Case 5
Systemic Antibiotics and Enzyme Suppression Therapy
Medical History
The patient reported that she had been diagnosed with type II diabetes three weeks prior to presenting for dental care. Her physician initiated a regimen of metformin 500 mg twice a day and advised her to return in six weeks for reassessment. Review of the patient’s family medical history revealed that both her mother and her mother’s sister are type II diabetics. The patient does not have a relationship with her father and is unaware of his medical history.
Review of Systems
- Vital signs
- Blood pressure: 126/76 mmHg
- Pulse rate: 73 beats/min
- Respiration: 15 breaths/min
Dental History
The patient reports that she has not seen a dentist in about eight years and that she only sees a dentist when she is in pain. The patient reports brushing twice a day and states that she has never flossed.
Social History
The patient reports that she has smoked a pack of cigarettes per day since age 15 (33 pack years), uses marijuana three times a week, and drinks alcohol occasionally.
Extraoral and Intraoral Examination
There were no significant extraoral findings, no swellings, or masses detected. Limited intraoral examination revealed a fluctuant buccal swelling associated with tooth #19. Periodontal probing of tooth #19 revealed deep probing depths (5–9 mm), a deep Class II (possibly Class III) furcation defect with a 9 mm vertical component. Probing of the buccal furcation region elicited a mixed purulent serosanguinous discharge. Uneven marginal ridges and an open proximal contact between teeth #19 and #20 were noted. Radiographic examination revealed previous endodontic therapy #19 and restoration with a ceramometal crown. Large periapical radiolucencies were associated with both roots of tooth #19 (see Figures 5.5.1 through 5.5.4).
Figure 5.5.1: Radiographs of tooth #19.
Figure 5.5.2: Periodontal abscess #19.
Figure 5.5.3: 9 mm vertical component of defect.
Figure 5.5.4: Horizontal component of defect.
Diagnosis
Periodontal abscess #19, combined periodontic‐endodontic lesion #19 (Armitage 1999).
Treatment Plan
As tooth #19 was deemed to have a poor prognosis, extraction was recommended. The patient did not consent to extraction that day, but did consent to drainage of the infection. After inferior alveolar block anesthesia with one carpule 2% lidocaine with 1 : 100,000 epinephrine, drainage was established through the furcation with combined ultrasonic and curette instrumentation. Antibiotics (amoxicillin 500 mg TID for seven days) were prescribed and the patient was advised to return in one week for extraction of #19 and for a comprehensive oral evaluation. The patient did not return and has been lost to follow up.
Discussion
Periodontitis is a bacterially initiated series of inflammatory processes that result in the destruction of periodontal connective tissue attachment and supporting bone. Traditional therapy focuses on disruption of the subgingival biofilm mass by mechanical methods such as intensive home care, scaling and root planing, and surgical debridement. Biofilm removal is a difficult task and ultimately incomplete. Most patients demonstrate a favorable clinical response, while some subpopulations of patients respond poorly.
Attempts have been made to address the subgingival biofilm mass through the use of systemic antibiotics with the intention of removing the residual biofilm remaining after mechanical therapy. Multiple clinical studies have been performed to evaluate the potential benefits of adjunctive use of systemic antibiotics in the treatment of chronic periodontitis, aggressive periodontitis, and periodontitis unresponsive to conventional therapy, previously referred to as refractory periodontitis (The American Academy of Periodontology 1989). Variations in research methodology, including study design, antibiotics utilized, dosages, and duration of therapy make comparisons between studies difficult. A recent systematic review of the use of systemic antibiotics in periodontics could not establish definitive conclusions or treatment recommendations (Garcia Canas et al. 2015). Individual clinicians will need to decide if and when antibiotic therapy is appropriate. If antibiotics are to be used, scaling and root planing therapy with intense home care education should be provided first to lower the biofilm load (Jorgenson and Slots 2000). Antibiotic use is generally considered during instances of acute infection (abscesses), and possibly in patients with aggressive periodontitis.
