A recent study has once again put an allergy to amoxicillin and an increased chance of dental implant failure back into the spotlight. This recent retrospective study reviewed the charts of 838 patients who received dental implants, where 434 patients self-reported having a penicillin allergy and 404 patients did not, with a follow-up of at least a year.1 The patients who stated they did not have an allergy to penicillin were given amoxicillin prior to and after dental implant placement, while those who reported a penicillin allergy were given alternative antibiotics such as clindamycin, azithromycin, ciprofloxacin, or metronidazole.
The overall dental implant failure rate in this study was 12.9%. The failure rate in patients who reported no allergy to penicillin and took amoxicillin was 8.4%, while the failure rate in the allergy-reporting group was 17.1%. The failure rate for patients taking clindamycin was 19.9% and 30.8% for azithromycin. In addition, patients with a self-reported allergy to penicillin were more likely to experience earlier failure of their dental implant (failure at six months or less postplacement).
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These findings echoed the results of a study performed 18 years earlier where 1,925 implants were placed immediately in patients, with an overall failure rate of 3.7%. Patients with a self-reported allergy to penicillin were 3.34 times as likely to experience implant failure and 5.7 times more likely to experience implant failure secondary to infection if prescribed clindamycin rather than penicillin.2 Another similar study found that patients had twice the rate of dental implant failure with a reported allergy to penicillin (.8% no allergy versus 2.1% with allergy) but a 10 times higher failure rate if those implants were immediately placed (1% no allergy versus 10.5% allergy). The conclusion of this study is that a self-reported allergy to penicillin resulted in a higher infection and implant failure rate and primarily affected early/immediate implant placement.3
Is antibiotic coverage needed for dental implant placement?
One meta-analysis analyzing antibiotic coverage to prevent dental implant failure reviewed nine articles and found that only a single dose of preoperative amoxicillin (loading dose of 2 g) was efficacious in preventing implant failures. Antibiotic coverage post-implant placement did not have a statistical difference compared to no antibiotic coverage as it related to dental implant failure.4
Another similar study evaluating 14 studies with a total of 14,872 implants concluded that of the 8,603 implants placed in patients under antibiotic coverage, the failure rate was 3.53% compared with the 6,269 implants placed in patients without antibiotic coverage, which yielded a failure rate of 6.32%.5 Most of this benefit was in the form of antibiotic prophylaxis as the incidence of postoperative infection with or without antibiotic coverage did not yield any statistical differences.
The conclusion of this study, which coincides with the sentiments of multiple studies, was that antibiotic prophylaxis alone in the form of a single loading dose prior to dental implant placement reduced the rate of dental implant failure, but it did not affect postoperative infection rates or failure rates if antibiotic coverage was initiated after implant therapy in routine dental implant procedures.
What are the reasons for a higher dental implant failure rate in patients with penicillin allergies?
Although the exact mechanism behind why dental implants fail at a higher rate in patients with a penicillin allergy has not been pinpointed, there may be a few explanations.
1. There is no association between implant failure rates and penicillin allergy.
Approximately 10%–20% of patients in the United States currently report an allergy or reaction to penicillin; however, these are rarely hypersensitivity or immunoglobulin E (IgE)-mediated reactions, so these drugs could be administered safely.6 In other words, 80%–99% of the patients with a self-reported penicillin allergy were not considered allergic to penicillin after allergy testing.7 With this rationale in mind, most patients in these studies who reported penicillin allergies and had dental implant failure were most likely not allergic to penicillin, thus nullifying the association between implant failure and penicillin allergy.
2. Antibiotic coverage for dental implant placement other than penicillin is suboptimal.
Antibiotics other than penicillin may favor the rise in species that result in dental implant failure, especially clindamycin. Certain Prevotella species in saliva have shown resistance to clindamycin,8 which can be problematic as P. intermedia and P. aeruginosa are often found in implants with peri-implantitis.9
Another in vitro study found that one or more pathogenic species found in implants with peri-implantitis, especially Prevotella intermedia, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans, are resistant to clindamycin at therapeutic concentrations in 47% of cases. In addition, several studies have linked the prescription of antibiotics other than beta-lactams to an increase in methicillin-resistant Staphylococcus aureus (MRSA), and S. aureus has been associated with peri-implantitis. This finding of suboptimal coverage with antibiotics other than penicillin has been replicated in the orthopedic literature, with both hip and knee replacements showing higher failure rates in patients covered with clindamycin and vancomycin due to reported penicillin allergies.10
3. Penicillin allergy may indicate a genetic predisposition toward dental implant failure.
People with penicillin allergies have a potential genetic variant in two human leukocyte antigen (HLA) genes: HLA-B major histocompatibility complex gene and the other in the PTPN22 gene.11 Carriers of this HLA-B*55:01 allele not only have a higher likelihood of having a penicillin allergy but also higher acute and chronic levels of inflammatory disease, which is a risk factor for dental implant failure.12 Current studies are looking into this association to see if it is clinically relevant.
4. Clindamycin negatively influences osseointegration.
In vitro studies have shown that, at high concentrations, clindamycin reduces the activity of alkaline phosphatase and the calcification of the extracellular matrix, which is a sign of altered bone metabolism.13 Another study has shown clindamycin to impair cell mitochondria and have cytotoxic effects on human osteoblasts, which can affect bone metabolism and hence dental implant osseointegration.14 Further studies are needed in this area of research.
