Abstract | PURPOSE: 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.
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Authors | Caitlin 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 |
Journal | Intensive care medicine
(Intensive Care Med)
Vol. 38
Issue 12
Pg. 2063-71
(Dec 2012)
ISSN: 1432-1238 [Electronic] United States |
PMID | 23111805
(Publication Type: Evaluation Study, Journal Article)
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Chemical References |
- Anti-Bacterial Agents
- Glucocorticoids
- Mineralocorticoids
- Desoxycorticosterone
- Dexamethasone
- Oxacillin
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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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