© The authors, 2025

Introduction

Antimicrobial resistance is currently one of the most pressing topics in public health [1,2]. A recent report published in The Lancet estimated that resistant bacterial species contribute to 4.95 million deaths annually, with 1.27 million deaths directly attributable to these infections [3]. Since the early 2000s, the World Health Organization (WHO) has been actively raising awareness about this issue through various campaigns [4] and the development of global guidelines [5]. One of the primary strategies for combating antimicrobial resistance is ensuring the correct administration of antimicrobial medications.

Antibiotic prophylaxis refers to the perioperative administration of antibiotics, typically before surgery, to prevent potential infections at the surgical site or at distant location [6]. This practice differs from antibiotic therapy, which involves prescribing antibiotics to treat an active infection and usually requires a longer course of treatment [7].

Despite extensive research into the use of antibiotics in dentistry, a clear consensus has yet to be reached [8–10]. Current scientific guidelines recommend that antibiotic use in dentistry be restricted to well-defined clinical indications [11,12]. However, in implant dentistry, antibiotics are frequently prescribed, often inappropriately, not only to prevent systemic complications but also to reduce the bacterial load at the implant site [13,14]. Postoperative infection at the implant site is recognized as a potential cause of early implant failure [15]. Other contributing factors include insufficient primary stability, micromovements during healing, excessive surgical trauma, poor bone quality, and unfavourable patient habits such as smoking or inadequate oral hygiene [16–18].

Antibiotic prophylaxis is commonly used to prevent early implant failure resulting from postoperative infections. Although several systematic reviews have addressed this topic, the evidence remains inconclusive regarding its efficacy and optimal administration protocols. While some studies report a reduction in early implant failure rates with prophylactic antibiotic use [19], others find no significant benefit [20]. A recent review further emphasized the lack of definitive evidence concerning the ideal antibiotic type and dosage for prophylaxis in implant dentistry [21].

To help clarify the current evidence, this systematic review aims to assess the efficacy of antibiotic prophylaxis in immunocompetent patients undergoing dental implant surgery. Specifically, it addresses the following research question:

“Is antibiotic prophylaxis administered prior to implant surgery, in comparison with a placebo, effective in preventing early osseointegration complications and failure in immunocompetent patients?”

Material and methods

Protocol

This systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [22].

Before the start of this study, the protocol was registered on PROSPERO (CRD42023427802).

Inclusion and exclusion criteria

The inclusion criteria of this systematic review were organized by the PICOS system:

• (P) Population: patients, partially or totally edentulous, without immunodepression (immunocompetent) or high-risk heart disease for infective endocarditis undergoing dental implant placement treatment.

• (I) Intervention: any type of antibiotics administered pre-operatively (antibiotic prophylaxis) at any dose and for any duration.

• (C) Comparison: placebo.

• (O) Type of outcome measures. Primary outcome: early implant failure (due to lack of osteointegration) within the first 6 months after surgery. Secondary outcome: surgical complications (wound dehiscence, suppuration, fistula formation, and abscesses), patient-reported adverse events (erythema, urticaria, nausea, vomiting, and diarrhea) and pain level. All prosthetic complications were excluded.

• (S) Types of studies: double-blind randomized controlled trials (RCTs) with a maximum follow-up of 6 months in English or French.

Search strategy

The electronic databases PubMed, Scopus, and Web of Science were used for the systematic search of articles. No handsearching or grey literature analysis was performed.

The search process began and was completed on May 18, 2023.

Medical Subject Headings (MeSH) descriptors related to the key concepts, as well as free terms, were used (Tab. I) and search equations designed to each database were developed as follows:

• PubMed: (“Antibiotic Prophylaxis”[Mesh] OR Antibiotic* OR “Antibiotic prophylaxis” OR Antibioprophylaxis OR “Antibiotic premedication” OR Antibiotherap*) AND (“Dental Implants”[Mesh] OR Implantology* OR “Implant surger*” OR “Dental implant*” OR “Implant dental”) AND (“Osseointegration”[Mesh] OR Osseointegration OR Complication* OR Failure* OR Sequel* OR Survival OR Success).

• Scopus: TITLE-ABS-KEY (antibiotic* OR “Antibiotic prophylaxis” OR antibioprophylaxis OR “Antibiotic premedication” OR Antibiotherap) AND TITLE-ABS-KEY (implantology* OR “Implant surger*” OR “Dental implant*” OR “Implant dental*”) AND TITLE-ABS-KEY (complication* OR failure* OR sequel* OR Survival OR Success OR Osseointegration).

