Adjunctive Corticosteroids in Gram-Negative Bacteremia
Adjunctive corticosteroids are NOT recommended for gram-negative bacteremia and may increase mortality, particularly when used at high doses (≥4g/day hydrocortisone equivalent). 1
Evidence Against Corticosteroid Use
The strongest clinical evidence demonstrates harm rather than benefit:
A large 10-year observational study of 612 patients with gram-negative bacteremia found that corticosteroid therapy in patients with shock did not enhance survival. Treatment with an average of 4.0 g/day of hydrocortisone or its equivalents was associated with a significant increase in fatality rates. 1
Prior corticosteroid therapy diminished the febrile response to bacteremia, which itself was associated with worse outcomes—failure to mount a fever >99.6°F within the first 24 hours significantly increased fatality rates. 1
A comprehensive meta-analysis of 10 prospective, randomized, controlled trials found no overall beneficial effect of corticosteroids in patients with septic shock (rate difference: -0.2%, 95% CI: -9.2% to 8.8%). 2
Nuanced Findings on Gram-Negative Specific Infections
While the meta-analysis showed no overall benefit, there was a slight but non-significant trend toward better outcomes in the gram-negative subgroup (-5.6% vs. 1.8% for gram-positive), but this did not reach statistical significance and should not change clinical practice. 2
No differences were observed when comparing low-dose versus high-dose corticosteroids or by type of corticosteroid used. 2
What Actually Reduces Mortality in Gram-Negative Bacteremia
Focus on these evidence-based interventions instead:
Appropriate antibiotic therapy reduces fatality by approximately 50% across all categories of underlying disease severity. 1
Early appropriate antibiotic therapy reduces shock development by 50% and significantly reduces fatality even after shock has developed. 1, 3
Empirical broad-spectrum coverage with anti-pseudomonal beta-lactams (piperacillin-tazobactam, carbapenems, or antipseudomonal cephalosporins) should be initiated immediately. 4, 5
Dual therapy (beta-lactam plus aminoglycoside) is recommended for critically ill patients, those with neutropenia, septic shock, or suspected multidrug-resistant organisms. 4, 5
Source control including removal of infected catheters, drainage of abscesses, and removal of infected foreign bodies is paramount. 6, 3
Common Pitfalls
Do not use corticosteroids as adjunctive therapy for gram-negative bacteremia based on the assumption they will improve outcomes—the evidence shows potential harm. 1, 2
Do not delay appropriate antibiotics while considering adjunctive therapies—early appropriate antibiotic therapy is the single most important intervention. 1, 3
Adverse events from steroids (gastrointestinal bleeding, secondary infections, hyperglycemia) occurred at similar rates to controls in trials, but the lack of benefit combined with potential for increased mortality makes their use unjustified. 2