Triple antibiotic paste shows stronger antimicrobial performance than calcium hydroxide for persistent endodontic infections

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Frontiers in Medicine Published May 30, 2026 Medically reviewed May 30, 2026 Study authors: Carlos M. Ardila, Eliana Pineda-Vélez, Anny Marcela Vivares-Builes DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider that antibiotic-based medicaments may offer stronger antimicrobial performance for persistent endodontic infections, but evidence is limited and heterogeneous.

This is a systematic review with structured domain-based interpretative synthesis and an exploratory meta-analysis of twelve studies on intracanal medicaments for persistent endodontic infections. The review focused on antimicrobial effectiveness against E. faecalis, with secondary outcomes including biofilm-related outcomes and bacterial reduction. The authors synthesized that antibiotic-based medicaments, particularly triple antibiotic paste, generally showed comparatively stronger antimicrobial performance. Calcium hydroxide showed variable and generally lower efficacy, especially in deeper dentinal regions. Combination therapies showed improved performance, and novel agents showed promising but heterogeneous results. The exploratory meta-analysis revealed extreme heterogeneity with imprecise estimates. The authors noted limitations including substantial heterogeneity, limited high-quality clinical evidence, and that quantitative pooling was limited to two studies. They concluded that findings suggest potential improvements in intracanal disinfection strategies, pending further standardized and clinically robust investigations, with overall certainty of evidence ranging from low to moderate.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

Persistent endodontic infections are frequently associated with Enterococcus faecalis, a pathogen capable of biofilm formation and dentinal tubule penetration, contributing to treatment failure. This systematic review aimed to evaluate the antimicrobial effectiveness of intracanal medicaments against E. faecalis, compare different formulations, and explore patterns of bacterial resistance and tolerance using a structured domain-based interpretative synthesis and exploratory meta-analysis. A systematic review was conducted following PRISMA 2020 guidelines. Searches were performed in PubMed/MEDLINE, Scopus, and Embase. Eligible studies included in vitro, ex vivo, and clinical investigations reporting quantitative antimicrobial outcomes. A structured domain-based interpretative synthesis was performed across key domains, and meta-analysis was conducted when feasible. Twelve studies were included. Antibiotic-based medicaments, particularly triple antibiotic paste, generally showed comparatively stronger antimicrobial performance, especially in studies assessing bacterial reduction and biofilm-related outcomes. Calcium hydroxide showed variable and generally lower efficacy, especially in deeper dentinal regions, though combination therapies improved performance. Novel agents, including nanoparticle-based systems and bioactive compounds, showed promising but heterogeneous results. Quantitative pooling was limited to two studies and revealed extreme heterogeneity with imprecise estimates. Overall certainty of evidence ranged from low to moderate. Intracanal medicaments exhibit consistent antimicrobial activity against E. faecalis, with comparatively stronger performance observed for antibiotic-based formulations in the available experimental evidence. However, substantial heterogeneity and limited high-quality clinical evidence constrain definitive conclusions. These findings suggest potential improvements in intracanal disinfection strategies, pending further standardized and clinically robust investigations. https://www.crd.york.ac.uk/PROSPERO/recorddashboard, identifier CRD420261345958.