• WOS: (((((TS=((Antibiotic* OR “Antibiotic prophylaxis” OR Antibioprophylaxis OR “Antibiotic premedication”OR Antibiotherap*))) AND TS=((Implantology* OR “Implant surger*” OR “Dental implant*” OR “Implant dental*”))) AND TS=((Complication* OR Failure* OR sequel* OR Survival OR Success OR Osseointegration))))).

Study selection

No filters, other than the search equations, were applied in the databases during the article search.

Articles were imported into the bibliographic management software Zotero© (https://www.zotero.org) and duplicates were removed.

Then, using the Rayyan software (https://www.rayyan.ai), a double-blind selection involving two reviewers (JD, SC) was conducted on the titles and abstracts of the collected articles. The final eligibility of the articles selected for this systematic literature review was assessed on the full text, also in a double-blind manner, by the two reviewers. At each stage, articles for which opinions differed were discussed by the two reviewers to reach an agreement.

Data extraction

The data were extracted by two authors independently (JD, SC) and synthesized into tables. In case of disagreement, a discussion was held to reach a final agreement.

Information for data extraction included:

• Lead author, publication year, country;

• Recruitment setting, trial design and follow-up duration;

• External funding;

• Type of antibiotic tested and administration protocol of the antibiotic and the placebo;

• Co-treatments: any additional treatment performed before and after the surgery;

• Number of participants;

• Main results on the evaluated outcomes.

Risk of bias assessment

The quality of the studies was assessed by a single reviewer (JD) using the 'Risk of Bias 2' (RoB 2) tool, developed by the Cochrane Collection [23].

This tool allows for the evaluation of bias risks in RCTs.

Afterall, the studies were classified following three different possibilities: low risk of bias, some concerns and high risk of bias.

No study was excluded based on the risk of bias assessment.

Results

Study selection

The electronic search in the three databases yielded 1,852 results. After removing duplicates, 1,047 articles remained, of which 20 articles were retained after evaluation of titles and abstracts.

Following a second double-blind assessment, based on a full-text review, 13 studies were excluded:

• 3 due to lack of full-text availability, even after contacting the authors;

• 4 of them were not clinical trials (2 literature reviews and 2 editorials);

• 3 of them were clinical trials without a placebo group;

• 1 study had a follow-up duration exceeding 6 months;

• 1 study was a RCT but not double-blinded;

• 1 study compared the effects of antibiotics on bacterial flora rather than on postoperative complications or early failures of implant surgery.

Only one article inspired disagreement between the two reviewers, which was resolved by discussion [24].

Succeeding the study selection process 7 articles were selected [24–30].

The selection process is described in Figure 1.

Fig. 1 PRISMA flow diagram.

Study methods and characteristics

The main characteristics of the 7 included studies are summarized in Table II.

The studies were conducted between 2008 and 2023. Six of the studies were carried out in Europe [25–27,28–30]. The two trials conducted in Italy were made by the same research group led by Esposito et al. [25,27], while the two conducted in Spain were directed by different teams [26,30]. Regarding the other trials, one was done in Sweden [29], one was conducted in Ireland [28] and one was a multicentric international study [24].

The common aim of each of the seven trials was to evaluate the effectiveness of antibiotic prophylaxis before the placement of dental implants to improve clinical outcomes and preventing early postoperative complications.

The patients were selected from both private dental clinics and University hospitals and presented with one or several edentulous areas. Two trials include patients receiving concomitant bone grafting during implant surgery act [26,29].

The exclusion criteria identified in the different studies selected were as follows:

• Heart disease;

• Presence of orthopedic or cardiac prostheses;

• Immunodeficiency;

• Uncontrolled diabetes;

• Patients who had undergone radiotherapy to the head or neck;

• Chronic or acute infection near the implant site;

• Patients already receiving antibiotic treatment for unrelated systemic issues;

• Pregnant patients;

• Patients treated with bisphosphonates;

• Patients with blood coagulation disorders.

In three studies, only one implant was placed per patient [24,26,30], while in the other four studies [25,27,28,29], patients underwent either single or multiple implant placements. In total, the seven trials included 1,846 participants. In all studies, both the antibiotic and placebo groups had an equivalent number of patients.

