Systemic Antibiotics in Periodontal therapy.ppt

Systemic Antimicrobials in
Periodontal therapy

Introduction
• The various periodontal diseases result from
susceptible hosts having their periodontal
tissues colonized by specific oral pathogens in
numbers sufficient to overwhelm their tissue
defenses.
• Clinical success in the treatment of these
diseases thus requires reduction of the
bacterial load or enhancement of the host
tissues' ability to defend or repair itself.

Introduction
• Traditionally, the foundations of clinical success
include oral hygiene education; nonsurgical
mechanical root debridement, surgical therapy to
remove sub-gingival bacteria and their accretions
from root surfaces; and SPT.
• In certain types of periodontal disease including
chronic advanced periodontitis, refractory
periodontitis, aggressive periodontitis, and
periodontitis as a manifestations of systemic
diseases, adjunctive chemotherapeutic agents may
be necessary to control the disease process.

Definitions
• Chemotherapeutic agent - general
term for a chemical substance that
provides a clinical therapeutic benefit.
• Antimicrobial/antiinfective agent -
chemotherapeutic agent that works by
reducing the number of bacteria
present.

Definitions
• Antibiotic - naturally occurring,
semisynthetic or synthetic type of
antiinfective agent that destroys or
inhibits the growth of selective
microorganisms, generally at low
concentrations.

• Chemotherapeutic agents can be
administered locally, orally, or parenterally. In
either case, their purpose is to reduce the
number of bacteria present in the diseased
periodontal pocket.
• Systemic antibiotics may be a necessary
adjunct in controlling bacterial infection
because bacteria can invade periodontal
tissues, making mechanical therapy alone
sometimes ineffective.

Classification
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 etc.
4.-lactam antibiotics: Penicillins, Cephalosporins, Monobactams,
Carbapenems.
5.Tetracyclines: Oxytetracyclines, Doxycycline etc.
6.Nitrobenzene derivative: Chloramphenicol.
7.Aminoglycosides: Streptomycin, Gentamycin, Neomycin etc.
8.Macrolide antibiotics: Erythromycin, Roxithromycin, Azithromycin
etc.

Classification
9.Polypeptide antibiotics: Polymyxin-B, Colistin, Bacitracin,
Tyrothricin.
10.Nitrofuran derivatives: Nitrofurantoin, Furazolidone.
11.Nitroimidazoles: Metronidazole, Tinidazole.
12.Nicotinic acid derivatives: Isoniazid, Pyrazinamide, Ethionamide.
13. Polyene antibiotics: Nystatin, Amphotericin-B, Hamycin.
14. Imidazole derivatives: Miconazole, Clotrimazole, Ketoconazole,
Fluconazole.
15. Others: Rifampin, Lincomycin, Clindamycin, Spectinomycin,
Vancomycin, Sodium fusidate, Cycloserine, Viomycin,
Ethambutol, Thiacetazone, Clofazimine, Griseofulvin.

Classification
Mechanism of action
– Inhibit cell wall synthesis: Penicillins,
Cephalosporins, Cycloserine, Vancomycin,
Bacitracin.
– Cause leakage from cell walls:
• Polypeptides- Polymyxins, Colistin, Bacitracin.
• Polyenes- Amphotericin-B, Nystatin, Hamycin.
– Inhibit protein synthesis: Tetracyclines,
Chloramphenicol, Erythromycin, Clindamycin.

Classification
– Cause misreading of m-RNA code and affect
permeability: Aminoglycosides – Streptomycin,
Gentamycin etc.
– Inhibit DNA gyrase: Fluoroquinolones-
Ciprofloxacin.
– Interfere with DNA function: Rifampin,
Metronidazole.
– Interfere with DNA synthesis: Idoxuridine,
Acyclovir, Zidovudine.
– Interfere with intermediary metabolism:
Sulfonamides, Sulfones, PAS, Trimethoprim,
Pyrimethamine, Ethambutol.

Classification
• Type of organisms against which
primarily active
– Antibacterial: Penicillins, Aminoglycosides,
Erythromycin etc.
– Antifungal: Griseofulvin, Amphotericin B,
Ketoconazole etc.
– Antiviral: Idoxyuriidine, Acyclovir, Zidovudine,
Amantadine etc.
– Antiprotozoal: Chloroquine, Pyrimethamine,
Metronidazole, Diloxanide etc.
– Anthelminthic: Mebendazole, Pyrantel,
Niclosamide, Diethyl carbamazine etc.

Classification
• Spectrum of activity
Narrow Spectrum Broad spectrum
• Penicillin G Tetracyclines
• Streptomycin Chloramphenicol
• Erythromycin

Classification
• Type of action
Primarily bacteriostatic Primarily bactericidal
• Sulfonamides Penicillins Cephalosporins
• Tetracyclines Aminoglycosides Vancomycin
• Chloramphenicol Polypeptides Nalidixic acid
• Erythromycin Rifampin Ciprofloxacin
• Ethambutol Cotrimoxazole Isoniazid

Classification
• Antibiotics are obtained from:
Fungi Bacteria Actinomycetes
Penicillin Polymyxin B Tyrothricin Aminoglycosides
Macrolides
Cephalosporin Colistin Aztreonam Tetracyclines
Polyenes
Griseofulvin Bacitracin Chloramphenicol

SYSTEMIC ADMINISTRATION OF ANTIBIOTICS
Background and rationale
• The treatment of periodontal diseases is based on the infectious
nature of these diseases.
• Ideally, the causative microorganism(s) should be identified and
the most effective agent selected using antibiotic sensitivity
tests. The difficulty lies primarily in identifying specific etiologic
microorganism(s) rather than microorganisms simply associated
with various periodontal disorders.
• The possible clinical benefits of administering antibiotics to help
control periodontal disease must be weighed against possible
adverse reactions - allergic/anaphylactic reactions,
superinfections, development of resistant bacteria, interactions
with other medications, upset stomach, nausea, vomiting.

• Common and indiscriminate use of antibiotics
worldwide has contributed to increasing
numbers of resistant bacterial strains
over the last 15 to 20 years, and this trend is
likely to continue given the widespread use of
antibiotics.
• The overuse, misuse, and widespread
prophylactic application of antimicrobial drugs
are some of the factors that have led to the
emergence of resistant microorganisms.

An ideal antibiotic for use in prevention and
treatment of periodontal diseases should be -
• specific for periodontal pathogens,
• nontoxic,
• substantive,
• not in general use for treatment of other diseases,
• and inexpensive.
Although oral bacteria are susceptible to many
antibiotics, no single antibiotic at concentrations
achieved in body fluids inhibits all putative
periodontal pathogens. A combination of antibiotics
may be necessary to eliminate all putative pathogens
from some periodontal pockets.

