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Does the Use of Prophylactic Antibiotics Decrease Implant Failure?
Does the Use of P ro p h y l a c t i c A n t i b i o t i c s D e c re a s e I m p l a n t F a i l u re? Basel Sharaf, DDS, MDa,*, Thomas B. Dodson, DMD, MPHb KEYWORDS Prophylactic antibiotics Implant dentistry Implant failure Dental implants
MATERIAL AND METHODS To answer the question, the authors searched the Medline English language literature with PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL). The authors searched using the following Medical Subject Headings (MeSH): antimicrobial agents, antibiotics or prophylactic antibiotics, and dental implants. All relevant studies published in English through December 2010 were included. Fifty-nine articles met the initial screening criteria. Abstracts from the search query were reviewed. Articles meeting the following criteria were selected: (1) randomized controlled clinical trials, (2) meta-analysis or systematic review. The primary predictor variable was antibiotic therapy, classified as a preoperative dose of antibiotics, preoperative and postoperative antibiotic treatment, and no antibiotics. The primary outcome variable was implant failure. The secondary outcome variable was postoperative infection. Each article was reviewed and data summarized for the following variables: sample size, antibiotic use, implant failure, and postoperative infections. The treatment effect was measured using absolute risk reduction (ARR), which is defined
a Department of Surgery, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo General Hospital, Buffalo, NY, USA b Department of Oral and Maxillofacial Surgery, Center for Applied Clinical Investigation, Harvard School of Dental Medicine and Massachusetts General Hospital, Warren Building-Suite 1201, 55 Fruit Street, Boston, MA 02114, USA * Corresponding author. Department of Surgery, Buffalo General Hospital, 100 High Street Room C381, Buffalo, NY 14203. E-mail address: [email protected]
Oral Maxillofacial Surg Clin N Am 23 (2011) 547–550 doi:10.1016/j.coms.2011.07.008 1042-3699/11/$ – see front matter Ó 2011 Elsevier Inc. All rights reserved.
oralmaxsurgery.theclinics.com
The use of dental implants in oral rehabilitation is widely accepted, with an estimated 1 million dental implants placed annually worldwide.1–5 Despite a high success rate, implant failures do occur. Failure of dental implants can be attributable to implant-related, patient-related, and surgical technique–related factors.5 Bacterial colonization of the implant surface and surgical site infection have been implicated in early implant failure.6 Once an infection ensues at the implant site, eradication of the infection is usually difficult, which may lead to the ultimate removal of the implant.6 For this reason, various antibiotic regimens, including multiday perioperative regimens to a single preoperative dose have been suggested to minimize early infections after dental implant placement. However, the routine use of antibiotics is not without risks. Complications including gastrointestinal symptoms to more serious allergic reactions are not uncommon. In addition, the selection of antibiotic-resistant bacteria is a major public health concern. The purpose of this article is to answer the following question: “In patients receiving dental implants, does the administration of prophylactic antibiotics reduce early implant failure?”
548
Sharaf & Dodson as the absolute difference in failure rates between the intervention and control groups. The number needed to treat (NNT), calculated as the reciprocal of ARR, is defined as the number of implants that must be placed with antibiotic use to prevent 1 implant failure.
RESULTS Five articles were selected for review.7–11 Four studies were randomized controlled trials (RCTs, level of evidence 1b),12 and are summarized in Table 1. One study was a meta-analysis (Cochrane systematic review) of these 4 RCTs (level of evidence 1a).11 The first RCT, by Abu Ta’a and colleagues,7 compared 1 g of amoxicillin given 1 hour preoperatively and 500 mg of amoxicillin 4 times daily given for 2 days postoperatively versus no antibiotics. All patients rinsed with chlorhexidine once before implant placement and twice daily for 7 to 10 days postoperatively. Each group included 40 patients and there were a total of 247 implants inserted. At 5 months follow-up, 5 implants failed in 3 patients who did not receive antibiotics (5 of 119 implants failed; ARR 4.2%). There were no failures in the antibiotic group. Four patients in the untreated group and 1 patient in the antibiotic group developed postoperative infection. The differences were not statistically significant between the 2 groups for any of the outcome measures. Esposito and colleagues,8,9 in 2 consecutive RCTs, compared the effect of 2 g of amoxicillin given 1 hour preoperatively with placebo tablets. All patients received oral hygiene instructions and professional dental debridement 1 week before implant insertion. In addition, all patients rinsed with chlorhexidine preoperatively and twice daily for 7 days postoperatively. In the first study,8 165 patients were included in each group with a total of 696 implants placed. There were 9 implant failures in the control group and 2 implant failures in the antibiotic group (ARR 1.9%). Three patients in the antibiotic group developed infection versus 2 patients in the placebo group. In the second study,9 252 patients were included in the antibiotic group and 254 patients in the control group, with a total of 972 implants placed. Five patients in the antibiotic group experienced 7 implant failures, whereas 12 patients in the placebo group had 13 implant failures (ARR 1.3%). In both studies, there were no statistically significant differences for implant failure or postoperative infection between the 2 groups. Anitua and colleagues10 compared 2 g of amoxicillin given 1 hour preoperatively with placebo tablets. All patients received oral hygiene instructions
and dental prophylaxis a few days before implant placement. Patients rinsed with chlorhexidine before surgery. Only single implants placed in mediumquality bone were included. In addition, implants were treated with autologous plasma rich in growth factors. Fifty-two patients were included in the antibiotic group and 53 patients in the control group. Two patients in each group lost their implants and 6 patients in each group had postoperative infections. There were no statistically significant differences in outcome measured between the 2 groups. A meta-analysis of the 4 RCTs included 1007 patients and a total of 2020 implants.11 There were more implant failures in the control group (not receiving antibiotics), with a statistically significant difference between the 2 groups after pooling the patient groups from the 4 RCTs (risk ratio 0.40, 95% confidence interval [CI] 0.19–0.84). The number of patients needed to be treated with antibiotics to prevent 1 patient from having implant failure was 33 (95% CI 17–100).11 There were no statistically significant differences for the other outcomes, including prosthesis failure, postoperative infection, and adverse events.
DISCUSSION The purpose of this study was to answer the question: Does antibiotic therapy, when given either as a single dose preoperatively or multiday treatment postoperatively, decrease the failure rate of dental implants? To answer this question, the authors used a comprehensive literature review. Three of the 4 individual RCTs showed a trend toward reduction of implant failure when antibiotics were used, although the differences between the groups were not statistically significant. This is consistent with our findings in a previous literature review.13 One RCT included patients with medium-quality bone in whom a single implant was placed in conjunction with plasma rich in growth factors. This study failed to show a difference between the 2 groups. When the 4 RCTs were combined in a meta-analysis, however, a statistically significant reduction in implant failure was observed when patients received 2 g of amoxicillin 1 hour preoperatively or 1 g of amoxicillin administered 1 hour preoperatively and 500 mg 4 times daily for 2 days postoperatively. The number of patients needed to be treated with antibiotics to prevent 1 patient from early implant loss was 33. There were no major adverse effects related to antibiotic use reported in the 4 RCTs. There is paucity of evidence to support the routine use of postoperative antibiotics. This is reflected by 2 prospective studies comparing the effect of preoperative antibiotics versus postoperative antibiotics only.1,4
Table 1 Summary of randomized controlled trials Study
Preop Ab % Failure
5
N/Ab
4 3 4
247 (implants) 80 (patients) 696 (implants) 316 (patients) 105 (implants) 105 (patients) 972 (implants) 506 (patients)
4.2% (5/119 implants) 7.5% (3/40 patients) 2.5% (9/355 implants) 5.1% (8/158 patients) 3.8% (2/53 implants)
Preop & Postop Ab % Failure
ARR
NNT
0% (0/128 implants) 4.2% (implants) 24 (implants) 0% (0/40 patients) 7.5% (patients) 13 (patients) 0.6% (2/341 implants) N/A 1.9% (implants) 52 (implants) 1.3% (2/159 patients) 3.8% (patients) 27 (patients) 3.8% (2/52 implants) N/A N/A N/A
2.7% (13/483 implants) 1.4% (7/489 implants) N/A 4.7% (12/254 patients) 2% (5/252 patients)
1.3% (implants) 76 (implants) 2.7% (patients) 37 (patients)
Abbreviations: Ab, Antibiotics; ARR, absolute risk reduction; NNT, number of implants needed to be placed in conjunction with antibiotics to prevent 1 implant failure. a Percentage failure is the number of failed implants divided by total implants in the group. b Not applicable.