The antibiotic prophylactic protocols varied between the studies as follows:

• One study compared the administration of 3 grams of amoxicillin 1 h before the procedure to a placebo administered at the same time [28].

• Four studies compared the oral administration of 2 grams of amoxicillin 1 h before the procedure to a placebo [25–27,29].

• One study evaluated four different dosing regimens [24]: the positive control group received 2 grams of amoxicillin orally 1 h before the procedure; test group 1 received 2 grams of amoxicillin immediately postoperatively; test group 2 received 2 grams of amoxicillin 1 h before the procedure, followed by 500 milligrams three times a day for 2-3 days; the control group received 2 grams of placebo 1 h before the procedure.

• One study compared the oral administration of clindamycin (600 mg) in two capsules taken 1 h before the procedure, with two placebo capsules given to the control group [30].

Overall, of the seven trials, six used amoxicillin as the antibiotic, while only one trial evaluated clindamycin.

In three trials, participants received no additional instructions or treatments beyond the antibiotic prophylaxis [24,29,30]. Preceding the surgery, patients underwent professional debridement, only if necessary, and at least one session of oral hygiene training in four trials [25–27,28]. Moreover, prior to implant placement, participants in all studies rinsed with 0.2% chlorhexidine digluconate for 1 min. In three studies, participants were instructed to use chlorhexidine mouthwash for one week postoperatively, rinsing two to three times a day [25,27,28].

Three trials implemented a postoperative pain management protocol, prescribing paracetamol (1g) or ibuprofen (600mg) as needed [26,28,30]. No details were provided by the other trials on this topic.

In one study, implants were treated with plasma rich in growth factors (PRGF) before placement in both groups [26].

In order to evaluate early implant failure, all seven trials assessed implant osseointegration through clinical evaluation, defined by implant mobility or infection necessitating removal. The Ostell™ system was used in two trials to assess implant stability at two months [30] or three months [26]. Two other studies assessed implant stability after four months by tightening the implant abutment to 28 N/cm with a manual wrench [25,27].

None of the trials found a statistically significant difference in implant failure rate between the antibiotic and placebo groups, with all reported p-values > 0.05 (see Tab. III for a summary).

Nolan et al. highlighted that all the implant losses occurred during multiple implant placement surgeries [28]. The same authors identified a correlation between surgery duration and implant success as a potential risk factor [28].

Postoperative complications were assessed one and two weeks after implant placement in two studies [27,29], while one study performed evaluations at 1, 7, 14, 28, and 56 days postoperatively [26]. Three studies performed implant evaluations at two [24], three [28], or both three and six months [29] postoperatively, but in these studies, the details of the evaluation methods were not specified. All trials monitored the complications such as wound dehiscence, suppuration, fistula formation, and abscesses, while patient-reported adverse events included erythema, urticaria, nausea, vomiting, and diarrhea. None of the trials found a statistically significant difference in postoperative complications between the antibiotic and placebo groups, with all reported p-values > 0.05 (see Tab. III for a summary).

Postoperative pain was evaluated using the Visual Analog Scale (VAS) in three studies [24,28,30]. Among these studies, only the one published by Nolan et al. reported a significant reduction in post-surgical pain levels in the antibiotic prophylaxis group compared to the placebo group [28].

Risk of bias within studies

Figure 2 presents the risk of bias assessment for the selected RCTs.

Overall, four studies were found to have a low risk of bias [25–27,30], while three studies raised some concerns [24,28,29]. The domains D3 (Bias due to missing outcome data) and D5 (Bias in the selection of the reported result) exhibited the highest percentage of risk. In contrast, domains D1 (Bias arising from the randomization process) and D4 (Bias in the measurement of the outcome) showed the lowest risk of bias.

Fig. 2 Risk of bias summary.

Discussion

Various antibiotic prophylaxis protocols have been described in the literature, yet no consensus exists on the most effective approach. Amoxicillin is the most widely used antibiotic, with six of the studies included in this review employing it [24,28,29]. Romandini et al. concluded that current evidence is insufficient to recommend a specific dosage [21], while Esposito et al. suggested administering 2–3 g of antibiotics prior to implant surgery under strict aseptic conditions to reduce the risk of implant failure [19].