Biologic implications
• Systemic antibiotics are released from
the pocket wall into GCF. The putative
periodontal pathogens (Red complex)
tend to reside in the section of the
biofilm attached to the epithelial surface
of the periodontal pocket. The
susceptibility of bacteria to antibiotics
may be the key to the efficacy of
systemic antibiotics in the treatment of
periodontal diseases.

Biologic implications
• Systemic antibiotic therapy also has the
potential to suppress periodontal pathogens
residing on the tongue or other oral surfaces,
thereby delaying subgingival recolonization of
pathogens.
• A recent systematic review concluded that
when a patient uses systemic antibiotic, it is
likely to be of benefit for the treatment of
the patient’s periodontal infection (Haffajee
AD, Socransky SS, Gunsolly JC, 2003).

Association between putative periodontal
pathogens and periodontal disease.
Very strong Strong Moderate Early stage of
investigation
P gingivalis,
A
actinomycetemc
omitans,
T forsythensis,
Spirochetes of
NUG
P intermedia
T denticola
E nodatum
Dialister invisus
C rectus
P micros
F nucleatum
Selenomonas
noxia
E corrodens
Beta hemolytic
streptococci.
Gram negative
enteric rods,
Pseudomonas
species
Staphylococcus
species
Enterococcus
fecalis
Candida
albicans.

Patients
• who exhibit continuing loss of periodontal attachment
despite diligent conventional mechanical therapy.
Recurrent or refractory periodontitis is often related
to persistent subgingival pathogens and impaired
host resistance.
• with aggressive types of periodontitis.
• With medical conditions predisposing to periodontitis.
• with acute or severe periodontal infections (abscess,
ANUG/ANUP).
• Evidence is strongest in the treatment of aggressive
localized periodontitis (Slots et al. 1979, Pavicic et al.
1991, Saxen & Asikainen,1993).

Patients
• Moderate evidence for the value of antibiotics is in
aggressive generalized periodontitis (Rams & Keyes
1983, Gordon et al. 1985, McCulloch et al.1989,
1990)
• and periodontal abscesses (Hafstrom et al. 1994).
Limited evidence for antibiotics in periodontics
• Adjunct to periodontal flap surgery
• Peri-implantitis
• Regenerative surgical procedures
(Haffajee et. al, 1988, 1995 )

Drugs
Important pharmacological
determinants include-
 body weight
 degree of absorption
 rate of metabolism
 duration of effective antimicrobial levels
at the site of infection.

Drugs
Efficacy of the antimicrobial therapy is determined by the
antimicrobial spectrum, pharmacokinetic characteristics of the
drug, and by local environmental factors including
• drug binding to tissues
• protection of pathogens through binding, consumption or
degrading of the drug by non-target organisms.
• subgingival plaque biofilm protecting the pathogens
• total bacterial load relative to the maximum achievable
antibiotic concentration.
• effectiveness of host defenses
• pathogens in periodontal tissues, root surfaces and extra dental
oral sites not affected by the therapy.

Guidelines for use of antibiotics in
periodontal therapy
• Clinical diagnosis & situation dictate the need for possible
antibiotic therapy as an adjunct in controlling active periodontal
disease. The patient's diagnosis can change over time. E.g., a
patient that presents with generalized slight chronic
periodontitis can return to a diagnosis of periodontal health
after initial therapy. However, if this patient has been treated
appropriately and continues to have active disease, the
diagnosis can change to refractory periodontitis.
• Continuing disease activity, as measured by continuing
attachment loss, purulent exudate, & /or continuing periodontal
pockets of ≥ 5 mm, that bleed on probing, is an indication for
periodontal intervention and possible microbial analysis through
plaque sampling. Also, cases of refractory or aggressive
periodontitis may indicate the need for antimicrobial therapy.

periodontal therapy
• When used to treat periodontal disease, antibiotics are selected
based on the microbial composition of the plaque, the patient's
medical and dental status, current medications, and results of
microbial analysis if performed.
• Microbiologic plaque sampling may be performed according to
the instructions of the reference microbiologic laboratory.
Commonly, the samples are taken at the beginning of an
appointment before instrumentation of the pocket.
Supragingival plaque is removed and an endodontic paper point
is inserted subgingivally into the deepest pocket(s) present to
absorb bacteria in the loosely associated plaque. This is placed
in reduced transfer fluid and sent overnight to the laboratory.
The laboratory will then send the referring dentist a report that
includes the pathogens present and any appropriate antibiotic
regimen.

periodontal therapy
• Plaque sampling can be performed at the initial
examination, root planing, reevaluation, or SPT
appointment. Clinical indications for microbial testing
include aggressive periodontal disease, diseases
refractory to standard mechanical therapy, and
periodontitis associated with systemic conditions.
• Antibiotics have been shown to have value in
reducing the need for periodontal surgery in patients
with chronic periodontitis.

periodontal therapy
• Antibiotic therapy should not be used as a
monotherapy. That is, it must be part of the
comprehensive periodontal treatment plan. This
therapy should have debridement of root surfaces,
optimal oral hygiene, and frequent SPT at the center
of therapy.
• An antibiotic strength 500 times the systemic
therapeutic dose may be required to be effective
against the bacteria arranged in biofilms. It is
therefore important to disrupt this biofilm physically
so that the antibiotic agents can have access to the
periodontal pathogens.

periodontal therapy
• Slots and co-workers have described a series of steps using
antimicrobial agents for enhancing regenerative healing. They
recommend starting antibiotics 1 to 2 days before surgery and
continuing for a total of at-least 8 days. However, the value of
this regimen has not been well documented, further studies are
encouraged.
• Using evidence based techniques, meta-analysis has shown
statistically significant improvements in attachment loss when
tetracyclines and metronidazole are used as adjuncts to SRP.
Clindamycin and doxycycline also showed statistically significant
increases in attachment levels. There was borderline significance
using amoxicillin plus metronidazole because of smaller number of
pooled subjects in the meta-analysis. Spiramycin and penicillin
appeared to give the least improvement.

periodontal therapy
Improvements in attachment levels were consistent for chronic
and aggressive periodontitis, although aggressive periodontitis
patients benefited more from the antibiotics. Haffajee et. al.
concluded that data support similar effects for most antibiotics.
Therefore, the selection of an antibiotic must be made based on
other factors.
The clinician must make the final decision with the
patient. Risks and benefits concerning antibiotics as adjuncts to
periodontal therapy must be discussed with the patient before
antibiotics are used.
Dosage adjustment of all antibiotics is required in
children to avoid excessive concentrations, and in the elderly
since advanced age may be associated with altered
pharmacokinetics of antibiotics.

periodontal therapy

Tetracyclines
• Tetracyclines have been widely used in the
treatment of periodontal diseases.
• Frequently used in treating refractory
periodontitis, including localized
aggressive periodontitis.
• Have the ability to concentrate in the
periodontal tissues and inhibit the growth of
Actinobacillus actinomycetemcomitans.
• Also exert an anticollagenase effect that can
inhibit tissue destruction and may aid bone
regeneration (Host Modulation).

