Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Methylprednisolone decreased mortality and respiratory failure in severe Pneumocystis carinii pneumonia

ACP J Club. 1991 Mar-April;114:42. doi:10.7326/ACPJC-1991-114-2-042


Source Citation

Gagnon S, Boota AM, Fischl MA, et al. Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A double-blind, placebo-controlled trial. N Engl J Med. 1990;323:1444-50.


Abstract

Objective

To determine whether patients with Pneumocystis carinii pneumonia, treated with corticosteroids early in their illness, will have an increased rate of survival and a decreased rate of respiratory failure and time spent in intensive care.

Design

Randomized, double-blind, placebo-controlled trial, with patients evaluated weekly in the hospital and followed for 4 to 14 months after discharge.

Setting

Jackson Memorial Hospital, Miami, Florida, USA.

Patients

All patients had severe P. carinii pneumonia, confirmed histologically, and were seropositive for human immunodeficiency virus (HIV) type 1. Intubated patients and patients who had received more than 72 hours of antibiotic treatment were excluded. 24 patients were selected for the trial and 23 were randomized (mean age 38 y, 83% men).. 48% of patients reported acquiring HIV positivity heterosexually.

Intervention

All patients were given trimethoprim-sulfamethoxazole for 21 days at a dose of 15 mg/d trimethoprim per kilogram of body weight. Methylprednisolone was given intravenously to the corticosteroid group, 40 mg in a 100-ml bolus of saline every 6 hours for 7 days (n = 12), whereas the placebo group (n = 11) received saline only. Patients who relapsed after the course of treatment were given 3 more days of a tapered dose.

Main outcome measures

Survival to hospital discharge, respiratory failure requiring intubation, and the completion of antibiotic therapy.

Main results

Treatment with methylprednisolone began a mean of 1.1 days after starting antibiotic therapy (83% vs 36%, P < 0.024) {ARI 47%; NNT 2, CI 1 to 14; RRI 129%, CI 13% to 463%}*. 9 patients (75%) survived to hospital discharge in the corticosteroid group compared with 2 (18%) in the control group (P < 0.008) {this absolute risk improvement of 57% means that 2 patients would need to be treated (NNT) with corticosteroids (compared with placebo) to have 1 additional patient survive to hospital discharge, 95% CI 1 to 6; the relative risk improvement was 313%, CI 40% to 1402%}*. 9 patients (82%) in the placebo group compared with 3 (25%) in the corticosteroid group had respiratory failure (P < 0.008). {Absolute risk reduction 57%; 2 patients would need to be treated with corticosteroids (compared with placebo) to prevent 1 additional case of respiratory failure, CI 1 to 6; relative risk reduction 69%, CI 29% to 89%.}* More patients assigned to corticosteroids (10 vs 4 on placebo) completed 21 days of antibiotic therapy (83% vs 36%, P < 0.24) {ARI 47%; NNT 2, CI 1 to 14; RRI 129%, CI 13% to 463%}*. In the first 7 days, patients on corticosteroids improved more in terms of fever, dyspnea, and arterial blood gas measurements. Patients assigned to corticosteroids spent, on average, less time in the intensive care unit (1.2 days vs 6.3 days, P < 0.001), but recipients of placebo spent an average of 13 days in the hospital compared with 21 days for patients who received corticosteroids (P < 0.12).

Conclusions

Adjunctive therapy with methylprednisolone for P. carinii pneumonia improved survival rate and decreased respiratory failure in the first 7 days. Side effects of the treatment could not be assessed because of the low rate of survival in the placebo group.

Source of funding: In part, Alliance Against AIDS.

Address for article reprint: Dr. S. Gagnon, University of Kansas School of Medicine, 1010 N. Kansas, Wichita, KS 67214, USA.

*Numbers calculated from data in article.


Commentary

This is a timely study, contributing important information that could improve the treatment of Pneumocystis carinii pneumonia. Together with other recent studies on the same problem, it strongly suppors the clinical policy of prescribing corticosteroids early in the course of treating P. carinii pneumonia.

The timing of initiation of corticosteroid therapy in relation to starting antibiotic treatment is important for understanding the rationale for the effectiveness of treatment. In this study, corticosteroids were given within 72 hours after starting antibiotics. This would be consistent with the possibility that corticosteroids work by reducing the obstruction to oxygenation that could occur secondary to an inflammatory reaction associated with lysis of the organisms. This immediate benefit of corticosteroids would outweigh the long-term risks, including immunosuppression, associated with their use. Another possibility is that patients who have associated adrenal insufficiency may benefit from corticosteroids.

This article should be read in conjunction with the other article (1) (see also "Prednisone decreased mortality and respiratory failure in moderate-to-severe Pneumocystis carinii pneumonia") and Special Report (2) on the same topic in the same issue of The New England Journal of Medicine.

Marise S. Gottlieb, MD
Tulane University School of MedicineNew Orleans, Louisiana, USA


References

1. Bozzette SA, Sattler FR, Chiu J, et al. A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. N Engl J Med. 1990;323:1451-7.

2. National Institutes of Health-University of California Expert Panel for Corticosteroids as Adjunctive Therapy for Pneumocystis Pneumonia. Consensus statement on the use of corticosteroids as adjunctive therapy for pneumocystis pneumonia in the acquired immunodeficiency syndrome. N Engl J Med. 1990;323:1500-4.