Drug Topics - January 2009 - (Page 36) Continuing Education COMMUNITY-ACQUIRED MRSA TABLE 3 Dosing and adverse event pro le for agents that are active against MRSA Antibiotic Clindamycin (Cleocin) Tetracyclines: doxycycline (Doryx), minocycline (Minocin) Trimethoprim/ sulfamethoxazole (Septra, Bactrim) Rifampin (Rifadin) Linezolid (Zyvox) Vancomycin (Vancocin) Daptomycin (Cubicin) Tigecycline (Tygacil) Quinupristin/ dalfopristin (Synercid) Dosage Form IV or PO PO Dosing Schedule Q6-8h Q12h Dose Adjustments None Not defined Adverse Events Gastrointestinal effects, including pseudomembranous colitis Gastrointestinal upset and photosensitivity; not for use in pregnancy or children <8 years old IV or PO Q12h Renal dose adjustment Avoid use in hepatic impairment None Adjust according to therapeutic drug levels Renal dose adjustment Hepatic dose adjustment None Hypersensitivity, rash, hyperkalemia IV or PO BID Discoloration of body fluids, hepatotoxicity, significant drug interactions Neuropathy, thrombocytopenia, myelosuppression, serotonin syndrome Hypotension, red-man syndrome, rare renal failure Creatine kinase elevations, rhabdomyolysis Gastrointestinal upset, injection-site reactions, nausea, vomiting Myalgias, venous irritation, hyperbilirubinemia IV or PO IV BID Varies IV IV IV Q24h Q12h Q8h after receiving doxycycline at a dose of 100 mg twice a day for seven days. In light of the outcomes of these two studies, it is important that we keep the tetracyclines near the forefront of options when treating outpatient CA-MRSA. Trimethoprim/sulfamethoxazole (TMP/SMX) TMP/SMX is a two-component antibiotic that works through inhibition of folic acid synthesis at two distinct points in the pathway. Interference with folic acid synthesis results in inhibition of bacterial DNA synthesis. TMP/SMX has demonstrated activity against susceptible S. aureus isolates, including both MSSA and MRSA. Most CA-MRSA isolates show susceptibility to TMP/SMX in vitro. Clinical data on use of TMP/SMX for treating CA-MRSA are sparse. Most of the efficacy quoted is from one trial, which evaluated the use of intravenous vancomycin versus TMP/ SMX in treatment of a variety of S. aureus infections. Both antibiotics demonstrated a 100 percent cure rate in the MRSA population. In this trial, TMP was dosed 320 mg twice a day; vancomycin was dosed at 1 gm every 12 hours. In a later trial evaluating treatment of skin and soft-tissue infections, TMP/SMX demonstrated an 85 percent success rate in the MRSA subgroup. The dose of TMP in the study was 160 mg twice a day. These authors concluded that TMP/SMX would need to be evaluated in a larger clinical trial and with a higher dose of TMP before a solid recommendation could be made for the use of TMP/SMX. As mentioned above, the use of TMP/SMX has increased over the past few years as incidence rates of CA-MRSA have increased. Despite favorable in vitro susceptibility data and initial clinical outcomes, clinicians remain concerned about the potential for treatment failure, emergence of resistance, and risk of hypersensitivity reactions to the sulfa moiety. Also, hyperkalemia can occur in up to 20 percent of patients, especially if they have a baseline serum creatinine of 1.2 mg/dL or higher. At present, TMP/SMX is recommended for the treatment of skin and soft-tissue infections when intravenous therapy is not indicated, but caution should be taken, owing to its lack of streptococcus coverage. Rifampin Rifampin acts by inhibiting bacterial RNA synthesis and exhibits bactericidal activity against MRSA. When rifampin is used as monotherapy, the selection of resistant mutants occurs rapidly. Therefore, the utility of rifampin is limited to combination therapy. Rifampin is most commonly used in combination with other antibiotics, such as vancomycin, for synergy and for its improved activity within biofilms. The potential for significant drug interactions and the development of resistance limit the use of rifampin for the treatment of CA-MRSA. W W W.D R U GTO P I C S .C O M 36 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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