Tetracyclines
Pharmacology.
• A group of antibiotics having a nucleus of 4 cyclic rings,
produced naturally from certain species of Streptomyces or
derived semisynthetically.
• Bacteriostatic and are effective against rapidly multiplying
bacteria.
• Generally are more effective against gram-positive bacteria than
gram-negative bacteria.
• Effective in treating periodontal diseases in part because their
concentration in the gingival crevice is 2 to 10 times
that in serum. This allows a high drug concentration to be
delivered into periodontal pockets. In addition, several studies
have demonstrated that tetracyclines at a low gingival crevicular
fluid concentration(2 to 4 g/ml) are very effective against
many periodontal pathogens.

Tetracyclines
On the basis of chronology of development,
convenience of description, they may be
divided into three groups
• Group I Group II Group III
Chlortetracycline Demeclocycline Doxycycline
Oxytetracycline Methacycline Minocycline
Tetracycline Lemecycline

Tetracyclines
Mechanism of action-
• Primarily bacteriostatic.
• Inhibit protein synthesis by binding to 30S ribosomes
in susceptible organism. Thus, attachment of
aminoacyl-t-RNA to the mRNA-ribosome complex is
interfered with. As a result, peptide chains fail to
grow.
• The sensitive organisms have an energy dependant
active transport process which concentrates
tetracyclines intracellularly.

Tetracyclines
• In gram negative bacteria, tetracyclines diffuse
through porin channels as well. The more lipid
soluble members (doxycycline, minocycline) enter by
passive diffusion also (this is partially responsible for
their higher potency).
• The carrier involved in active transport of
tetracyclines is absent in the host cells. Moreover,
protein synthesizing apparatus of host cells is less
sensitive to tetracyclines. These two factors are
responsible for the selective toxicity of tetracyclines
for the microbes.

Tetracyclines
• Resistance develops in a slow, graded manner. In
such bacteria, usually the tetracycline concentrating
mechanism becomes less efficient or the bacteria
acquire the capacity to pump it out.
• Another mechanism is plasmid mediated synthesis of
a ‘protection’ protein which protects the ribosomal
binding site from tetracycline. However some
organisms not responding to other tetracyclines may
be inhibited by therapeutically attained
concentrations of minocycline.

Tetracyclines
Clinical Use
• Investigated as adjuncts in the treatment of localized aggressive
periodontitis (LAP). A. actinomycetemcomitans is a frequent
causative microorganism in LAP & is tissue invasive. Therefore
mechanical removal of calculus & plaque from root surfaces
may not eliminate this bacterium from the periodontal tissues.
Systemic tetracycline can eliminate tissue bacteria & has been
shown to arrest bone loss & suppress A.
actinomycetemcomitans levels in conjunction with SRP.
• This combined form of therapy allows mechanical removal of
root surface deposits and elimination of pathogenic bacteria
from within the tissues. Increased post treatment bone levels
have been noted using this method.

Tetracyclines
• Long-term use of low doses of tetracyclines has been advocated
in the past. One long-term study of patients taking low doses of
tetracycline (250 mg per day for 2 to 7 years) showed
persistence of deep pockets that did not bleed on probing.
These sites contained high proportions of tetracycline-resistant,
gram-negative rods (i.e., Fusobacterium nucleatum). After the
antibiotic was discontinued, the flora was characteristic of sites
with disease.
• Therefore it is not advisable to engage in long-term regimens of
tetracyclines because of the possible development of resistant
bacterial strains. Although commonly used in the past as
antimicrobial agents, especially for LAP and other types of
aggressive periodontitis, tetracyclines now tend to be replaced
by more effective combination antibiotics.

Tetracyclines
• Because of increased resistence to
tetracyclines, metronidazole or
amoxicillin with metronidazole has been
found more effective in treating
aggressive periodontitis in children.
• Some investigators believe
metronidazole combined with
amoxicilin-clavulanic acid is the
preferable antibiotic.

Tetracyclines
• Pharmacokinetics- older tetracyclines are incompletely
absorbed from the GIT; absorption is better if taken on empty
stomach. Doxycycline & minocycline are completely absorbed
irrespective of food.
• Concentrate in liver, spleen and bind to connective tissue in
bone and teeth. Intracellularly, they bind to mitochondria.
Minocycline accumulates in body fat. CSF concentration is about
1/4th plasma concentration.
• Most tetracyclines are primarily excreted in urine by glomerular
filteration. Thus, dose has to be reduced in renal failure;
doxycycline being an exception to this. Partially metabolized &
significant amount enters bile- some degree of enterohepatic
circulation occurs.
• Secreted in milk in sufficient amount to effect the suckling
infant.

Tetracyclines
Drug interactions-
• Enzyme inducers like phenobarbitone and
phenytoin, and carbamazepine enhance
metabolism and reduce the t1/2 of
doxycycline.
• have a chelating property- they form
insoluble complexes with calcium and other
metals. Milk, iron preparations, nonsystemic
antacids and sucralfate reduce their
absorption.
• increase the serum levels of digoxin.

Tetracyclines
Adverse effects-
Irritative effects - epigastric pain, nausea, vomiting
and diahorrea due to the irritant property.
Dose related toxicity-
• liver damage- fatty infiltration of liver and jaundice.
Can precipitate acute hepatic necrosis in pregnant
women.
• kidney damage- prominent in the presence of
existing kidney disease. All tetracyclines except
doxycycline, accumulate and enhance renal failure.

Tetracyclines
• phototoxicity- a sunburn like, skin reaction on
exposed parts is seen in some individuals. A higher
incidence is noted with demeclocycline and
doxycycline.
• teeth and bones- have a chelating property.
Calcium-tetracycline chelate gets deposited in
developing teeth and bones. Mid-pregnancy to 5
months of extra-uterine life, deciduous teeth are
affected, brown discoloration and ill-formed teeth. 3
month to 5 years of age, permanent anterior
dentition is affected. Late pregnancy or childhood,
temporary suppression of bone growth can occur.
The ultimate effect on stature is mostly insignificant.

