title: High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria.
abstract: BACKGROUND
  The high incidence of multidrug-resistant (MDR) bacteria among patients admitted to ICUs has determined an increase of tigecycline (TGC) use for the treatment of severe infections. Many concerns have been raised about the efficacy of this molecule and increased dosages have been proposed. Our purpose is to investigate TGC safety and efficacy at higher than standard doses.
  
  
  METHODS
  We conducted a retrospective study of prospectively collected data in the ICU of a teaching hospital in Rome. Data from all patients treated with TGC for a microbiologically confirmed infection were analyzed. The safety profile and efficacy of high dosing regimen use were investigated.
  
  
  RESULTS
  Over the study period, 54 patients (pts) received TGC at a standard dose (SD group: 50 mg every 12 hours) and 46 at a high dose (HD group: 100 mg every 12 hours). Carbapenem-resistant Acinetobacter.baumannii (blaOXA-58 and blaOXA-23 genes) and Klebsiella pneumoniae (blaKPC-3 gene) were the main isolated pathogens (n = 79). There were no patients requiring TGC discontinuation or dose reduction because of adverse events. In the ventilation-associated pneumonia population (VAP) subgroup (63 patients: 30 received SD and 33 HD), the only independent predictor of clinical cure was the use of high tigecycline dose (odds ratio (OR) 6.25; 95% confidence interval (CI) 1.59 to 24.57; P = 0.009) whilst initial inadequate antimicrobial treatment (IIAT) (OR 0.18; 95% CI 0.05 to 0.68; P = 0.01) and higher Sequential Organ Failure Assessment (SOFA) score (OR 0.66; 95% CI 0.51 to 0.87; P = 0.003) were independently associated with clinical failure.
  
  
  CONCLUSIONS
  TGC was well tolerated at a higher than standard dose in a cohort of critically ill patients with severe infections. In the VAP subgroup the high-dose regimen was associated with better outcomes than conventional administration due to Gram-negative MDR bacteria.
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Pascale
authors.forename: Luca
authors.initials: L
authors.lastname: Montini
authors.forename: Mariano
authors.initials: M
authors.lastname: Pennisi
authors.forename: Valentina
authors.initials: V
authors.lastname: Bernini
authors.forename: Riccardo
authors.initials: R
authors.lastname: Maviglia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bello
authors.forename: Teresa
authors.initials: T
authors.lastname: Spanu
authors.forename: Mario
authors.initials: M
authors.lastname: Tumbarello
authors.forename: Massimo
authors.initials: M
authors.lastname: Antonelli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016638:Critical Illness / Q000628:therapy*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000502:physiology; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011446:Prospective Studies; D012189:Retrospective Studies; D012720:Severity of Illness Index; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline