It’s difficult for me to recall but I believe that the first half of the lecture this morning (8/14/17) focused on periodontitis and the microbiology behind it and the second part dealt with antibiotics used to treat periodontitis. It is prudent that we first have a fundamental understanding of the microbiology associated with oral pathology if we have any hope of treating these diseases with antibiotics. Therefore, this paper will be split into two parts. The first will establish an understanding of the microbes associated with the oral cavity and the second will be a brief discussion of the proper antibiotics used to treat these diseases. It should go without saying that this topic can not be covered with any type of justice in a mere 500-600 word essay. So in the event that I am required to write additional essays for my two days of ‘excused’ absences, perhaps this paper will suffice.
Let us first start by identifying beneficial species of oral bacteria and how they contribute to periodontal health. Beneficial bacteria can help prevent the growth of pathogenic bacteria by passively occupying a niche, limiting adhesion of pathogenic bacteria, affecting the vitality and/or growth of pathogenic bacteria, affecting the ability of bacteria to produce virulence factors or actively degrading the virulence factors produced by bacteria. A classic example of a beneficial bacteria is S. Sanguinis which produces hydrogen peroxide. Hydrogen peroxide kills the virulent bacteria A. actinomycetemcomitans (AA). (2) Generalizations have been observed when a patient makes a transition from health to periodontitis. Typically, one will observe a shift from gram-positive to gram negative, cocci to rods/spirochetes, nonmotile to motile, facultative anaerobes to obligate anaerobes, and fermenting to proteolytic species. Bacteria that are highly prevalent in periodontally healthy patients are primarily gram-positive facultative species associated with the genera streptococcus and actinomyces. This includes: S. sanguinis, S. mitis, A oris, A. israelii, A. gerencseriae, A. viscosus, A. naeslundii. Some gram-negative species associated with periodontal health include: P. intermedia, F. nucleatum, Spp. Polymorphem, F. periodonticum, Capnocytophaga spp., Neissera spp., Veillonella spp. It is worth noting that a few spirochetes and motile rods may also be present in periodontal health. (1) Even though these bacteria can be found in a healthy periodontal microbiological niche, only a few bacteria have been found to be protective or beneficial to the host. These bacteria include: S. sanguinis, Veillonella parvula and C. ochracea. A study by Socransky et. al. showed that sites with increased attachment gain post therapy had high levels of C. ochracea and S. sanguinis which supports the theory that they are protective to the periodontium. (3)
Let us now move our concentration to pathogenic bacteria. A small group of bacteria have been strongly associated with periodontal disease. This includes AA, T. forsynthia, Treponema denticola and P. gingivalis. Other bacteria mildly associated with periodontal disease are P. intermedia, Prevotella nigrescens, C. rectus, Parvimonas micra, F. nucleatum, Eubacterium nodatum and various spirochetes. The presence of these bacteria alone do not guarantee periodontal disease, instead, the number of these bacteria have to reach a critical mass to initiate the pathogenic process. (1)
Experimental gingivitis has been extensively studied by Loe et. al. They first established periodontal heath through rigorous oral hygiene measures. They then abstained from oral hygiene for 21 days. They found that after the first hour and through the next 24 hours the concentration of bacteria on the tooth surface will increase exponentially followed by clinically visible plaque 36 hours later. The initial colonizers are gram-positive rods/cocci and gram-negative cocci. When inflammatory changes become present, so does the presence of gram-negative rods and filaments followed by spirochetal and motile microbiota. (4) The subgingival microbiota of plaque-induced gingivitis consists of roughly equal proportions of gram-negative and gram-positive as well as facultative and anaerobic microorganisms. (5) Refer to Table 1. for a complete list of bacteria associated with gingivitis and various forms of periodontitis. Pregnancy-associated gingivitis is associated with an increase in P. intermedia and C. rectus which use the increased levels of steroid hormone in the crevicular fluid as growth factors. (6) Gingivitis is not just a mere result of increased levels of plaque but rather caused by selective alterations in the microbiological composition of plaque. Finally, gingivitis does not always proceed periodontitis. (1)
