dalfopristin group vs. a 50 percent rate in the comparator groups. Although effective, the use of this medication is limited by its potential for drug interactions (including with all medications metabolized by the CYP450 3A4 system) and the need for administration through a central line to improve tolerability. However, as the development of resistance persists, quinupristin/dalfopristin will continue to be used. Tigecycline Tigecycline is a glycylcycline antimicrobial that exhibits bacteriostatic activity against a wide spectrum of aerobic and anaerobic bacteria. With a mechanism of action similar to that of the tetracyclines, it binds to the 30S ribosomal subunit, ultimately resulting in inhibition of protein synthesis. Tigecycline was structurally modified to improve its efficacy against tetracycline-resistant organisms, including MRSA. Three comparison trials studied the efficacy of tigecycline for the treatment of skin and soft-tissue infections. Intravenous administration of tigecycline was given at 100 mg for the first dose, then 50 mg twice a day for up to 14 days. In the MRSA subgroup, clinical and microbiologic success rates were 83 percent, compared to 50 percent in the vancomycin/aztreonam group. The authors concluded that tigecycline is safe and effective. Investigational treatment options Several antimicrobials with activity against MRSA are in development. The classes with the most promising clinical data are the lipoglycopeptides and cephalosporins. The three lipoglycopeptides — oritavancin, telavancin, and dalbavancin — are similar to vancomycin in their mechanisms of action. Some clinical data have been published on the efficacy of this new class of antimicrobials. Each one has been studied in the treatment of skin and soft-tissue infections. Oritavancin Oritavancin possesses bactericidal activity in vitro against resistant and susceptible gram-positive bacteria, including MRSA. Oritavancin has exhibited efficacy comparable to that of vancomycin for the treatment of skin and soft-tissue infections and has also demonstrated efficacy in a variety of animal models of gram-positive infections. In 2008, a new drug application was filed with the FDA; however, more clinical trials need to be published to determine the role of oritavancin. W W W.D R U GTO P I C S .C O M 38 DRUG TOPICS Januar y 2009 http://WWW.DRUGTOPICS.COM
Table of Contents Feed for the Digital Edition of Drug Topics - January 2009 Drug Topics - January 2009 Contents Letters Up Front Up Front in Depth Community Practice Drug Pipeline: What to Watch in 2009 OTC Community-Aquired MRSA Infections New Products Viewpoint Drug Topics - January 2009 Drug Topics - January 2009 - Drug Topics - January 2009 (Page Cover1) Drug Topics - January 2009 - Drug Topics - January 2009 (Page Cover2) Drug Topics - January 2009 - Drug Topics - January 2009 (Page 1) Drug Topics - January 2009 - Drug Topics - January 2009 (Page 2) Drug Topics - January 2009 - Drug Topics - January 2009 (Page 3) Drug Topics - January 2009 - Contents (Page 4) Drug Topics - January 2009 - Contents (Page 5) Drug Topics - January 2009 - Contents (Page 6) Drug Topics - January 2009 - Contents (Page 7) Drug Topics - January 2009 - Contents (Page 8) Drug Topics - January 2009 - Contents (Page 9) Drug Topics - January 2009 - Contents (Page 10) Drug Topics - January 2009 - Contents (Page H1) Drug Topics - January 2009 - Contents (Page H2) Drug Topics - January 2009 - Contents (Page H1) Drug Topics - January 2009 - Contents (Page H2) Drug Topics - January 2009 - Contents (Page H3) Drug Topics - January 2009 - Contents (Page H4) Drug Topics - January 2009 - Contents (Page H5) Drug Topics - January 2009 - Contents (Page H6) Drug Topics - January 2009 - Contents (Page H7) Drug Topics - January 2009 - Contents (Page H8) Drug Topics - January 2009 - Contents (Page 13) Drug Topics - January 2009 - Up Front (Page 14) Drug Topics - January 2009 - Up Front (Page 15) Drug Topics - January 2009 - Up Front (Page 16) Drug Topics - January 2009 - Up Front (Page 17) Drug Topics - January 2009 - Up Front in Depth (Page 18) Drug Topics - January 2009 - Up Front in Depth (Page 19) Drug Topics - January 2009 - Community Practice (Page 20) Drug Topics - January 2009 - Community Practice (Page 20a) Drug Topics - January 2009 - Community Practice (Page 20b) Drug Topics - January 2009 - Community Practice (Page 21) Drug Topics - January 2009 - Drug Pipeline: What to Watch in 2009 (Page 22) Drug Topics - January 2009 - Drug Pipeline: What to Watch in 2009 (Page 23) Drug Topics - January 2009 - Drug Pipeline: What to Watch in 2009 (Page 24) Drug Topics - January 2009 - Drug Pipeline: What to Watch in 2009 (Page 25) Drug Topics - January 2009 - Drug Pipeline: What to Watch in 2009 (Page 26) Drug Topics - January 2009 - Drug Pipeline: What to Watch in 2009 (Page 27) Drug Topics - January 2009 - OTC (Page 28) Drug Topics - January 2009 - OTC (Page 29) Drug Topics - January 2009 - OTC (Page 30) Drug Topics - January 2009 - OTC (Page 31) Drug Topics - January 2009 - Community-Aquired MRSA Infections (Page 32) Drug Topics - January 2009 - Community-Aquired MRSA Infections (Page 33) Drug Topics - January 2009 - Community-Aquired MRSA Infections (Page 34) Drug Topics - January 2009 - Community-Aquired MRSA Infections (Page 35) Drug Topics - January 2009 - Community-Aquired MRSA Infections (Page 36) Drug Topics - January 2009 - Community-Aquired MRSA Infections (Page 37) Drug Topics - January 2009 - Community-Aquired MRSA Infections (Page 38) Drug Topics - January 2009 - Community-Aquired MRSA Infections (Page 39) Drug Topics - January 2009 - Community-Aquired MRSA Infections (Page 40) Drug Topics - January 2009 - Community-Aquired MRSA Infections (Page 41) Drug Topics - January 2009 - New Products (Page 42) Drug Topics - January 2009 - New Products (Page 43) Drug Topics - January 2009 - New Products (Page 44) Drug Topics - January 2009 - New Products (Page 45) Drug Topics - January 2009 - New Products (Page 46) Drug Topics - January 2009 - New Products (Page 47) Drug Topics - January 2009 - Viewpoint (Page 48) Drug Topics - January 2009 - Viewpoint (Page Cover3) Drug Topics - January 2009 - Viewpoint (Page Cover4)
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