## 4 Discussion
Even considering only the administration of amoxicillin in the postoperative modality, the results suggest a significant benefit in favor of prophylaxis but with a high heterogeneity (75%, \(p<0.01\)) and an NNT equal to 12. In addition, in this analysis, although the result is significantly in favor of antibiotic prophylaxis, the high heterogeneity indicates that the studies conducted report discordant results. Post-surgical administration analysis considering only non-penicillin antibiotics did not find a significant difference between prophylaxis and placebo; furthermore, this analysis was conducted on only two studies of which one did not report any postoperative infection and therefore it was not possible to evaluate its heterogeneity (see Figure S10 in the Supplementary material section). Overall, administration in the post-surgical mode showed significant efficacy in the prevention of surgical site infections, but the studies in the literature did not show concordant results. Overall, therefore, the prophylactic administration of antibiotics was found to be effective in the prevention of surgical site infections and, among the various modalities, the exclusively pre-surgical administration seems to be the one most supported by the literature. The analysis of the data in the literature allows us to state that pre- and post-surgical antibiotic prophylaxis is less effective than the exclusively pre-surgical modality. These data are in contrast with the logic, since a greater coverage with antibiotics should reduce the risk of developing a post-operative infection of the wound. One possible explanation is that in case of exclusively pre-surgical administration, the dose of antibiotic administered was double in most cases [26; 27; 30; 33] and therefore, during the operation, the blood concentration of the antibiotic was greater. Even though the analysis of the data in the literature concerning post-surgical administration alone indicates a benefit from antibiotic prophylaxis, it also shows a lower benefit than other possible methods of administration and also reveals that the results of the studies do not agree. For an effective prophylaxis, the antimicrobial has to be delivered to the operative site before contamination occurs. Thus, the antimicrobial serum and tissue concentrations should exceed the minimum inhibitory concentration (MIC) for the potential infective agent, for the duration of the entire procedure [35]. An appropriate administration of prophylaxis, including the appropriate drug, dose, and timing of administration, is essential to reduce surgical wound infections (SWIs). For most procedures, continuation of antibiotic prophylaxis after surgery is not required; nonetheless, this is frequently not adhered to, resulting in additional costs, an increased risk of antimicrobial resistance and side-effects including acute kidney injury and Clostrridioides difficile infection [36]. In fact, there is growing evidence that postoperative antimicrobial administration is not necessary for most procedures [35; 37; 38; 39]. However, if post-surgical administration was deemed necessary, the duration of the therapy should be less than 24 h, in order to avoid the insurgence of bacterial resistance [35]; as a general rule, avoiding unnecessary use of antibiotics helps in diminishing the occurrence of adverse effects and antibiotic resistance development [40]. Therefore, it is possible to state from the data in the literature that antibiotic prophylaxis for the prevention of surgical site infections is useful and should be administered pre-surgically. In the present review, a meta-analysis was also carried out considering only data on surgeries for which the odontomy or osteotomy was explicitly reported. This analysis was chosen on a clinical experience basis which indicates, in case of odontomy or osteotomy, a greater trauma on soft and hard tissues and therefore a greater risk of infection [41].