Prophylactic Antibiotics and Implant Placement
Abu-Ta’a et al,7 2008 Esposito et al,8 2008 Anitua et al,10 2009 Esposito et al,9 2010
Follow-up Sample Size No Ab % Period (months) (Implants, Patients) Failurea
549
550
Sharaf & Dodson Dent and colleagues1 demonstrated that when preoperative antibiotics were used, there was 1.5% implant failure compared with a 4.0% failure rate when only postoperative antibiotics were used in an 800-patient study. Laskin and colleagues4 reported higher failure rates (10%) when only postoperative antibiotics were given compared with preoperative antibiotics (4.6%). There are some drawbacks to the RCTs reviewed. The follow-up time varied from 3 months in 1 trial10 and 4 months in 2 trials4,9 to 5 months in 1 trial.3 Decreasing the follow-up period may decrease the number of failed implants and may overestimate the effect of antibiotics on the primary outcome variable: implant failure. Another drawback is the use of bone substitutes and other bone-regenerative procedures at the time of implant placement, which may affect implant healing and failure rates. The use of bone-regenerative procedures was reported in 2 studies.7,10 In addition, the effect of timing of implant placement (delayed or immediately after extraction) may potentially increase implant failure rates. Esposito and colleagues9 demonstrated in a logistic regression analysis that patients in the RCT who received immediate postextraction implants had a 9% failure rate versus 2% in the delayed group, regardless of antibiotic use (P<.001).9
SUMMARY Based on the 4 reviewed RCTs and the metaanalysis, there is evidence that the use of a single preoperative dose of 2 g amoxicillin 1 hour before implant placement or 1 g amoxicillin 1 hour preoperatively and 500 mg 4 times daily for 2 days postoperatively can significantly reduce the rate of early implant failure. To prevent 1 patient from implant failure, 33 patients must be treated with antibiotics. The use of antibiotics has no statistically significant effect on postoperative infections after implant placement. Based on these findings, the authors recommend the following: in otherwise healthy patients who are not allergic to penicillin, a 2 g preoperative dose of amoxicillin, or a 1 g preoperative dose of amoxicillin and 500 mg 4 times daily for 2 days postoperatively is recommended to prevent early implant failure. In clinical settings that diverge from that scenario, the clinician’s own judgment of each individual patient is essential in tailoring antibiotic use to prevent implant infection and failure. A large double-blind, randomized controlled trial comparing the use of a standardized antibiotic regimen (preoperative and/or postoperative) versus placebo is needed to further elucidate the most
efficacious antibiotic regimen in reducing early dental implant failure.13
REFERENCES 1. Dent CD, Olson JW, Farish SE, et al. The influence of preoperative antibiotics on success of endosseous implants up to and including stage II surgery: a study of 2,641 implants. J Oral Maxillofac Surg 1997;55(12 Suppl 5):19–24. 2. Gynther GW, Ko¨ndell PA, Moberg LE, et al. Dental implant installation without antibiotic prophylaxis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85(5):509–11. 3. Binahmed A, Stoykewych A, Peterson L. Single preoperative dose versus long-term prophylactic antibiotic regimens in dental implant surgery. Int J Oral Maxillofac Implants 2005;20(1):115–7. 4. Laskin DM, Dent CD, Morris HF, et al. The influence of preoperative antibiotics on success of endosseous implants at 36 months. Ann Periodontol 2000;5(1):166–74. 5. Pye AD, Lockhart DE, Dawson MP, et al. A review of dental implants and infection. J Hosp Infect 2009; 72:104–10. 6. Esposito M, Hirsch JM, Lekholm U, et al. Biological factors contributing to failures of osseointegrated oral implants. (II) Etiopathogenesis. Eur J Oral Sci 1998;106:721–64. 7. Abu-Ta’a M, Quirynen M, Teughels W, et al. Asepsis during periodontal surgery involving oral implants and the usefulness of peri-operative antibiotics: a prospective, randomized, controlled clinical trial. J Clin Periodontol 2008;35(1):58–63. 8. Esposito M, Cannizzaro G, Bozzoli P, et al. Efficacy of prophylactic antibiotics for dental implants: a multicentre placebo-controlled randomised clinical trial. Eur J Oral Implantol 2008;1:23–31. 9. Esposito M, Cannizzaro G, Bozzoli P, et al. Effectiveness of prophylactic antibiotics at placement of dental implants: a pragmatic multicenter placebocontrolled randomized clinical trial. Eur J Oral Implantol 2010;3(2):135–43. 10. Anitua E, Aguirre JJ, Gorosable A, et al. A multicenter placebo-controlled randomized clinical trial of antibiotic prophylaxis for placement of single dental implants. Eur J Oral Implantol 2009;2:283–92. 11. Esposito M, Worthington HV, Loli V, et al. Interventions for replacing missing teeth: antibiotics at dental implant placement to prevent complications (Review). Cochrane Database Syst Rev 2010;7:CD004152. 12. Center of Evidence Based Medicine. Available at: http://www.cebm.net/levels_of_evidence. Accessed January 27, 2011. 13. Sharaf B, Jandali Rifai M, Dodson TB. Do perioperative antibiotics decrease implant failure? J Oral Maxillofac Surg 2011;69(9):2345–50.
MATERIAL AND METHODS To answer the question, the authors searched the Medline English language literature with PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL). The authors searched using the following Medical Subject Headings (MeSH): antimicrobial agents, antibiotics or prophylactic antibiotics, and dental implants. All relevant studies published in English through December 2010 were included. Fifty-nine articles met the initial screening criteria. Abstracts from the search query were reviewed. Articles meeting the following criteria were selected: (1) randomized controlled clinical trials, (2) meta-analysis or systematic review. The primary predictor variable was antibiotic therapy, classified as a preoperative dose of antibiotics, preoperative and postoperative antibiotic treatment, and no antibiotics. The primary outcome variable was implant failure. The secondary outcome variable was postoperative infection. Each article was reviewed and data summarized for the following variables: sample size, antibiotic use, implant failure, and postoperative infections. The treatment effect was measured using absolute risk reduction (ARR), which is defined
a Department of Surgery, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo General Hospital, Buffalo, NY, USA b Department of Oral and Maxillofacial Surgery, Center for Applied Clinical Investigation, Harvard School of Dental Medicine and Massachusetts General Hospital, Warren Building-Suite 1201, 55 Fruit Street, Boston, MA 02114, USA * Corresponding author. Department of Surgery, Buffalo General Hospital, 100 High Street Room C381, Buffalo, NY 14203. E-mail address: [email protected]
Oral Maxillofacial Surg Clin N Am 23 (2011) 547–550 doi:10.1016/j.coms.2011.07.008 1042-3699/11/$ – see front matter Ó 2011 Elsevier Inc. All rights reserved.
