The Periodontal Disease Challenge

• An estimated £2.8 billion per annum is spent on periodontal disease treatment in the UK (NHS Stats).
• Periodontitis can result in loss of teeth, which may impact on quality of life. Periodontitis is also associated with systemic disease such as diabetes and cardiovascular diseases.
• Factors to consider in the pathogenesis of periodontitis: Host inflammatory response (hyper inflammatory response, reduced antioxidant defences), biofilm/bacteria (composition move to pathogenic flora, bacterial load) and risk factors e.g. smoking, systemic disease, local risk factors. Essentially antimicrobials target the biofilm.

Antibiotics – The Biology

• Modes of action – may be bactericidal (lyse bacteria e.g. metronidazole, augmentin) or bacteriostatic (stop bacteria dividing e.g. tetracycline). Antibiotics can act on bacteria by inhibiting cell wall synthesis, inhibiting protein synthesis, altering cell membranes, inhibiting nucleic acid synthesis or they may have anti-metabolite activity.
• Challenges – getting antibiotic to the site of infection, achieving a therapeutic dose, maintaining that dose for sufficient time, choosing the correct antibiotic, avoiding resistance, ensuring patient compliance and ensuring appropriate use.
• In the periodontal pocket, the more anaerobic bacteria will be at the base of the pocket and the more aerobic bacteria supragingivally. Bacteria don’t exist on their own – they will be part of a biofilm which is multicellular and complex. This biofilm will need to be disrupted to allow antibiotics to penetrate effectively.
• There has been a steep increase in the use of antibiotics over the last decade. High intensity farming (meat production) contributes to a large part of the problem of resistance but as a health professional who prescribe, we must play our part in appropriate prescribing and minimising the risks of bacterial resistance.

Antibiotics – Don’t abuse

• Before even considering prescribing antibiotics, it is important to minimise bacterial colonisation in other ways e.g. focusing on local risk factors (restorative work – ensure no overhangs/plaque traps, partial dentures – hygienic design, removal of calculus through debridement).
• Antibacterial resistance is on the rise and may create a health catastrophe. The highest rates of resistance are in southern Europe.
• In the mid-late 80s there was an antibiotic discovery void. Before that, many were being produced to work against resistance. The void was largely as a result of the cost required to develop new antibiotics as well as the focus on antiretroviral therapy at the time. We are now essentially playing catch-up.
• Human microbiome is made up of 10K more bacteria than host cells. If there are resistant bacteria in that patient and broad spectrum antibiotics are taken (prescribed/food chain), you select out those resistant bacteria (kill off the other bacteria) and those resistant bacteria then multiply and colonise. Bacteria may also transfer resistance to other bacteria species. Therefore resistance is easily and quickly developed.
• Mechanisms through which bacteria resist antibiotics include: blocked entry, alteration of target molecule, production of inactivation enzymes, pumping of the antibiotic back out of the bacteria and creation of alternative target binding sites.
• An antibiotic resistance cycle develops whereby there is increased antibiotic use (due to reduced effectiveness), this leads to increased resistance, which leads to ineffective treatment and therefore increased healthcare demand, resulting in increased morbidity.

