Prophylactic Antibiotics: Do They Prevent Postoperative Complications Following Impacted Third Molar Removal?

The removal of impacted third molars has become a standard procedure for oral and maxillofacial surgeons as well as for some general dentists. Generally, their surgical removal is completed without difficulty; however, there sometimes can be intraoperative as well as postoperative complications. Although rare, intraoperative damage to adjacent teeth, sensory nerve damage, and mandibular fracture have been reported. (Table 1)

The most common postoperative sequelae are pain, swelling and trismus. Less common complications include alveolar osteitis (AO), or dry socket, infection and hemorrhage. The prevalence of alveolar osteitis has been reported to range from 0.5% to 68.4% but a rate of about 6% seems more typical.¹ It is generally considered an inflammatory response of the alveolar bone to a traumatic stimulus rather than a bacterial infection; however, its etiology is closely associated with bacterial contamination and fibrinolysis of the blood clot in the socket.²

Postoperative surgical site infections (SSI) are a more serious complication. The overall incidence of such infections after the removal of impacted third molars has been reported to be in the range of 0%-27%.³ However, most studies cite an incidence of less than 5%.⁴ Severe infections involving the fascial spaces and requiring hospitalization are not common but may occur in about 1% of cases.⁵

Even with the low rates of occurrence of alveolar osteitis and surgical site infections, the number of these complications is important because of the large volume of patients undergoing the removal of impacted third molars.⁴ It is estimated that ten million impacted teeth are removed each year in the United States.⁶ Because the occurrence of these conditions can have an adverse effect on the quality of life and productivity, as well as an economic effect, there have been numerous attempts over the years to find a way to prevent or limit their occurrence. Most of these studies have involved the use of prophylactic antibiotics. In 1966, Kay showed a significant decrease in the incidence of AO with the administration of a single dose of penicillin before surgery.⁷ This article served as the impetus for the subsequent widespread prescribing of various antibiotics following third molar surgery.² Lang has reported that most oral surgeons in the UK, and over 50% of the oral surgeons in the US, routinely prescribe antibiotics for third molar surgery.⁸

Antibiotic prophylaxis in third molar surgery is believed to reduce postoperative complications caused by microorganisms present in the oral cavity. However, their use is controversial, with multiple studies claiming both positive and negative results. Moreover, prophylactic antibiotic therapy puts patients at risk for adverse drug reactions, and it may also contribute to the development of antibiotic resistance.⁹ It is estimated that 7% of patients receiving antibiotics experience some sort of adverse reaction.¹⁰ The purpose of this report is to analyze the current literature in an attempt to determine whether the advantages of using prophylactic antibiotics to prevent postoperative complications following the removal of impacted third molars outweigh these negative aspects.

Studies supporting the use of prophylactic antibiotics
There are many studies that have looked at the possible benefits of prophylactic antibiotic use in third molar surgery. Ren and Malstrom² conducted a systematic quantitative review of randomized controlled trials on the effectiveness of antibiotic prophylaxis in reducing AO and SSI. They evaluated 16 clinical trials involving 2932 patients that reported AO as an outcome and found that the group treated with systemic antibiotics had an AO rate of 6.2%, whereas the control groups (placebo or no treatment) had a rate of 14.4%. Their meta-analysis indicated that antibiotic therapy was statistically significant in reducing the AO rate. A subgroup analysis revealed that both broad spectrum (amoxicillin) and narrow spectrum anti-anerobics (metronidazole) were equally effective, and preoperative dosing was more effective than postoperative dosing, which had no statistically significant effect on the AO rate. They also evaluated SSI in 12 clinical trials involving 2396 patients randomized to an antibiotic or placebo group. They found that the treatment group had an infection rate of 4.0% whereas the control group had a rate of 6.1%, and their meta-analysis found that there was a statistically significant reduction in SSI in the treated group. They also found that preoperative and multiday postoperative antibiotics were more effective than just preoperative single dosing. Although the authors felt that there is a role for systemic antibiotic prophylaxis in third molar surgery, they suggested that it may be prudent to use them only in patients judged to have increased risks of postoperative complications and the decision is ultimately the responsibility of the surgeon.