Only seven studies met the inclusion criteria for this systematic review, and their limited number necessitates a cautious interpretation of the findings. Nonetheless, the consistency in study protocols and follow-up periods (ranging from 2 to 6 months) lends support to the validity of their results. Overall, the synthesized literature in this review does not support the hypothesis that antibiotic prophylaxis is effective in preventing early osseointegration complications or implant failures in immunocompetent patients when compared to a placebo.

To ensure that the findings were representative of a generally healthy population; while maintaining diversity in age, sex, lifestyle, and medical history, we verified the equivalence of sample sizes and participant characteristics across all groups. Notably, some included studies did not exclude smokers, thereby enhancing the generalizability of the findings [31].

The recommendations issued by AFSSAPS in 2011 advise against the use of prophylactic antibiotics prior to implant placement in healthy patients [32]. Similarly, the European Association for Osseointegration (EAO) Consensus Conference in 2015 discouraged the use of prophylactic antibiotics for systemically healthy individuals undergoing implant surgery [33]. More recently, the ITI Consensus Conference recommended the administration of antibiotics only after assessing the patient's overall medical risk [34]. The findings of this systematic review are in agreement with these recommendations.

Furthermore, our conclusions align with those of a 2023 systematic review and meta-analysis that assessed 12 high-quality studies and found that antibiotics do not significantly reduce early postoperative complications [20]. However, unlike the present review, the study by Torof et al. included cases where antibiotics were administered postoperatively and included patients with systemic conditions. Additionally, no restriction was placed on follow-up duration, which accounts for the larger number of studies included. By focusing exclusively on preoperative antibiotic prescriptions in healthy individuals, our review specifically addresses the efficacy of commonly used prophylactic protocols.

In contrast, some literature presents divergent conclusions [35–37]. For instance, Tan et al. concluded in their meta-analysis that 2 g of amoxicillin may reduce early implant failures [35]. However, nine out of the fifteen studies included were assessed as having a high risk of bias, highlighting the need for more rigorous research. Similarly, Roca-Millan et al. supported the use of a single prophylactic dose in healthy patients [36], though only four of their eleven included studies were judged to have a low risk of bias. By contrast, the present review exclusively included double-blind, placebo-controlled trials, leading to a low risk of bias classification in key domains (D1 and D4) for all included studies, as shown in Figure 2.

Despite the lack of supporting evidence, antibiotic prophylaxis remains commonly prescribed in clinical practice, often driven by clinicians' concerns about infections, implant failure, patient discomfort, economic consequences, and the desire to ensure perfect clinical outcomes. However, non-compliance with evidence-based guidelines contributes to the rise of antimicrobial resistance, increased healthcare costs, and the risk of adverse effects associated with antibiotic therapy [3]. Postoperative antibiotic administration, in particular, does not appear to be justified [21].

Interestingly, the number of implants placed simultaneously may be a risk factor for early implant failure. One study found that all patients with implant failures had received multiple implants during a single surgery [28]. This study also identified a correlation between longer surgical duration and increased risk of failure and complications; all failures occurred in procedures exceeding 1 h [28]. Conversely, Anitua et al., who limited their analysis to single-implant placements, found no significant association between procedure time and implant failure [26].

Clean surgical techniques and clinician expertise remain critical for implant success. Recent studies suggest that routine clean protocols may be sufficient to ensure favourable outcomes, and strict aseptic conditions may not significantly improve success rates in procedures without bone grafting [38].

Limitations of this review include the use of only three electronic databases, which may have limited the comprehensiveness of the search. Additionally, the risk of bias was assessed by a single reviewer; a double-blind risk assessment process would have enhanced the reliability of this evaluation.

Conclusion

The results of this systematic literature review support the non-recommendation of antibiotic prophylaxis in healthy patients before implant surgery. In the context of a global fight against antibiotic resistance, it is essential and urgent to further clarify and guide practitioners' therapeutic decisions.

Indeed, the hypothetical benefits of routine antibiotic prophylaxis before implant surgery do not justify its use in light of the global threat posed by antibiotic resistance.

Funding

This research did not receive any specific funding.

Conflicts of interest

The authors declare that they have no conflict of interest.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Author contribution statement

Dubedout J : Data analysis; Podda G: Data analysis; Fricain JC: Manuscript correction and scientific support; Fénelon M: Manuscript correction and scientific support; Chuy V: Statistical analysis; Catros S: Study planning, data analysis, and supervision.

References

All Tables

All Figures

	Fig. 1 PRISMA flow diagram.
In the text

	Fig. 2 Risk of bias summary.
In the text