Prevalence of metronidazole resistance genes in Porphyromonas gingivalis: A systematic review

The rising prevalence of antimicrobial resistance among periodontal pathogens poses a significant threat to the effectiveness of periodontal therapy. Porphyromonas gingivalis, a key pathogen in periodontitis, has historically been susceptible to metronidazole. However, emerging reports of phenotypic resistance and the potential presence of resistance genes, such as the nim gene, raise concerns regarding its continued efficacy. The objective of the study was to evaluate the prevalence of metronidazole resistance in P. gingivalis, focusing on both phenotypic resistance and molecular detection of resistance genes. This systematic review was registered in PROSPERO (ID: 1070147) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. A comprehensive literature search was performed in PubMed, Scopus, and Web of Science for the studies published between January 2005 and April 2025. Studies reporting phenotypic or genotypic metronidazole resistance in P. gingivalis among human subjects with periodontitis were included. Study quality was assessed using the Newcastle-Ottawa Scale and Risk of Bias in Nonrandomized Studies of Interventions-I tool. Due to methodological heterogeneity, results were synthesized qualitatively rather than through meta-analysis. Eight studies were included. Three studies reported phenotypic resistance to metronidazole exceeding 25%, whereas the others identified genotypic resistance with a prevalence of around 30%. Molecular analyses indicated that nim genes were rarely detected or absent. The presence of phenotypic resistance without consistent genotypic evidence suggests alternative mechanisms, such as biofilm-associated tolerance or efflux activity. Variations in geographic location, antimicrobial susceptibility testing methods, and prior antibiotic exposure contributed to heterogeneity across studies. This review suggests that phenotypic metronidazole resistance in P. gingivalis occurs in certain populations, with low resistance in surveillance settings, where nim genes are rarely detected. However, this evidence is limited by heterogeneity in study design and resistance assessment and findings should be interpreted cautiously.