Comparison Between Two Different Antibiotic Regimens for the Placement of Dental Implants: a Randomized Clinical Trial

Introduction

After the discovery of penicillin as an antimicrobial agent in 1928, and later methicillin, an important improvement of the prognosis of antimicrobial therapies occurred. However, an increased trend in antibiotic resistance among community-acquired pathogens has been observed over the past two decades (1, 2). For example, over a short period of time, S. aureus developed resistance to the β-lactam compounds found in penicillin families, and by 2003, more than 50% of S. aureus isolates recovered in U.S. hospitals were methicillin-resistant Staphylococcus aureus (3). When a resistant bacterium is involved in any clinical infection, the prognosis of the antimicrobial treatment drops significantly and the patient affected might not always survive such infection. As health care professionals, it is important to minimize the exposure of our patients to antibiotics since the emergence of resistance in the oral microflora has started to become a threat in our modern society. This could be explained by the improper use of antibiotics, in terms of either dosage (duration of treatment too long or dose too weak) or indication (4, 5). To support this statement, three studies have shown that low dosage and/or long treatment duration increase the risk of carriage of antibiotic-resistant strains (6-8).

The demand for dental implants has been increasing in the population due to their high success rate and significant improvements in the quality of life. On the other hand, the use of antibiotics is very common in the practice of oral implantology. In order to prevent infections, it has been initially established in the implant placement protocol that pre- and postoperative antibiotics should be prescribed to the patient receiving dental implants 9. There have been many antibiotic regimens used in the attempt to minimize the risks of infections and consequently, increasing the survival rate of dental implants. Initially, it was recommended to give antibiotics at least 1 hour before implant placement followed by daily doses for 10 days (9). Later on, a retrospective study demonstrated that there were no advantages in giving antibiotics 1 hour before implant placement and post-operatively for 10 days regarding the implant survival rates (10). A multicenter retrospective study of 2,973 implants showed a significant higher survival rate in patients who had received preoperative antibiotics (11). The subjects were followed up to 36 months after implant placement. In that study, 96% of cases received post-operative antibiotics and that decision to prescribe antibiotic coverage and the regimen to follow were left to the discretion of the surgeons. Another retrospective study found that there were no significant differences in failure rates between implants placed in patients receiving a 1-day single-dose administration of antibiotic and those placed in patients taking a 1-week post-operative regimen of antibiotics (12). The authors also stated that a single dose of antibiotics to prevent dental implant infections was efficient enough to prevent the risks of the emergence of antimicrobial-resistant bacterial strains. Two recent meta-analyses of 4 randomized clinical trials comparing implants placed in patients who received antibiotics pre- and/or post-operatively showed a statistically significant higher number of patients experiencing implant failures in the group not receiving any antibiotics (13, 14). To illustrate the controversy surrounding antibiotic prophylaxes for dental implant patients, a survey of private dental practices in UK found that there was a wide variation of antibiotic regimens: prophylactic, postoperative, and combination of both pre- and postoperative antibiotics (15). Consequently, in order to prevent the overuse of antibiotics and the potential emergence of drug resistant bacteria, it would be advisable to find an optimal protocol including an antibiotic therapy with a minimal duration while the implant survival rate would remain unchanged.

Very few clinical trials have looked at the patient-based outcomes. Indeed, the patients' pain and discomfort experience has not been taken into account in most of dental implant clinical trials and little is known about its prevalence and intensity after surgery, especially with regard to different antibiotics regimens. Moreover, it was shown that individuals taking postoperative antibiotics exhibited less crestal bone loss 6 months after implant placement when compared to those who did not take any antibiotics postoperatively (16). However, no information is available on the effect of antibiotics on crestal bone loss with the newer design of implants exhibiting the platform switching concept. Crestal bone loss around dental implants was recently associated with higher peri-implant crevicular fluid (PICF) concentration of biomarkers (pg/μL) involved in the bone metabolism such as metalloproteinases (MMPs), and osteoprotegerin (OPG)(17, 18). The membrane bound and soluble RANKL (sRANKL) was found in significantly higher PICF levels in peri-implantitis sites compared to healthy sites (19). To our knowledge, no prospective study in oral implantology comparing two antibiotics regimens has looked at subject-based outcomes, clinical, radiographic and immunological outcomes simultaneously.

Therefore, the aim of this prospective two-arm randomized clinical trial is to compare the crestal bone loss, the PICF concentration of three selected biomarkers for bone loss, pain experience and interference with daily activities, and the postoperative morbidity (swelling, bruising, wound dehiscence and suppuration) between 2 different antibiotics regimens in patients undergoing dental implant surgery.