Marcussen et al.¹¹ evaluated the timing of prophylactic antibiotic use on the incidence of SSI and AO in third molar removal involving ostectomy. A systematic review and meta-analysis were performed on 10 random controlled trials that included 1390 patients. They found that a single preoperative dose of amoxicillin 2g statistically decreased the rate of SSI. They also found that a single 800 mg dose of penicillin V statistically decreased the incidence of AO, whereas a single dose of amoxicillin or metronidazole did not.

Morrow et al.¹ implemented a prospective cohort study and evaluated 1877 patients having third molars removed in an ambulatory setting by oral surgeons participating in a practice-based research collaborative over a period of one year. The purpose was to measure the association between postoperative antibiotic use alone and the frequency of postoperative inflammatory complications (AO or SSI). 61% of patients received a postoperative antibiotic. They found that the frequency of AO in the postoperative antibiotic group was 4.0% compared to 6.3% in the non-antibiotic group, which was statistically significant. The frequency of SSI in the postoperative antibiotic group was 0.4% compared to 1.4% in the non-antibiotic group. They also found that males, smokers and increasing surgical difficulty were statistically associated with inflammatory complications. There was no standardization of the type, dose, frequency or length of postoperative antibiotic administration. The authors attempted to standardize diagnostic criteria for AO and SSI, but other factors such as surgery length, level of tissue trauma, operator experience, and frequency of postoperative evaluations were not evaluated. The authors concluded that postoperative antibiotics alone, regardless of the delivery pattern, was associated with only a marginal decrease in postoperative inflammatory complications.

A Cochrane review by Lodi et al.¹² evaluated 18 double-blind placebo-controlled trials with a total of 2456 participants to determine the effect of antibiotic prophylaxis on the development of infectious complications following tooth extraction. They found that compared to placebo, antibiotics probably reduce the risk of infection in patients undergoing third molar extractions by about 70%. They also found that antibiotics may reduce the risk of dry socket by 38%. Patients in the antibiotic group tended to have less pain overall 7 days after the extraction, probably a direct result of fewer inflammatory complications. Antibiotic use was associated with generally mild and transient effects compared to placebo.

Menon et al.¹³ performed a systematic review involving 11 randomized controlled studies assessing the efficacy of amoxicillin/amoxicillin-clavulanic acid for reducing the risk of postoperative infection after third molar surgery in healthy volunteers. They found that both antibiotics significantly reduced the risk of infection. When evaluating for adverse effects, the amoxicillin-clavulanic group was associated with a higher risk of adverse effects, but this was only associated with postoperative use.

Studies not supporting the use of prophylactic antibiotics
There are also numerous studies, meta-analyses, clinical trials and review papers in the literature that raise doubts about the effectiveness of prophylactic antibiotics in third molar surgery. In a 5-year retrospective case record study that included 992 patients who had impacted third molars removed, Menon et al.¹⁴ assessed the effect of postoperative antibiotics on the rate of SSI. The most common postoperative antibiotic used was amoxicillin. They found that there was no difference in the rate of infection in the treated and nontreated groups.

A randomized three-arm, double-blind controlled trial assessing the efficacy of antibiotics post third molar surgery was performed by Milani et al.¹⁵ A total of 80 healthy patients were assigned to 3 drug protocols. One group received a preoperative dose and a 7-day postoperative course of amoxicillin, the second group received preoperative amoxicillin and a 7- day postoperative course of a placebo, and the third group received a preoperative placebo and a 7-day postoperative course of a placebo. The authors assessed postoperative pain, swelling and trismus at postoperative day 4 and 7. They found no statistically significant difference in any of the outcome variables between the groups. The authors concluded that there was no advantage in administering antibiotics to healthy patients undergoing extraction of third molars.

