Comparing the Antimicrobial In Vitro Efficacy of Amoxicillin/Metronidazole against Azithromycin—A Systematic Review
Periodontitis can be described as a common inflammatory and infectious disease that will lead to the destruction of the main structures that support the tooth and, if untreated, can also lead to the loss of the tooth itself. This destructive mechanism is mainly related to the formation of a complex and thick biofilm that has been formed by many bacteria that attach to the surface of the tooth. This situation must be kept under control because it might lead to more serious complications such as: bacterial shifts (spread of the bacteria in different areas), dysbiosis (mechanism related to microbial imbalance or maladaptation) and transition from gingivitis to periodontitis may also occur.
WHAT LIMITATES THE MICROBIAL EFFECT: BENEFITS VERSUS RISKS
Nowadays the prescription of different antibiotics is the best option. In particular, the combination of systemically administrated amoxicillin (AMX) and metronidazole (MTZ) has been frequently chosen for the non-operative periodontal therapy. AMX is a bacteriolytical lactame-antibiotic with a wide spectrum and a half-life of 1 to 1.5 hours and MTZ is especially effective against anaerobes and protozoa with a half-life of 6 to 7 hours. Nevertheless, the effectiveness of this combination is strongly limited by its side effects such as: potential drawbacks of this regimen and problems with the compliance. These problems led to an ongoing search for alternatives.
HAVE WE FOUND ANY ALTERNATIVES TO SOLVE THE PROBLEM?
Azithromycin (AZM), a macrolide antibiotic extensively used in general medicine, has recently found its niche in periodontal therapy as well and has been proposed as a possible alternative. This antibiotic is interesting for periodontal therapy due to several potential benefits, including a broad antimicrobial spectrum, anti-inflammatory activity, a lower intake dosage and duration/frequency of intake. Furthermore, recent systematic review found clear evidence for AZM as a second alternative to the combination of AMX + MTZ in chronic periodontitis patients.
SO… WHAT TREATMENT IS BETTER?
In order to answer this question many literature searches have been performed. The data collected up to and including 29 March 2018, come from studies that matched the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic reviews. At the end of the comparative process three publications have been included in the systematic analysis. Many laboratory studies have been compared and their aim was to evaluate the antimicrobial efficacy in vitro of AMX + MTZ vs. AZM. These studies hypothesized that both antibiotic therapies were equally effective in eliminating in vitro the growth of bacteria associated with periodontal disease.
WHAT STUDIES HAVE BEEN MADE?
The purpose of these studies was to evaluate the efficacy of AZM, compared to the combination of AMX + MTZ. Even though the main limitation was the fact that just a few studies were carried out in order to support these outcomes, the combination of AMX + MTZ was shown to have a higher antimicrobial efficacy in vitro, compared to AZM.
- Belibasakis and Thurnheer (2014) tested in vitro subgingival biofilm model with 10 species. After culturing the bacteria for 40.5 h, the biofilms were exposed to the following antibiotics for another 24 hours at concentrations detected in the pocket environment following systematic administration.
- Ong and co-workers (2017) evaluated the efficacy of AZM on mono- and polymicrobial biofilm formations consisting of P. gingivalis, T. denticola, and T. forsythia in comparison to AMX + MTZ in combination in vitro.
- Soares and co-workers (2015) tested the antimicrobial effects of AZM and the combination of AMX + MTZ on a polymicrobial biofilm model with 35 subgingival bacterial species, including S. oralis, F. nucleatum, P. gingivalis, P. intermedia, A. actinomycetemcomitans (a periodontal pathogen closely associated with the causative agents of rapid periodontitis progression) and T. forsythia.
WHAT IS THE FINAL RESULT?
The conclusions stated that AMX + MTZ compared to AZM in in vitro biofilm models have more pronounced antimicrobial effects such as biofilm reduction, growth inhibition, and reduction of metabolic activity. All the studies showed that AMX + MTZ reduced the biofilm 27% more than AZM. The metabolic activity through AMX + MTZ was reduced by the 84% whereas only by 17% through AZM.
In conclusion, the combination of AMX + MTZ performed in 3 out of 3 studies better and seemed to have a higher antimicrobial efficacy in vitro as compared to AZM, further studies are required to evaluate the comparative laboratory susceptibility and, in particular, the clinical relevance of AZM.
This blog entry was written by Francesca Capucci and Francesca Covini, 2nd year Dentistry Students in Pharmacology at University CEU Cardenal Herrera.