The Journal of Contemporary Dental Practice
Volume 21 | Issue 4 | Year 2020

Antibiotics for Periodontal Infections: Biological and Clinical Perspectives

Simpy Amit Mahuli1, Ali M Zorair2, Mohammed Abdurabu Jafer3, Alnomari Sultan4, Gargi Sarode5, Hosam Ali Baeshen6, A Thirumal Raj7, Sachin Sarode8, Shankargouda Patil9

1Public Health Dentist, Ranchi, Jharkhand, India
2Pharmacy Comprehensive Specialized Clinics of Security Forces of Jazan, Jazan, Kingdom of Saudi Arabia
3Department of Preventive Dental Science, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia; Department of Health Promotion, CAPHRI, Maastricht University, Maastricht, Netherlands
4Ministry of Health-Primary Health Care, Jazan, Kingdom of Saudi Arabia
5Department of Oral Pathology and Microbiology, Dr DY Patil Dental College and Hospital, Dr DY Patil Vidyapeeth, Pune, Maharashtra, India
6Department of Orthodontics, College of Dentistry, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
7Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Chennai, Tamil Nadu, India
8Department of Oral Pathology and Microbiology, Dr DY Patil Dental College and Hospital, Dr DY Patil Vidyapeeth, Pune, Maharashtra, India
9Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia

Corresponding Author: Shankargouda Patil, Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia, Phone: +966 507633755, e-mail:

How to cite this article Mahuli SA, Zorair AM, Jafer MA, et al. Antibiotics for Periodontal Infections: Biological and Clinical Perspectives. J Contemp Dent Pract 2020;21(4):372–376.

Source of support: Nil

Conflict of interest: None


Aim: The review is to highlight the use of antibiotics in periodontal infections and prevent indiscriminate use of antibiotics.

Background: Periodontitis is the most common disease of the periodontal attachment apparatus, and its etiological factor can be related to the existence of virulent microorganisms in the dental plaque biofilm which harbors millions of microorganisms. In addition, the pathogenesis of this disease is greatly influenced by the host immune response that leads to the cyclic destruction and healing pattern.

Review results: Periodontitis is mostly treated through mechanical debridement using surgical and nonsurgical therapy. However, many times, this treatment does not render desired results due to poor patient compliance, altered immune response, or other host-related factors. This leads to the administration of antibiotics as an adjunct to mechanical debridement. Antibiotics are useful in eliminating periodontopathic microbes, but these agents should be cautiously used and prescribed only if indicated.

Conclusion: Indiscriminate use of antibiotics can lead to unforeseen adverse effects as well as the development of resistant strains of microorganisms.

Clinical significance: Hence, it is crucial for the dentists to know the indications, contraindications, undesirable effects, correct choice, and dosage of the antimicrobial agent before prescribing it to their patients thereby ensuring the success of periodontal therapy. Thus, the clinician should keep in mind that the antibiotics are merely adjuncts to mechanical therapy and not its replacement.

Keywords: Antibiotic, Periodontitis, Plaque control, Periodontal pathogen.


Dental plaque is “the nonmineralized microbial accumulation that adheres tenaciously to tooth surface, restorations, and prosthetic appliances, shows structural organization with predominance of filamentous forms, is composed of an organic matrix derived from salivary glycoproteins and extracellular microbial products, and cannot be removed by rinsing or water spray”.1 Biofilms are “matrix-enclosed bacterial population’s adherent to each other and/or to surfaces or interfaces.”2 The extracellular polymeric component on interaction with the host tissue will result in disease.3 The prolonged and unattended presence of the plaque in the oral cavity can lead to periodontitis and dental caries.4

The presence of dental plaque leading to disease in the oral cavity is explained by the following theories:

The periodontal disease is an inflammatory entity of microbial etiology affecting the periodontal apparatus leading to loss of attachment mostly seen in the elderly population. It is majorly classified into two types: gingivitis and periodontitis. Gingivitis is a reversible condition that affects the gingiva and is commonly seen among all age groups, whereas periodontitis affects the entire periodontal architecture leading to periodontal destruction, pocket formation, recession, and subsequently loss of a tooth. It has been postulated that pathogenesis of periodontitis occurs in a cyclic manner with periods of exacerbation, remission, and latency that is a result of the host immune response.8

The most common form of periodontitis is chronic periodontitis which leads to slow progression of bone loss and attachment loss.9,10 Supra and subgingival deposits are the main causes of periodontal disease; hence, mechanical debridement is the first line of treatment as it reduces the microbial load. However, despite the mechanical plaque removal, the residual presence of microorganism persists, making the antibiotic therapy desirable to fight the pathogens and stop disease progression.9,11


Diseases of the periodontium are divided into chronic periodontitis and aggressive periodontitis; both of which termed as localized or generalized depending on their site of occurrence. Furthermore, it is classified as: periodontitis associated with systemic diseases, necrotizing ulcerative gingivitis, and endodontic lesions.12 Among all these above-mentioned entities, chronic periodontitis is the most commonly observed type in adults. The predisposing risk factors for periodontal disease are subgingival plaque accumulation, stress, smoking, immunological disorders, nutritional deficiency, traumatic occlusion, etc.13 The subgingival plaque is a complex microbial ecosystem with more than 500 microbial species of microorganisms.14 Some of these microbial species have been identified as the causative organisms for the periodontal disease under the effect of local and systemic causes. Among the oral flora, the most important are Porphyromonas gingivalis (seen in chronic periodontitis), Aggregatibacter actinomycetemcomitans (seen in aggressive periodontitis), Bacteroides sp., Treponema sp., Fusobacterium sp., Prevotella sp., Campylobacter sp., and Eikenella. The Socransky complexes, red and orange complex microorganisms, were commonly seen in 5 mm and more periodontal depth and attachment loss cases.1517

These periodontal microorganisms play a vital role in the occurrence of the disease; however, it is not the only factor responsible. The host immune response plays a vital role in the pathogenesis of periodontal disease causing the cyclic pattern of remission and exacerbation.18 The increased levels of inflammatory mediators, such as interleukin-1β, prostaglandins, and tumor necrosis factor α, lead to the chronic and persistent inflammation that causes the destruction of periodontal tissues.19,20 These mediators result in the destruction of alveolar bone mediated by the activation of tissue degradation factors like polymorphonuclear serine proteases, plasminogen, and matrix metalloproteinases.21,22

Mechanical periodontal therapy, i.e., surgical and nonsurgical debridement of the dental plaque along with patient education for maintenance of good personal oral hygiene and follow-up and thereby removal of local irritating factors is the mainstay for treatment of periodontal disease. The strength and success of this approach have been proven time and again by longitudinal studies. The potency of the approach is evaluated by the resolution of clinical signs and symptoms, removal of periodontal microbes, and repopulation of the oral cavity by beneficial microorganisms. Conventional mechanical therapy does not yield favorable results with all patients or sites. The antibiotics use is recommended during certain kinds of periodontal disease because of their infective nature and the limitations of conventional mechanical therapy.23,24

The debate over the significance of an exclusive microbial etiology of periodontal infections may never be completely dissolved. Nevertheless, there is a slight question that certain specific microorganisms are related to certain phases of periodontal diseases.6 The sustained and total elimination of periodontal pathogens is a very difficult endeavor as all these pathogens belong to the indigenous flora of the oral cavity; hence, there is immediate repopulation and oral biofilm formation soon after completion of mechanical periodontal debridement.2527 Nevertheless, in periodontitis, one of the specific manifestations is the faster loss of connective tissue leading to deep pockets with gram-negative and highly virulent strains of bacteria. In such cases, antimicrobials would prove to be valuable adjuncts to mechanical therapy as professional debridement alone may not be capable of effectively eliminating all the microbes in the periodontal tissues (Table 1).28,29

Ideal properties of antibiotic:


The success of antibiotic therapy depends on the potency of the agent used against the culprit microbe. The choice of antibiotic regimen is difficult to periodontal disease as it is a mixed microbe disease. Antibiotics are target specific, i.e., each acts on a particular part of the oral biofilm. For instance, T. denticola, F. nucleatum, P. gingivalis, and B. forsythia, belonging to the red and orange Socransky complexes are gram-negative strict anaerobes and are specifically targeted by metronidazole, whereas it marginally affects genera Actinomyces, Streptococcus, and Capnocytophaga that belong to the green complex.3032 Metronidazole also has a limited effect on facultative anaerobe, for example, A. actinomycetemcomitans. A broad-spectrum drug is amoxicillin that affects both gram-negative anaerobes and Actinomyces species.31,33 A large array of antibiotics are used as adjuncts to nonsurgical and surgical therapy in the treatment of periodontal disease. The commonly used antimicrobials in periodontal therapy are tetracycline, metronidazole, penicillin, macrolides, ciprofloxacin, and clindamycin. Metronidazole and amoxicillin are reported to be the most commonly used combination antibiotic regimen.31

Table 1: Classification of antibiotics on the basis of the mechanism of action30
Mechanism of actionExample
Inhibition of synthesis of bacterial cell wallsPenicillin and cephalosporin
Affecting permeability by interference with the cell membrane of the microorganismAntifungal agents
Inhibition of protein synthesis by affecting the function of the 30S or 50S ribosomal subunitsTetracycline, macrolides, and clindamycin
Blocking of important metabolic stepsSulfonamides and trimethoprim
Interference with nucleic acid synthesisMetronidazole and quinolones


An extensive search of the literature reveals that there is no agreement on the ideal regimen, dosage, and duration of antibiotic therapy for periodontal disease. According to the guidelines of antibiotic therapy, the onset of antibiotic therapy with respect to mechanical therapy is of high relevance. Indirect evidence hints, antibiotic therapy should begin on the last day of mechanical therapy and for a short time, except in patients with the immunocompromised state where prophylactic antibiotics are recommended.31,34Table 2 shows some of the commonly prescribed antibiotic regimes for periodontitis.


The issue of patient consistency has been rarely tended in the literature, specifically in assessing the impacts of systemic antimicrobials. Studies have reported that merely 20% of patients conform to the regimen prescribed.31,35 Azithromycin is preferred because of its long half-life and pharmacologic properties. One tablet (500 mg) every day for three continuous days instead of multiple antimicrobial regimens.31,36 Compliance as far as oral cleanliness and upkeep consideration is ought to be understood. Studies where positive results emulating adjunctive anti-infection agents were accounted for, patients had received periodic maintenance and had acceptable oral hygiene. In the event where the patient is noncompliant with oral cleanliness measures, a positive treatment result taking after adjunctive antimicrobial agents may not be possible. Antibiotic therapy is not an alternative but only an adjuvant to good oral hygiene and regular maintenance.31

Table 2: Commonly prescribed antibiotic regimen for periodontitis
Metronidazole500 mg/t.i.d./8 days
Clindamycin300 mg//t.i.d./8 days
Doxycycline/minocycline100–200 mg/q.d./21 days
Ciprofloxacin500 mg/b.i.d./8 days
Azithromycin500 mg/q.d./4–7 days
Metronidazole + amoxicillin250 mg/t.i.d./8 days (each drug)
Metronidazole + ciprofloxacin500/b.i.d./8 days (each drug)


An extensive literature search has revealed several lacunae in the area concerning reporting of adverse events following the use of antibiotic therapy in the treatment of periodontal disease. Most adverse effects account for minor gastrointestinal tract disturbances, such as diarrhea and nausea. However, genuine adverse occasions, for example, hypersensitive and anaphylactic response and pseudomembranous colitis, are reported, and patients have to be educated to the potential risks while prescribing systemic antibiotics. The adverse effects of penicillin witnessed are often mild like rashes, urticaria, dermatitis, and joint pains. The anaphylactic reaction in response to penicillin occurs approximately one in every 10,000 patients encountered, and about 10% of these prove to be fatal.31,37 Utilization of antibiotics is ought to be painstakingly considered by selecting antimicrobials that expand antimicrobial action and minimize potential medication interactions and adverse effects. An extensive medicinal history should be taken preceding antibiotic prescription.

The most commonly prescribed pharmaceutical agents in the current medical practice are antibiotics, and it is imperative for a periodontist to be well aware of the contraindications and possible adverse effects of the antibiotics used in the treatment of periodontal diseases. The contraindications for use of antibiotics are related to their pharmacokinetics and pharmacodynamics properties. Hence, caution should be exercised while prescribing antibiotics to patients with impaired renal or hepatic functions. An exhaustive medical history will also help in ruling out the instances of allergies and anaphylactic reactions related to antibiotics such as penicillin.38


Biofilms have significantly high antimicrobial resistance when compared with their free-floating counterparts, which spawns severe concerns in the treatment procedure. Antimicrobial resistance of microorganisms inherent or arise as a result of the emergence of resistant strains of bacteria.31 A few studies have evaluated the increase in antimicrobial resistance in oral biofilm post-antimicrobial therapy. Feres et al. have reported patients of chronic periodontitis treated by nonsurgical periodontal treatment followed by oral antimicrobial therapy to have antibiotic-resistant species in saliva and plaque samples.39 An increase in microbial resistance has been reported in countries where antibiotics are sold over the counter without a prescription in comparison with where antibiotics sale is more restricted and only with prescription.40 This highlights the significance of microbial resistance in antibiotics, thereby making it use more responsibly to prevent the spread of resistant microbial strains globally.31

Intrinsic, mutational, and acquired resistance are the three major mechanisms by which antimicrobial resistance occurs.30,41,42 Intrinsic resistance is the inherent naturally occurring resistance of an organism to an antibiotic. Mutational resistance occurs due to the formation of a genetically different microbial population as a result of spontaneous chromosomal alteration. This kind of resistance has been observed for aminoglycosides and rifampin where a change in a single nucleotide base has occurred in microorganism.30,41 Finally, acquired resistance occurs by transduction, transformation, or conjugation where there is horizontal acquisition of a genetic element. Transduction involves the intervention of a bacteriophage that facilitates the transfer of exogenous DNA from one microbe to another, whereas during transformation, the microorganisms take up available DNA from the surrounding environment. Conjugation is the most common mechanism by which transfer of antibiotic resistance genes occurs, where there is a direct cell-to-cell contact for the transfer of genetic material.30,41,42 Hence, the three main strategies used by bacteria for resistance to different antimicrobials are prevention of the drug from reaching its target, alteration of the target, and inactivation of the particular antimicrobial agent.4348

Experts have postulated different mechanisms to explain the higher resistance of antibiotics in oral biofilms. The defensive mechanisms employed in the biofilm seem to be discrete from those, which are accountable for conventional antimicrobial resistance.

They all appear during the final stage of biofilm maturation.49,50 The presence of enzymes, β-lactamases, leads to less penetration of the antibiotic in the oral biofilm. The secretion of the exopolysaccharide matrix further prevents penetration of antimicrobials by forming a protective coating or binding the antimicrobial.49,5154 Several authors have documented the presence of various microenvironments in the biofilms, and they differ in their metabolism, oxygenation, and pH, thereby providing evidence of the complex heterogeneity within biofilms.55,56 The oral biofilm is a biologically programmed structural growth on a surface that has specific metabolic, interactive, physiological functions, and genetic expressions that are quite unique. This diversity is termed as the “biofilm phenotype” and is reported to be the underlying cause of antimicrobial resistance in biofilms.5760 Increased resistance to antimicrobials in biofilms is a result of a combination of all or some of these mechanisms acting together as a multilayered defense during biofilm maturation. These mechanisms function in a reversible and transient way adding to the higher antimicrobial resistance. The following factors have an influence on the development of drug resistance:


Herrera et al. concluded that antibiotics should be used with periodontal therapy only when indicated and act as an adjunct to mechanical treatment.34 Nevertheless, indirect evidence ropes in the disagreement that antibiotic therapy should be started on the last day of mechanical debridement and be for a brief duration of time (<1 week) to ensure patient compliance. Mechanical plaque control is the mainstay for the prevention and treatment of periodontal disease, but it requires immense patient cooperation and motivation; therefore, antimicrobial therapy acts as a useful adjuvant for achieving the desired results. Hence, it is imperative for the clinician to know the effect of these agents so that they can provide the patients with tailor-made prescriptions and make periodontal therapy a success.61 Furthermore, antimicrobial therapy should be prescribed with caution keeping in mind the adverse effects and the increasing microbial resistance. There need to be standard guidelines in periodontal and peri-implant conditions.62


Hence, it is crucial for the dentists to know the indications, contraindications, undesirable effects, correct choice, and dosage of the antimicrobial agent before prescribing it to their patients, thereby ensuring the success of periodontal therapy. Thus, the clinician should keep in mind that the antibiotics are merely adjuncts to mechanical therapy and not its replacement.


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