Prescription of antibiotics for the prevention of failures and postoperative infections in oral implantology: a literature review

peer reviewed award

Précis: The evidence does not support routine antis. Clinicians should consider the local, systemic and procedural risk factors for each patient before deciding to prescribe prophylactic antibiotics.

Journal of the Irish Dental Association August/September 2021; 67 (4): 207-212

FIGURE 1: Classification of implant failure.

Introduction
The increased success and survival of dental implants reported in the literature has led them to become increasingly popular. Albrektsson estimated that more than 12 million implants are placed annually around the globe.1 A recent systematic review reported a mean survival value of 94.6% and success rates ranging from 34.9-100% over a mean follow-up period of 13 years.2
Antibiotics are a type of antimicrobial agent that kill or slow the growth of bacteria, and they are prescribed by health professionals to treat and prevent infections. Surgical antibiotic prophylaxis can be defined as “the use of antibiotics to prevent infections at the surgical site”.3 There are currently no clear guidelines on antibiotic prophylaxis for implant surgery and antibiotic prophylaxis remains a controversial topic.

Dental implant failure
Dental Implant failures are subdivided into early and late failures (Figure 1). Early failure of implants occurs due to lack of osseointegration, while late failures occur because osseointegration could not be maintained. Late failures usually occur within the first two years of implant service. Confounding factors that can precipitate infection or implant failure include: the experience of the operator; the degree of asepsis and surgical time; tobacco smoking; certain types of medication; the patient’s overall health; and, the patient’s oral hygiene practices.4-6

Problems with antibiotic prescription
Reports suggest that around 30% of antibiotics prescribed in primary care settings are unnecessary.7 The prescription of antibiotics is associated with risks to both the individual and the economy. In addition to the risk of side effects or allergic reactions to the patient, over prescription of antibiotics is associated with the emergence of resistant strains of bacteria.8 Resistant infections can become fatal and the process of developing new antibiotics active against the resistant strains is expensive.

Methods
A literature search was performed in MEDLINE through the PubMed database of the US National Library of Medicine and the Web of Science for articles published until May 2019 using Medical Subject Heading search terms [MESH] + free text terms alone and in different combinations. Key articles that were unavailable electronically were searched manually.

Results
Antibiotic prophylaxis and dental implants
Antibiotic prophylaxis is recommended for surgical procedures in which infection is likely and for surgery where infection results in severe consequences even though it is unlikely.9 The prevalence of postoperative infection following dental implant surgery ranges from 1.6% to 11.5%.10 Dental implant infections are difficult to treat, and a lot of infected implants end up being removed.10 In an attempt to avoid this complication, it has been reported that about 50% of dentists prescribe preoperative and/or postoperative antibiotics to all patients during implant placement.11-18
The first two published studies looking at the effect of antibiotic prescription on the outcome of dental implant placement provided conflicting results. Dent et al. (1997), in a prospective clinical trial, observed that when preoperative antibiotics were not used, the risk of implant failure increased two to three times (1.5% with preoperative antibiotics vs 4% without preoperative antibiotics).19 On the other hand, Gynther et al. (1998) reported in a retrospective study that antibiotic prophylaxis does not offer any obvious advantage in the routine placement of implants in healthy patients.20

RCT comparing one preoperative antibiotic regimen vs no antibiotic (Table 1)
The randomised controlled trial (RCT) published by Kashani et al. (2019) is the only one to show a statistically significant difference in implant failure rates between the antibiotic and no antibiotic groups.21 However, this trial was not placebo controlled and both the randomisation process and blinding are unclear. Additionally, a sub-analysis by the author showed that confounding factors associated with the surgical procedure affected the outcome.

Table 1

RCTs comparing one preoperative antibiotic regimen vs placebo (Table 1)
Results from four double-blinded RCTs show that a single preoperative dose of antibiotics has no statistically significant effect on the incidence of postoperative infection or implant failure in healthy patients.22-25 Thankfully, results also show that the risk of adverse events with antibiotic use is extremely low.22
The RCT published by Nolan et al. (2014) utilised 3g amoxicillin preoperatively as the intervention.23 Although the differences were not statistically significant, failures and infections occurred only in the placebo group. Results demonstrated that longer surgical time and placement of multiple implants resulted in more implants failing to integrate. This could be explained by the fact that the implants were placed by postgraduate students and operator experience has previously been reported to have an effect on the survival of dental implants.26
Similar findings were reported by Anitua et al. (2009)24 and Esposito et al. (2008, 2010).22,25 It is important to note that in the study by Anitua and co-workers, the sample size was low and only patients requiring single implants were included.24 Additionally, the implants were covered in plasma-rich growth factors (PRGFs) before placement. It has been demonstrated that PRGFs play a role in healing and bone regeneration, and thus this action might have skewed the results. In the two studies by Esposito and co-workers, different surgical approaches and loading times were followed.22,25Interestingly, it was found that immediate implants were more likely to fail regardless of antibiotic use.25

RCT comparing preoperative plus postoperative antibiotics vs no antibiotics (Table 1)
Abu Ta’a et al. (2008) used 1g of amoxicillin one hour preoperatively plus 500mg amoxicillin four times a day for two days postoperatively as their intervention.27 Implant failure was only noted in those participants who did not receive antibiotics (five implants in three participants). One patient smoked more than 40 cigarettes a day and for the other patient a one-stage protocol was used and the patient had parafunctional habits. Postoperative infection was only detected in one participant in the antibiotic group and in four in the control group.