Prior to using systemic antibiotics, the clinician has the obligation to consider multiple patient factors (see Table 5.5.1). A comprehensive review of the patient’s history is necessary with regard to allergies, comorbid medical conditions, current medication profile, and scheduled medical tests or procedures. Possible adverse drug reactions (side effects) of the antibiotics should be considered, as well as potential drug interactions with the patient’s other medications. Most antibiotics can cause nausea and diarrhea, with resultant dehydration raising the blood levels of other medications. Indiscriminate antibiotic use may contribute to the development of bacterial resistance to antimicrobials. Patient compliance with the drug regimen and the economic cost should be considered. Finally, as with all medications, one must consider whether the use of the medication is expected to alter the overall clinical outcome of the disease.
Table 5.5.1: Considerations prior to initiating antibiotic therapy.
| Patient’s medical history (allergies, comorbidities) |
| Potential drug interactions with patient’s other medications |
| Side effects of the proposed antibiotic therapy |
| Patient’s compliance with the antibiotic regimen |
| Risk of contributing to the development of bacterial resistance to antibiotics |
| Risk of alterations of the normal flora |
| Will the drug therapy alter the overall clinical outcome of the disease? |
| Economic issues |
Amoxicillin is a broad‐spectrum penicillin that is bactericidal to both gram‐positive and gram‐negative bacteria (see Table 5.5.2). It is well absorbed orally and can be taken irrespective of meals. It is usually dosed at 500 mg every eight hours. As there is a great overuse of penicillin globally, there is potential for both bacterial resistance and allergic responses. It is susceptible to the bacterial enzyme beta‐lactamase, which renders it ineffective. For that reason, a product has been developed that combines amoxicillin with a beta‐lactamase inhibitor called clavulanic acid. The amoxicillin‐clavulanic acid combination is marketed as the product Augmentin with recommended dosage 500 mg every 12 hours (Ciancio and Mariotti 2014).
Table 5.5.2: Antibiotics used to treat periodontal diseases.
| Class | Drug | Dosage |
| Penicillin | Amoxicillin | 500 mg Q8H × 8 days |
| Penicillin + beta‐lactamase inhibitor | Amoxicillin + clavulanic acid | 500 mg Q12H × 8 days |
| Tetracycline | Doxycycline | 100 mg once a day |
| Nitroimidazole | Metronidazole | 500 mg Q8H × 8 days |
| Lincomycin | Clindamycin | 300 mg Q8H ×10 days |
| Fluoroquinolone | Ciprofloxacin | 500 mg Q12H × 8 days |
| Macrolide | Azithromycin | 500 mg once a day for 4–7 days |
| Penicillin/Nitroimidazole Combination Therapy | Amoxicillin+ Metronidazole | 250 mg of each Q8H × 8 days |
Doxycycline is a tetracycline derivative that is bacteriostatic against gram‐positive, gram‐negative, spirochetes, and motile rods. The usual dose is 100 mg daily, but a dose of 100 mg twice a day for the first day and then 100 mg daily is not uncommon. Known side effects are photosensitivity and staining of the developing teeth of fetuses and nursing infants, leading to concerns about use in women of child bearing age (Slots and Ting 2002; Ciancio and Mariotti 2014).
Metronidazole is a nitroimidizole compound that is bactericidal to anaerobes, including spirochetes. It has been used to treat patients with necrotizing ulcerative gingivitis who present with systemic symptoms. It is usually dosed at 500 mg every eight hours. To increase its effectiveness against Aggregatibacter actinomycetemcomitans, it may be combined with amoxicillin at a dose of 250–500 mg of both agents every eight hours (Jorgenson and Slots 2000; Slots and Ting 2002). It has the unique side effect of a disulfiram reaction, in that it may induce severe vomiting when used with alcohol (See Table 5.5.3).
Table 5.5.3: Unique adverse drug reactions (ADRs) of antibiotics.
| Drug | ADR |
| Tetracyclines | Photosensitivity, staining of developing teeth of children and fetuses |
| Clindamycin | Pseudomembranous enterocolitis |
| Fluoroquinolones | Photosensitivity |
| Metronidazole | Disulfiram type reaction (severe vomiting when used with alcohol) |
Clindamycin is a lincomycin derivative commonly used in patients with allergies to penicillin. It is bacteriostatic against anaerobes. A common dosage when used in periodontics is 300 mg every eight hours. A potentially fatal side effect of pseudomembranous colitis due to the overgrowth of Clostridium difficile is associated with clindamycin, although the condition may also occur with the use of other antibiotics (Jorgenson and Slots 2000). Clindamycin should not be used in patients with colitis.
