The extraction of lower third molars is a very common procedure with an estimated incidence of surgical site infection of between 1-13% and between 0.5 – 5% for dry socket (alveolar osteitis). While antibiotic prophylaxis has been shown to reduce dry socket and site-specific infection the routine use of antibiotic prophylaxis for third molar surgery in healthy patients is questionable in the light of increasing antibiotic resistance.
The aim of this review was to assess the role of different antibiotic prophylactic treatments in relation to the risk of developing dry socket (DS) and site-specific infection (SSI) after lower third molar extraction.
Methods
A protocol was registered with the PROSPERO database. Searches were conducted in the Cochrane Library, Medline/PubMed and Scopus databases. Randomised controlled trials in patients undergoing lower third molar extractions receiving prophylactic antibiotics or placebo/no treatment published between 1999 and 2021 were considered. Three reviewers independently searched and selected studies with data being extracted by two reviewers independently. Two reviewers assessed risk of bias using the Cochrane RoB2 tool. A pair-wise meta-analysis was conducted with outcomes reported as odds ratio (ORs) with the 95% confidence interval (95% CI) followed by a network meta-analysis (NMA) The efficacy (DS and SSI) and safety of the different treatments was calculated using the surface under the cumulative ranking (SUCRA) curve with values ranging from 0% to 100%, with higher values suggesting better performance. The certainty of evidence was assessed using the GRADE approach.
Results
- 16 RCTs (15 parallel, 1 cross-over) involving 2158 patients (2428 third molars) were included.
- 7 RCTs compared amoxicillin+ clavulanic acid, 6 studies amoxicillin, two metronidazole and single studies azithromycin, and clindamycin against no treatment /placebo.
Dry Socket (DS)
- 12 RCTs (1755 patients, 1995 third molars) assessed DS.
- Meta-analyses favoured antibiotics over placebo/no treatment, OR = 0.54 (95%CI: 0.33 to 0.90). Number needed to treat (NNT) = 25.
- The NMA model did not reveal any significant differences between the different antibiotics.
- The SUCRA rankings are shown in the table 1 below.
- The certainty of evidence was assessed as low.
Table1. – SUCRA rankings for dry socket.
| Antibiotic | SUCRA value |
| clindamycin preoperative | 73.7% |
| azithromycin preoperative | 71.3% |
| amoxicillin preoperative | 66.3% |
| amoxicillin–clavulanic acid pre- and postoperative | 55.1% |
| clindamycin pre- and postoperative | 50.2% |
| amoxicillin postoperative | 49.1% |
| amoxicillin–clavulanic acid postoperative | 43.7% |
| clindamycin postoperative | 38.8% |
| metronidazole preoperative | 34.0% |
| placebo/no treatment | 17.8% |
Surgical site infection (SSI)
- 12 parallel and one cross-over RCT (1746 patients, 1986 third molars) assessed SSI.
- Meta-analyses favoured antibiotics over placebo/no treatment, OR = 0.36 (95%CI: 0.22 to 0.57) Number needed to treat (NNT) = 18.
- The NMA showed a statistically significant difference when comparing amoxicillin plus clavulanic acid given pre- and postoperatively with placebo/no treatment.
- The SUCRA rankings are shown in the table 2 below.
- The certainty of evidence was assessed as low.
Table 2. – SUCRA rankings for surgical site infection.
| Antibiotic | SUCRA value |
| amoxicillin postoperative | 77.7% |
| metronidazole pre-operative | 74.2% |
| amoxicillin–clavulanic acid pre- and postoperative | 72.7% |
| azithromycin preoperative | 67.5% |
| amoxicillin–clavulanic acid pre-operative | 50.9% |
| amoxicillin–clavulanic acid postoperative | 49.7% |
| amoxicillin preoperative | 43.6% |
| clindamycin post- operative | 25.1% |
| amoxicillin pre- operative and postoperative | 23.7% |
| placebo/no treatment | 15.0% |
Adverse Effects
- The most common adverse events were diarrhoea, nausea, vomiting, gastric pain, headache, and mycosis.
- Analysis of 7 RCTs (1484 patients, 1724 third molars) found no statistically significant difference in adverse events between antibiotic and control groups, OR = 0.73 (95%CI: 0.51 to 1.03).
- The certainty of evidence was assessed as very low.
Conclusions
The authors concluded: –
Although antibiotic prophylaxis was observed to significantly reduce the risk of dry socket and surgical site infections in healthy patients undergoing lower third molar extraction in the present review, the number of patients needed to treat was high. The preoperative administration of clindamycin was found to be the most effective treatment to prevent dry socket, while the postoperative administration of amoxicillin was found to be the most effective treatment to prevent surgical site infections. Since antimicrobial resistance is considered an important threat to global health, dentists should evaluate the need to prescribe antibiotics for each individual patient, taking into consideration the presence of systemic conditions and the case-specific risk of developing postoperative infections and/or dry socket after lower third molar removal.
Comments
The authors registered their review with the PROSPERO database and followed a typical systematic review and NMA approach with study inclusion limited to publications between 1999 and 2021. Previously we had considered another NMA by Falci et al., (Dental Elf – 24th Jun 2022) with no date restrictions which included 34 RCTs and a Cochrane review by Lodi et al., (Dental Elf – 3rd Mar 2021). While the Cochrane review related to prevention of complications following tooth extraction 21 out of the 23 studies related to third molar extraction.
These reviews shown that the use of antibiotics does reduce the post-operative infection and dry socket. However, the numbers of patients needed to treat to prevent one infection are high and concerns related to antibiotic resistance are increasing. Consequently, the routine use of prophylactic antibiotics for third molar surgery should be avoided with use being considered only after a careful assessment of an individual patient’s risk.
Links
Primary Paper
Camps-Font O, Sábado-Bundó H, Toledano-Serrabona J, Valmaseda-de-la-Rosa N, Figueiredo R, Valmaseda-Castellón E. Antibiotic prophylaxis in the prevention of dry socket and surgical site infection after lower third molar extraction: a network meta-analysis. Int J Oral Maxillofac Surg. 2023 Aug 21:S0901-5027(23)00188-1. doi: 10.1016/j.ijom.2023.08.001. Epub ahead of print. PMID: 37612199.
Review protocol in PROSPERO database
Other references
Dental Elf – 24th Jun 2022
Dental Elf – 3rd Mar 2021
Dental Elf – 12th Aug 2016
Dental Elf – Third Molar blogs
