By Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC

Synopsis: A randomized clinical trial from Kenya found that adult patients with community-acquired pneumonia who received standard care plus a 10-day course of glucocorticoids had a modest decrease in 30-day mortality compared to standard care alone (22.6% vs. 26.0%, respectively; P = 0.02).

Source: Lucinde RK, Gathuri H, Mwaniki P, et al. A pragmatic trial of glucocorticoids for community-acquired pneumonia. N Engl J Med. 2025;393:2187-2197.

The role for steroids in community-acquired pneumonia (CAP) has been debated for decades. Some recent studies have shown a benefit, at least for certain patients, while others have not.^1-3 Most of the evidence showing an improvement in mortality is derived from studies conducted in intensive care units (ICUs), which are limited in availability in sub-Saharan Africa. Moreover, these studies exclude patients with human immunodeficiency virus (HIV) and tuberculosis, which are common co-existing illnesses in sub-Saharan Africa, because of concern about the immunomodulating effect of steroids. Therefore, Lucinde and colleagues sought to determine the efficacy and safety of adjunctive steroids in adults hospitalized with CAP in Kenya.

The study was an open-label, randomized controlled trial conducted at 18 public hospitals in Kenya. Patients were included who were at least 18 years of age and diagnosed with CAP. They were enrolled within the first 48 hours after hospitalization. The diagnosis of CAP was based on symptoms (e.g., cough, fever, dyspnea, hemoptysis, chest pain) and signs (e.g., crackles on lung examination). Imaging and laboratory testing frequently were unavailable and, therefore, were not included in the study protocol. Patients were excluded who had a contraindication to steroids, were pregnant or breast-feeding, had hospital-acquired pneumonia, or had a condition that warranted the use of steroids (e.g., an exacerbation of chronic obstructive pulmonary disease or COVID-19).

Enrolled patients were randomized 1:1 to receive standard care or standard care along with 10 days of a low-dose steroid. Intravenous steroids were prescribed at enrollment if an oral steroid was not an option, although oral steroids were given to all patients at the time of discharge. Standard care was determined by the attending physicians and included administration of a β-lactam antibiotic (i.e., benzylpenicillin or a cephalosporin) plus a macrolide (i.e., azithromycin or erythromycin) according to World Health Organization (WHO) guidelines. Follow-up occurred on days 14 and 30 after enrollment through telephone calls. The primary endpoint was death by any cause within 30 days after study enrollment. Adverse events and serious adverse events were the safety outcomes.

There were 2,180 patients enrolled in the trial; 1,089 were assigned to the standard care plus steroid group and 1,091 to the standard care alone group. The median age for both groups was 53 years (range, 38 to 72 years). The two groups were similar in terms of demographics, antibiotics received, and adherence to treatment. The most common coexisting illnesses were HIV (344 patients, 15.8%) and hypertension (300 patients, 13.8%). The median duration of steroid treatment in the hospital was four days (range, two to eight days). There were five patients (0.2%) who were transferred to an ICU during their hospitalization. Hypoxia (O₂ saturation < 90%) was present on enrollment in 808 patients (37.1%), and 92 patients (8.4%) had hypotension (systolic blood pressure < 90 mmHg).

A total of 530 patients (24.3%) died within the 30-day follow-up period. Of these, 246 (22.6%) were in the standard care plus steroid group and 284 (26.0%) were in the standard care group. The patients who received steroids had a lower 30-day mortality compared to those who received standard therapy (hazard ratio, 0.84; 95% confidence interval, 0.73 to 0.97; P = 0.02).

There were 385 adverse events reported during the study, 211 in the steroid plus standard care group and 174 in the standard care group. The most common events in the steroid plus standard care group were hyperglycemia (35 events, 16.6%) and pulmonary tuberculosis (34 events, 16.1%). Common adverse events in the standard care group were pulmonary tuberculosis (35 events, 20.1%) and acute kidney injury (14 events, 8.0%). There were 96 serious adverse events reported. The most common in both groups was progression to severe CAP. This occurred in nine of 45 patients (20.0%) in the steroid plus standard care group and in five of 51 patients (9.8%) in the standard care group.

Commentary

This was a pragmatic study conducted in a resource-limited setting that showed a mortality benefit for steroids in patients with CAP. While the absolute difference of 3.4 percentage points in 30-day mortality appears modest, it may represent a significant effect on public health in a region where mortality from CAP is high. The severity of CAP was not assessed in the trial. However, 37% of the patients had hypoxia and 8.4% had hypotension, suggesting that a substantial number had severe disease.

Hyperglycemia occurred in 16% of the patients who received steroids. While clinicians in sub-Saharan Africa are able to manage hyperglycemia, blood glucose monitoring is burdensome to these hospitals because of limited resources. Moreover, the presence of diabetes is increasing in Africa, so escalating steroid usage may put patients at increased risk. Thus, the potential mortality benefit from steroids in CAP must be weighed carefully against the likelihood of increased metabolic complications.

There were a few limitations to the study. First, clinical trials with open-label designs are at risk for ascertainment and reporting bias. Second, the median age of the participants was 53 years, which is lower than in most studies. This may limit the generalizability of the findings to older adults. Finally, although patients underwent randomization within 48 hours after hospital admission, the timing of when steroids were initiated was not recorded.

This study provides evidence that low-dose steroids, a widely available and inexpensive intervention, can reduce mortality from CAP in Africa. Continued safety monitoring of steroids, especially for hyperglycemia, is warranted. Additional clinical trials are needed in Africa to ascertain the mortality benefits from steroids in subgroups of patients with CAP, such as those with hypoxia or HIV. A risk-adapted strategy for steroid use may be more reasonable than a universal approach. However, designing and executing such studies is challenging because of limited resources and infrastructure, highlighting current health inequities between nations.

Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC, is Professor of Medicine, Division of Infectious Diseases, Northeast Ohio Medical University, Rootstown, OH.

References

1. Caballero LA, Aijaz A, Paryani N, et al. Comparing the efficacy of corticosteroids among patients with community-acquired pneumonia in the ICU versus non-ICU settings: A systematic review and meta-analysis. Steroids. 202;205:109389.

2. Pitre T, Pauley E, Chaudhuri D, et al. Corticosteroids for adult patients hospitalised with non-viral community-acquired pneumonia: A systematic review and meta-analysis. Intensive Care Med. 2025;51:917-929.

3. REMAP-CAP Investigators; Angus DC. Effect of hydrocortisone on mortality in patients with severe community-acquired pneumonia: The REMAP-CAP Corticosteroid Domain Randomized Clinical Trial. Intensive Care Med. 2025;51:665-680.