A systematic review and meta-analysis were performed by Isordia-Espinoza et al.³ to assess the risk of surgical wound infection and the adverse effects of amoxicillin in healthy patients having third molars removed. They evaluated 351 patients that were placed in either a treatment group receiving amoxicillin before or after the operation or a placebo or no treatment group. They found that there was no significant reduction in the risk of infection in the amoxicillin group when compared to the untreated/placebo group. Also, the pre or postoperative timing of antibiotic administration did not show any difference in reducing the risk of infection compared to the placebo/untreated group. In addition, they found that there was no increased risk of adverse effects between the amoxicillin group and the placebo/untreated group. The authors concluded that neither the prophylactic nor the postoperative use of amoxicillin in healthy patients undergoing third molar removal is recommended.

Bezerra et al.¹⁶ conducted a single center, randomized, double-blind clinical trial with a split-mouth design on 34 patients using either a preoperative dose of amoxicillin or a placebo. Patients were evaluated on postoperative days 3, 7 and 14. They found no significant difference in inflammatory/infectious complications, edema or pain between the two treatment groups. The only difference was a greater mouth opening in the treatment group at day 3. The authors concluded that prophylactic antibiotics do not seem to impose additional benefits for a young healthy population.

Xue et al.¹⁷ also performed a split-mouth, randomized, double-blind trial on 192 patients given amoxicillin (or clindamycin if penicillin allergic) preoperatively as well as 3 days postoperatively. Patients were evaluated on postoperative days 2 and 10 for inflammatory/infectious reactions, pain, swelling and mouth opening. They found no significant difference in any of the variables studied except for a difference in pain levels between the two groups on day 10, which they believe was due to differences in timing/use of painkillers.

Another split-mouth, randomized, double-blind placebo-controlled clinical trial was performed by Siddiqi et al.¹⁸ 95 patients were randomly assigned to 2 groups. Initially one group received prophylactic amoxicillin and the other a placebo. Then, 3 weeks later, the groups were switched. The patients were evaluated at postoperative days 3, 7 and 14 and there was no statistically significant difference in the infection rate, pain, swelling or trismus between the two groups. The authors concluded that prophylactic antibiotics should not be routinely administered to non-immunocompromised patients.

Discussion
A basic factor in determining if a patient should or should not be given prophylactic antibiotics is whether the procedure involved has a significant risk of infection. Another factor is that the benefits of using the antibiotic should outweigh the risks. On this basis, although the findings regarding the effectiveness of using prophylactic antibiotics to prevent AO and infections in patients having impacted third molars removed still remains somewhat equivocal, these other factors do not support its routine use. Studies have shown that the incidence of AO ranges from 1%–6.3% and postoperative infections, most of which are minor, occur in less than 6% of patients. On the other hand, it has been shown that up to 7% of patients receiving an antibiotic have an adverse reaction¹⁰. Moreover, the indiscriminate use of antibiotics has also been shown to lead to the development of resistant organisms and superinfections. Therefore, the possible benefits of prophylactic antibiotics in healthy patients do not justify the potential risks.

However, there are other steps that can be taken to minimize AO and postoperative infections. These include the following:

• Have the patient rinse with 0.12% chlorhexidine preoperatively.
• Use as atraumatic a surgical technique as possible.
• Use proper irrigation to avoid overheating the bone.
• Instruct the patient on proper postoperative wound care, oral hygiene and diet.

Some other factors that should be considered in the decision to use prophylactic antibiotics are the difficulty of surgery, presence of pericoronitis, poor oral hygiene, smoking, an immuno-compromised patient and increasing age. When used in such circumstances, they should always be started preoperatively.

Oral Health welcomes this original article.