Tetracyclines
• antianabolic effect- reduce protein synthesis & have an
overall catabolic effect. They induce a negative nitrogen
balance and can increase blood urea.
• vestibular toxicity- minocycline has produced ataxia, vertigo,
nystagmus , which subside when discontinued.
Hypersensitivity – though uncommon with tetracyclines,
skin rashes, urticaria, glossitis and pruritis have been
reported.
Superinfection – most common antibiotics responsible for
superinfection, because they cause marked suppression of
resident microflora. Intestinal superinfection is the most
prominent; pseudomembranous enterocolitis being most
serious. Doxycycline and minocycline are less liable to cause
diarrhea because only small amounts reach the lower bowel
in active form.

Specific Agents
• Tetracycline, Minocycline, and Doxycycline- all
semisynthetic members of the tetracycline
group-have been used in periodontal therapy.
TETRACYCLINE.
• Tetracycline requires administration of 250
mg q.i.d. It is inexpensive, but compliance
may be reduced by having to take four
capsules per day. Plasma t1/2- 6-10 hrs.
• Achromycin, Hostacyclin, Idilin – 250, 500 mg cap.

MINOCYCLINE.
• Effective against a broad spectrum of
µorganisms.
• In patients with adult periodontitis, it
suppresses spirochetes and motile rods as
effectively as SRP, with suppression
remaining evident for up to 3 months after
therapy.
• Can be given twice a day, thus facilitating
compliance when compared with tetracycline.

MINOCYCLINE.
• Although associated with less photo- and
renal toxicity than tetracycline, it may cause
reversible vertigo.
• Administered in a dosage of 200 mg per day
for 1 week results in a reduction in total
bacterial counts, complete elimination of
spirochetes for periods of up to 2 months,
and improvement in all clinical parameters.
• Plasma t1/2- 18-24 hrs.
• Cyanomycin – 50, 100 mg caps.

DOXYCYCLINE
• Has the same spectrum of activity as
minocycline and may be equally as effective.
• Because it can be given only once daily (qd),
patients may be more compliant.
• Compliance is also favored because its
absorption from the GIT is not altered by
calcium, metal ions, or antacids, as is
absorption of other tetracyclines.

DOXYCYCLINE
• Recommended dosage when used as an antimicrobial
agent is 100 mg twice daily the first day, then 100
mg once daily. To reduce GI upset, 50 mg can be
taken BD.
• When used in a subantimicrobial dose to inhibit
collagenase, it is recommended in a 20-mg dose
twice daily. Periostat (Collagenex Pharmaceutical Inc)
& generic forms are available in a dose of 20 mg
doxycycline.
• Plasma t1/2- 18-24 hrs.
• % absorption after oral administration- 93
• Peak serum level 2-4 µg/ml.
• Dox T, Microdox, Tetradox, Doxycaps – 100 mg

HOST MODULATION
Doxycycline Hyclate
• The U.S. Food and Drug Administration recently granted
marketing approval for doxycycline hyclate (Periostat) for the
adjunctive treatment of periodontitis.
• Periostat, available as a 20-mg capsule of doxycycline hyclate, is
prescribed for use by patients twice daily.
• The mechanism of action is by suppression of the activity of
collagenase, particularly that produced by PMNs.
• Although this drug is in the antibiotic family, it does not produce
antibacterial effects because the dose of 20 mg twice daily is
too low to affect bacteria.
• As a result, resistance to this medication has not been seen.

HOST MODULATION
• Four double-blind, clinical, multicenter studies of more than 650
patients have demonstrated that doxycycline hyclate improves
the effectiveness of professional periodontal care and slows the
progression of the disease process.
• The results of the first three studies showed that doxycycline
hyclate resulted in approximately a 50% improvement in clinical
attachment levels in pockets with probing depths (PD) of 4 to 6
mm and a 34% improvement in pockets with probing depths ≥7
mm.
• It was also noted that attachment loss was prevented in sites
with normal probing depths (0 to 3 mm), whereas the placebo
groups lost 0.13 mm at 12 months (p = 0.05).
(Caton et. al., Ciancio et. al. )

HOST MODULATION
• Caton and co-workers have shown statistically
significant reductions in probing depths and increases
in clinical attachment levels with adjunctive Periostat
in conjunction with root planing at 3-, 6-, and 9-
month evaluations compared with placebo groups
undergoing root planing alone. Although statistically
significant, the net changes were considered limited
alterations in patients with moderate to severe
chronic periodontitis.
• Results of safety studies showed the use of 20-mg
Periostat BID either with or without mechanical
therapy (SRP) did not exert an antimicrobial effect on
the periodontal microflora and did not result in a
detrimental shift in the normal flora.

HOST MODULATION
• The colonization or overgrowth of the
periodontal pocket by bacteria resistant
to doxycycline, tetracycline,
minocycline, amoxicillin, erythromycin,
or clindamycin has not been observed.
• In addition, no evidence of any
tendency toward the acquisition of
multiantibiotic resistance was found.

Metronidazole
Pharmacology
• A nitroimidazole compound developed in France in 1959 to treat
protozoal infections.
• Bactericidal to anaerobic organisms and does not affect aerobic
bacteria.
• Not the drug of choice for treating A.actinomycetemcomitans
infections, but it may be effective at therapeutic levels owing to
its hydroxy metabolite.
• However, it is effective against
A.actinomycetemcomitans when used in combination
with other antibiotics.
• Also effective against anaerobes such as Porphyromonas
gingivalis and Prevotella intermedia.

Metronidazole
Mechanism of action-
• Not well understood.
• After entering the microorganism by diffusion, its
nitro group is reduced to intermediate compounds
which cause cytotoxicity probably by disrupting
bacterial DNA synthesis in conditions in which a low
reduction potential is present.
• Its selectively high activity against anaerobic
organisms has suggested interference with electron
transport from NADPH to other reduced substrates.

Metronidazole
Pharmacokinetics
• Almost completely absorbed from the small
intestines: little unabsorbed drug reaches the colon.
• Widely distributed in the body and attains therapeutic
concentration in the saliva.
• Metabolized in the liver primarily by oxidation and
glucoronide conjugation, and excreted in the urine.
• Plasma t1/2 is 8 hrs.
• % administration after oral absorption- 90
• Peak serum level- 20-25 µg/ml.

