**3. The use of antibiotics for the treatment of peri-implant infection**

When a dental implant is inserted into the oral cavity, it provides a new and physically different surface for the colonization of microorganisms. The development of this new biofilm is a process strongly resembling biofilm formation on natural teeth [46–51]. The colonization of microorganisms on this new surface has been shown to start within hours after insertion, with a microflora already resident in the oral cavity [52, 53].

Peri-implantitis was initially defined as "a site-specific infection with many features in common with chronic adult periodontitis" [54] and/or as "an inflammatory, bacterial-driven destruction of the implant supporting tissues" [55]. Both definitions imply that bacteria may play a crucial role in the initiation and progression of peri-implantitis. With time varying from months to years, the implant microflora has shown to become more complex if soft tissue inflammation and pocket formation develop around a dental implant (i.e., clinical signs of periimplantitis) [56].

Studies have shown that when comparing clinically healthy peri-implant sites to sites with peri-implantitis, a transition in microflora composition can be seen [57, 58]. A shift from predominantly nonmotile, aerobic, and facultative anaerobic bacteria to a biofilm with a high proportion of gram-negative, motile, anaerobic bacteria has occurred [59, 60]. Moreover, residual teeth (not edentulous or partially edentulous) and clinical condition (periodontally healthy teeth or persisting ongoing periodontitis with residual probing) have been shown to influence the development of the subgingival microflora around dental implants [61, 62]. In partially edentulous patients, the adjacent teeth play a role in the periodontal pathogen colonization [63–65]. Accumulation of a microbial biofilm on the implant surface promotes an inflammatory response in the peri-implant mucosa, resulting in peri-implant mucositis. This is characterized as a reversible inflammation of the soft tissues, with reddening, swelling, and bleeding on probing [66–68]. Persistence of inflammation may result in the loss of peri-implant supporting tissues which is defined as peri-implantitis [42, 54, 55, 68]. Peri-implantitis appears to be associated with a similar microflora as that found in chronic periodontitis such as *Porphyromonas gingivalis, Tannerella forsythia,* and *Aggregatibacter actinomycetemcomitans* [69– 73]*.* However, compared with periodontitis, some bacteria, which are not part of the typical periodontopathic microbiota, have been found in peri-implantitis lesions such as staphylo‐ cocci, enteric rods, and Candida [74, 75].

Peri-implantitis has become a prevalent, notable disease, affecting a substantial number of patients [76]. However, a recent review indicates a wide variation in the incidence and prevalence of peri-implantitis [76]. This variation is most likely due to patient/case selection, diagnostic criteria used, and varying time of follow-up. Tomasi and Derks [76] in a recent review stated that the prevalence of peri-implantitis varies between 8.9 and 47% of implants. In 2012, the EAO Consensus Conference stated that peri-implantitis occurred in one of five patients within 5 years following implant placement [77].

Treatment of peri-implantitis is directed towards removing the biofilm, resolving the inflam‐ mation, and arresting the progression of bone loss. Various protocols have been suggested as a method for achieving this [78]. The primary objective was to alter the microbiota and induce the host immune system to eliminate putative pathogens [79]. Mechanical debridement and disinfection of implant surfaces are directed to remove the oral biofilm and perio-pathogenic microbes to a certain extent [80]. Indeed, the surface characteristics and the screw-shaped configuration of most current implants may influence the resolution of the inflammation in the surrounding tissues [79]. Conventional mechanical therapies currently used in the treatment of periodontitis may therefore be difficult to apply around dental implants [79].

**3. The use of antibiotics for the treatment of peri-implant infection**

a microflora already resident in the oral cavity [52, 53].

cocci, enteric rods, and Candida [74, 75].

patients within 5 years following implant placement [77].

implantitis) [56].

