title: Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia.
abstract: OBJECTIVE
  The effects of stress-dose corticosteroid therapy were studied in a canine staphylococcal pneumonia model of septic shock.
  
  
  METHODS
  Immediately following intrabronchial bacterial challenge, purpose-bred beagles were treated with stress doses of desoxycorticosterone (DOC), a mineralocorticoid agonist, and dexamethasone (DEX), a glucocorticoid agonist, or with placebo for 96 h. Oxacillin (30 mg/kg every 8 h) was started 4 h after infection onset. Bacterial dose was titrated to achieve 80-90 % lethality (n = 20) using an adaptive design; additional animals (n = 18) were investigated using the highest bacterial dose.
  
  
  RESULTS
  Initial analysis of all animals (n = 38) demonstrated that the effects of DOC + DEX were significantly altered by bacterial dose (p = 0.04). The treatment effects of DOC + DEX were different in animals administered high or relatively lower bacterial doses in terms of survival (p = 0.05), shock reversal (p = 0.02), interleukin-6 levels (p = 0.02), and temperature (p = 0.01). DOC + DEX significantly improved the above parameters (p ≤ 0.03 for all) and lung injury scores (p = 0.02) after high-dose bacterial challenges, but not after lower challenges (p = not significant for all). Oxacillin trough levels were below the minimum inhibitory concentration of the infecting organism, and DOC + DEX increased the frequency of persistent staphylococcal bacteremia (odds ratio 3.09; 95 % confidence interval 1.05-9.11; p = 0.04).
  
  
  CONCLUSIONS
  Stress-dose corticosteroids were only beneficial in cases of sepsis with high risk for death and even short courses may interfere with host mechanisms of bacterial clearance.
authors.affiliation: Department of General Surgery, The Johns Hopkins Hospital, Baltimore, MD 21287, USA. cmh@jhmi.edu
authors.forename: Caitlin W
authors.initials: CW
authors.lastname: Hicks
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Sweeney
authors.forename: Robert L
authors.initials: RL
authors.lastname: Danner
authors.forename: Peter Q
authors.initials: PQ
authors.lastname: Eichacker
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Suffredini
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.forename: Junfeng
authors.initials: J
authors.lastname: Sun
authors.forename: Brad
authors.initials: B
authors.lastname: Moriyama
authors.forename: Robert
authors.initials: R
authors.lastname: Wesley
authors.forename: Ellen N
authors.initials: EN
authors.lastname: Behrend
authors.forename: Steven B
authors.initials: SB
authors.lastname: Solomon
authors.forename: Charles
authors.initials: C
authors.lastname: Natanson
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D058491:Bacterial Load; D016887:Cardiopulmonary Resuscitation; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D003900:Desoxycorticosterone / Q000008:administration & dosage / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008901:Mineralocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D010068:Oxacillin / Q000493:pharmacokinetics; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000382:microbiology; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000188:drug therapy* / Q000382:microbiology; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D005938:Glucocorticoids; D008901:Mineralocorticoids; D003900:Desoxycorticosterone; D003907:Dexamethasone; D010068:Oxacillin