Reducing Treatment Failure in Community-Acquired Pneumonia Patients with Corticosteroids

Jonathan Frazier, PharmD Candidate 2015

Community-acquired pneumonia (CAP) (along with the flu) is one of the top ten leading causes of death in the country ranking at seven. It affects more than 5 million adults and accounts for more than 1 million hospital admissions each year in the United States. Multiple healthcare organizations all agree that CAP patients who are admitted represent a major concern and that specific therapeutic approaches should be taken as early as possible to treat and improve clinical outcomes.1

Title:Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients With Severe Community-Acquired Pneumonia and High Inflammatory Response: A Randomized Clinical Trail
Design Randomized, double-blind, placebo controlled, intent-to-treat; 120 patients
Objective To assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response.
Study groups Two groups randomized on 1:1 allocation to either receive:
• IV bolus of 0.5mg/kg per 12 hours of methylprednisolone
• Placebo
for 5 days starting within 36 hours of hospital admission.
Methods All patients were treated with antibiotics according to international guidelines. Standard laboratory and microbiological exams were performed at the time of clinical presentation. Interleukin 6, IL-8, IL-10, procalcitonin and CRP levels were obtained on the first day and after 3 and 7 days of treatment.
Duration 5 day trial periods lasting from June 2004 to February 2012
Primary Outcome Measure The rate of treatment failure: early, late, or at both times. Early treatment failure was defined as clinical deterioration within 72 hours of treatment. Late treatment failure was defined as radiographic progression, persistence of severe respiratory failure, development of shock, need for invasive mechanical ventilation not present at baseline, or death between 72 and 120 hours after treatment.
Baseline Characteristics Methylprednisolone (n = 61) Placebo (n = 59)
Age, mean (SD) 64.5 (19.1) 66.1 (20.1)
Male sex, No. (%) 35 (57) 39 (66)
Current Smoker, No. (%) 15 (25) 17 (29)
Chronic Pulmonary Disease, No. (%) 7 (11) 12 (20)
Fever, No. (%) 48 (79) 41 (69)
Cough, No. (%) 46 (75) 40 (68)
Chest Pain, No. (%) 21 (34) 26 (44)
Glucose, mg/dl (IQR) 131 (106-159) 113.5 (107-180)
C-reactive Protein, mg/dl (IQR) 273 (202-292) 244 (172-289)
Results Primary Clinical Outcome Methylprednisolone (n = 61) Placebo (n=59) P Value Difference Between Groups, % (95% CI)
Treatment failure, No. (%) 8 (13) 18 (31) 0.02 18 (3 to 32)
Early treatment failure (0-72h), No. (%) 6 (10) 6 (10) 0.95 0 (-10 to 11)
Late treatment failure, No. (%) 2 (3) 15 (25) 0.001 22 (10 to 34)

Overall there was less treatment failure in the methylprednisolone group compared to the placebo group. This was largely due to less late treatment failures in the methylprednisolone group.

Adverse Events Common Adverse Events: Adverse Event Methylprednisolone (n = 61) Placebo (n =59) P Value
Hyperglycemia, No. (%) 11 (18) 7 (12) 0.34
Superinfection,No. (%) 1 (2) 0 (0) >0.99
GI bleeding, No. (%) 0 (0) 1 (2) 0.50
Delirium, No. (%) 1 (2) 0 (0) >0.99
Acute Kidney Injury, No. (%) 8 (13) 8 (14) 0.85
Acute Hepatic Failure, No. (%) 1 (2) 0 (0) >0.99
Percentage that Discontinued due to Adverse Evens:None Reported
Study Author Conclusions Based on the results from this clinical trial, the author concludes that the acute use of methylprednisolone is associated with less treatment failure and lower inflammatory response in patients with both severe community acquired pneumonia and a high inflammatory response. As such, the author concludes that if these findings were replicated they would support the use of corticosteroids as adjunctive therapy in this clinical population.

While the author is correct in that if their findings were replicated again, the data would support the use of corticosteroids in this particular patient population, the problem is that is the only population it supports the use in. While the data shows that the use of corticosteroids reduce treatment failure in patients with severe CAP and high inflammatory response, the results cannot be generalized to all patients with CAP. The other problem with this study are the limitations such as the lack of a gradual taper and 72 hours C-reactive protein level measurement, to ensure no rebound inflammation, there were no set rules or guidelines for antibiotic dose adjustments, and lastly the 5 day dose of methylprednisolone even though previous studies suggest the benefit in prolonged use. This study does benefit clinical practice in that it gives us perspective and insight into a treatment modality that can potentiality be used to help decrease the amount of deaths from CAP each year not only in the treatment failure population but in the generalized population as well. So while there certainly is potential for the use of corticosteroids in patients with CAP more studies need to be performed before it can be considered for use.

References

1. Restrepo MI, Mortensen EM, Velez JA, et al. A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU. Chest. 2008;133(3):610-617.
2. Torres A, Sibila O, Ferrer M, et al. Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients With Severe Community-Acquired Pneumonia and High Inflammatory Response: A Randomized Clinical Trail. JAMA. 2015;313(7)677-686.

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