Several studies on chronic periodontitis have found two models of attachment loss; the gradual model and the burst model. These models have reviled the fact that some sites progress while others improve and this continues in a cyclical pattern. (7) Examination of the microbiology associated with chronic periodontitis has consistently shown elevated proportions of spirochetes. They have also found that most bacteria are anaerobic gram-negative. Some studies have also found a correlation between viral microorganisms of the herpesvirus group and chronic periodontitis. Most notably Epstein Barr Virus-1 and human Cytomegalovirus. (8) This suggests that viruses may contribute to periodontal infections but the role of viruses requires more investigation. (1)
Localized aggressive periodontitis (LAP) is characterized by rapid and severe attachment loss that occurs during or before puberty. Often found in females and/or individuals with immunological defects. Symptoms of LAP can often be detected in primary dentition around canines and second molars. The microbiota associated with LAP is composed of gram-negative, capnophilic, anaerobic rods. The main offender being AA. (9) A clone of A.A. with high leukotoxin is uniquely associated with aggressive forms of periodontitis. Also, P. gingivalis and AA are known to invade host tissue cells, which may be significant in aggressive forms of periodontitis. This why mechanical debridement alone is not enough to control LAP but requires adjunctive antibiotic therapy. (1)
Necrotizing periodontal diseases (NPD) present with acute inflammation of the gingival/ periodontal tissue and necrosis of the marginal gingiva/interdental papillae. Often associated with stress or HIV. Clinically, signs of malodor, lymphadenopathy, fever and malaise can be seen. Microbiological studies have shown that the main offenders are P. intermedia, spirochetes and F. nucleatum. Spirochetes can penetrate necrotic tissue and unaffected connective tissue which supports the need for adjunctive antibiotic therapy. (10)(1)
Periodontal abscesses are acute lesions that result in rapid destruction of the periodontal tissues. Often, they occur in patients with untreated periodontitis but may also occur in the absence of periodontitis when there is an impacted foreign objects or endodontic pathology. Periodontal abscesses may appear clinically with pain, swelling, suppuration, BOP and tooth mobility. If the abscess has become systemically involved, signs of cervical lymphadenopathy and elevated WBC count may be observed. (11) Studies have found elevated levels of F. nucleatum, P. intermedia, P. gingivalis, P. micra and T. forsynthia in periodontal abscesses. (1) If the abscess is secondary to an endodontic infection then streptococcus spp. is also usually detected. (12)
Now that we have a fundamental grasp on the microbiology associated with the various forms of periodontitis, gingivitis and periodontal abscesses, we can begin discussing ‘adjunctive’ antibiotic therapy to assist in the treatment of these pathologies. I stress the word ‘adjunctive’ because studies have shown that when bacteria become arranged in biofilms, antibiotic strength up to 500x greater than the usual therapeutic dose is required to be effective. (1) Therefore, antibiotics should only be used alongside mechanical therapy and/or incision & drainage (I&D) and/or extraction. Antibiotics have no place as a stand alone therapy for oral pathology. This is a fundamental concept commonly forgotten in the dental community.
Let’s first discuss systemic antibiotics used for periodontal therapy. Tetracyclines, Metronidazole, Penicillins, Cephalosporins, Clindamycin, Ciprofloxacin, and Macrolides are the common antibiotics known to the dental community. Most of these antibiotics are administered orally with the understanding that they carried to the gingival crevicular fluid (GCF). Systemic antibiotics should be reserved for cases of aggressive periodontitis, NUG and NPD because as I described earlier, these diseases are associated with bacteria that can invade periodontal tissue rendering mechanical therapy alone ineffective.
