Steroids Offer No Help for Pneumonia
Steroids Offer No Help for Pneumonia
By John Gever, Senior Editor, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit
for reading medical news
Action Points
* Explain to interested patients that corticosteroids are used to reduce inflammation, which is a prominent feature of many infections including pneumonia.
* Explain that some previous studies had suggested a benefit for corticosteroids in pneumonia but the evidence was not strong. But this relatively large randomized trial, a strong form of evidence, showed that corticosteroids provided no benefit in most cases, and may have fostered recurrence of pneumonia in some.
* Explain that some patients may nevertheless benefit from corticosteroids despite the findings of this study. Treatments must be determined for each patient individually.
Adding prednisolone to antibiotics in patients with community-acquired pneumonia (CAP) did not improve outcomes and may actually have worsened them, according to researchers conducting a placebo-controlled trial.
Clinical cure rates and most other outcomes were similar in hospitalized CAP patients treated for one week with prednisolone at 40 mg/day versus placebo, but late failure was significantly more common in the prednisolone group, according to Dominic Snijders, MD, of Medical Centre Alkmaar in the Netherlands, and colleagues.
Patients taking prednisolone suffered late failure (recurrence of pneumonia symptoms at least three days after admission) at a rate of 19.2%, compared with 6.4% among patients in the placebo group (P=0.04), the researchers reported online in the American Journal of Respiratory and Critical Care Medicine.
"Prednisolone should not be recommended as routine adjunctive treatment in CAP," they concluded.
Corticosteroids have shown some benefit in other serious infections such as sepsis, though not consistently, the researchers indicated.
One study in pneumococcal pneumonia showed such a strong positive effect for supplemental corticosteroids that the trial was stopped prematurely. Steroids have also appeared to be beneficial in CAP patients in a retrospective analysis.
Consequently, Snijders and colleagues conducted a randomized trial involving 213 patients hospitalized with clinically and radiologically diagnosed CAP.
Pneumonia severities of all grades were represented, with most clustered in Pneumonia Severity Index classes 2 to 4. About 14% of patients had class I illness and the same number had class 5 illness.
Mean patient age was about 63, and slightly more than half were men, while 30% were current smokers.
Some 20% had chronic obstructive pulmonary disease. From 7% to 22% had other comorbid illnesses such as diabetes, asthma, and ischemic or chronic heart disease.
These were about equally common in the two treatment groups, except that significantly more in the placebo group had chronic heart disease (22% versus 10%, P=0.01).
Antibiotic regimens, including the choice of drugs as well as the route of administration, varied among patients. About 57% received amoxicillin, while 37% received moxifloxacin, and some 4% had a combination of amoxicillin and clavulanic acid.
Patients were randomly assigned to receive prednisolone or placebo, and by the same route as the antibiotics (intravenous or oral).
The primary study endpoint, seven-day clinical cure, was met by 80.8% of those taking prednisolone and 85.3% of the placebo group (P=0.38).
There was no clear winner, either, in secondary endpoints (intention to treat, P>0.10 except as noted):
* 30-day clinical cure: 66.3% prednisolone, 77.1% placebo (P=0.08)
* 30-day mortality: 5.8% prednisolone, 5.5% placebo
* Mean length of stay: 10.0 days prednisolone, 10.6 days placebo
* Mean time to clinical stability: 4.9 days for both groups
* Early failure rate: 13.5% prednisolone, 12.8% placebo
Results were similar among the 83% of patients who completed treatment as scheduled. There was also no sign that prednisolone was effective in patients with more severe illness, as defined by high Pneumonia Severity Index and CURB-65 scores.
Nevertheless, Snijders and colleagues cautioned that a benefit for the drug in severe cases "cannot be excluded."
Prednisolone did appear to have benefits in certain surrogate outcomes.
Serum C-reactive protein (CRP) levels declined significantly faster in the corticosteroid group initially, with mean levels about half those seen in the placebo group on days five to seven. By day 14, though, CRP levels in the placebo group dropped significantly below those in the prednisolone patients.
Fever also abated more quickly with prednisolone, with mean temperatures reduced by as much as 0.5° C relative to the placebo group in the first few days of treatment. There was no difference in mean temperature by day seven.
Adverse effects attributable to treatment were infrequent and did not differ between groups.
Snijders and colleagues indicated that the higher rate of late clinical failures with prednisolone and the higher levels of CRP at day 14, after initial suppression, may reflect a rebound phenomenon.
Although superinfection might also account for these observations, the researchers said there was no evidence for additional infections in these patients.
The researchers suggested that tapering corticosteroids, rather than stopping them abruptly as was done in the current study, might protect against rebound.
They also cited several limitations to the study. The primary outcome and some of the secondary endpoints were somewhat subjective, Snijders and colleagues pointed out.
Also, they did not evaluate patients' adrenal functions, and the number of patients with COPD in the sample was too small to permit conclusions about the effect of corticosteroids in that subpopulation.
Finally, the researchers indicated that the once-daily dosing of prednisolone could have reduced the drug's efficacy.
The study was funded by AstraZeneca.
The authors declared they had no potential conflicts of interest.
Primary source: American Journal of Respiratory and Critical Care Medicine
Source reference:
Snijders D, et al "Efficacy of corticosteroids in community-acquired pneumonia -- a randomized double blinded clinical trial" Am J Respir Crit Care Med 2010; DOI: 10.1164/rccm.200905-0808OC.