References

1. Morrow AJ, Dodson, TB, Gonzalez ML, et al. Do postoperative antibiotics decrease the frequency of inflammatory complications following third molar removal? J Oral Maxillofac Surg 76:700-708, 2018.
2. Ren Y-F, Malstrom HS. Effectiveness of antibiotic prophylaxis in third molar surgery: a meta- analysis of randomized controlled clinical trials. J Oral Maxillofac Surg 65: 1909-1921, 2007.
3. Isordia-Espinoa MA, Aragon-Martinez, Martinez-Morales, Zapata-Morales. Risk of wound infection and safety profile of amoxicillin in healthy patients which required third molar surgery: a systematic review and meta-analysis. Br J Oral Max Surg 53:796-804, 2015.
4. Reiland MD, Ettinger KS, Lohse CM, Viozzi CF. Does administration of oral versus intravenous antibiotics have an effect on the incidence of alveolar osteitis or postoperative surgical site infections? J Oral Maxillofac Surg 75: 1801-1808, 2017.
5. Yoshi T, Hamamoto Y, Muraoka S, et al.: Incidence of deep fascial space infection after surgical removal of the mandibular third molars. J Infect Chemother 7:55, 2001.
6. Chidambaram R. The effects of intravenous antibiotic administration during the surgical removal of third molar: systematic review. J Young Pharm 11: 3, 2019.
7. Kay LW. Investigation into the nature of pericoronitis. Br J Oral Surg 4:52, 1966.
8. Lang MS, Gonzalez ML, Dodson TB. Do antibiotics decrease the risk of inflammatory complication after third molar removal in community practices? J Oral Maxillofac Surg 75:249255, 2017.
9. Ramos E, Santamaria J, Santamaria G, et al. Do systemic antibiotics prevent dry socket and infection after third molar extraction? A systematic review and meta-analysis. Oral Surg Oral Med Oral Pathol Oral Radiol 122: 403-425, 2016.
10. Alanis A, Weinstein AJ. Adverse reactions associated with the use of oral penicillins and cephalosporins. Med Clin North Am 67: 113, 1983.
11. Marcussen KB, Laulund AS, Jorgensen HL, et al. A systematic review on the effects of single-dose preoperative antibiotics at surgical osteotomy extraction of lower third molars. J Oral Maxillofac Surg 74: 693-703, 2016.
12. Lodi G, Sardella A, Carrassi A, et al. Antibiotics to prevent complications following tooth extractions(review). Cochrane Database of Systematic Reviews 11: CD003811, 2012.
13. Menon, RK, Gopinath D, Li, KY, et al. Does the use of amoxicillin/amoxicillin-clavulanic acid in third molar surgery reduce the risk of postoperative infection? A systematic review with meta-analysis. Int J Oral Maxillofac Surg 48: 263-273, 2019.
14. Menon, RK, Yan LK, Gopinath D, et al.: Is there a need for postoperative antibiotics after third molar surgery? A 5-year retrospective study. J Invest Clin Dent 10(4): e12460, 2019.
15. Milani BA, Bauer HC, Sampaio-Filho H, et al. Antibiotic therapy in fully impacted third molar surgery: randomized three-arm, double blind, controlled trial. Oral Maxillofac Surg 19: 341-346, 2015.
16. Bezerra, TP, Studart-Soares EC, Scaparo HC, et al. Prophylaxis versus placebo treatment for infective and inflammatory complications of surgical third molar removal: a split-mouth, double-blind, controlled, clinical trial with amoxicillin (500 mg). J Oral Maxillofac Surg 69: 333-339, 2011.
17. Xue P, Wamg J, Wu Y, et al.: Efficacy of antibiotic prophylaxis on postoperative inflammatory complications in Chinese patients having impacted mandibular third molars removed: a split-mouth, double-blind, self-controlled, clinical trial. Br J Oral and Maxillofac Surg 53: 416-420, 2015.
18. Siddiqi A, Morkel JA, Zafar S. Antibiotic prophylaxis in third molar surgery: a randomized double-blind placebo-controlled clinical trial using split-mouth technique. Int J Oral Maxillofac Surg 39: 107-114, 2010.

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About the Author

Robert A. Green Oral and Maxillofacial Surgeon, Stoney Creek, Ontario. Email: oralmaxsurg@gmail.com.

 

 

 

Bruce R. Pynn Oral and Maxillofacial Surgeon, Thunder Bay, Ontario, Email: b.pynn@shaw.ca.

 

 

 

Daniel M. Laskin Professor and Chairman Emeritus. Department of Oral and Maxillofacial Surgery, Virginia Commonwealth University School of Dentistry. Richmond, Virginia. Email: dmlaskin@vcu.edu

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