Azithromycin vs the sledgehammer

One protocol for the use of adjunctive antibiotics in the treatment of advanced periodontal infections involves the prescription of amoxicillin (500mg) together with metronidazole (500mg) (Gareth et al J Clinical Periodontology 2011 38:43-49 Amoxicillin and metronidazole as an adjunctive treatment in generalized aggressive periodontitis at initial therapy or re-treatment: a randomized controlled clinical trial (pages 43–49).

Azithromycin has both antibiotic capabilities against periodontopathogens AND anti-inflammatory and immuno-modulating properties;  neither amoxicillin, metronidazole nor the combination of the two, have the latter properties.  

The following chart shows the antibiotic dosage of the two antibiotic regimens over the recommended course (3 days for azithromycin vs 7 days for amoxicillin and metronidazole).

As the dosage of azithromycin is approximately 12 times less than amoxicillin + metronidazole and the time patients are exposed to the antibiotic is significantly less (3 vs 7 days) it is my conjecture that the likelihood of  bacterial resistance developing is much higher for the amoxicillin + metronidazole than the azithromycin regimen.

Furthermore, a significant number of people taking amoxicillin + metronidazole have side effects compared with azithromycin.  Compliance is likely to be better with azithromycin (3 tablets vs 42 tablets of amoxicillin + metronidazole ) especially when side effects are common.

Given the efficacy of azithromycin in reducing the signs and symptoms of advanced periodontitis over a long period of time after a single course with a very low incidence of side effects, I can no longer justify using the sledgehammer of amoxicillin + metronidazole in my patients.

Towards an 'azithromycin in periodontal treatment' protocol

As the result of observations of the responses of patients with advanced periodontal problems to azithromycin, I now use the following protocol.  This protocol is being refined as new observations are made over time.  

As a result of applying this protocol, it is very rare for me to see 'downhill' or extreme downhill' patients in my practice.  I have observed a fundamental change in periodontal treatment needs (most advanced cases are now successfully managed with subgingival debridement only) and conversion of previously downhill cases to stable in the long term ie at least 2 years following a single course of azithromycin.

Advanced/ terminal chronic periodontitis

Aggressive periodontitis

Prescribe azithromycin at initial consultation, review patient after 4-6 weeks to formulate definitive periodontal treatment plan based on reduction of inflammation, periodontal pocketing, tooth mobility and patient's symptoms.

Patients report that gingival bleeding on brushing stops 1-2 weeks after taking azithromycin, reduced mobility.  Clinically, periodontal improvement is generally noted after 4-6 weeks, pocket depth decreases as a result of resolution of inflammation and gingival recession.  Pus exudate also stops during this time.   Continuing beneficial effects are observed over long period of time (4-8-12-18 months) with gingival recontouring and further pocket depth reduction.  

Concurrent periodontal treatment (4-6 weeks after first precribing azithromycin):

• Extract extremely hopeless teeth.
• Splint very loose teeth.
• Monthly subgingival debridement with power scaler and curettes, OHI, continue while tissues heal, pocket depths decrease and gingival tissues recontour.
• Monitor bone consolidation/ regeneration with PA/OPG 6-12 months.
• Periodontal surgery rarely necessary as pockets heal and gingival inflammation subsides.

Patients not responding to supportive periodontal therapy (SPT)

Prescribe azithromycin once patients have been identified as downhill after conventional periodontal therapy and on-going SPT.  

Patients report that gingival bleeding on brushing stops 1-2 weeks after taking azithromycin.  Periodontal pockets decrease and gingival inflammation is resolved. Downhill cases are converted to stable.

Continue SPT, I have noticed that intervals between SPT increase significantly (typically patients with ongoing inflammation and pocketing who used to attend 2-3 monthly now need to be seen 4-6 monthly and have achieved periodontal stability.

Moderate- severe gingival overgrowth related to calcium channel blocker medications

If drug substitution is not possible, consider prescribing a single course of azithromycin at the intitial consultation. 

Regression of overgrowth observed at 6-12 weeks after azithromycin, this effect continues over many months.  6-12 weeks after prescribing azithromycin, simple subgingival debridement of the calculus deposits that were formerly subgingival is indicated.  Periodontal surgery is not usually required as the gingival tissues are significantly remodeled presumably as a result of long-term activity/effect of azithromycin on gingival fibroblasts.

Peri-implantitis

Depending on severity, prescribe azithromycin at initial visit or after poor response to conventional treatment for peri-implantitis.

Protocol similar as for advanced chronic periodontitis.  Of the limited number of cases I have treated, resolution of inflammation and reduction of pocket depth is observed in the same time frame as for resolution of periodontitis.

Further periodontal healing after azithromycin

Further improvement in periodontal health after a single course of azithromycin has occurred since the first posting about this patient (A case of rapid improvement in gingival health).  The patient had been prescribed azithromycin at the initial consultation, given the severity of his periodontal condition and its inflammatory nature. 