In order to utilized antibiotics effectively, the causative microorganisms must be identified. Once identified, antibiotic-sensitivity testing should be done in order to select the most effective therapy. This however, is easier said than done because it is difficult to differentiate between the etiological agents and microorganisms associated with various periodontal disorders. (13) Even if one does identify the virulent microorganisms, selecting the appropriate antibiotic can prove to be difficult as there is currently nothing on the market that eliminates all known periodontal pathogens. This is why combination therapy is often necessary. (1)
Tetracycline (including Minocycline and Doxycycline) has been widely used for the treatment of LAP. This is because it is very effective against A.A. This category of antibiotics has also been shown to inhibit matrix metalloproteinases and reactive oxygen species. (14) These byproducts of the inflammatory process are responsible for bone resorption and inhibition of them can prove useful in the battle against periodontal disease. Due to the detrimental side effects of tetracyclines (teeth staining, GI upset, photosensitivity, etc.) and increased resistance, they are not widely used anymore and have been replaced with more effective combination antibiotics like amoxicillin-clavulanic acid/metronidazole. (1)
Metronidazole is used clinically to treat gingivitis, NUG, NPD, and chronic periodontitis. I should reiterate from the previous paragraph that metronidazole is not effective against AA infections alone and must be used in combination therapy. It is however effective against P. gingivalis and P. intermedia. The major side effect associated with this antibiotic comes when it is consumed with alcohol. It also has the ability to decrease anticoagulant therapy and should not be used on patients taking blood thinners. (1)(15)
Penicillins are a widely used antibiotic for the treatment of dental infection but it has not been proven to increase periodontal attachment levels. Therefore, they are not used as adjunctive therapy for the treatment of periodontitis. Amoxicillin (or Augmentin) has a broader spectrum of action and, as previously described, can be used in combination therapy with metronidazole for the management of aggressive periodontitis. Must be careful not to use on patients who are allergic to this drug emphasizing the importance of a through medical history. (1)
Cephalosporins are in the same family as penicillins but are not typically used to treat infections related to dentistry. This is because penicillins are much more effective against oral pathogens and should therefore be selected for treatment over cephalosporins. (13)
Ciprofloxin is the only antibiotic that is effective against all strains of AA. It is also effective against gram-negative rods and anaerobes. The best thing about this antibiotic is that it does not really effect beneficial microorganisms associated with the oral cavity which means it has the ability to promote a healthy oral microflora. (1)
Clindamycin is commonly used as an alternative antibiotic in patients who are allergic to penicillin. It is effective against anaerobic bacteria and has been shown to be useful against patients with periodontitis that is unresponsive to tetracycline therapy. This antibiotic is notorious for causing pseudomembranous colitis (I have had personal experience with a family member) and must be used with caution. (13)
Macrolides like erythromycin do not concentrate in the GCF and are not used to treat periodontal diseases. Azithromycin has however been shown to increase attachment levels when used as an adjunctive therapy for periodontal disease. (16) Carranza maintains that more studies need to be done to support the efficacy of azithromycin for the treatment of periodontal disease. (1)
Many of these systemic antibiotics have been packaged in vesicles intended for the local delivery. This includes Atridox (doxycycline), Arestin (minocycline), and Actisite (tetracycline). PerioChip (chlorohexidine) is also used but does not fall under the category of antibiotic. The idea behind this is to increase the concentration of antibiotics directly at the site where it is most needed. Every single one of these local delivery methods has research supporting their efficacy in the treatment of periodontal disease with respect to restoring clinical attachment. (17) However, they are only shown to be effective when used alongside SRP therapy. (1)
To crudely summarize, an effective clinician is only effective when he/she knows thy enemy. One must fully understand the microflora of the oral cavity associated with health and disease. They must also have a complete understanding of their arsenal so as to know which weapons are effective against which enemy. Furthermore, they must also have a full understanding of their patients, their patient’s history and the clinical outcome that can reasonably be expected as a result of treatment. Only then can an educated decision be made as to how they are to proceed with treatment in a way that will give the most predictable and successful outcome.