oralmaxsurgery.theclinics.com
The use of dental implants in oral rehabilitation is widely accepted, with an estimated 1 million dental implants placed annually worldwide.1–5 Despite a high success rate, implant failures do occur. Failure of dental implants can be attributable to implant-related, patient-related, and surgical technique–related factors.5 Bacterial colonization of the implant surface and surgical site infection have been implicated in early implant failure.6 Once an infection ensues at the implant site, eradication of the infection is usually difficult, which may lead to the ultimate removal of the implant.6 For this reason, various antibiotic regimens, including multiday perioperative regimens to a single preoperative dose have been suggested to minimize early infections after dental implant placement. However, the routine use of antibiotics is not without risks. Complications including gastrointestinal symptoms to more serious allergic reactions are not uncommon. In addition, the selection of antibiotic-resistant bacteria is a major public health concern. The purpose of this article is to answer the following question: “In patients receiving dental implants, does the administration of prophylactic antibiotics reduce early implant failure?”
548
Sharaf & Dodson as the absolute difference in failure rates between the intervention and control groups. The number needed to treat (NNT), calculated as the reciprocal of ARR, is defined as the number of implants that must be placed with antibiotic use to prevent 1 implant failure.
RESULTS Five articles were selected for review.7–11 Four studies were randomized controlled trials (RCTs, level of evidence 1b),12 and are summarized in Table 1. One study was a meta-analysis (Cochrane systematic review) of these 4 RCTs (level of evidence 1a).11 The first RCT, by Abu Ta’a and colleagues,7 compared 1 g of amoxicillin given 1 hour preoperatively and 500 mg of amoxicillin 4 times daily given for 2 days postoperatively versus no antibiotics. All patients rinsed with chlorhexidine once before implant placement and twice daily for 7 to 10 days postoperatively. Each group included 40 patients and there were a total of 247 implants inserted. At 5 months follow-up, 5 implants failed in 3 patients who did not receive antibiotics (5 of 119 implants failed; ARR 4.2%). There were no failures in the antibiotic group. Four patients in the untreated group and 1 patient in the antibiotic group developed postoperative infection. The differences were not statistically significant between the 2 groups for any of the outcome measures. Esposito and colleagues,8,9 in 2 consecutive RCTs, compared the effect of 2 g of amoxicillin given 1 hour preoperatively with placebo tablets. All patients received oral hygiene instructions and professional dental debridement 1 week before implant insertion. In addition, all patients rinsed with chlorhexidine preoperatively and twice daily for 7 days postoperatively. In the first study,8 165 patients were included in each group with a total of 696 implants placed. There were 9 implant failures in the control group and 2 implant failures in the antibiotic group (ARR 1.9%). Three patients in the antibiotic group developed infection versus 2 patients in the placebo group. In the second study,9 252 patients were included in the antibiotic group and 254 patients in the control group, with a total of 972 implants placed. Five patients in the antibiotic group experienced 7 implant failures, whereas 12 patients in the placebo group had 13 implant failures (ARR 1.3%). In both studies, there were no statistically significant differences for implant failure or postoperative infection between the 2 groups. Anitua and colleagues10 compared 2 g of amoxicillin given 1 hour preoperatively with placebo tablets. All patients received oral hygiene instructions
and dental prophylaxis a few days before implant placement. Patients rinsed with chlorhexidine before surgery. Only single implants placed in mediumquality bone were included. In addition, implants were treated with autologous plasma rich in growth factors. Fifty-two patients were included in the antibiotic group and 53 patients in the control group. Two patients in each group lost their implants and 6 patients in each group had postoperative infections. There were no statistically significant differences in outcome measured between the 2 groups. A meta-analysis of the 4 RCTs included 1007 patients and a total of 2020 implants.11 There were more implant failures in the control group (not receiving antibiotics), with a statistically significant difference between the 2 groups after pooling the patient groups from the 4 RCTs (risk ratio 0.40, 95% confidence interval [CI] 0.19–0.84). The number of patients needed to be treated with antibiotics to prevent 1 patient from having implant failure was 33 (95% CI 17–100).11 There were no statistically significant differences for the other outcomes, including prosthesis failure, postoperative infection, and adverse events.
