FROM JAMA

A 5-day course of methylprednisolone reduced the rate of treatment failure in adults with severe community-acquired pneumonia and a high initial inflammatory response, according to a report published online Feb. 17 in JAMA.

“If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population,” said Dr. Antoni Torres of Institut Clinic del Torax, Hospital Clinic, Barcelona, and his associates.

The use of corticosteroids in community-acquired pneumonia is controversial. Some studies show that corticosteroids decrease radiographic progression of the disease, prevent shock, prevent respiratory failure, decrease length of stay, and reduce mortality. Other studies show no benefit. Dr. Torres and his colleagues studied the use of corticosteroids in the subgroup of patients who present with severe disease and a proinflammatory profile characterized by a serum CRP level over 150 mg/dL – the patients most likely to benefit from anti-inflammatories and least likely to be harmed by steroid-induced superinfection.

In a randomized double-blind trial at three teaching hospitals in Spain, 120 such patients were randomly assigned to receive 5 days of either IV methylprednisolone (61 patients) at a dose of 0.5 mg/kg every 12 hours or a matching placebo (59 patients), in addition to antibiotics. The most common cause of pneumonia in both study groups was Streptococcus pneumoniae, and the most frequent empiric antimicrobial treatment was a combination of ceftriaxone, levofloxacin, and azithromycin.

As expected, CRP and IL-10 levels decreased more in patients who received the corticosteroid than in those who received placebo.

The primary efficacy endpoint was the rate of treatment failure, both within 72 hours (early) and at 72-120 hours (late) after initiation of therapy. This rate was significantly lower in patients who received methylprednisolone (8 patients, or 13%) than in those who received placebo (18, or 31%). This reduction was largely attributed to the prevention of radiographic progression and late septic shock.

However, there were no significant differences in the secondary outcomes of time to clinical stabilization, length of ICU stay, length of hospitalization, and in-hospital mortality, the investigators said (JAMA 2015 Feb. 17 [doi:10.1001/jama.2015.88]). Adverse events were similar between the two study groups and included hyperglycemia (18% with methylprednisolone vs 12% with placebo) and acute kidney injury (13% vs. 14%). One patient taking methylprednisolone developed a superinfection. Other serious adverse events included one case of delirium and one of acute hepatic failure in the methylprednisolone group and one case of GI hemorrhage in the placebo group.

It is likely that the most feared adverse effect of corticosteroid therapy – immunosuppression leading to superinfection – wasn’t an issue in this study because of the short course of treatment and the relatively low dose of methylprednisolone used, the researchers said.

These findings are important because any efficacious adjunctive treatment may help reduce the high mortality associated with severe community-acquired pneumonia. It is estimated that despite effective antibiotic treatment, 12%-36% of patients admitted to an ICU with this disease will die within a short period, Dr. Torres and his associates noted.

They are conducting another study to confirm these results, in part because the small difference between the two study groups in the number of treatment failures – only 10 patients – indicates that replication is needed.

This study was supported by the Sociedad Españolade Neumologia, Societat Catalanade Pneumologia, Fundació Catalanade Pneumologia, Grup de Recercade Qualitatdela Generalitatde Catalunya, Fondode Investigación Sanitaria, Institut d’Investigacions Biomèdiques August Pii Sunyer, and Centrode Investigación Biomédica En Red-Enfermedades Respiratorias. Dr. Torres reported having no financial disclosures; his associates reported ties to GlaxoSmithKline, Dey Pharma, Pfizer, Boehringer Ingelheim, Bayer, Sherin Pharma, AstraZeneca, Cubist, Thermo Diagnostics, and Theravance.

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