Metronidazole
Clinical Usage
• Has been used clinically to treat gingivitis,
acute necrotizing ulcerative gingivitis, chronic
periodontitis, and aggressive periodontitis. It
has been used as monotherapy and also in
combination with both root planing and
surgery or with other antibiotics.
• Has been used successfully for treating NUG.

Metronidazole
• Studies in humans (Lekovic et. al, 1983;
Loesche et. al, 1992) have demonstrated the
efficacy of metronidazole in the treatment of
gingivitis and periodontitis.
• A single dose (250 mg orally) appears in both serum
and gingival fluid in sufficient quantities to inhibit a
wide range of suspected periodontal pathogens.
• Administered systemically (750 to 1000 mg/day for 2
weeks), this drug reduces the growth of anaerobic
flora, including spirochetes, and decreases the clinical
and histopathologic signs of periodontitis.

Metronidazole
• Most commonly prescribed regimen- 250 mg thrice daily (tid)
for 7 days.
• Loesche and co-workers found that 250 mg of metronidazole
given three times daily for 1 week was of benefit to patients
with a diagnosed anaerobic periodontal infection.
• In this study, an infection was considered anaerobic when
spirochetes composed 20% or more of the total microbial count.
Metronidazole used as a supplement to rigorous scaling and
root planing resulted in a significantly reduced need for surgery
when compared with root planing alone. The bacteriologic data
of this study showed that only the spirochete count was
significantly reduced.
• Currently, the critical level of spirochetes needed to diagnose an
anaerobic infection, the appropriate time to give metronidazole,
and the ideal dosage or duration of therapy are unknown.

Metronidazole
• As monotherapy, inferior and at best only equivalent to root
planing.
• Offers some benefit in the treatment of refractory
periodontitis, particularly when used in combination with
amoxicillin.
• Soder and co-workers showed that metronidazole was more
effective than placebo in the management of sites unresponsive
to root planing. Nevertheless, many patients still had sites that
bled on probing despite metronidazole therapy.
• Studies have suggested that when combined with amoxicillin or
amoxicillin-clavulanate potassium, metronidazole may be of
value in the management of patients with localized aggressive
or refractory periodontitis.

Metronidazole
Side Effects
• Anorexia, nausea, metallic taste and
abdominal cramps are the most common.
Looseness of stool is occasional.
• less frequent side effects are- headache,
glossitis, dryness of mouth, dizziness, rashes
and transient neutropenia.
• prolonged administration may cause
peripheral neuropathy and CNS effects.
Seizures have followed very high doses.

Metronidazole
Drug interactions
• Has an antabuse effect when alcohol is ingested. Response
generally proportional to the amount ingested and can result in
severe cramps, nausea, and vomiting. Products containing
alcohol should be avoided during therapy and for at least 1 day
after therapy is discontinued.
• Also inhibits warfarin metabolism.
• Patients undergoing anticoagulant therapy should avoid it
because it prolongs prothrombin time.
• Should be avoided in patients who are taking lithium since it is
found to decrease renal elimination of lithium.
• barbiturates and hydantoin decrease the effectiveness of
metronidazole.

Metronidazole
Contraindications- neurological
disease, blood dyscrasias, first trimester
of pregnancy (possible risk of
teratogenicity), chronic alcoholism.
• Flagyl, Metrogyl, Aldezole, Aristogyl, Metron - 200, 400 mg tab.

Penicillins
Pharmacology
• Drugs of choice for the treatment of many serious infections in
humans and are the most widely used antibiotics.
• Natural and semisynthetic derivatives of broth cultures of the
Penicillium mold.
• The penicillin nucleus consists of fused thiazolidine and -lactam
rings to which side chains are attached through an amide
linkage.
• The side chain of natural penicillin can be split by an amidase to
produce 6-amino-penicillanic acid.
• Other side chains can be attached to it resulting in different
semisynthetic penicillins with unique antibacterial activities and
different pharmacokinetic profiles.

Penicillins
Mechanism of action
• Interfere with the synthesis of bacterial cell wall
by interfering with cross linking (which maintains the
close knit structure of cell wall) & are bactericidal.
Penicillin binding proteins (PBPs) have been located
in the bacterial cell membrane. Each organism has
several PPBs & PPBs obtained from different
organisms differ in their affinity towards -lactam
antibiotics. This fact probably explains their differing
sensitivity to the various -lactam antibiotics.
• When bacteria divide in the presence of a -lactam
antibiotic, cell wall deficient forms are produced.
Because the interior of the bacterium is
hyperosmotic, the CWD forms swell and burst,
resulting in bacterial lysis.

Penicillins
• The peptidoglycan cell wall is unique to
bacteria. No such substance is synthesized by
higher animals. Therefore, penicillin is
practically non-toxic to man.
• In gram positive bacteria, the cell wall is
almost entirely made of peptidoglycan. In
gram negative bacteria, it consists of
alternating layers of lipoprotein and
peptidoglycan. This may be the reason for a
higher susceptibility of gram positive bacteria
to penicillin.

Penicillins
Clinical Usage
• Penicillins other than amoxicillin and
amoxicillin-clavulanate potassium
(Augmentin) have not been evaluated, and
their use in periodontal therapy does not
appear to be justified.
Side Effects
• May induce allergic reactions and bacterial
resistance; up to 10% of patients may be
allergic to penicillin.

Penicillins
Amoxicillin
• A semisynthetic penicillin with an extended antimicrobial
spectrum that includes gram-positive and gram-negative bacteria.
• It is an amino penicillin, i.e. it has an amino substitution in the side
chain.
• Demonstrates excellent absorption after oral administration.
Amoxicillin is susceptible to penicillinase, a - lactamase produced
by certain bacteria that breaks the penicillin ring structure and
thereby renders penicillins ineffective.
• May be useful in the management of patients with aggressive
periodontitis, both in the localized and generalized forms.
Recommended dosage is 500 mg tid for 8 days.
• Plasma t1/2 is 1 hour. % administration after oral absorption- 75
• Peak serum level- 5-8 µg/ml.
• Novamox, Synamox, Mox, Amoxyl – 250, 500 mg caps.

