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Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia.

AbstractPURPOSE:
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.
AuthorsCaitlin W Hicks, Daniel A Sweeney, Robert L Danner, Peter Q Eichacker, Anthony F Suffredini, Jing Feng, Junfeng Sun, Brad Moriyama, Robert Wesley, Ellen N Behrend, Steven B Solomon, Charles Natanson
JournalIntensive care medicine (Intensive Care Med) Vol. 38 Issue 12 Pg. 2063-71 (Dec 2012) ISSN: 1432-1238 [Electronic] United States
PMID23111805 (Publication Type: Evaluation Study, Journal Article)
Chemical References
  • Anti-Bacterial Agents
  • Glucocorticoids
  • Mineralocorticoids
  • Desoxycorticosterone
  • Dexamethasone
  • Oxacillin
Topics
  • Animals
  • Anti-Bacterial Agents (pharmacokinetics)
  • Bacterial Load
  • Cardiopulmonary Resuscitation
  • Cross Infection (drug therapy, microbiology)
  • Desoxycorticosterone (administration & dosage, pharmacology)
  • Dexamethasone (administration & dosage, pharmacology)
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Therapy, Combination
  • Glucocorticoids (administration & dosage, pharmacology)
  • Microbial Sensitivity Tests
  • Mineralocorticoids (administration & dosage, pharmacology)
  • Oxacillin (pharmacokinetics)
  • Pneumonia, Staphylococcal (drug therapy, microbiology)
  • Severity of Illness Index
  • Shock, Septic (drug therapy, microbiology)
  • Survival Analysis

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