Ciprofloxacin is a fluoroquinolone antibiotic effective against anaerobes. It is the only product effective against all strains of A. actinomycetemcomitans. Its usual dose when used in periodontics is 500 mg every 12 hours (Ciancio and Mariotti 2014). It may cause photosensitivity.
Azithromycin is a macrolide effective against anaerobes and gram‐negative bacilli. The usual dose is 500 mg once a day (Ciancio and Mariotti 2014).
While systemic antibiotics are used with the intent of altering the subgingival biofilm mass, a reduced dose of the tetracycline derivative doxycycline, referred to as subantimicrobial dose doxycycline (SDD), is used with the intent of modifying the patient’s host response to the biofilm challenge (see Table 5.5.4). Doxycycline is an effective inhibitor of the matrix metalloprotease enzymes (MMPs) that are responsible for the degradation of collagen, which leads the loss of periodontal connective tissue attachment and bone loss. At a dose of 20 mg twice a day, subantimicrobial dose doxycycline has demonstrated statistically significant and some minor clinically significant effects on periodontal probing depths and clinical attachment levels in selected patients with generalized severe chronic periodontitis (Caton et al. 2000). Less impressive effects are seen in patients with mild or moderate chronic periodontitis. The effects on probing depths and clinical attachment levels were not to the extent that would alter clinical decision making. Available as the prescription product Periostat, it is meant to be used for a minimum of 90 days.
Table 5.5.4: Features of subantimicrobial dose doxycycline (SDD).
| Does not have antimicrobial properties |
| Lowers matrix metalloprotease (MMP) levels |
| Long‐term use does not lead to changes in antimicrobial susceptibility |
| Long‐term use exerts no antibacterial effect on the subgingival microflora |
| Long‐term use has no effect on the microflora of the GI tract, the GU tract, or the skin |
At the recommended dose of 20 mg twice a day, doxycycline demonstrates no antimicrobial properties, and as such does not lead to any changes in the normal flora of the oral cavity, gastrointestinal tract, genitourinary tract, or skin. It does not lead to changes in bacterial sensitivity or resistance to tetracyclines. Since it is tetracycline derivative, there are concerns about its use in women of child bearing age due to its potential for staining of teeth in developing fetuses or nursing infants. It may cause photosensitivity.
Take‐Home Hints
- Prior to considering prescribing any medication, the responsible clinician would have reviewed the patient’s medical history and would be aware of the potential for an adverse drug reaction (including allergic reaction) or drug interaction. Clindamycin is from the lincomycin class of drugs. Doxycycline is from the tetracycline class of drugs. Metronidazole is from the nitroimidazole class of drugs. Amoxicillin is from the penicillin class of drugs and should be avoided in a patient with known allergy to penicillin.
- Most periodontal conditions are effectively treated without the use of systemic antimicrobials. Generalized mild chronic periodontitis is treated with a combination of home care education and scaling and root planing. Medication associated gingival overgrowth is treated with a combination of home care education, scaling (or scaling and root planing if attachment loss is present), and possible periodontal surgery. Consultation with the patient’s physician, with a possible change in drug therapy, may be appropriate. Herpetic gingivostomatitis is self‐limiting and is usually treated with palliative care and occasional antivirals. A periodontal abscess is usually treated with definitive care: extraction if the tooth is nonmaintainable, or drainage of the infection. In those cases where definitive care is not possible or if the patient presents with uncontrolled risk factors (diabetes, smoking, immunosuppression, etc.) use of an antimicrobial may be appropriate.
- The concept behind the use of subantimicrobial dose doxycycline is that the product can block the matrix metalloprotease enzyme collagenase without antimicrobial effects. Doxycycline at a dose of 20 mg twice a day demonstrates no antimicrobial properties. At doses of 50 mg or greater, doxycycline acts as an antimicrobial.
- Even with long‐term use, a subantimicrobial dose of doxycycline does not contribute to bacterial resistance as the product does not have any antimicrobial properties. Doxycycline is from the tetracycline class of medications and should not be used in patient allergic to tetracycline. The mechanism of action of low dose doxycycline is the inhibition of the matrix metalloprotease enzyme collagenase, not the reduction of Streptococcus mutans. There are concerns about the use of the product in women of child bearing age because tetracyclines are known to cause staining of the teeth of a developing fetus.
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