RCTs comparing multiple regimens of antibiotic prophylaxis (Table 1)
Two multicentre RCTs comparing different antibiotic regimens to each other and to no antibiotics showed no significant difference in the incidence of postoperative infection or implant failures.
In the study by Caiazzo et al. (2011), no postoperative infections were noted over follow-up of eight weeks.28 However, the only two implant failures in the study occurred in the no antibiotic group. In the study by Tan et al. (2014), there was no suppuration noted in the no antibiotic group. However, that group had the one and only implant failure in the study.29

Systematic reviews and meta-analyses (Table 2)
The latest systematic review and meta-analysis by Khouly et al. (2019) used the incidence of postoperative infection as the primary outcome rather than implant failure.30 Results showed no statistically significant difference in the incidence of postoperative infection between the control group and the antibiotic group. Furthermore, no statistically significant difference was reported when the authors compared the different antibiotic regimens, which included preoperative only, preoperative and postoperative, and postoperative only, to the control group. Lobos et al. (2015) reported similar findings.31
Another systematic review did not support the routine administration of antibiotic prophylaxis to healthy patients undergoing implant surgery, as the majority of included studies showed no statistical difference in terms of prosthetic failure, implant failure or postoperative infection. The two studies that supported the use of antibiotics were assessed as having a high risk of bias.32
Other systematic reviews and meta-analyses showed that prophylactic antibiotics significantly reduce implant failure33-39 but have no significant effect on the incidence of postoperative infection.33,35-37,39 The numbers needed to treat (NNT) to prevent implant failure in one patient ranged from 25 to 67 across these studies (Table 3). Even though a statistically significant difference was found between the antibiotic and control groups in their meta-analysis, Braun et al. (2019) concluded that routine use of antibiotics is still not warranted and further evidence is needed.38 Sanchez et al. (2018) concluded that a single dose of preoperative antibiotics (SDOAP) is effective at preventing implant failures (risk difference of 1.3%) but was of no significance in preventing postoperative infection.39 They reported that the NNT to prevent one patient from developing postoperative infection using SDOAP was 100.39 They also failed to find a significant benefit from administering postoperative antibiotics (both with preoperative or solely postoperative), which is similar to what was reported later by Romandini et al. (2019).40 The advantage of the complex systematic review and meta-analysis by Lund et al. (2015) was that a sub-analysis of two studies that had reduced clinical heterogeneity was done, which led to the conclusion that antibiotic prophylaxis provided no benefit in uncomplicated surgery.34

Table 2

Discussion
Associating antibiotics directly with implant failure can be misleading, as implant failure is a complex and multifactorial process, in which postoperative infection is one of several causes. Furthermore, a new definition of osseointegration states that “osseointegration is a foreign body reaction where interfacial bone is formed as a defence reaction to shield off the implant from the tissues”.41 A mild response, along with mild inflammation, can be considered normal. However, overactivation of the immune system can increase osteoclastic activity, which will result in bone loss and loosening of the implant. This is usually independent of bacteria and it is reported that bacterial causes of implant loosening account for as little as 1% of operated cases.42 More important factors identified include: smoking; genetic deficiencies; poor clinical handling; corrosion of the implant; residual cement; and, use of certain pharmaceutical products such as selective serotonin reuptake inhibitors (SSRIs) and proton pump inhibitors (PPIs).42,43
Chlorhexidine mouth rinse was a confounding variable in a number of the studies.22-25,27-29 This antimicrobial agent has been shown to be efficacious against a variety of microorganisms including gram-positive and gram-negative bacteria, yeasts, and viruses.44 In addition, it has high substantivity, which enables a prolonged effect. Thus, it is difficult to rule out the influence of chlorhexidine rinse on the results. It is important that future studies consider this and study the effects of antibiotics and chlorhexidine independently of one another.
Overall, it is very difficult to conduct a well-controlled RCT as a large sample size is needed. Most studies that had a pre-calculated sample size failed to reach their target. Furthermore, there are many confounding variables such as smoking status, number of implants placed per patient, location of implants placed, implant placement and loading protocols, which all need to be controlled for. Additionally, there is no consensus regarding which is the most appropriate antibiotic as well as the dose to be used.
It is also important to note that postoperative infections in the published literature were detected clinically as suppuration with or without pain, swelling and fever. It has been suggested that low-grade infections that are not detected clinically can account for some implant failures and so the actual occurrence of infection may be underestimated.36

Conclusion
Based on the best available evidence, routine antibiotic prophylaxis to prevent dental implant infections in healthy patients may not be indicated. Further large, multicentre, double-blinded RCTs are needed. The authors’ advice to clinicians is to consider the local, systemic and procedural risk factors for each patient before deciding to prescribe prophylactic antibiotics.

References

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Mohamed El Azrak

Dr Mohamed El Azrak BA BDentSc

Dr Ioannis Polyzois
Associate Professor/Consultant in Periodontology
Dublin Dental University Hospital

Corresponding author: Dr Mohamed El Azrak E: elazrakm@tcd.ie

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