title: High and increasing Oxa-51 DNA load predict mortality in Acinetobacter baumannii bacteremia: implication for pathogenesis and evaluation of therapy.
abstract: BACKGROUND
  While quantification of viral loads has been successfully employed in clinical medicine and has provided valuable insights and useful markers for several viral diseases, the potential of measuring bacterial DNA load to predict outcome or monitor therapeutic responses remains largely unexplored. We tested this possibility by investigating bacterial loads in Acinetobacter baumannii bacteremia, a rapidly increasing nosocomial infection characterized by high mortality, drug resistance, multiple and complicated risk factors, all of which urged the need of good markers to evaluate therapeutics.
  
  
  RESULTS
  We established a quantitative real-time PCR assay based on an A. baumannii-specific gene, Oxa-51, and conducted a prospective study to examine A. baumannii loads in 318 sequential blood samples from 51 adults patients (17 survivors, 34 nonsurvivors) with culture-proven A. baumannii bacteremia in the intensive care units. Oxa-51 DNA loads were significantly higher in the nonsurvivors than survivors on day 1, 2 and 3 (P=0.03, 0.001 and 0.006, respectively). Compared with survivors, nonsurvivors had higher maximum Oxa-51 DNA load and a trend of increase from day 0 to day 3 (P<0.001), which together with Pitt bacteremia score were independent predictors for mortality by multivariate analysis (P=0.014 and 0.016, for maximum Oxa-51 DNA and change of Oxa-51 DNA, respectively). Kaplan-Meier analysis revealed significantly different survival curves in patients with different maximum Oxa-51 DNA and change of Oxa-51 DNA from day 0 to day 3.
  
  
  CONCLUSIONS
  High Oxa-51 DNA load and its initial increase could predict mortality. Moreover, monitoring Oxa-51 DNA load in blood may provide direct parameters for evaluating new regimens against A. baumannii in future clinical studies.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, and Institute of Microbiology, College of Medicine, National Taiwan University, Tapei, Taiwan.
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Chuang
authors.forename: Shan-Chwen
authors.initials: SC
authors.lastname: Chang
authors.forename: Wei-Kung
authors.initials: WK
authors.lastname: Wang
mesh_terms: D000151:Acinetobacter Infections / Q000097:blood / Q000382:microbiology* / Q000401:mortality; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000235:genetics*; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016470:Bacteremia / Q000097:blood / Q000382:microbiology* / Q000401:mortality; D001426:Bacterial Proteins / Q000235:genetics*; D004269:DNA, Bacterial / Q000097:blood / Q000235:genetics*; D005260:Female; D005798:Genes, Bacterial / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial