ANTI-MICROBIAL

AGENTS IN
PERIODONTAL DISASE
INTRODUCTION

• All living organisms are vulnerable to infection

• Human beings, with no exception, are susceptible to disease caused by bacteria, virus, fungi,
protozoa, helminths.
• In the beginning of 20th century, Ehrlich coined the term “Chemotherapeutic agents”

CHEMOTHERAPEUTIC ANTIMICROBIAL
AGENTS AGENTS

ANTIBIOTICS
CLASSIFICATION OF ANTIMICROBIAL AGENTS
A. Chemical structure
1. Sulfonamides and related drugs: Sulfadiazine and others, Sulfones—Dapsone (DDS), Paraaminosalicylic acid (PAS).
2. Diaminopyrimidines: Trimethoprim, Pyrimethamine.
3. Quinolones: Nalidixic acid, Norfloxacin,Ciprofloxacin, Prulifloxacin, etc.
4. β-Lactam antibiotics: Penicillins, Cephalosporins, Monobactams, Carbapenems.
5. Tetracyclines: Oxytetracycline, Doxycycline, etc.
6. Nitrobenzene derivative: Chloramphenicol.
7. Aminoglycosides: Streptomycin, Gentamicin, Amikacin, Neomycin, etc.
8. Macrolide antibiotics: Erythromycin, Clarithromycin, Azithromycin, etc.
9. Lincosamide antibiotics: Lincomycin, Clindamycin.
10. Nitroimidazoles: Metronidazole, Tinidazole, etc.
11. Polyene antibiotics: Nystatin, Amphotericin- B, Hamycin.
12. Azole derivatives: Miconazole, Clotrimazole, Ketoconazole, Fluconazole.
13. Others: Rifampicin, Isoniazid, Cycloserine
 B. MECHANISM OF ACTION

Inhibit DNA Inhibit

Inhibit cell wall Leakage from Inhibit protein Misreading of Inihibit DNA
function and intermediate
synthesis cell membrane synthesis mRNA codes gyrase
synthesis metabolism

Aminoglycosides
Penicillin Bacitracin Tetracycline Ciprofloxacin Rifampicin, Sulphonamide
-Streptomycin

Cephalosporin Amphotericin B Chloramphenicol Norfloxacin Acyclovir Metronidazole

Bacitracin Erythromycin
 SPECTRUM OF
TYPE OF ACTION
ACTIVITY

BACTERIOSTATI NARROW BROAD

BACTERICIDAL
C SPECTRUM SPECTRUM

TYPE OF
ORGANISM

ANTI
ANTI FUNGAL ANTI VIRAL
BACTERIAL
BETA LACTUM ANTIBIOTICS

• Have beta lactum ring

• Major groups – Penicillin and Cephalosporins
• Add on – Monobactums, carbapenams, beta lactamase inhibitors were added
PENICILLIN
• First clinically used antibiotics in 1941 by
Alexander Flemming
• P. notatum, P. chyrsogenum
• Mech of action:
– blocks d-alanine ring
– Prevents transpeptidation
• Bactericidal action
• Gram positive > Gram negative
 BETA LACTAMASE
PENICILLIN
INHIBITOR

• PHARMACOKINETICS:
CLAVULINIC ACID,
NATURAL SEMISYNTHETIC SULBACTUM, – PENICILLIN G – only i.v administration
TAZOBACTUM

– Benzathine and Procaine penicillin – i.m

PENICILLIN G ACID RESISTANT
PENICILLINASE
RESISTANT
EXTENDED
SPECTRUM admistration – delayed absorption –
PENICILLIN
prolonged duration of action

PENICILLIN V METHICILLIN AMPICILLIN

– Penicillin is rapidly excreted by kidney,
bile or liver.

PROCAINE
– Plasma half life is 1hour.
CLOXACILLIN AMOXICILLIN
PENICILLIN

PIPERACILIN

CARBENICILLIN
USES:
• Streptococcal infection
• Pneumococcal infection
• Meningococcal infection
• Gonococcal infection
• Syphilis
• Tetanus, gas gangrene
• Diphtheria
• ANUG – penicillin along with
metronidazole is given.
ADVERSE EFFECTS:
• Local irritation
• Hypersensitivity - rash, itching,
urticaria and fever.
• Super infection
• Jarisch Herxheimer reaction – in
Syphilitic patients – shivering,
fever, myalgia, exacerbation of
lesions, even vascular collapse.
• Amphicillin – Pseudomembranous
colitis, diarrhoea
BETA LACTAMASE INHIBITORS

• Beta lactamase enzyme present in bacteria can cause resistant to

gram positive and gram negative bacteria
• Beta lactamase inhibitors – Clavulanic acid, sulbactum, tazobactum
• Clavulanic acid – Progressive/suicide inhibitor of beta lactamase
enzyme
– Mostly given along with amoxicillin
– Amox 250mg + Clavulanic acid 125mg TDS
– Amox 500mg + Clavulanic acid 125mg TDS
– Amox 875mg + Clavulanic acid 125mg TDS
CEPHALOSPORINS
• USES: • ADVERSE EFFECTS
– Various aerobic and anaerobic – Toxicity
infections – Hypersensitivity
– 1st generantion acts mostly on gram – Diarrhoea
+ve
– Nephrotoxicity
– As generation progress – gram –ve
– Cefoperazone – disulfiram like
– Respiratory, urinary, cutaneous, gastro reaction
intestinal infection
– Bleeding
– Methicillin resistant staphylococcal
infections
– Hospital acquired infections
– Mixed aerobic and anaerobic
infections
QUINOLONES

• Synthetic antimicrobials – mostly against gram negative bacteria

• First discovered was Nalidixic acid in 1980’s
• USES: • ADVERSE EFFECTS:
– Most susceptible: aerobic gram –ve bacilli – Rare
– Moderately susceptible: gram +ve – Gastro intestinal irritation
– Resistant : bacteriodes, anaerobic cocci – Rashes itches
– Typhoid fever – Hypersensitivity
– Urinary tract infection
– Gastroenteritis
– Gonorrhoea
– Tuberculosis
– meningitis
TETRACYCLINES

• Broad spectrum antibiotic – bacteriostatic

• Inhibits protein synthesis by binding to 30S subunit
of ribosome blocking peptide formation
• Tetracyclines are active against many gram-positive
and gram negative bacteria, including certain
anaerobes, rickettsiae, chlamydiae, and
mycoplasmas.
• Pharmacokinetics:
– Easily absorbed orally and excreted in urine and feces
• Short-acting (chlortetracycline, tetracycline, oxytetracycline)
• Intermediate-acting (demeclocycline and methacycline)
• Long-acting (doxycycline and minocycline)
• USES:
– Chlamydia, lymphogranuloma
– Atypical pneumonia
– Cholera
– Brucellosis
– Plague, rickettsiae
• ADVERSE EFFECTS:
– Hepatotoxic, Nephrotoxic
– Phototoxic
– Affects teeth and bones
– Ototoxic
– Hypersensitivity
– Superinfections
AMINOGLYCOSIDES

• Bactericidal effect
• Mechanism of action – Inhibits protein
synthesis by binding to 30S or 50S subunit
of ribosomes
• USES:
– Mycobacterial infections
– Non tuberculous infections
– Gram –ve meningitis
– Topical – ocular infections

• ADVERSE EFFECTS:
– Ototoxicity
– Nephrotoxicity
MACROLIDES

• Low doses – bacteriostatic

• High doses – bactericidal ERYTHROMYCIN 250-500mg qid
• Mechanism of action: binds to 50S
ribosomal subunit and inhibits protein ROXITHROMYCIN 150-300mg BD
synthesis CLARITHROMYCIN 250mg BD
• Erythromycin was discovered in 1952
AZITHROMYCIN 500mg OD
• Later Azithromycin, Clarithromycin,
Roxithromycin were developed.
• USES: • ADVERSE EFFECTS:
– Alternative to penicillin – GI disturbances
– Upper respiratory tract – Ototoxic
infections – Hypersensitivity
– Syphilis, gonorrhoea,
meningitis
– Sinusitis
– Toxoplasmosis
METRONIDAZOLE

• Nitroimidazole group
• Highly active amoebicide
• Kills anaerobic protozoa
• Has wide spectrum of action on anaerobic
bacteria
• Readily absorbed from intestine and
excreted by kidney
• DOSE: 200-300mg TDS for 7 days
• USES: • ADVERSE EFFECTS:
– Amoebiasis – Anorexia
– Giardiasis – Metallic taste
– Trichomonas – Headache
– Anaerobic bacterial infections – Dry mouth
– Pseudomembranous colitis – Disulfiram like reaction in
– ANUG Chronic alcoholic patients.
– H.pylori
ANTIBIOTICS IN PERIODONTAL THERAPY
BIOFILM
SYSTEMIC ANTIMICROBIAL THERAPY

• Periodontal treatment aims at restoring the microbiota compatible with periodontal health.
• Effective periodontal treatment implies a reduction of pathogenic levels of indigenous oral
micro organisms and elimination of exogenous pathogens
• Mechanical periodontal treatment - reduce total supra and sub gingival bacterial mass,
• Periodontal antibiotic therapy aims to reinforce mechanical periodontal
RATIONALE OF ANTIBIOTICS

• Specific and stronger associations of certain bacterial complexes in periodontitis ( Tanner et al ,1998).
• Mechanical debridement alone has failed in eliminating distinct periodontal pathogens from subgingival niche
– Due to limited access to root surface and other extracrevicular sites
– Tissue invading skills of organisms. (Mombelli et al ,2000)
• Can induce a microbial shift ( Feres et al,2001).
• Can eradicate pathogens such as Aa for a longer period (24 months). (Ehmke et al , 2005)
• Can decrease the amount of periodontal surgery (Loeshe et al , 1992).
• Minimize effects of periodontitis on systemic conditions.
• Eliminate certain key pathogens in family units and thus can contribute to prevention of disease.
SELECTION OF AN EFECTIVE ANTI
MICROBIAL AGENT
• AgP
• CP
• NPD
• Abscess

Local Patient
factors selection

Medical Drug
status selection
• Renal, hepatic, diabetic, • Spectrum
age, pregnancy and • Pharmacokinetics
lactation, CVS disorders
Two critical factors should be specifically considered in selecting a systemic antibiotic in
periodontal therapy:
1. Gingival fluid concentration 
2. Minimum inhibitory concentration (MIC)
1. The gingival fluid concentration (CGCF) provides information on the peak levels achieved by
systemic delivery at the primary ecological niche for periodontal pathogens, the periodontal
pocket.
2. The 90% minimum inhibitory concentration (MIC90) is an in vitro determination of the
concentration that will inhibit growth of 90% of the bacterial strains of a species that are
tested. Antimicrobial activity can be defined as a relationship between CGCF and MIC90
100 (CGCF/MIC90) = antimicrobial activity expressed as a percentage for each antibiotic and each
organism.
ADVANTAGES
• Through serum  reaches base of dep
pockets and furcation, gingival epithelium
and connective tissue, dentinal tubules
• Kills bacterial in other ecological niches
• It also kills bacteria in saliva and GCF

DISADVANTAGES
• Bacterial resistance for antibiotics develops
• Superinfection and opportunistic infections
• Tetracycline – discoloration of teeth, affects
tooth development in children
• Patients non compliance
GUIDELINES FOR USE OF ANTIMICROBIAL THERAPY

CLINICAL DIAGNOSIS

AGGRESSIVE ,
CHRONIC REFRACTORY OR
PERIODONTITIS MEDICALLY RELATED
PERIODONTITIS

MICROBIAL
ANALYSIS
ORAL HYGIENE,
ROOT
DEBRIDEMENT INEFFECTIV
SPT, SURGERY E
EFFECTIV
ANTIBIOTICS E

SPT
TIMING OF ANTIBIOTIC
ADMINISTRATION
 SINGLE
ANTIBIOTIC
COMBINED
REGIMEN
ANTIBIOTIC
REGIMEN
SINGLE ANTIBIOTIC REGIMEN
COMBINATION THERAPY

Localised aggressive periodontitis- A.a & P.g

• Metronidazole–amoxicillin: 250 mg t.i.d. for 8 days (each)
• metronidazole–amoxicillin–clavulanate potassium
Against A.a
•  Metronidazole–ciprofloxacin : 500 mg b.i.d. for 8 days
• This combination provides a therapeutic benefit by reducing or eliminating pathogenic
microorganisms and offers a prophylactic benefit by giving rise to predominantly streptococcal
microflora.
• Winkel et al., 2001- observed that patients with P. gingivalis at baseline treated with
metronidazole+amoxicillin - half the number of >5 mm pockets after therapy 

• Guerreo et al. 2005 used metronidazole+amoxicillin in aggressive periodontitis- showed

improvement in clinical parameters
 Broaden
antimicrobial
range of
therapeutic
regimn

Why
combination
therapy?

Lower the
Prevent
dose of
bacterial
individual
resistance
antibiotics
 Increased adverse
reactions
Disadvantages of
combination therapy Antagonistic drug
interactions with
improperly selected
antibiotics
 Associated Microflora Antibiotic of Choice
Gram-Positive Organisms Amoxicillin-Clavulanate potassium
(Augmentin) (Walker et al 1993)
Gram-negative organisms Clindamycin (Gordon et al 1990)

Nonoral gram – negative Ciprofloxacin (Magnusson et al

facultative rods, 1994)
Pseudomonads,Staphylococci
Black-pigmented bacteria and Metronidazole (van Winkelhoff et
spirochetes al 1992)
Prevotella intermedia, Tetracycline (Pavicic MJ et al
Porphyromonas gingivalis 1995)

A. actinomycetemcomitans Metronidazole/amoxicillin ( van

Winkelhoff et al 1992)
Metronidazole / Ciprofloxacin
(Rams & Slots 1992)
Tetracycline (Lisgarten et al 1993)
P. gingivalis Azithromycin (Pajukanta R 1993)
SYSTEMIC ANTIBIOTIC DOSING REGIMENS
Single Agent Regimen Dosage/Duration
Amoxicillin 500 mg Three times per day × 8
days
Azithromycin 500 mg Once daily × 4–7 days
Ciprofloxacin 500 mg Twice daily × 8 days
Clindamycin 300 mg Three times daily × 10 days
Doxycycline or 100–200 mg Once daily × 21 days
Minocycline
Metronidazole 500 mg Three times daily × 8 days
Combination Therapy
Metronidazole + 250 mg of each Three times daily × 8 days
Amoxicillin
Metronidazole + 500 mg of each Twice daily × 8 days
Ciprofloxacin
POST OPERATIVE USE OF
ANTIBIOTICS
SURGICAL HOST
COMPLICATIONS IMMUNOCOMP
ROMISED
1) Procedures that go beyond 2 hours
2) Injury of anatomical structures (eg.
sinus perforations)
3) Fascial planes entered
4) Surgeries performed in inflamed
tissues
ANTIBIOTICS
• Decision to routinely use antibiotics as part of the periodontal surgical procedure cannot be
substantiated.
• A low rate of postoperative infection following periodontal surgical procedures (CA Powell et
al , 2005).
• There may be no benefit in using antibiotics for the sole purpose of preventing post-surgical
infections
ANTIBIOTIC PROPHYLAXIS

• Cardiac valve diseases, prosthetic heart valves,

pacemakers
• Hip, knee, total joint replacement
• Renal dialysis shunt
• Cerebrospinal fluid shunt
• Vascular grafts
• Immunosuppression patients – Leukemia, cancer,
cancer chemotherapy
• Asplenic patients
• Transplantation patients
• HIV patients
PROBLEMS THAT HAVE SLOWED PROGRESS OF
ANTIBIOTIC THERAPY

1. Periodontal diseases are heterogeneous;

2. Clinical diagnoses are made on the basis of clinical signs, not molecular pathology
3. The actual causal factors have not been definitively identified
4. No microbiological sampling.
5. There are many different antibiotic protocols but few well designed, randomized controlled
trials that test the efficacy of these protocols.
6. Systems for culture and sensitivity testing of bacterial plaque are not readily available.
7. Host response plays a major role in the pathogenesis of periodontitis.
 ANTIBIOTIC SUSCEPTABILITY &
RESISTANCE
• Antimicrobial susceptibility variation of 50 anaerobic
periopathogens in aggressive periodontitis: an
interindividual variability study; Lakhssassi N et al -
Oral Microbiol Immunol. 2005 Aug;20(4):244-52.
 CHECKING FOR SENSITIVITY
• Antibiotic sensitivity can be done by 4 methods :

1) Disc –diffusion method (Kirby-Bauer)

2) Strokes method

3) E-test ( based on disc diffusion method)

4) Agar-or broth dilution tests ( check MIC)

ANTIBIOTIC FAILURE

• Inappropriate choice of antibiotic

• Antibiotic resistant microbes
• Too low blood concentration of antibiotic
• Slow growth rate of micro organisms
• Impaired host defense
• Patient non compliance
• Antibiotic antagonism
• Inability of the drug to penetrate to the site of infection
• Limited vascularity and unfavourable local factors
• Failure to eradicate the source of infection
TO SUMMARIZE
• Antibiotics do have some added benefit in treating periodontitis in conjunction with
scaling and root planning.
• Aggressive periodontitis
• Should only be used in acute periodontal conditions where drainage or debridement is
impossible and when there is local spread of infection and systemic upset has occurred.
• There is not enough evidence to support their use with periodontal surgery. ( Herrera Et
. al , 2008)
• Offer very little if any adjunctive benefit to the treatment of periodontal disease in patients
who smoke.
WHICH ANTIBIOTIC OR ANTIBIOTIC COMBINATION IS MOST
APPROPRIATE FOR WHICH FORM OF PERIODONTAL INFECTION?

• Tetracycline- 250 mg four times daily for 2 weeks, used as an adjunct to full mouth SRP.

• Currently metronidazole (400 mg 3 times daily) and amoxicillin (250 mg 3 times daily) for
7 days should be used as an adjunct to full mouth SRP when treating localized /generalized AP.
CONCLUSION

Systemic periodontal antibiotic therapy aims to

reinforce mechanical periodontal treatment and
to support the host defense system in overcoming
the infection by killing subgingival pathogens that
remain after conventional mechanical periodontal
therapy.