Amoxicillin-Clavulanate (Augmentin).
• The combination of amoxicillin with clavulanate
potassium makes Augmentin resistant to penicillinase
enzymes produced by some bacteria.
• May be useful in the management of patients with
refractory or localized aggressive periodontitis.
• Bueno and co-workers reported that Augmentin
arrested alveolar bone loss in patients with
periodontal disease that was refractory to treatment
with other antibiotics including tetracycline,
metronidazole, and clindamycin.
• Contains amoxicillin 250mg + clavulanic acid 125 mg.
• Augmentin, Enhancin, Amonate, Mox clav – 375 mg tab

Clindamycin
Pharmacology
• Lincosamide antibiotic similar in mechanism of action
and spectrum of activity to erythromycin.
• Effective against anaerobic bacteria. Effective in
situations in which the patient is allergic to penicillin.
• Oral absorption good.
• Penetrates to most skeletal and soft tissues, but not
to brain and CSF; accumulates in neutrophils and
macrophages.
• Is largely metabolized and metabolites are excreted
in urine and bile.
• t1/2 is 3 hours. % absorption after oral admin. 90.
• Peak serum level- 5 µg/ml

Clindamycin
Clinical Usage
• Has shown efficacy in patients with
periodontitis refractory to tetracycline
therapy.
• Walker and co-workers have shown aid in
stabilizing refractory patients. Dosage used in
their studies was 150 mg q.i.d for 10 days.
• Jorgensen and Slots have recommended a
regimen of 300 mg twice daily for 8 days.

Clindamycin
Side Effects
• Has been associated with pseudomembranous colitis, but the
incidence is higher with cephalosporins and ampicillin. When
needed, it can be used with caution. It is not indicated in
patients with a history of colitis. Diarrhea or cramping that
develops during the use of clindamycin may be indicative of
colitis, and clindamycin should be discontinued. Metronidazole
can be used as an alternative.
Drug interactions
• Anti-diarrheals (kaolin) decrease the absorption of clindamycin.
• Muscle relaxants (diazepam) - increased frequency and duration
of respiratory paralysis.
• Erythromycin- mutual antagonism.
• Dalcap, dalcin – 150 mg cap.

Ciprofloxacin
Pharmacology
• a quinolone active against gram-negative
rods, including all facultative and some
anaerobic putative periodontal pathogens.
• Quinolones are entirely synthetic
antimicrobials.
• Ciprofloxacin is the most potent first
generation fluoroquinolone.
• Fluoroquinolones are quinolone antimicrobials
having one or more fluorine substitutions.

Ciprofloxacin
Mechanism of action
• They inhibit the bacterial enzyme DNA gyrase which
nicks double stranded DNA, introduces negative
supercoils and then reseals the nicked ends.
• The bactericidal action probably results from
digestion of DNA by exonucleases whose production
is signaled by the damaged DNA.
• In place of DNA gyrase, the mammalian cells possess
an enzyme tropoisomerase II which has a very low
affinity for FQs- hence low toxicity to the host cells.

Ciprofloxacin
Pharmacokinetics-
• Rapidly absorbed orally, but food delays absorption
and 1st pass metabolism occurs.
• The most prominent feature is high tissue
penetrability: concentration in lung, sputum, muscle,
bone, prostrate and phagocytes exceeds that in
plasma, but CSF and aqueous levels are lower.
• It is primarily excreted in urine, both by glomerular
filtration and tubular secretion.
• Urinary and biliary concentrations are 10-50 fold that
in plasma.

Ciprofloxacin
• Oral bioavailability(%)- 60-80
• plasma protein binding- 20-35
• Vol. of distribution (L/Kg)- 3-4
• Percentage absorption after oral
administration - 70
• elimination t1/2 (hr) – 3-5
• Peak serum level- 1.5 µg/ml
• routes of administration- oral, i.v.
• dose mg BD oral - 250-750
i.v. - 100- 200

Ciprofloxacin
Clinical Usage.
• Because it demonstrates minimal effect on
Streptococcus species, which are associated
with periodontal health, ciprofloxacin therapy
may facilitate the establishment of a
microflora associated with periodontal health.
• At present, ciprofloxacin is the only antibiotic
in periodontal therapy to which all strains of
A. actinomycetemcomitans are susceptible.
• It also has been used in combination with
metronidazole.

Ciprofloxacin
Side Effects.
• Have a good safety record. Side effects occur
in about 10% patients but are generally mild;
withdrawal needed only in about 1.5%
patients.
• Nausea, headache, anxiety, restlessness,
vomiting and abdominal discomfort have
been associated with ciprofloxacin.
• Known to cause arthropathy in animals,
hence avoided in pregnancy.

Ciprofloxacin
Drug interactions
• Quinolones inhibit the metabolism of theophylline, and caffeine
and concurrent administration can produce toxicity.
• Quinolones have also been reported to enhance the effect of
warfarin and other anticoagulants.
• Cimetidine- increased serum levels of fluoroquinolones.
• Cyclosporine- increased serum levels of cyclosporine.
• NSAIDs- increased risk of stimulation of CNS.
• Probenecid- decreased ciprofloxacin clearance.
• Sucralfate- decreased absorption of quinolones.
• Ciplox, ciproflox, cifran, quintor – 250, 500 mg tab.

Macrolides
Pharmacology.
• Contain a many-membered lactone ring to
which one or more deoxy sugars are
attached.
• Inhibit protein synthesis by binding to the
50S ribosomal subunits of sensitive
microorganisms.
• Can be bacteriostatic or bactericidal,
depending on the concentration of the drug
and the nature of the microorganism.

Macrolides
Drug interactions
• Carbamazepine – increased serum levels of carbamazepine with
nystagmus nausea, vomiting and ataxia.
• Cisapride- increased cisapride concentration with risk of
arrhythmias.
• Cyclosporine- increased serum levels of cyclosporine with
toxicity.
• Methylprednisolone- increased steroid concentration.
• Non sedating antihistamines (terfenadine, astemizole)-
increased antihistamine concentration with life threatening
arrhythmias.
• Theophylline – increased serum levels of theophylline with
nausea, vomiting, seizures and apnea.
• Oral anticoagulants (warfarin)- increased anticoagulant effect.

Macrolides
Clinical Usage.
• Erythromycin does not concentrate in
gingival crevicular fluid, and it is not
effective against most putative
periodontal pathogens.
• For these reasons, it is not
recommended as an adjunct to
periodontal therapy.

Azithromycin
• A member of the azalide class of macrolides.
• Effective against anaerobes and gram-negative bacilli.
• After an oral dosage of 500 mg once daily for three consecutive
days, significant levels of azithromycin can be detected in most
tissues for 7 to 10 days.
• Its concentration in tissue specimens from periodontal lesions is
significantly higher than that of normal gingiva.
• It has been proposed that azithromycin penetrates fibroblasts
and phagocytes in concentrations 100 to 200 times greater than
that of the extracellular compartment.
• Actively transported to sites of inflammation by phagocytes and
then released directly into the sites of inflammation as the
phagocytes rupture during phagocytosis.
• Therapeutic use requires a single dose of 250 mg per day for 5
days after an initial loading dose of 500 mg.

