title: The late phase of sepsis is characterized by an increased microbiological burden and death rate.
abstract: BACKGROUND
  Recent models capturing the pathophysiology of sepsis and ex-vivo data from patients are speculating about immunosuppression in the so-called late phase of sepsis. Clinical data regarding survival and microbiological burden are missing. The aim of this study was to determine the clinical significance of the 'late phase' of sepsis with respect to overall survival and occurrence of microbiological findings.
  
  
  METHODS
  In a retrospective trial, 16,041 patient charts from a university intensive care unit were screened, and 999 patients with severe sepsis or septic shock were identified. Three phases were established according to the mortality peaks which were separated by two distinct nadirs: phase I (days 1 to 5), phase II (days 6 to 15) and phase III (days 16 to 150). Patients were analyzed for outcome, SOFA scores, procalcitonin levels, antimicrobial treatment, dialysis, mechanical ventilation and results of blood cultures during their hospital stay.
  
  
  RESULTS
  Out of 999 enrolled patients, 308 died during the course of sepsis presenting a characteristic mortality rate (30.8%) with three distinct mortality peaks (at days 2, 7 and 17). Overall 36.7% of all deaths occurred in the early phase (phase I) and 63.3% during the later phases (phase II + III). In total 2,117 blood cultures were drawn. In phase I, 882 blood cultures were drawn, representing a sampling rate of 88% with a positive rate of 14.9%. In phase II, 461 samples were taken, indicating a sampling rate of 52% and a positive rate of 11.3%. Within phase III, 524 samples were obtained representing a sampling rate of 66% with a positive rate of 15.3%, which was significantly higher compared to the positive rate of phase II and similar to phase I. In particular, the rate of typically opportunistic bacteria increased significantly from 9% in phase I up to 18% in phase III. The same is true for Candida spp. (phase I 13%, phase III 30%).
  
  
  CONCLUSIONS
  The later phase of sepsis is associated with a significant re-increase of positive blood culture results, especially regarding opportunistic bacteria and fungi. These observations warrant further studies focusing on the underlying mechanisms resulting in this outcome burden in the later phase of sepsis.
authors.affiliation: Clinic for Anesthesiology and Intensive Care, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Gordon P
authors.initials: GP
authors.lastname: Otto
authors.forename: Maik
authors.initials: M
authors.lastname: Sossdorf
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Claus
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rödel
authors.forename: Katja
authors.initials: K
authors.lastname: Menge
authors.forename: Konrad
authors.initials: K
authors.lastname: Reinhart
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.forename: Niels C
authors.initials: NC
authors.lastname: Riedemann
mesh_terms: D000368:Aged; D000890:Anti-Infective Agents / Q000627:therapeutic use; D005260:Female; D005858:Germany / Q000453:epidemiology; D017052:Hospital Mortality / Q000639:trends*; D006801:Humans; D008297:Male; D008485:Medical Audit; D008875:Middle Aged; D012189:Retrospective Studies; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality* / Q000503:physiopathology; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D000890:Anti-Infective Agents