By John Gever, Senior Editor, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit
for reading medical news
Action Points
* Explain to interested patients that corticosteroids are used to reduce inflammation, which is a prominent feature of many infections including pneumonia.
* Explain that some previous studies had suggested a benefit for corticosteroids in pneumonia but the evidence was not strong. But this relatively large randomized trial, a strong form of evidence, showed that corticosteroids provided no benefit in most cases, and may have fostered recurrence of pneumonia in some.
* Explain that some patients may nevertheless benefit from corticosteroids despite the findings of this study. Treatments must be determined for each patient individually.
Adding prednisolone to antibiotics in patients with community-acquired pneumonia (CAP) did not improve outcomes and may actually have worsened them, according to researchers conducting a placebo-controlled trial.
Clinical cure rates and most other outcomes were similar in hospitalized CAP patients treated for one week with prednisolone at 40 mg/day versus placebo, but late failure was significantly more common in the prednisolone group, according to Dominic Snijders, MD, of Medical Centre Alkmaar in the Netherlands, and colleagues.
Patients taking prednisolone suffered late failure (recurrence of pneumonia symptoms at least three days after admission) at a rate of 19.2%, compared with 6.4% among patients in the placebo group (P=0.04), the researchers reported online in the American Journal of Respiratory and Critical Care Medicine.
"Prednisolone should not be recommended as routine adjunctive treatment in CAP," they concluded.
Corticosteroids have shown some benefit in other serious infections such as sepsis, though not consistently, the researchers indicated.
One study in pneumococcal pneumonia showed such a strong positive effect for supplemental corticosteroids that the trial was stopped prematurely. Steroids have also appeared to be beneficial in CAP patients in a retrospective analysis.
Consequently, Snijders and colleagues conducted a randomized trial involving 213 patients hospitalized with clinically and radiologically diagnosed CAP.
Pneumonia severities of all grades were represented, with most clustered in Pneumonia Severity Index classes 2 to 4. About 14% of patients had class I illness and the same number had class 5 illness.
Mean patient age was about 63, and slightly more than half were men, while 30% were current smokers.
Some 20% had chronic obstructive pulmonary disease. From 7% to 22% had other comorbid illnesses such as diabetes, asthma, and ischemic or chronic heart disease.
These were about equally common in the two treatment groups, except that significantly more in the placebo group had chronic heart disease (22% versus 10%, P=0.01).
Antibiotic regimens, including the choice of drugs as well as the route of administration, varied among patients. About 57% received amoxicillin, while 37% received moxifloxacin, and some 4% had a combination of amoxicillin and clavulanic acid.
Patients were randomly assigned to receive prednisolone or placebo, and by the same route as the antibiotics (intravenous or oral).
The primary study endpoint, seven-day clinical cure, was met by 80.8% of those taking prednisolone and 85.3% of the placebo group (P=0.38).
There was no clear winner, either, in secondary endpoints (intention to treat, P>0.10 except as noted):
* 30-day clinical cure: 66.3% prednisolone, 77.1% placebo (P=0.08)
* 30-day mortality: 5.8% prednisolone, 5.5% placebo
* Mean length of stay: 10.0 days prednisolone, 10.6 days placebo
* Mean time to clinical stability: 4.9 days for both groups
* Early failure rate: 13.5% prednisolone, 12.8% placebo
Results were similar among the 83% of patients who completed treatment as scheduled. There was also no sign that prednisolone was effective in patients with more severe illness, as defined by high Pneumonia Severity Index and CURB-65 scores.
Nevertheless, Snijders and colleagues cautioned that a benefit for the drug in severe cases "cannot be excluded."
Prednisolone did appear to have benefits in certain surrogate outcomes.
Serum C-reactive protein (CRP) levels declined significantly faster in the corticosteroid group initially, with mean levels about half those seen in the placebo group on days five to seven. By day 14, though, CRP levels in the placebo group dropped significantly below those in the prednisolone patients.
Fever also abated more quickly with prednisolone, with mean temperatures reduced by as much as 0.5° C relative to the placebo group in the first few days of treatment. There was no difference in mean temperature by day seven.
Adverse effects attributable to treatment were infrequent and did not differ between groups.
Snijders and colleagues indicated that the higher rate of late clinical failures with prednisolone and the higher levels of CRP at day 14, after initial suppression, may reflect a rebound phenomenon.
Although superinfection might also account for these observations, the researchers said there was no evidence for additional infections in these patients.
The researchers suggested that tapering corticosteroids, rather than stopping them abruptly as was done in the current study, might protect against rebound.
They also cited several limitations to the study. The primary outcome and some of the secondary endpoints were somewhat subjective, Snijders and colleagues pointed out.
Also, they did not evaluate patients' adrenal functions, and the number of patients with COPD in the sample was too small to permit conclusions about the effect of corticosteroids in that subpopulation.
Finally, the researchers indicated that the once-daily dosing of prednisolone could have reduced the drug's efficacy.
The study was funded by AstraZeneca.
The authors declared they had no potential conflicts of interest.
Primary source: American Journal of Respiratory and Critical Care Medicine
Source reference:
Snijders D, et al "Efficacy of corticosteroids in community-acquired pneumonia -- a randomized double blinded clinical trial" Am J Respir Crit Care Med 2010; DOI: 10.1164/rccm.200905-0808OC.
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