## 4 Discussion  
First of all, it is important to highlight that the present review and meta-analysis evaluated the effectiveness of antibiotic prophylaxis in the prevention of infectious complications on the operative site only in case of mandibular third molar extraction. For the meta-analysis, all the data taken as a whole were first considered, and then, subgroup analysis was carried out in case it was possible to extrapolate the data. Therefore, the effectiveness of antibiotic prophylaxis was evaluated even in case of only pre-surgical administration, pre- and post-surgical administration, and only post-surgical administration. This choice was made due to the different possible methods of administration: on the one hand, for example, pre- or pre- and post-surgical administration as for endocarditis prophylaxis; on the other hand, a reasonable clinical approach could be to administer antibiotic prophylaxis only after the completion of the surgery in case of difficult extraction, according to the judgment of the oral surgeon. Furthermore, an initial evaluation was carried out regarding all types of antibiotics, and then, if possible, the literature data were stratified according to the type of antibiotic administered: only amoxicillin (with clavulanic acid) and only other antibiotics that were not penicillin. This choice was made to assess whether there was a benefit of one group of antibiotics over the others. In fact, amoxicillin is considered the most suitable broad-spectrum antibiotic for antibiotic prophylaxis, also for the prophylaxis of secondary infections such as bacterial endocarditis. In addition, when possible, an analysis of data regarding osteotomy or odontotomy interventions was carried out, considering these elements as a risk factor linked to the use of high-speed drills and therefore to the possible formation of bone necrosis. With regards to the qualitative analysis, each article was assessed using the final [PERSON]'s instrument. Just one article was assigned with only 1 point ([PERSON] and [PERSON]. [30]), four articles obtained 2 points ([PERSON] and [PERSON]. [22], [PERSON] and [PERSON]. [23], [PERSON] and [PERSON]. [24], [PERSON] and [PERSON]. [32]), four articles gained 3 points ([PERSON] and [PERSON]. [27], [PERSON] and [PERSON]. [29], [PERSON] and [PERSON]. [33], [PERSON] and [PERSON]. [34]), and six articles got 4 points ([PERSON] and [PERSON]. [20], [PERSON] and [PERSON]. [21], [PERSON] and [PERSON]. [25], [PERSON] and [PERSON]. [26], [PERSON] and [PERSON]. [28], [PERSON] & [PERSON] [31]). The systematic review of the literature made it possible to identify 15 articles in order to carry out a meta-analysis, for a total of 2726 surgeries performed. The meta-analysis carried out on all articles showed a benefit in the use of prophylactic antibiotics for the prevention of infectious complications with both the fixed and random analysis. This analysis entailed a moderate degree of heterogeneity, with a \(p<0.1\) (see Figure S1 in the Supplementary material section). This heterogeneity can be explained by the fact that all the methods of administration and all the drugs were considered together. Later in the discussion, it will be shown that some methods of recruitment have had a wider heterogeneity than others. The necessary number of patients to be treated to benefit from the administration of antibiotic prophylaxis, considering all the modalities and all types of antibiotics together, was equal to 15. The meta-analysis of the data regarding antibiotic prophylaxis with all types of antibiotics, considering exclusively the pre-surgical administration, included 8 studies for a total of 652 surgeries performed (see Figure S2 in the Supplementary material section). In this case, the RR (0.29) significantly favored the prophylaxis both with the fixed and random models. Furthermore, the heterogeneity of the data was found to be zero and the number of patients to be treated to obtain a therapeutic benefit was equal to 9.