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      Telavancin for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA)

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          Abstract

          Telavancin is a bactericidal lipoglycopeptide antibiotic that is structurally related to vancomycin. It demonstrates in vitro activity against a variety of Gram-positive pathogens including, but not limited to, methicillin-resistant Staphylococcus aureus (MRSA). Telavancin is currently FDA-approved for the treatment of complicated skin and skin-structure infections. Recently, two randomized clinical trials demonstrated the efficacy and safety of telavancin compared to vancomycin for the treatment of nosocomial pneumonia. Overall, telavancin has a favorable safety profile. However, mild gastrointestinal disturbances and reversible increases in serum creatinine were observed in clinical studies. Additional clinical studies are needed to evaluate telavancin’s efficacy and safety in comparison to other antistaphylococcal agents for the treatment of infections such as bacteremia and endocarditis.

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          Most cited references 41

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          Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia.

          Traditionally, pneumonia developing in patients outside the hospital is categorized as community acquired, even if these patients have been receiving health care in an outpatient facility. Accumulating evidence suggests that health-care-associated infections are distinct from those that are truly community acquired. To characterize the microbiology and outcomes among patients with culture-positive community-acquired pneumonia (CAP), health-care-associated pneumonia (HCAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). A retrospective cohort study based on a large US inpatient database. A total of 4,543 patients with culture-positive pneumonia admitted into 59 US hospitals between January 1, 2002, and December 31, 2003, and recorded in a large, multi-institutional database of US acute-care hospitals (Cardinal Health-Atlas Research Database; Cardinal Health Clinical Knowledge Services; Marlborough, MA). Culture data (respiratory and blood), in-hospital mortality, length of hospital stay (LOS), and billed hospital charges. Approximately one half of hospitalized patients with pneumonia had CAP, and > 20% had HCAP. Staphylococcus aureus was a major pathogen in all pneumonia types, with its occurrence markedly higher in the non-CAP groups than in the CAP group. Mortality rates associated with HCAP (19.8%) and HAP (18.8%) were comparable (p > 0.05), and both were significantly higher than that for CAP (10%, all p < 0.0001) and lower than that for VAP (29.3%, all p < 0.0001). Mean LOS varied significantly with pneumonia category (in order of ascending values: CAP, HCAP, HAP, and VAP; all p < 0.0001). Similarly, mean hospital charge varied significantly with pneumonia category (in order of ascending value: CAP, HCAP, HAP, and VAP; all p < 0.0001). The present analysis justified HCAP as a new category of pneumonia. S aureus was a major pathogen of all pneumonias with higher rates in non-CAP pneumonias. Compared with CAP, non-CAP was associated with more severe disease, higher mortality rate, greater LOS, and increased cost.
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            Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia.

            We attempted to find a relationship between the microbiological properties of bloodstream isolates of methicillin-resistant Staphylococcus aureus (MRSA) and the efficacy of vancomycin in the treatment of bacteremia. Vancomycin susceptibility testing was performed, and bactericidal activity was determined for 30 isolates from 30 different patients with MRSA bacteremia for whom clinical and microbiological outcome data were available. The majority of these patients had been previously enrolled in multicenter prospective studies of MRSA bacteremia refractory to conventional vancomycin therapy. Logistic regression found a statistically significant relationship between treatment success with vancomycin and decreases in both vancomycin MICs ( 6.27 [n = 8], 50%). We conclude that a significant risk for vancomycin treatment failure in MRSA bacteremia begins to emerge with increasing vancomycin MICs well within the susceptible range. Elucidating the mechanisms involved in intermediate-level glycopeptide resistance in S. aureus should begin by examining bacteria that begin to show changes in vancomycin susceptibility before the development of obvious resistance. Prognostic information for vancomycin treatment outcome in MRSA bacteremia may also be obtained by testing the in vitro bactericidal potency of vancomycin.
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              Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study.

              Post hoc analyses of clinical trial data suggested that linezolid may be more effective than vancomycin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. This study prospectively assessed efficacy and safety of linezolid, compared with a dose-optimized vancomycin regimen, for treatment of MRSA nosocomial pneumonia. This was a prospective, double-blind, controlled, multicenter trial involving hospitalized adult patients with hospital-acquired or healthcare-associated MRSA pneumonia. Patients were randomized to receive intravenous linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) for 7-14 days. Vancomycin dose was adjusted on the basis of trough levels. The primary end point was clinical outcome at end of study (EOS) in evaluable per-protocol (PP) patients. Prespecified secondary end points included response in the modified intent-to-treat (mITT) population at end of treatment (EOT) and EOS and microbiologic response in the PP and mITT populations at EOT and EOS. Survival and safety were also evaluated. Of 1184 patients treated, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042). All-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%). For the treatment of MRSA nosocomial pneumonia, clinical response at EOS in the PP population was significantly higher with linezolid than with vancomycin, although 60-day mortality was similar.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2012
                2012
                16 March 2012
                : 8
                : 131-137
                Affiliations
                Department of Pharmacy, Clinical and Administrative Sciences, University of Oklahoma Health Sciences Center College of Pharmacy, Oklahoma City, OK, USA
                Author notes
                Correspondence: Candace Y Hooper, PGY2 Internal Medicine Pharmacy Resident, University of Oklahoma Health Sciences Center College of Pharmacy, PO Box 26901, Oklahoma City, OK 73126, USA, Tel +1 405 271 6484, ext 47175, Fax +1 405 271 6750, Email candace-hooper@ 123456ouhsc.edu
                Article
                tcrm-8-131
                10.2147/TCRM.S23247
                3333464
                22547931
                © 2012 Hooper and Smith, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

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