Azithromycin
Pharmacokinetics-
• Acid stable, has a rapid oral absorption, marked tissue
distribution and intracellular penetration. Concentration in most
tissues exceeds that in plasma.
• Particularly high concentrations are attained inside fibroblasts
and macrophages: volume of distribution is about 30L/Kg. Slow
release from the intracellular sites contributes to its long
terminal t1/2 of more than 50hr. It is largely excreted in bile,
renal excretion being less than 10%.
• Side effects- mild gastric upset, abdominal pain (less than
erythromycin), headache, dizziness.
• Plasma t1/2- 12 hrs, % absorption after oral adminstration- 37
• Peak serum level- 0.4 µg/ml.
• Aziwok, azithral, zithromac- 250 mg tab.

SERIAL AND COMBINATION
ANTIBIOTIC THERAPY
Rationale
• Because periodontal infections may contain a wide diversity of
bacteria, no single antibiotic is effective against all putative
pathogens.
• Differences exist in the microbial flora associated with the
various periodontal disease syndromes. These "mixed"
infections can include a variety of aerobic, microaerophilic, and
anaerobic bacteria, both gram negative and gram positive.
• In these instances, it may be necessary to use more than one
antibiotic, either serially or in combination.
• However, before combinations of antibiotics are used, the
periodontal pathogen(s) being treated must be identified and
antibiotic susceptibility testing performed.

ANTIBIOTIC THERAPY
Clinical Use
• Antibiotics that are bacteriostatic (e.g., tetracycline) should not be used
simultaneously with bactericidal antibiotic (e.g., amoxicillin) because
the bactericidal agents exert activity during cell division which is
impaired by the bacteriostatic drug. (antagonistic action)
• When both types of drugs are required, they are best given serially,
not in combination.
• Rams and Slots reviewed combination therapy using systemic
metronidazole along with amoxicillin, Augmentin, or ciprofloxacin. The
metronidazole-amoxicillin and metronidazole-Augmentin combinations
provided excellent elimination of many organisms in adult and localized
aggressive periodontitis that had been treated unsuccessfully with
tetracyclines and mechanical debridement. These drugs have an
additive effect regarding suppression of A. actinomycetemcomitans.

ANTIBIOTIC THERAPY
• Tinoco and coworkers found metronidazole and
amoxicillin to be clinically effective in treating LAP,
although 50% of patients harbored A.
actinomycetemcomitans one year later.
• Metronidazole-ciprofloxacin combination is effective
against A. actinomycetemcomitans. Metronidazole
targets obligate anaerobes, and ciprofloxacin targets
facultative anaerobes. This is a powerful combination
against mixed infections. Studies of this drug
combination in the treatment of refractory
periodontitis have documented marked clinical
improvement.

ANTIBIOTIC THERAPY
• This combination may provide a therapeutic benefit
by reducing or eliminating pathogenic organisms and
a prophylactic benefit by giving rise to a
predominantly streptococcal microflora.
• Systemic antibiotic therapy combined with
mechanical therapy appears valuable in the
treatment of recalcitrant periodontal infections and
LAP infections involving A. actinomycetemcomitans.
• Antibiotic treatment should be reserved for specific
subsets of periodontal patients who do not respond
to conventional therapy. Selection of specific agents
should be guided by the results of cultures and
sensitivity tests for subgingival plaque µorganisms.

Selection of antibiotics
• Relatively few studies have been performed
regarding which antibiotics should be selected
for aggressive periodontitis patients in whom
the subgingival microbiota have been
characterized through microbiological testing.
• In addition, the optimal dose of antibiotics
remains unclear since most current antibiotic
regimens are empirically developed rather
than through systematic research.

• Metronidazole may arrest the disease
progression in recalcitrant periodontitis
patients with P gingivalis or P
intermedia infections with few or no
other potential pathogens (Loesche et
al, 1992).
• It can readily attain effective
antibacterial concentrations in GCF and
gingival tissue.

• Clindamycin has demonstrated efficacy
in recurrent periodontitis and may be
considered in periodontal infections of
Peptostreptococcus, β- hemolytic
streptococci and various oral gram
negative anaerobic rods (Walker C,
Gordon J, 1990).
• E. corrodens is resistant to clindamycin.

• Tetracyclines may be indicated in periodontal infections in which
A actinomycetemcomitans is a prominent pathogen.
• However, they may not be sufficient in case of mixed infections.
• They also have the possible benefit of inhibiting the gingival
collagenases.
• Doxycycline has the highest protein binding capacity and
longest half life; and Minocycline has best absorption and tissue
penetration of the tetracyclines.
• Recently, the GCF concentration of systemically administered
tetracyclines was reported to be less than that of plasma
concentration and vary widely among individuals (between 0
and 8 µg/ml), with approximately 50% of samples not achieving
a level of 1 µg/ml, possibly explaining much of the
variability in clinical response to systemic tetracyclines observed
in practice.

• Fluoroquinolones are effective against
enteric rods, pseudomonads, A
actinomycetemcomitans, staphylococci
and other periodontal microorganisms.
• They penetrate readily into diseased
periodontal tissues and GCF and may
reach higher concentration than that of
serum.

• Azithromycin exhibits an excellent
ability to penetrate both healthy and
diseased periodontal tissues.
• It is highly active against many
periodontal pathogens although some
enterococcus, staphylococcus, E
corrodens, F nucleatum and
peptosteptococcus strains may exhibit
resistance.

• Metronidazole plus amoxicillin provides a relatively predictable
eradication of A actinomycetemcomitans and marked
suppression of P. gingivalis in aggressive forms of adolescent
periodontitis and recalcitrant adult periodontitis.
• Metronidazole plus ciprofloxacin may substitute for
metronidazole plus amoxicillin in individuals who are allergic to
β-lactam drugs and are at least 18 years of age.
• This is also a valuable drug combination in periodontitis patients
having mixed anaerobic enteric rod infections.
• Non periodonopathic viridans streptococcal species that have
the potential to inhibit several pathogenic species (beneficial
organisms) are resistant to the metronidazole-ciprofloxacin
combination and may recolonize in treated subgingival sites.

