title: Telavancin hospital-acquired pneumonia trials: impact of Gram-negative infections and inadequate Gram-negative coverage on clinical efficacy and all-cause mortality.
abstract: BACKGROUND
  When hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP) is caused by gram-positive and gram-negative pathogens or both (mixed infections), the adequacy of gram-negative coverage (GNC) can confound the assessment of a gram-positive agent under study. This analysis examines the influence of gram-negative infections and the adequacy of GNC on clinical efficacy and all-cause mortality in the telavancin HABP/VABP phase 3 ATTAIN trials (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia).
  
  
  METHODS
  This post hoc analysis evaluated 3 patient groups from ATTAIN: (1) gram-positive-only infections, (2) gram-positive-only and mixed infections-adequate GNC, and (3) gram-negative-only infections and mixed infections with inadequate GNC. For each, clinical efficacy at test of cure and all-cause mortality at day 28 were compared for telavancin and vancomycin.
  
  
  CONCLUSIONS
  In the ATTAIN safety population there were 16 more deaths in the telavancin arms than in the vancomycin arms. Of these, 13 were in patients with gram-negative-only infections (n = 9) or with mixed infections and inadequate GNC (n = 4) and all had estimated baseline creatinine clearances of <30ml/min. Based on this analysis, clinical response and all-cause mortality could be confounded because there were more patients with gram-negative pathogens at baseline and more patients received inadequate treatment of these gram-negative infections in the telavancin groups.
authors: Theravance Biopharma US, South San Francisco, California.
authors: Melinda K
authors: MK
authors: Lacy
authors: Department of Medicine, Section of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" (CEMIC), Ciudad Autónoma de Buenos Aires, Argentina.
authors: Martin E
authors: ME
authors: Stryjewski
authors: Theravance Biopharma US, South San Francisco, California.
authors: Whedy
authors: W
authors: Wang
authors: Theravance Biopharma US, South San Francisco, California.
authors: Thomas C
authors: TC
authors: Hardin
authors: Theravance Biopharma US, South San Francisco, California.
authors: Boris
authors: B
authors: Nogid
authors: Theravance Biopharma US, South San Francisco, California.
authors: David R
authors: DR
authors: Luke
authors: Pulmonary and Critical Care Medicine, Washington Hospital Center, Washington D.C.
authors: Andrew F
authors: AF
authors: Shorr
authors: Department of Medicine, Duke Clinical Research Institute, Durham, North Carolina.
authors: G Ralph
authors: GR
authors: Corey
authors: Theravance Biopharma US, South San Francisco, California.
authors: Steven L
authors: SL
authors: Barriere
mesh_terms: D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D060085:Coinfection / Q000188:drug therapy / Q000401:mortality; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D017052:Hospital Mortality; D006801:Humans; D000077427:Lipoglycopeptides; D008297:Male; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; D014640:Vancomycin; C487637:telavancin
keywords: ATTAIN; hospital-acquired; mortality; pneumonia; telavancin