Headlines
The microbiota in the oral cavity has the potential to act as a reservoir for antibiotic resistance genes.
The use of systemic antibiotics in the treatment of periodontal and peri-implant disease may thus be harmful for the ecosystems of the individual and its surroundings.
Considering the questionable positive and limited long-term effect in periodontal treatment, the use of systemic antibiotics should be restricted to aggressive periodontitis and/or unresponsive cases of advanced periodontitis.
Microbiological analysis including susceptibility testing are recommended in cases where antibiotics are considered as an adjunct to systematic periodontal treatment.«
The scientific evidence on the use of systemic antibiotics as an adjunctive treatment for peri-implantitis is scarce with no proven effective treatment protocol.
This article will discuss the updated rationale for the supplementary use of systemic antibiotics (antibiotics administered per os) in periodontal and peri-implant infections in the light of the recent global antibiotic resistance threat. As a consequence, different aspects of clinical and microbiological considerations including relevant groups of antibiotics and their antimicrobial resistance, will be discussed. Aggressive and chronic periodontitis which comprise heterogeneous constellations of destructive periodontal disease, are included in the periodontitis section (). The reader should be aware of the recently modified classification of periodontal diseases () where the two principal forms above have been put into the diagnosis «Periodontitis» (reclassified based on stages and grading). With the diverse clinical picture of periodontitis, the clinician will with either classification have to carefully evaluate each patient and decide an individual treatment plan. The general rule for adjunctive antibiotics must be restrictive, and the knowledge about the antibiotic resistance profile from microbiological testing is an important tool for a good treatment decision.
History of systemic antibiotics in periodontology
The basic approach for treatment of plaque-induced periodontitis has been established as anti-infective therapy; without the use of antibiotics Long-term clinical studies have documented that infection control by mechanical periodontal treatment can be maintained with regular supportive care for most patients. The cornerstones in the maintenance are to monitor the quality of the patient's oral hygiene, the clinical symptoms (bleeding on probing (BOP) and pocket probing depths (PPD) and X-ray information on a regular basis Furthermore, periodontal therapy are dependent on skilled clinicians (dentists and dental hygients) who are able to diagnose and treat according to accepted guidelines ().
Systemically administered antibiotics in this field was introduced in 1976 or even earlier when metronidazole was used for targeting anaerobic bacteria in dental infections (). Tetracyclines were also tested experimentally (-) and used in cases of «juvenile periodontitis» (), before amoxicillin or the combination of amoxicilin and metronidazole were shown to improve the treatment results Later, studies by Loesche and coworkers showed a clinical benefit of metronidazole, used in addition to scaling and root planing (SRP), which seemed to reduce the need for periodontal surgery
At the same time, Slots and coworkers reported on advanced cases of periodontitis where the treatment did not halt the periodontal breakdown. Such cases assigned as «refractory» or «therapy-resistant» may have originated from periodontal disease originally diagnosed as «chronic periodontitis». According to Armitage (), «refractory periodontitis» could be a heterogenous group including multiple forms of nonresponsive periodontitis
The observations of the periodontal microbiota «superinfected» with non-oral Gram negative facultative rods (Escherichia coli, Klebsiella pneumoniae, Serratia spp. Pseudomonas spp), yeasts, and even Staphylococcus aureus, often corresponded with these non-responsive cases. In vitro antibiotic resistance profiles to several antibiotics could also be detected as typical characteristics reflecting that the periodontal microbiota could be a reservoir of bacterial resistance. More than 20 years later, data from microbiological samples of untreated periodontitis patients show a high prevalence of antibiotic resistance in the microbiota, supporting its role as a reservoir of antibiotic resistance genes
Periodontitis
Aggressive periodontitis and chronic periodontitis
In the classification from 1999 «juvenile periodontitis» was placed in the aggressive periodontitis group () due to characteristics with early onset and rapid attachment loss. Treatment of these cases have for many years been accepted as a challenge for the clinician. If treatment is to succeed tooth loss should be limited as much as possible and be intensive and careful with the clinician's knowledge of etiology, pathogenesis, microbiology and clinical features. Patients included in these categories are those who may benefit from the use of systemic antibiotics as a supplement to conventional periodontal treatment However, antibiotics should only be prescribed to patients with severe periodontal breakdown in order to treat the patients individually and reduce antibiotic use to the minimum.
Localized and generalized aggressive periodontitis have several common clinical characteristics, including a 3 - 4 fold higher speed of progression/destruction rate compared to chronic periodontitis Periods of progression are followed by periods of regression (). The treatment should always include an initial periodontal therapy phase, a second phase that may include the use of antibiotics together with SRP or SRP plus periodontal surgery, with a carefully planned supportive therapy (maintenance) in all cases. Since the biofilm is 100 - 1000 times more resistant to antibiotics than planktonic bacterial cells the biofilm must be broken mechanically to make the antibiotics sufficiently effective in reaching the target.
The rationale for the use of antibiotics is that pathogens after mechanical debridement persist in the periodontal tissue, in furcation involvements, root concavities or dentin tubules and may recolonize as the basis for recurrent disease. The presence of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis in the microbiota in patients with aggressive periodontitis may have increased indication for the use of supplementary antibiotics due to their ability to invade host tissue cells (epithelial and connective tissue cells If antibiotics are to be prescribed, it should be administered during a short period of disease activity/progression, and considered only for patients with sufficient oral hygiene (plaque index not exceeding 15 %) after initial treatment. These criteria for antibiotics should be met: Presence of several probable pockets of? 6mm (at least 2 sites in patients with localized aggressive periodontitis), persistent inflammation registered as BOP and/or suppuration, increased loss of attachment, verified progression of bone loss on radiographs and an unfavorable subgingival microbiota (). Thus, the adjunctive use of antibiotics in patients with aggressive periodontitis has become part of the national antibiotic guidelines in several countries due to the reported effect of systemic antibiotic therapy with a mean difference in PPD and CAL of 1.05 mm and 1.08 mm 6-month post-treatment, respectively
If antibiotics are considered in the treatment of periodontits, it should always be administered as a supplement to conventional therapy
Many studies with variable observation periods and results have during the last twenty years been performed to evaluate the effect of adjunctive systemic antibiotics as part of the initial treatment of chronic periodontitis. Several treatment schemes have been used followed by discussions and arguments of pro et contra of how to implement these drugs with the best effect, and several types of antibiotics have also been tested. Most prevalent is the combination of amoxicillin and metronidazole ().
According to a meta-analysis from 2003 analyzing 29 studies, the authors () concluded that systemic antibiotics had a statistically significant positive effect on clinical attachment loss with the greatest effect in patients with aggressive periodontitis compared to those with chronic periodontitis. This study, other systematic reviews and meta-analyses of non-surgical periodontal therapy supplemented with systemic antibiotics in patients with untreated chronic periodontitis () indicate only a minimal clinical measurable effect in previously untreated patients. In earlier studies, patients with chronic periodontitis responded well to mechanical debridement when the oral hygiene was sufficient, and the disease was diagnosed in time Recent studies support that there was no significant long-term effect after 5 years on PPD, CAL or tooth loss when metronidazole was used alone as a supplement to SRP
Peri-implantitis
The inflammatory process, potentially leading to destruction of the supportive bone around osseointegrated dental implants, is also related to formation of oral biofilms on inert implant surfaces (). Therefore, a personalized oral hygiene protocol and controlled maintenance care intervals after implantation are crucial in the primary prevention of peri-implant diseases The wide variation in prevalence of peri-implantitis in several reports may be explained by different criteria for the amount of alveolar bone loss defined as pathological and for the follow-up time of implants in function. Since there is an increasing trend to use dental implants to replace missing teeth instead of conventional prosthodontic reconstructions, there will be a continuous need for efficient treatment options for peri-implant diseases, especially peri-implantitis. It has been estimated that more than 12 million implants are placed globally every year (). At patient level, a meta-analysis presented weighted mean values of 42.9 % for peri-implant mucositis and of 21.7 % for peri-implantitis (). In Sweden, it was recently shown that during a time period of nine years, 14.5 % of the patients treated with dental implants developed a moderate to severe form of peri-implantitis ().
Periodontitis versus peri-implantitis - similar or different?
Periodontitis and peri-implantitis are both infections linked to the formation of biofilms located at the gingival margin where the subgingival/submucosal sites of an affected tooth/implant have similar major risk factors, such as poor oral hygiene, smoking, and diabetes Periodontitis per se forms an increased risk for peri-implantitis One drastic difference is a non-linear, accelerating pattern of bone destruction and its fast progression in peri-implantitis In addition, the type of implant surface seems to have an impact on the susceptibility to develop peri-implantitis and on the resolution of infection
The periodontal pathogens have been considered causative agents also in peri-implantitis due to the potential transmission of pathogenic species from periodontal pockets to peri-implant sites Factors that determine the compostion of the periodontal microbiota are defined by the microbial ecological niche (). Essential for subgingival bacterial growth is the anaerobic conditions, the supply of nutrients from the gingival crevicular fluid, temperature and other factors which favor the composition of the microbiota in that niche.
The microbiota of chronic periodontitis has been characterized by different bacterial complexes that cooperate in the pathogenesis (). The red complex consists of Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola and with the members of the orange complex (a number of other anaerobic, Gram negative species) have been proposed to be responsible for disease progression (figure 1). The established subgingival biofilm in periodontitis is dominated by facultative and strict anaerobic species including Prevotella spp. Fusobacterium spp. Porphyromonas spp.; Treponema spp. and others. Recent studies indicate that Porphyromonas gingivalis represents a «keystone pathogen» which is able to modulate the subgingival biofilm into dysbiosis, thus exerting the whole bacterial community into disfavor of the host A. actinomycetemcomitans associated with local aggressive periodontitis («juvenile periodontitis») may also be detected in other forms of periodontal disease. Thus, the virulence factors of these species represent
