Corticosteroids reduce treatment failure in severe community acquired pneumonia, trial shows

Corticosteroid therapy significantly reduces treatment failure in patients hospitalised with severe community acquired pneumonia who have high inflammatory response, a study has found.

Community acquired pneumonia is currently the leading cause of death from infectious disease in developed countries. Mortality is high in patients who are hospitalised with the condition, particularly in those with severe pneumonia and in the 10-20% whose treatment fails.

The trial, reported in JAMA,1 included 120 patients admitted to three Spanish teaching hospitals with severe community acquired pneumonia and high levels of inflammation (C reactive protein levels higher than 150 mg/L at admission). They were randomised to corticosteroid therapy (intravenous bolus of 0.5 mg/kg every 12 hours) or placebo for five days started within 36 hours of hospital admission, in addition to antibiotics recommended by guidelines.

Patients treated with corticosteroid therapy were significantly less likely to experience treatment failure than those in the placebo group. Only eight patients (13%) treated with corticosteroids had treatment failure, compared with 18 (31%) in the placebo group (odds ratio 0.34 (95% confidence interval 0.14 to 0.87) P=0.02).

Treatment failure was defined as a composite of early failure (clinical deterioration indicated by development of shock, need for invasive mechanical ventilation, or death within 72 hours) and late failure (radiographic progression, persistence of severe respiratory failure, shock, ventilation, or death 72-120 hours after starting treatment).

“Among patients with severe community acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone . . . decreased treatment failure,” said the researchers, led by Antoni Torres, of the Hospital Clinic in Barcelona, Spain. “If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population.”

Further results showed no difference in mortality between the two groups, with six deaths (10%) among patients treated with methylprednisolone and nine (15%) in the placebo group (P=0.37). Adverse events occurred at similar rates in the two groups: hyperglycaemia occurred in 11 patients from the corticosteroid group and in seven from the placebo group (P=0.34).

In an accompanying editorial2 Richard Wunderink, of Northwestern University’s Feinberg School of Medicine in Chicago, USA, noted that radiographic progression from 72 hours to five days was the primary driver of treatment differences. He said this might mean that corticosteroids block the effects of high concentrations of cytokines that can occur shortly after starting antibiotics in patients with high levels of bacterial infection. He cautioned that treatment should be individualised for each patient.

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