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

      Therapeutics and Clinical Risk Management
      Dove Medical Press
      nosocomial pneumonia, mrsa, hospital-acquired pneumonia, health care-associated pneumonia, telavancin, ventilator-associated pneumonia

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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.

          Most cited references41

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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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            Guidelines for preventing health-care--associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee.

            This report updates, expands, and replaces the previously published CDC "Guideline for Prevention of Nosocomial Pneumonia". The new guidelines are designed to reduce the incidence of pneumonia and other severe, acute lower respiratory tract infections in acute-care hospitals and in other health-care settings (e.g., ambulatory and long-term care institutions) and other facilities where health care is provided. Among the changes in the recommendations to prevent bacterial pneumonia, especially ventilator-associated pneumonia, are the preferential use of oro-tracheal rather than naso-tracheal tubes in patients who receive mechanically assisted ventilation, the use of noninvasive ventilation to reduce the need for and duration of endotracheal intubation, changing the breathing circuits of ventilators when they malfunction or are visibly contaminated, and (when feasible) the use of an endotracheal tube with a dorsal lumen to allow drainage of respiratory secretions; no recommendations were made about the use of sucralfate, histamine-2 receptor antagonists, or antacids for stress-bleeding prophylaxis. For prevention of health-care--associated Legionnaires disease, the changes include maintaining potable hot water at temperatures not suitable for amplification of Legionella spp., considering routine culturing of water samples from the potable water system of a facility's organ-transplant unit when it is done as part of the facility's comprehensive program to prevent and control health-care--associated Legionnaires disease, and initiating an investigation for the source of Legionella spp. when one definite or one possible case of laboratory-confirmed health-care--associated Legionnaires disease is identified in an inpatient hemopoietic stem-cell transplant (HSCT) recipient or in two or more HSCT recipients who had visited an outpatient HSCT unit during all or part of the 2-10 day period before illness onset. In the section on aspergillosis, the revised recommendations include the use of a room with high-efficiency particulate air filters rather than laminar airflow as the protective environment for allogeneic HSCT recipients and the use of high-efficiency respiratory-protection devices (e.g., N95 respirators) by severely immunocompromised patients when they leave their rooms when dust-generating activities are ongoing in the facility. In the respiratory syncytial virus (RSV) section, the new recommendation is to determine, on a case-by-case basis, whether to administer monoclonal antibody (palivizumab) to certain infants and children aged <24 months who were born prematurely and are at high risk for RSV infection. In the section on influenza, the new recommendations include the addition of oseltamivir (to amantadine and rimantadine) for prophylaxis of all patients without influenza illness and oseltamivir and zanamivir (to amantadine and rimantadine) as treatment for patients who are acutely ill with influenza in a unit where an influenza outbreak is recognized. In addition to the revised recommendations, the guideline contains new sections on pertussis and lower respiratory tract infections caused by adenovirus and human parainfluenza viruses and refers readers to the source of updated information about prevention and control of severe acute respiratory syndrome.
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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
                22547931
                3333464
                10.2147/TCRM.S23247
                https://creativecommons.org/licenses/by-nc/3.0/

                Medicine
                nosocomial pneumonia,mrsa,hospital-acquired pneumonia,health care-associated pneumonia,telavancin,ventilator-associated pneumonia

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