Clinical translation and actionable advice
Implant candidates who self-report an allergy to penicillin may benefit from independent allergy testing to ascertain a true allergy to the antibiotic. There are many different types of skin testing and dose challenge tests available that can be used to test potential implant candidates who claim to have a penicillin allergy.15 In addition, there are many different questions to ask during the patient intake exam that can ascertain a true penicillin allergy versus a coincidental confounding penicillin reaction.16
Patients who may be sensitive to penicillin or have gastrointestinal issues associated with multiple-day antibiotic use may benefit from a single loading prophylactic dose prior to implant therapy to reduce the failure rate as opposed to antibiotic coverage for seven to 10 days. The evidence suggests that for routine dental implant placement, most of the antibiotic coverage is in the prophylactic form as a single dose versus a multiday sustained dose. Finally, antibiotic alternatives to clindamycin for patients with true penicillin allergies who are receiving dental implants should be explored as clindamycin appears to have the least effect in lowering dental implant failure rates.
Editor’s note: This article originally appeared in Perio-Implant Advisory, a chairside resource for dentists and hygienists that focuses on periodontal- and implant-related issues. Read more articles and subscribe to the newsletter.
- Bagheri Z, Barrese N, Rubinshtein G, Zahedi D, Malvin NJ, Froum S. Dental implant failure rates in patients with self-reported allergy to penicillin. Clin Implant Dent Relat Res. 2022;1-6. doi:10.1111/cid.13082
- Wagenberg B, Froum SJ. A retrospective study of 1925 consecutively placed immediate implants from 1988 to 2004. Int J Oral Maxillofac Implants. 2006;21(1):71-80.
- French D, Noroozi M, Shariati B, Larjava H. Clinical retrospective study of self-reported penicillin allergy on dental implant failures and infections. Quintessence Int.2016;47(10):861-70. doi:3290/j.qi.a36887
- Sánchez FR, Andrés CR, Arteagoitia I. Which antibiotic regimen prevents implant failure or infection after dental implant surgery? A systematic review and meta-analysis. J Craniomaxillofac Surg. 2018;46(4):722-736. doi:1016/j.jcms.2018.02.004
- Keenan JR, Veitz-Keenan A. Antibiotic prophylaxis for dental implant placement? Evid Based Dent. 2015;16(2):52-53. doi:1038/sj.ebd.6401097
- Inglis JM, Caughey GE, Smith W, Shakib S. Documentation of penicillin adverse drug reactions in electronic health records: inconsistent use of allergy and intolerance labels. Intern Med J.2017;47(11):1292-1297.doi:1111/imj.13558
- Trubiano JA, Thursky KA, Stewardson AJ, et al. Impact of an integrated antibiotic allergy testing program on antimicrobial stewardship: a multicenter evaluation. Clin Infect Dis. 2017;65(1):166-174. doi:1093/cid/cix244
- Rashid MU, Weintraub A, Nord CE. Development of antimicrobial resistance in the normal anaerobic microbiota during one year after administration of clindamycin or ciprofloxacin. 2015;31:72-77. doi:10.1016/j.anaerobe.2014.10.004
- Lafaurie GI, Sabogal MA, Castillo DM, et al. Microbiome and microbial biofilm profiles of peri-implantitis: a systematic review. J Periodontol.2017;88(10:1066-1089. doi:1902/jop.2017.170123
- Tan TL, Springer BD, Ruder JA, Ruffolo MR, Chen AF. Is vancomycin-only prophylaxis for patients with penicillin allergy associated with increased risk of infection after arthroplasty? Clin Orthop Relat Res. 2016;474(7):1601-1606. doi:10.1007/s11999-015-4672-4
- Krebs K, Bovijn J, Zheng N, et al. Genome-wide study identifies association between HLA-B(∗)55:01 and self-reported penicillin allergy. Am J Hum Genet.2020;107(4):612-621. doi:1016/j.ajhg.2020.08.008
- Raslan HM, Attia HR, Salama I, et al. Association of PTPN22 1858C→T polymorphism, HLA-DRB1 shared epitope and autoantibodies with rheumatoid arthritis. Rheumatol Int. 2016;36(8):1167-1175. doi:10.1007/s00296-016-3511-6
- Naal FD, Salzmann GM, von Knoch F, et al. The effects of clindamycin on human osteoblasts in vitro. Arch Orthop Trauma Surg. 2008;128(3):317-323. doi:10.1007/s00402-007-0561-y
- Duewelhenke N, Krut O, Eysel P. Influence on mitochondria and cytotoxicity of different antibiotics administered in high concentrations on primary human osteoblasts and cell lines. Antimicrob Agents Chemother. 2007;51(1):54-63. doi:10.1128/AAC.00729-05
- Penicillin allergy. Diagnosis and treatment. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/penicillin-allergy/diagnosis-treatment/drc-20376226#:~:text=With%20a%20skin%20test%2C%20the,high%20likelihood%20of%20penicillin%20allergy
- Is it really a penicillin allergy? Evaluation and diagnosis of penicillin allergy for healthcare professionals. Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Infectious Diseases. https://www.cdc.gov/antibiotic-use/community/pdfs/penicillin-factsheet.pdf