Benefits, But No Specific Benefits, of Amoxicillin-Metronidazole in Aggregatibacter-associated Periodontitis

I have noted in the past couple of years a tendency of broadening the so far limited indication for adjunct systemic antibiotics for the treatment of chronic periodontitis. This is mainly due to systematic reviews with a special focused question on periodontal probing depth reduction and clinical attachment gain as outcome. New randomized controlled clinical trial have been published as well and have now discussed also an old concept, i.e. reducing the need for periodontal surgery. On the sad occasion of the demise of Walter J. Loesche I had emphasized that it was he, already in the 1980s, who had introduced this slightly provocative outcome.

For some time (and I have to admit that I had contributed to the topic about 15 years ago), periodontal infection with Aggregatibacter actinomycetemcomitans (the species which has mainly been implicated in localized and generalized aggressive periodontitis) had been one possible indication for systemic metronidazole and amoxicillin as adjunct to non-surgical periodontal therapy of chronic periodontitis. About 25 years ago, certain pundits (including me) had endorsed even the concept that periodontal infections with this gram-negative, facultative rod were so special as regards severity of periodontal disease and substantial problems of eliminating it by mechanical means from the oral cavity, would justify a certain category of “Aggregatibacter actinomycetemcomitans-associated periodontitis”. Well, among others, our group had spent considerable time and effort to show that this bacterium is a common commensal in the oral cavity of young adults without destructive periodontal disease. In an upcoming review article by Könönen and Müller (2013) we showed that there is in fact evidence that a particularly toxic clone of A. actinomycetemcomitans is associated with the onset of aggressive periodontitis in teenagers in Morocco, and Hujoel et al. (2013) recently emphasized that not-so-toxic clones of the bacterium maybe associated with periodontitis “in non-Caucasian pediatric populations living in some geographic areas with high child mortality rate”, but the evidence is weak for a causal role elsewhere.

Anyway, in a new clinical trial by Mombelli et al. (2013), the question was asked, are there specific benefits of amoxicillin-metronidazole in A. actinomycetemcomitans-associated periodontitis? As the paper tells, this was an extension of a previous trial (Cionca et al. 2010) where the focus was not explicitly on A. actinomycetemcomitans (the first 51 participants, ten had turned out to be A. actinomycetemcomitans-positiv), but on benefits of adjunct amoxicillin and metronidozle over nonsurgical periodontal therapy with placebo. The study then went on by screening for A. actinomycetemcomitans. Positive-for-the bacterium patients were randomized for receiving either scaling and root planing alone or in combination with systemic amoxicillin and metronidazole (500 mg and 375 mg respectively, 3 times per day for seven days). So, 41 patients were A. actinomycetemcomitans-positive and 41 -negative. Six-month results were reported. The primary outcome was persistence of sites with probing depth of >4 mm and bleeding on probing.

No doubt, regardless of presence of A. actinomycetemcomitans, the number of deep residual pockets of 5 mm or more was significantly further reduced when amoxicillin and metronidazole had been prescribed. Mean values of residual pockets bleeding on probing in Table 2 were 6.7 and 4.7 (A. actinomycetemcomitans-positive or -negative) in the placebo group and 2.6 and 1.6 in the test group. But more revealing information is provided in Fig. 2, displaying box plots which preserve more information. The median numbers of deep residual pockets in the placebo group were 3 and 2 as compared to 1 and 0 in the test group (for patients with and without A. actinomycetemcomitans, respectively). These are not dramatic differences. It is also clear that, in the placebo group, there was a patient with 33 residual pockets, two with 23 pockets, one with 17 and one with 16 residual pockets. Even in the antibiotic test group, one patient had, at six months, 18 residual pockets, and another with 13. It is remarkable that despite these “outliers”, the median value were low, 0-3 in any group (meaning, by the way, that 50% had even less). Up to three residual pockets after non-surgical periodontal therapy do not present much of a problem. Of concern is extent and severity of periodontal disease of “outliers”.

Surgery is not an inevitable indication at sites with a residual pocket of 5 mm or more. According to long-established understanding, access problems do present indications for periodontal surgery, infrabony lesions, furcations, posterior teeth, fibrous tissues in the tuberosity.  But the paper by Mombelli et al. is silent about these “true” indications. Whether antibiotic therapy would have lasting benefits in these lesions is doubtful. The difficult to access anatomical infrabony defects and furcation involvements won’t disappear after a course of antibiotics. How often are we supposed to repeat this “cure” in the coming years?

A true endpoint for any periodontal therapy should be tooth retention which can only be assessed after prolonged periods of time. Short-term (six month) results after adjunct antibiotic treatment (which, given the broad spectrum of a combination of amoxicillin and metronidazole, would lead more or less inevitably to slightly better results) is not convincing as long as no detailed analysis of the response at sites with a true indication for periodontal surgery is presented.

27 February @ 2:31 pm.

Last modified February 27, 2013.

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