DISCUSSION The purpose of this study was to answer the question: Does antibiotic therapy, when given either as a single dose preoperatively or multiday treatment postoperatively, decrease the failure rate of dental implants? To answer this question, the authors used a comprehensive literature review. Three of the 4 individual RCTs showed a trend toward reduction of implant failure when antibiotics were used, although the differences between the groups were not statistically significant. This is consistent with our findings in a previous literature review.13 One RCT included patients with medium-quality bone in whom a single implant was placed in conjunction with plasma rich in growth factors. This study failed to show a difference between the 2 groups. When the 4 RCTs were combined in a meta-analysis, however, a statistically significant reduction in implant failure was observed when patients received 2 g of amoxicillin 1 hour preoperatively or 1 g of amoxicillin administered 1 hour preoperatively and 500 mg 4 times daily for 2 days postoperatively. The number of patients needed to be treated with antibiotics to prevent 1 patient from early implant loss was 33. There were no major adverse effects related to antibiotic use reported in the 4 RCTs. There is paucity of evidence to support the routine use of postoperative antibiotics. This is reflected by 2 prospective studies comparing the effect of preoperative antibiotics versus postoperative antibiotics only.1,4
Table 1 Summary of randomized controlled trials Study
Preop Ab % Failure
5
N/Ab
4 3 4
247 (implants) 80 (patients) 696 (implants) 316 (patients) 105 (implants) 105 (patients) 972 (implants) 506 (patients)
4.2% (5/119 implants) 7.5% (3/40 patients) 2.5% (9/355 implants) 5.1% (8/158 patients) 3.8% (2/53 implants)
Preop & Postop Ab % Failure
ARR
NNT
0% (0/128 implants) 4.2% (implants) 24 (implants) 0% (0/40 patients) 7.5% (patients) 13 (patients) 0.6% (2/341 implants) N/A 1.9% (implants) 52 (implants) 1.3% (2/159 patients) 3.8% (patients) 27 (patients) 3.8% (2/52 implants) N/A N/A N/A
2.7% (13/483 implants) 1.4% (7/489 implants) N/A 4.7% (12/254 patients) 2% (5/252 patients)
1.3% (implants) 76 (implants) 2.7% (patients) 37 (patients)
Abbreviations: Ab, Antibiotics; ARR, absolute risk reduction; NNT, number of implants needed to be placed in conjunction with antibiotics to prevent 1 implant failure. a Percentage failure is the number of failed implants divided by total implants in the group. b Not applicable.
Prophylactic Antibiotics and Implant Placement
Abu-Ta’a et al,7 2008 Esposito et al,8 2008 Anitua et al,10 2009 Esposito et al,9 2010
Follow-up Sample Size No Ab % Period (months) (Implants, Patients) Failurea
549
550
Sharaf & Dodson Dent and colleagues1 demonstrated that when preoperative antibiotics were used, there was 1.5% implant failure compared with a 4.0% failure rate when only postoperative antibiotics were used in an 800-patient study. Laskin and colleagues4 reported higher failure rates (10%) when only postoperative antibiotics were given compared with preoperative antibiotics (4.6%). There are some drawbacks to the RCTs reviewed. The follow-up time varied from 3 months in 1 trial10 and 4 months in 2 trials4,9 to 5 months in 1 trial.3 Decreasing the follow-up period may decrease the number of failed implants and may overestimate the effect of antibiotics on the primary outcome variable: implant failure. Another drawback is the use of bone substitutes and other bone-regenerative procedures at the time of implant placement, which may affect implant healing and failure rates. The use of bone-regenerative procedures was reported in 2 studies.7,10 In addition, the effect of timing of implant placement (delayed or immediately after extraction) may potentially increase implant failure rates. Esposito and colleagues9 demonstrated in a logistic regression analysis that patients in the RCT who received immediate postextraction implants had a 9% failure rate versus 2% in the delayed group, regardless of antibiotic use (P<.001).9
