title: Empiric broad-spectrum antibiotic therapy of nosocomial pneumonia in the intensive care unit: a prospective observational study.
abstract: BACKGROUND
  Antibiotic de-escalation, which consists of the initial institution of empiric broad-spectrum antibiotics followed by antibiotic streamlining driven by microbiological documentation, is thought to provide maximum benefit for the individual patient, while reducing the selection pressure for resistance.
  
  
  METHODS
  To assess a carbapenem-based de-escalating strategy in nosocomial pneumonia (NP), a prospective observational study was conducted in critically ill patients with NP treated empirically with imipenem +/- aminoglycoside/glycopeptide in 24 intensive care units of Spanish general hospitals. Overall, 244 patients were assessable (91% with late-onset NP). The primary outcome was therapeutic success 7-9 days post therapy.
  
  
  RESULTS
  Microbial identification--based on cultures of tracheal aspirates in 82% of patients, cultures of protected specimen brush in 33%, and cultures of bronchoalveolar lavage in 4%--was only available for 131 (54%) patients. Initial antibiotics were inadequate for 23 (9%) patients. Of the remaining patients, antibiotics were streamlined in 56 (23%) patients and remained unchanged in 14 (6%) patients based on microbiology data, in 38 (16%) patients despite microbiology data favouring de-escalation, and in 113 (46%) patients due to unknown aetiology. Overall, de-escalation was implemented in only 23% of patients with potentially multiresistant pathogens, compared with 68% of patients with the remaining pathogens (P < 0.001). Response rates were 53% for patients continuously treated with imipenem-based regimens and 50% for the de-escalated patients. Higher Acute Physiology, Age, and Chronic Health Evaluation II scores were associated with greater mortality, whereas adequate empiric antibiotic therapy protected against fatal outcomes. No increase of superinfection rates caused by emerging pathogens was observed. The costs associated with de-escalation were mainly dependent on the duration of hospitalization.
  
  
  CONCLUSIONS
  This study mainly highlights the current practice of a specific algorithm of de-escalation solely based on the available microbiological data, and highlights the barriers to using it more widely. In this setting, de-escalation was less likely to occur in the presence of potentially multiresistant pathogens. Prior antibiotic administration and the low use of bronchoscopic techniques may have influenced negatively the implementation of de-escalation. Optimization of de-escalation strategies for NP should rely on a correct choice of empiric antibiotics, on appropriate microbiological investigations, and on a balanced interpretation of microbiological and clinical data.
authors.affiliation: Servicio de Medicina Intensiva, Hospital del Mar, Barcelona, Spain. Falvarez@imas.imim.es
authors.forename: Francisco
authors.initials: F
authors.lastname: Alvarez-Lerma
authors.forename: Bernabe
authors.initials: B
authors.lastname: Alvarez
authors.forename: Pilar
authors.initials: P
authors.lastname: Luque
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz
authors.forename: Jose-Maria
authors.initials: JM
authors.lastname: Dominguez-Roldan
authors.forename: Elisabet
authors.initials: E
authors.lastname: Quintana
authors.forename: Cesar
authors.initials: C
authors.lastname: Sanz-Rodriguez
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016638:Critical Illness / Q000401:mortality; D003428:Cross Infection / Q000188:drug therapy* / Q000401:mortality; D036262:Empirical Research; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy* / Q000401:mortality; D011446:Prospective Studies
chemical_list: D000900:Anti-Bacterial Agents