Corticosteroids Reduce Treatment Failure in Severe Pneumonia

Jenni Laidman

February 18, 2015

Corticosteroids were associated with reduced treatment failure among people with severe community-acquired pneumonia and excessive inflammatory response, a study published in the February 17 issue of JAMA reveals.

Antoni Torres, MD, PhD, director, Clinical Institute of Pulmonology and Thoracic Surgery (Institut Clínic de Pneumonologia i Cirurgia Toràcica), Hospital Clinic, Barcelona, Spain, and colleagues randomly assigned 120 patients with pneumonia and high inflammatory response to receive either a placebo (n = 59) or methylprednisolone (n = 61) for 5 days, beginning within 36 hours of admission. Patients in the double-blind trial also received antibiotics. The researchers defined high inflammatory response as C-reactive protein levels greater than 150 mg/L. Treatment failure was the primary trial outcome. In-hospital mortality was a secondary outcome.

Treatment failed for eight (13%) of the patients in the methylprednisolone group and 18 (31%) in the placebo group (P = .02), for an 18% difference between the groups (95% confidence interval [CI], 3% - 32%). Corticosteroids reduced the risk for treatment failure by 66% (odds ratio, 0.34; 95% CI, 0.14 - 0.87; P= .02). In-hospital mortality did not differ significantly between the two groups (P= .37), nor did levels of hyperglycemia (P = .34).

Treatment failure included shock, need for invasive mechanical ventilation, and death within 72 hours of treatment.

The authors report a reduction in late treatment failure with steroid therapy, principally as a result of decreased radiographic progression and late septic shock, both of which have been associated with higher mortality in severe community-acquired pneumonia.

Richard G. Wunderink, MD, from Northwestern University Feinberg School of Medicine, Chicago, Illinois, writes in an accompanying editorial that baseline imbalances between the two trial groups may explain a portion of the response, although the benefit of steroids in this study remained statistically significant in multivariable analysis. He notes that baseline cortisol levels were not measured, and that more patients in the placebo group had septic shock and required mechanical ventilation at the time of randomization.

He also points out that less than a quarter of the patients in either group (24% in the corticosteroid group and 23% in the placebo group) received macrolide combination antibiotic therapies, although several studies have suggested patients with severe community-acquired pneumonia experience better outcomes with this treatment.

"A more important question is what exactly are steroids preventing?" Dr Wunderink writes. "Because radiographic progression during the period between 72 hours and 5 days was the primary driver of treatment differences, understanding what this clinical finding represents is key to acceptance of the findings. The 2 logical explanations for radiographic progression are uncontrolled pneumonia and development of acute respiratory distress syndrome. Although the latter is supported by a body of literature, a beneficial effect on uncontrolled pneumonia is less logical. A more intriguing possibility is that corticosteroids block a Jarisch-Herxheimer-like reaction to initiation of antibiotics in patients with high genomic bacterial load."

One coauthor received honoraria for consultation and speaking from GlaxoSmithKline, Dey Pharma, Pfizer, Boehringer Ingelheim, Bayer-Shering Pharma, and AstraZeneca. Another coauthor received grant support and fees from Bayer and Cubist and received fees from Pfizer, Thermo Diagnostics, and Theravance. The other authors and Dr Wunderink have disclosed no relevant financial relationships.

JAMA. 2015;313:673-674, 677-686. Article abstract, Editorial extract

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