SUMMARY Based on the 4 reviewed RCTs and the metaanalysis, there is evidence that the use of a single preoperative dose of 2 g amoxicillin 1 hour before implant placement or 1 g amoxicillin 1 hour preoperatively and 500 mg 4 times daily for 2 days postoperatively can significantly reduce the rate of early implant failure. To prevent 1 patient from implant failure, 33 patients must be treated with antibiotics. The use of antibiotics has no statistically significant effect on postoperative infections after implant placement. Based on these findings, the authors recommend the following: in otherwise healthy patients who are not allergic to penicillin, a 2 g preoperative dose of amoxicillin, or a 1 g preoperative dose of amoxicillin and 500 mg 4 times daily for 2 days postoperatively is recommended to prevent early implant failure. In clinical settings that diverge from that scenario, the clinician’s own judgment of each individual patient is essential in tailoring antibiotic use to prevent implant infection and failure. A large double-blind, randomized controlled trial comparing the use of a standardized antibiotic regimen (preoperative and/or postoperative) versus placebo is needed to further elucidate the most
efficacious antibiotic regimen in reducing early dental implant failure.13
REFERENCES 1. Dent CD, Olson JW, Farish SE, et al. The influence of preoperative antibiotics on success of endosseous implants up to and including stage II surgery: a study of 2,641 implants. J Oral Maxillofac Surg 1997;55(12 Suppl 5):19–24. 2. Gynther GW, Ko¨ndell PA, Moberg LE, et al. Dental implant installation without antibiotic prophylaxis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85(5):509–11. 3. Binahmed A, Stoykewych A, Peterson L. Single preoperative dose versus long-term prophylactic antibiotic regimens in dental implant surgery. Int J Oral Maxillofac Implants 2005;20(1):115–7. 4. Laskin DM, Dent CD, Morris HF, et al. The influence of preoperative antibiotics on success of endosseous implants at 36 months. Ann Periodontol 2000;5(1):166–74. 5. Pye AD, Lockhart DE, Dawson MP, et al. A review of dental implants and infection. J Hosp Infect 2009; 72:104–10. 6. Esposito M, Hirsch JM, Lekholm U, et al. Biological factors contributing to failures of osseointegrated oral implants. (II) Etiopathogenesis. Eur J Oral Sci 1998;106:721–64. 7. Abu-Ta’a M, Quirynen M, Teughels W, et al. Asepsis during periodontal surgery involving oral implants and the usefulness of peri-operative antibiotics: a prospective, randomized, controlled clinical trial. J Clin Periodontol 2008;35(1):58–63. 8. Esposito M, Cannizzaro G, Bozzoli P, et al. Efficacy of prophylactic antibiotics for dental implants: a multicentre placebo-controlled randomised clinical trial. Eur J Oral Implantol 2008;1:23–31. 9. Esposito M, Cannizzaro G, Bozzoli P, et al. Effectiveness of prophylactic antibiotics at placement of dental implants: a pragmatic multicenter placebocontrolled randomized clinical trial. Eur J Oral Implantol 2010;3(2):135–43. 10. Anitua E, Aguirre JJ, Gorosable A, et al. A multicenter placebo-controlled randomized clinical trial of antibiotic prophylaxis for placement of single dental implants. Eur J Oral Implantol 2009;2:283–92. 11. Esposito M, Worthington HV, Loli V, et al. Interventions for replacing missing teeth: antibiotics at dental implant placement to prevent complications (Review). Cochrane Database Syst Rev 2010;7:CD004152. 12. Center of Evidence Based Medicine. Available at: http://www.cebm.net/levels_of_evidence. Accessed January 27, 2011. 13. Sharaf B, Jandali Rifai M, Dodson TB. Do perioperative antibiotics decrease implant failure? J Oral Maxillofac Surg 2011;69(9):2345–50.