Antibiotic therapy for small intestinal bacterial overgrowth: a systematic review of comparative efficacy, clinical-test discordance, and pediatric evidence gaps.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) and intestinal methanogen overgrowth (IMO) are heterogeneous conditions with poorly standardized antibiotic treatment. This review assessed clinical and test-based outcomes of SIBO therapy, phenotype-specific response, recurrence, and pediatric evidence on the same subject. METHODS: PubMed/MEDLINE, Scopus, and Web of Science Core Collection were searched for English-language human studies published between January 2000 and April 2026. Randomized, non-randomized interventional, and observational studies evaluating antibiotic-based treatment for SIBO or methane-positive/IMO phenotypes were included. Owing to substantial heterogeneity, findings were synthesized narratively. RESULTS: Thirty-nine studies were included. Rifaximin was the most frequently studied antibiotic, although outcomes varied considerably. In the only direct three-antibiotic comparison, metronidazole achieved the highest breath-test normalization, whereas rifaximin provided greater improvement in abdominal pain and bloating and fewer adverse events. Rifaximin plus neomycin showed the strongest comparative signal in methane-positive/IMO phenotypes. Clinical and test-based outcomes were frequently discordant, and pediatric evidence remained sparse and inconsistent. CONCLUSION: No antibiotic was universally superior. In adults, rifaximin appears to offer the most favorable overall balance between symptom improvement and tolerability, whereas metronidazole may achieve higher breath-test normalization in selected patients. Rifaximin plus neomycin showed the strongest comparative signal in methane-positive/IMO phenotypes. Evidence is insufficient to identify a preferred pediatric regimen. Treatment success should integrate symptoms, objective response, tolerability, recurrence, and patient phenotype.