Abstract
BACKGROUND: Antibiotics are widely overprescribed to treat upper respiratory tract infections (URTIs), even though viruses cause most URTIs. We aimed to evaluate the effectiveness of a clinical decision support algorithm (CDSA)- based intervention in reducing antibiotic prescriptions among ambulatory HIV-infected adult patients with acute URTI symptoms. METHODS: Between June and September 2024, we conducted a multicenter, two-arm parallel, cluster-randomized controlled trial in six primary healthcare facilities in Mozambique. The intervention included applying the CDSA, educating and supervising clinicians, and conducting prescription audits. We used Pearson’s chi-square test and relative risk to assess the effectiveness of the intervention in reducing antibiotic prescribing. RESULTS: Three hundred seventy-nine (97.9%) HIV-infected adult patients with URTI symptoms were recruited, 182 (48%) in the intervention arm and 197 (52%) in the control. Most were females (75.5%) and single (57%). Most appeared with common cold and flu-like symptoms. Participants in the intervention arm were less likely to receive an antibiotic prescription (RR 0.41, 95% CI: 0.31–0.55) and develop a complication (RR 0.44, 95% CI: 0.16–1.20) than those not exposed. The antibiotic prescribing rate was 23.1% for the intervention and 56.3% for the control. The intervention was associated with a significant reduction in antibiotic prescribing by 33.2% (p < 0.001) and a non-significant decrease in frequency of complications by 3.7% (p = 0.096). In both arms, most patients (78%) recovered completely within five days. Amoxicillin (47.8%), azithromycin (21.9%), and phenoxymethylpenicillin (14.1%) were the most prescribed antibiotics. CONCLUSIONS: Our CDSA, coupled with education and audits with feedback, effectively reduced antibiotic usage. Furthermore, withholding antibiotics for URTIs did not increase the frequency of complications. The intervention worked across our six sites, but larger studies with our CDSA across Mozambique are needed to see whether these findings also hold up elsewhere. TRIAL REGISTRATION: ISRCTN, ISRCTN88272350. Registered 16 May 2024, https://www.isrctn.com/ISRCTN88272350. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-026-13043-w.