22 Dental Implantology and Biomaterial

When a dental implant is inserted into the oral cavity, it provides a new and physically different surface for the colonization of microorganisms. The development of this new biofilm is a process strongly resembling biofilm formation on natural teeth [46–51]. The colonization of microorganisms on this new surface has been shown to start within hours after insertion, with

Peri-implantitis was initially defined as "a site-specific infection with many features in common with chronic adult periodontitis" [54] and/or as "an inflammatory, bacterial-driven destruction of the implant supporting tissues" [55]. Both definitions imply that bacteria may play a crucial role in the initiation and progression of peri-implantitis. With time varying from months to years, the implant microflora has shown to become more complex if soft tissue inflammation and pocket formation develop around a dental implant (i.e., clinical signs of peri-

Studies have shown that when comparing clinically healthy peri-implant sites to sites with peri-implantitis, a transition in microflora composition can be seen [57, 58]. A shift from predominantly nonmotile, aerobic, and facultative anaerobic bacteria to a biofilm with a high proportion of gram-negative, motile, anaerobic bacteria has occurred [59, 60]. Moreover, residual teeth (not edentulous or partially edentulous) and clinical condition (periodontally healthy teeth or persisting ongoing periodontitis with residual probing) have been shown to influence the development of the subgingival microflora around dental implants [61, 62]. In partially edentulous patients, the adjacent teeth play a role in the periodontal pathogen colonization [63–65]. Accumulation of a microbial biofilm on the implant surface promotes an inflammatory response in the peri-implant mucosa, resulting in peri-implant mucositis. This is characterized as a reversible inflammation of the soft tissues, with reddening, swelling, and bleeding on probing [66–68]. Persistence of inflammation may result in the loss of peri-implant supporting tissues which is defined as peri-implantitis [42, 54, 55, 68]. Peri-implantitis appears to be associated with a similar microflora as that found in chronic periodontitis such as *Porphyromonas gingivalis, Tannerella forsythia,* and *Aggregatibacter actinomycetemcomitans* [69– 73]*.* However, compared with periodontitis, some bacteria, which are not part of the typical periodontopathic microbiota, have been found in peri-implantitis lesions such as staphylo‐

Peri-implantitis has become a prevalent, notable disease, affecting a substantial number of patients [76]. However, a recent review indicates a wide variation in the incidence and prevalence of peri-implantitis [76]. This variation is most likely due to patient/case selection, diagnostic criteria used, and varying time of follow-up. Tomasi and Derks [76] in a recent review stated that the prevalence of peri-implantitis varies between 8.9 and 47% of implants. In 2012, the EAO Consensus Conference stated that peri-implantitis occurred in one of five

Treatment of peri-implantitis is directed towards removing the biofilm, resolving the inflam‐ mation, and arresting the progression of bone loss. Various protocols have been suggested as

It is therefore difficult to treat peri-implantitis, and the outcome may not be predictable [68]. To date, there is no standard protocol for the treatment of peri-implantitis. A nonsurgical treatment alone appears to be insufficient in resolving peri-implantitis lesions and is less successful in arresting disease recurrence in long-term follow-up [68, 81].

Surgical treatment of peri-implantitis allows better access for the removal of granulation tissue and decontamination of exposed implant surfaces [68]. Since the etiology of peri-implantitis is similar to periodontitis, the anti-infective protocol used with periodontitis has been adopted in the treatment of peri-implantitis. In the treatment of aggressive periodontitis, the use of adjunctive systematic antibiotics (amoxicillin and metronidazole) has shown an additional effect. The combination of amoxicillin and metronidazole has the potential to decrease a wide range of oral bacteria usually associated with peri-implantitis [82]. Studies including surgical treatment of peri-implantitis in combination with the use of amoxicillin (500 mg) and metro‐ nidazole (400 mg) for 7 days have shown a 58% success rate for implants with machined surfaces [83, 84]. However, in a majority of prospective clinical studies, the parallel effect of several procedures has been evaluated simultaneously [83–86]. These procedures include access flap procedures as well as reconstructive/regenerative procedures. Regardless of surgical technique, adjunctive treatment of systemically administered antibiotics has been used. Therefore, the knowledge of a single specific intervention, such as the adjunctive use of systematic antibiotic, is still limited [87, 88].

In a recent RCT including 100 patients, surgical treatment of peri-implantitis was performed with or without adjunctive systemic antibiotics [89]. The results of this study showed that the use of adjunctive systematic antibiotics combined with surgical treatment of peri-implantitis had a limited significant effect on implant success. However, there is an increase in the probability of treatment success of implants with a modified surface, but not at implants with a nonmodified/smooth surface [89]. The overall implant treatment success after a 1-year follow-up was 45% [89]. As presented in the scientific literature to date and concluded in a consensus from 2012 at the 8th European Workshop in Periodontology [88], the adjunctive use of systemic antibiotics on treatment outcome is still limited in the treatment of peri-implantitis.
