Drug Topics - January 2009 - (Page 37) CONTINUING EDUCATION A recently published review of the literature addressed the use of rifampin as an adjunct to other antibiotics for treatment of S. aureus infections. Unfortunately, the data on use of rifampin by human beings are limited and derive from small trials with inconsistent inclusion criteria, such as varied infection and disease states. These trials have shown conflicting results, making it difficult to form a solid recommendation for the use of rifampin in skin and soft-tissue infections. However, because of the capacity of S. aureus to form biofilms, use of rifampin in patients with implanted devices shows positive efficacy as an adjunct antibiotic. associated with long-term therapy, such as thrombocytopenia, may also limit its use. With linezolid, drug interactions are a concern. Serotonin syndrome has been reported when linezolid was combined with medications that have a serotonin mechanism, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, and the triptans. In addition, reports of S. aureus resistance to linezolid, although rare, emerged less than one year after it was approved for clinical use. This will need to be monitored in connection with future utility of linezolid. Fluoroquinolones Fluoroquinolones are bactericidal antibiotics that inhibit DNA gyrase to block bacterial DNA replication and transcription. The respiratory fluoroquinolones (e.g., levofloxacin, moxifloxacin, and gatifloxacin) also inhibit topoisomerase IV. Although many S. aureus isolates show susceptibility to the fluoroquinolones in vitro, resistance can develop rapidly through a single-step mutation in DNA gyrase. The dual mechanism has not maintained the fluoroquinolones’ susceptibility to S. aureus as it has done for other gram-positive pathogens. Some data suggest that fluoroquinolones may have contributed to the rise of MRSA through selective pressure and may increase the risk of MRSA colonization. Because of these concerns, fluoroquinolones are not currently recommended for the treatment of CA-MRSA infections. Inpatient treatment options While CA-MRSA infections of the skin and soft tissues can be treated on an outpatient basis, severe infections may require hospitalization and intravenous antibiotics. Some of the above-mentioned antibiotics used for outpatient treatment, such as TMP/SMX and linezolid, are also good options for inpatient therapy. In addition, vancomycin, daptomycin, tigecycline, and quinupristin/dalfopristin are also part of the armamentarium against CA-MRSA. Vancomycin Historically, vancomycin, a glycopeptide, has been considered the drug of choice for inpatient management of MRSA infections. Vancomycin exhibits bactericidal activity against MRSA by binding to the C-terminal end of late peptidoglycan precursors, preventing the effective formation of the bacterial cell wall. Vancomycin administered intravenously remains a treatment of choice for many types of diseases caused by MRSA, including the inpatient treatment of skin and soft-tissue infections. Generally, any new antibiotic for gram-positive infections is studied against vancomycin with or without a specific gram-negative antibiotic in clinical trials. Widespread use of vancomycin has led to development of resistance. Reports of vancomycin-intermediate strains of S. aureus (VISA) and VRSA have been increasing. Recent surveillance studies have demonstrated increases in the median minimum inhibitory concentrations (MIC) of vancomycin against S. aureus, which may result in treatment failures. Clinical trials have demonstrated that in patients with MRSA bacteremia, higher vancomycin MICs correlate with poorer outcomes. In patients infected with isolates exhibiting MICs ≤ 0.5 mcg/mL, the clinical success rate was approximately 55 percent. In contrast, clinical success rates with isolates having vancomycin MICs equal to 1 mcg/mL to 2 mcg/mL were only 9.5 percent. This trend of treatment failures that increase with increasing MICs is important to recognize, in light of the fact that an MIC ≤ 2 mcg/mL to vancomycin is still considered susceptible. Since the use of vancomycin to treat MRSA isolates with MICs ≥ 1 has been associated with increased treatment failures, its use for these isolates should be discouraged. The correlation of success rates with MICs of vancomycin has revitalized the Januar y 2009 Linezolid An oxazolidinone antibiotic, linezolid inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. Although the activity of linezolid is limited to gram-positive organisms, it demonstrates bacteriostatic activity against many multiply drug-resistant organisms such as MRSA, vancomycin-resistant S. aureus (VRSA), and vancomycin-resistant enterococcus (VRE). As noted above, linezolid shows activity against PVL production. This may play a role in future drug selection. Trials have found treatment with linezolid to be equivalent to or superior to vancomycin therapy in the treatment of MRSA skin and soft-tissue infections. Linezolid may also have an advantage compared to vancomycin in the treatment of MRSA pneumonia, as it has been shown to concentrate in plasma and in the fluid of the epithelial lining. A combined double-blind trial evaluating MRSA pneumonia has resulted in a higher rate of survival in the linezolid group (80 percent) than in the group treated with vancomycin (63.5 percent). Because questions have been raised concerning study design and clinical endpoints of some of the trials, linezolid has not emerged as the only first-line treatment for MRSA in the inpatient or outpatient setting. Linezolid is a viable option for outpatient treatment of skin and soft-tissue infections. The higher cost of the agent compared to other oral antibiotics may limit its use in some patient populations. (Earlier discharge of patients from the hospital can offset other healthcare expenditures.) Toxicities W W W.D R U GTO P I C S .C O M DRUG TOPICS 37 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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