Initial presentation

At his second visit a week later, significant improvement in gingival health was reported by the patient and obvious clinically.  At this time the lower anterior teeth were cleaned.

The patient returned 5 weeks later at which time the images below were taken.  Although no periodontal treatment had been given for the upper teeth, there has been further resolution of inflammation and pocketing.  Plaque and calculus has reformed around the lower anterior teeth.  There seems to be better gingival resolution around the upper teeth than the lowers.

It seems that the azithromycin is toning down the responses of the tissues to dental biofilm, resulting in resolution of gingival inflammation, gingival recession and pocket depth reduction.  The patient also reported that previously loose teeth were no longer mobile.

6 weeks after azithromycin

6 weeks after azithromycin showing periodontal healing on the
buccal and palatal aspects of the upper right anterior teeth;
no periodontal treatment had been given to these teeth.

Azithromycin and Periodontal Maintenance

Some patients who have had periodontal therapy (both conservative and surgical) and who attend for regular maintenance, struggle to keep their periodontal condition under control.  Their levels of gingival inflammation may be high, periodontal pockets persist or deepen and they may be loosing teeth along the way.  These cases have been described as 'downhill' or 'extreme downhill'.  Conventional re-treatment or maintenance does not seem to be able to stabilise their condition.

The use of a single course of azithromycin has, in my experience, turned cases such as these around .  Patients report rapid improvement in their periodontal symptoms and in the overall comfort of the teeth.  They express gratitude that, at last, they are making progress with their periodontal health.  Pocket depths significantly reduce after 6-8 weeks, there is much less bleeding on probing and the amount of blood arising during subsequent periodontal maintenance visits is minmal, as opposed to the copious bleeding that occurred previously during maintenance.  Intervals betweeen periodontal maintenance visits is usually extended from 2-3 monthly to 5-6 monthly for these cases.

Here are some extracts from my clinical notes of a patient I have been seeing since 1999 when she was 29.  She had aggressive generalised periodontitis and underwent extensive open flap debridement followed by periodontal maintenance over the years.  'June 2006: granulation tissue noted at the entrance of pockets, good OH but underlying gingival inflammation, deep pockets 16d, 14, 13, 12, 24 8mm.  Pockets debrided, review 2 months'.  And so it went until I prescribed a single course of azithromycin in December 2008.  Within 3 months, her periodontal situation had turned around, there were no pockets and no bleeding.  Recall intervals are now set at 6 months rather than 2-3 months.  It is now 2 years since she took the single course of azithromycin and her periodontal health has never been better (see image below). This person is very pleased with the outcome!

Clinical appearance 18 months after single course of azithromycin,
note the healthy quality of the gingival tissues

A case of rapid improvement in gingival health

At initial consultation

A 61 year old male presented with severe generalised gingivitis and advanced periodontitis.  There were no intercurrent diseases and he was a non-smoker.  Here is the periodontal condition at the intial visit.  Note the intensity and extent of gingival inflammation. A single course of azithromycin 500mg was prescribed.  Usually, I would subsequently see a person about 4-6 weeks after prescribing azithromycin; at this time I assess the periodontal response to azithromycin and then formulate a definitive periodontal treatment plan.

In the beginning

Azithromycin is an antibiotic that is closely related to erythromycin.  It was first formulated in 1980 but did not become available in Australia until 2004.  The properties of azithromycin are documented here.  In addition to being an effective antibiotic against a wide variety of bacteria (including Gram -ve periodontal pathogens), azithromycin has significant immuno-modulatory/ anti-inflammatory activity which is applied in the treatment of diseases that are not caused by bacteria, such as cystic fibrosis and asthma.  Azithromycin's anti-inflammatory properties make it a potentially useful agent in the management of inflammatory periodontal diseases as we move into the age of 'host modulation' in the treatment of these diseases.

The periodontal responses that will be documented in this blog have occurred following the prescription of a single course of azithromycin which is:  one 500mg tablet taken a day for 3 days, 2 hours after a meal.  The generic version in Australia is Zedd 500.  Azithromycin must not be prescribed to people with known allergy to erythromycin; 95% of patients do not report side effects.  Compliance is high because only 3 tablets are in the course and side effects are infrequent.

I intend to post clinical cases which highlight the periodontal responses to azithromycin as an adjunct to minimal periodontal intervention (usually oral hygiene instruction and subgingival debridement).  I will share the protocol I use to decide on case selection and timing of periodontal treatment after the patient takes the azithromycin.

Your constructive comments and queries are welcomed and I encourage you to post your own cases if you have clinical photographs or sequential radiographs, or simply descriptions of how your patients' periodontal condition changed over time, including what the patients report to you.