Azithromycin is a macrolide group of antibiotics with an extended spectrum against Gram -ve organisms than Erythromycin, which makes it suitable for periodontitis management, along with following advantages:
- High patient compliance with medication intake due to simple dosage (see the image below)
- It is bound to plasma proteins and released over 14 days to exert its antimicrobial effects over prolonged period of time despite simple dosage
- The medication is taken up selectively by inflammatory cells (macrophages) which increases the concentration of this drug in the area of infection/inflammation — where it is needed the most.
- It also has an anti-inflammatory effect.
It was very useful especially in patients with amoxicillin allergy or questionable compliance with medication intake.
Recently New England Journal of Medicine, which enjoys highest impact factor in medical literature (above 50 compared to highest impact factor of a dental journal in between 3-4) published a research by Ray and coworkers (NEJM 2012; 366: 1881-90), reporting 47 additiona cardiovascular death per 1 million prescriptions in patients receiving antibiotics as outpatients and 245 additional cardiovascular death in patients with risk of cardiovascular diseases. Apart from some short-falls like inclusion of only out-patients receiving antibiotics, lack of control for treatment of severe infections as an outpatient, determination of cardiovascular death from death certificate, rather than detailed assessment of medical records, this report has showed interesting relationship of antibiotics like Azithromycin and levofloxacillin (fluoroquinolone) with potentially fatal cardiac arrhythmia compared to amoxicillin and ciprofloxacillin. The effect of Azithromycin on cardiac rhythm has previously been reported in the internal studies of pharmaceutical company as well as per the FDA report below.
Subsequent to this publication, US Food and Drug Administration (FDA) has recently released a drug safety communication (dated 12th March, 2013) issued warning against azithromycin as a likely medication that can cause potentially fatal heart rhythms and warned health professionals to consider risk of torasades de pointes (a particular variety of ventricular arrhythmia) and fatal arrhythmia and possibly avoid this medication in patients with:
- known risk of prolonged heart beats (QT interval)
- patients on drugs known to prolong QT interval or receiving anti-arrhythmic agents,
- patients with ongoing proarrhythmic conditions such as low potassium or magnesium in blood or
- clinically significant bradycardia.
The warning specifically mentioned “elderly patients and patients with cardiac disease may be more susceptible…” and think before considering the use of this medication.
Before we address the core question of using this antibiotic for severe periodontitis management, we will review-refresh why or when we should consider antibiotics in management of severe periodontitis.
The use of antibiotics in management of periodontal disease is a complex issue. It is important to consider following factors:
- Should we prescribe the antibiotics routinely when treating patients with severe periodontal disease? What is the need?
- Should it be just a prescription of antibiotics (monotherapy) or used along with systematic periodontal debridement (adjunctive)
- Which antibiotics is found to have a positive effect, when used with debridement (adjunctive)?
- How does Azithromycin compares with other established regime?
What is the need of prescribing antibiotics in periodontal management?
To consider the answer of these questions, we need to look at the pathogenesis of periodontal disease.
It has been well established that plaque is essential for initiation of gingivitis, the progression of gingivitis to periodontitis and its further deterioration (Mild à Moderate à Severe) is related to immune-inflammatory imbalance. In simple words, it is the imbalance with a domination of aggressive host immuno-inflammatory response over reparative capacity or anti-inflammatory response of the body. When this balance is maintained or reparative response dominates, the disease does not progresses further (the periodontal pockets cannot heal without elimination of biofilm by debridement). The immune-inflammatory imbalance in favour of disease progression is driven by:
- Genetics, and also exogenous factors like
- smoking which impairs healing potential
- diabetes and obesity which enhances inflammatory response
- stress which may directly affect immune-inflammatory balance along with worsening of smoking and plaque control
While plaque is necessary for initiating process of periodontal disease, the disease progression is taken over by body’s immuno-inflammatory response (imbalance).
There are some bugs (microorganisms) which are infamous for their destructive potential and may possibly contribute to immune imbalance:
- P. gingivalis,
- T. forsythia,
- T. denticola (all three also known as Red Complex)
- A. actinomycetemcomitans.