Long-term impact of amoxicillin use to prevent postoperative infections after oral surgery on oral microbiome and resistome

Abstract

Background: Amoxicillin is currently one of the most popular antibiotics being used among dental practitioners worldwide to prevent postoperative infections after third molar surgery. However, the effectiveness of amoxicillin in preventing postoperative infections and the possible long-term adverse effects of its use for this procedure remains poorly understood. Methods: A three phase investigation was undertaken. A systematic review and meta-analysis was initially conducted to evaluate the current evidence on the effectiveness of amoxicillin in preventing postoperative surgical wound infections as well as the adverse outcomes of amoxicillin use. To further investigate the relative risk of postoperative infections with or without amoxicillin use, a five year retrospective study of case records was undertaken. Finally, two clinical trials were performed. The first was a pilot study (6 patients) and then a larger study of 57 patients were conducted in cohorts of patients who underwent third molar extractions with antibiotics (Group EA, n = 20) and without antibiotics (Group E, n = 20) along with a control group without antibiotics or extractions (Group C, n = 17). Analyses of salivary microbiome and resistance genes were performed using shotgun sequencing for the pilot study and further investigated in the larger study using 16S rRNA gene sequencing and quantitative PCR for 6 time points (Baseline, 1-, 2-, 3-, and 4-weeks, 3 months). The EA and E groups were followed up for a further 6 months. Results: The results of the systematic review and meta-analysis showed that amoxicillin when used alone was ineffective in preventing infections even though the short-term adverse effects of amoxicillin use were not significant. From the five year follow-up study of case records, we found that there was a minimal risk (2 %) for postoperative infection in this teaching hospital setting and that there was no recording or assessment of adverse effects related to antibiotic use. The pilot study examining the microbiome shift and resistome showed a higher level of Proteobacteria and beta lactamase resistance genes after extraction with antibiotics. These results were validated in the larger follow-up study. Unlike Group E and Group C, Group EA showed a 30% elevation in mean relative abundances of Proteobacteria and this change persisted up to 6 months. The combined number of operational taxonomic units (OTUs) that showed significant change from baseline to each time point over three months was: 67 for Group EA, 29 for Group E, and 13 for Group C. Group EA exhibited a 7.32-fold increase over 6 months, compared to a 2.41-fold increase in Group E and no increase for Group C at 3 months. Conclusion: Third molar extraction with amoxicillin use does not show a significant reduction in a risk for postoperative infection and resulted in prolonged changes in the oral microbiome and resistance genes when compared to extractions without amoxicillin use and controls. These findings are critical in modifying clinical antibiotic prescription patterns among dentists for third molar surgeries considering the fact that amoxicillin is the widely used antibiotic for this procedure.