The Use of Systemic antibiotics

• Systemic antibiotics should only be used in specific situations for managing periodontitis. Indications for use – aggressive periodontitis and necrotising periodontal diseases mainly. Very rarely used when patients not responding to treatment (following control of risk factors and excellent patient compliance with oral hygiene), for multiple lateral periodontal abscesses (but need to know cause) and spreading infection/systemic involvement.
• There is a minimum therapeutic concentration of an antibiotic and a maximum toxic concentration – an effective antibiotic dose aims to be between those two i.e. within the therapeutic window. The dosing regime i.e. OD/BDS/TDS/QDS maintain the antibiotic at the correct level.
• Tetracycline
  • Bacteriostatic
  • Doxycycline (200 mg loading dose then 100 mg per day for 3/52), minocycline (100 mg BD)
  • Contraindications – pregnancy, breast feeding, children <8 years, renal impairment, hepatic disease, SLE
  • Drug interactions – pencillin and other antimicrobials, antacids and iron preparations, insulin, digoxin, lithium carbonate, warfarin, carbamazepine and phenytoin, cimetidine
• Metronidazole
  • Bactericidal
  • 200/400 mg TDS for 3 days
  • Drug of choice for necrotising periodontal diseases
  • GCF levels 50% higher than serum
  • Effective against anaerobes
  • Avoid with pregnancy, alcohol and warfarin
• Metronidazole & Amoxicillin (combination therapy)
  • Metronidazole 400 mg TDS, Amoxicillin 500 mg TDS for 5-7 days
  • Good data on this combination (both clinically and at a microbial level
  • Used instead of Augmentin
  • Commonly used for aggressive periodontitis
• Azithromycin 500 mg OD for 3 days is now also used. Compliance is an obvious advantage of this drug. The evidence-base is not as strong as the amoxicillin and metronidazole combination.
• All systemic antibiotics should only be used as an adjunctive therapy, they should be prescribed on the day the debridement has been completed and debridement should ideally be completed in a short space of time. There is not enough evidence to support the use of antibiotics with periodontal surgery (EFP Workshop 2008).
• Systemic antibiotics should not be used for the routine management of chronic periodontitis

The Use of Local antimicrobials

• Local delivery/topical – antibiotics or antimicrobials that are delivered directly to the site of infection thereby limiting the systemic dose.
• Characteristics of an Ideal local delivery system: cost effective, ease of use, active against bacteria associated with periodontal disease, maximal retention in the periodontal pocket, anti-inflammatory, lack of significant side effects, biodegradable and biocompatible, low risk of bacterial resistance, inhibits periodontal breakdown and promotes healing, low systemic absorption, enhances clinical efficacy following nonsurgical therapy. Currently none of the ones available tick all of these boxes.
• Indications – the odd site that hasn’t responded to conventional periodontal treatment on more than one occasion, where the root surface has no detectable deposits, and the patient has good oral hygiene. Only then may the patient be considered for use of a local antimicrobial delivery system. Not used regularly by many periodontists due to the lack of significant clinical benefit.
• Contraindications – first line therapy, used in absence of non-surgical therapy, patient with poor oral hygiene, multiple sites, perio-endo lesions.
• Potential advantages of a local delivery system – reduced systemic dose, high local concentration, reduced systemic side effects, site specific, compliance isn’t an issue, can use agents that can’t be used systemically, super-infection and drug interactions unlikely.
• Disadvantages – expensive, often used inappropriately (relatively few indications).
• Examples of commercially available local delivery systems :
  • Antibiotics – Elyzol, Dentomycin, Atridox
  • Antimicrobials – PerioChip
• Approximate costs:
  • PerioChip (Chlorhexidine) £12.40 per chip
  • Dentomycin and Attridox (Tetracycline) £46 per syringe
  • Elyzol (Metronidazole) £42.50; 2 x 1g applications
• PerioChip
• Chlorhexidine 2.5 mg, biodegradable, gelatine-based
• Antiseptic, no systemic effect and controlled release properties
• Realised by diffusion over the first 24 hours (CHX 1,000ppm) then released over the next 3-10 days by host enzyme breakdown (CHX 100-500 ppm).

Alternate therapies

• PerioStat – 20 mg doxycycline BD, used 3 months systemically, used in a sub antimicrobial form but still as an adjunct mechanical instrumentation Periodontal disease leads to raised collagenase which is implicated in periodontal breakdown – at this dose, doxycycline has been shown to be a collagenase inhibitor. However, this is not used routinely, there may be small benefits but there is a variable response and long-term improvements have not been shown.
• Periowave – uses low dose laser, photodynamic therapy – photoactivator placed in the periodontal pocket, which is then activated by irradiation with a laser. The photosensitiser produced antibacterial molecules. There is currently limited evidence supporting this technique.

Periodontology