Background: Adjunctive corticosteroid therapy appears to be beneficial for adults with severe community-acquired pneumonia (CAP), but data on Mycoplasma pneumoniae CAP are limited. This study aimed to evaluate if adjunctive betamethasone reduced time to resolution of hypoxaemia in adults hospitalised with M. pneumoniae CAP.

Methods: An open-label, multicentre, randomised, controlled trial was conducted at eight Swedish hospitals. Adults admitted with M. pneumoniae CAP and hypoxaemia (SpO2 <93% and respiratory rate >20 breaths/min) were eligible. Exclusion criteria included asthma and diabetes mellitus. Participants were randomised (1:1) to either standard care without corticosteroids or adjunctive oral betamethasone (3 mg daily on days 1–2, and 2 mg daily on days 3–5). Antibiotic treatment was standardised to 200 mg doxycycline once daily for 10 days. The primary outcome was time to resolution of hypoxaemia in an intention-to-treat analysis. Safety was assessed in participants receiving at least one betamethasone dose. The study was registered with the EU Clinical Trials Register (EudraCT 2016-002585-32) and is completed.

Findings: Between March 1, 2018, and November 14, 2024, 70 participants were enrolled: 36 in the betamethasone group and 34 in the control group. The median age was 42 years (IQR 28–49) including 40 (57%) male and 30 (43%) female participants. All participants achieved resolution of hypoxaemia except two who withdrew consent. Time to resolution of hypoxaemia was shorter in the betamethasone group (HR 1.82 [95% CI 1.10–3.02], p = 0.020) compared to the standard of care group, with an estimated median of 2.3 (95% CI 1.8–2.7) and 3.6 (95% CI 1.9–5.3) days, respectively. Adverse events were similar between study groups. Severe adverse events were rare, and none were attributed to betamethasone treatment.

Interpretation: Adjunctive betamethasone was well tolerated and significantly shortened the duration of hypoxaemia in adults hospitalised with M. pneumoniae CAP in this open-label trial. Funding: The Swedish Society of Medicine.