• In addition to reducing the levels of treated periodontopathic
bacteria, systemic antibiotic therapy may lead to increased
levels of antibiotic resistant innocent or beneficial bacteria like
streptococci and actinomycetes.
• Subgingival overgrowth of periodontally harmless bacteria may
occupy niches previously inhabited by periodontal pathogens,
and because of antagonistic bacterial interactions delay or
prevent major gram negative pathogens from recolonizing
subgingival sites.
• Antibiotic therapy is indicated for periodontal abscess with
systemic manifestations (fever, malaise, lymphadenopathy).
Antibiotics for the treatment of abscesses should be prescribed
in conjunction with surgical incision and drainage.

Antibiotic regimen for adult patients with
acute periodontal abscesses
• Amoxicillin- loading dose of 1 g followed by 500 mg
tid for 3 days, followed by patient evaluation to
determine whether further antibiotic treatment or
dose adjustment is required.
• With allergy to β- lactam drugs-
• Azithromycin – loading dose of 1.0 g on day 1
followed by 500 mg/ q.d for days 2 and 3. or,
• Clindamycin – loading dose of 600 mg on day 1
followed by 300 mg qid for 3 days.

Antibiotics Used to Treat Periodontal Diseases:
Their Major Features and Indications
Category
/Family
Agent(s)
Used to
Treat
periodontal
disease
Major
Features
Indica-
tions
Penicillin
Amoxicillin
Extended spectrum of
antimicrobial
activity, excellent oral
adsorption; used
systemically.
LAP, GAP,
MRP, RP
Augmen-
tin
Effective against
penicillinase producing
microorganisms; used
systemically.
LAP, GAP,
MRP, RP

Tetracy
cline
Minocycline
Effective against broad
spectrum of microorganisms;
used systemically and
applied locally
(subgingivally).
LAP,
GAP,
MRP,
RP.
Doxycycline
spectrum of micro
organisms;
chemotherapeutically used in
subantimicrobial dose for
host modulation
Tetracycline
spectrum of
microorganisms; applied
locally.

Quinolone
Ciprofloxa-
cin
Effective against gram-
negative rods,
promotes health-associated
microflora.
LAP,
GAP,
MRP,
RP.
Macrolide Azithromy-
cin
Concentrates at sites of
inflammation;
used systemically.
Lincomy-
cin
derivative
Clindamy-
cin
Used in penicillin-allergic
patients;
effective against anaerobic
bacteria;
used systemically.

Nitro-
imida
zole
Metro-
nidazo
le
Effective against
anaerobic bacteria;
used systemically
and applied locally
(subgingivally) as a
gel.
LAP,
GAP,
MRP,
RP,
AP,
NUG

Common Antibiotic Regimens Used in Treating
Periodontal Diseases
Single agent Regimen Duration
Amoxicillin 500 mg 3 times
daily
8 days
azithromycin 500 mg once
daily
4-7 days
Ciprofloxacin 500 mg 2 times
daily
8 days
Clindamycin 300 mg 2 times
daily
8 days

Common Antibiotic Regimens Used in
Treating Periodontal Diseases
Single agent Regimen Duration
Doxycycline
or
minocycline
100- 200 mg
once daily
21 days
Metronida-
zole
250-500 mg 3
times daily
8 days

These regimens are prescribed with a review of the patient's medical history,
periodontal diagnosis, and antimicrobial testing. (Adapted from
Jorgensen MG, Slots J: Practical antimicrobial periodontal therapy.
Compend Contin Educ Dent 2000; 21:111.)
Combination
therapy
Regimen Duration
Metronidazole/
Amoxicillin
250 mg of each 3
times daily.
8 days
Metronidazole/
Ciprofloxacin
500 mg of each 2
times daily.
8 days

Antimicrobial agent Child dose(max)
Amoxicillin wt.< 20 kg- 20-40
mg/kg in divided doses
Clindamycin 8-12 mg/ kg in 3-4
equally divided doses.
Doxycycline or > 8 yrs, 4 mg/kg into
minocycline equally div doses b.i.d
1st day foll by 2mg/kg
single dose.

Antimicrobial agent Child dose(max)
Metronidazole not recommended for
children below 16.
Metronidazole/amoxicillin not recommended for
children below 16.
Metronidazole/ ciprofloxacin not recommended for
children below 16.

Development of antibiotic resistance
• Bacteria can be resistant in their natural state
(intrinsic) or become resistant (acquired) to
antibiotics in different ways.
• The emergence and spread of multiple resistant
organisms represent the convergence of a variety of
factors that include
• mutations,
• the exchange of genetic information among microorganisms and
• the development of environmental conditions (selective
pressure) that facilitate the development and spread of
antibiotic resistance
(Tenover, 2001).

• Intrinsic resistance refers to bacteria that are
insensitive, in their natural state, to an antibiotic
without the acquisition of resistance factors.
• Gram positive bacteria are surrounded by a thick
porous cell wall of peptidoglycans which offers little
or no resistance to the diffusion of small molecules
such as antibiotics.
• Gram-negative bacteria, however, have an additional
outer hydrophobic cell wall and a thin peptidoglycan
layer, which inhibits the diffusion of some unmodified
penicillins, conferring resistance to them.

• Indiscriminate antibiotic administration is contrary to
sound clinical practice and unnecessarily increases in
vivo resistance to antimicrobial agents that are
valuable in potentially fatal medical infections.
• Walker (1996) reported a significant increase in
tetracycline- and amoxicillin-resistant isolates in
subgingival samples from periodontitis patients
between 1990 and 1995.
• A number of authors recommend antimicrobial
susceptibility testing of isolated pathogens from non-
responding patients prior to systemic administration
of antibiotics.

• However, the subgingival microbial composition varies from pocket to
pocket (Mombelli et al, 2000), bacterial resistance can change during
biofilm growth and intra-strain differences in resistance profile exist,
and therefore the outcome of such susceptibility tests under planktonic
conditions, like dental plaque, remains questionable.
• The aggregation of bacteria in a biofilm indeed impairs the diffusion of
antibiotics or even inactivates them. High concentrations of the active
ingredient are needed before a beneficial effect can be expected.
• Estimations with biofilm experiments indicate that the necessary MICs
(minimal inhibitory concentration) of antimicrobials are at least 50X (or
even 210 000X) higher than for bacteria growing under planktonic
conditions (Anwar et al, 1992; Cargill et al, 1992; Brown and Gilbert,
1993; Slots and van Winkelhoff, 1993; Wilson, 1996; Gilbert
et al, 1997; Thrower et al, 1997; Kleinfelder et al, 1999).

Summary
• Severe periodontal infections represent such
a great threat to oral and possibly systemic
health that the prudent use of effective
antibiotics is ethically acceptable in
appropriately selected patients.
• However, the emerging antibiotic resistance
among human pathogens dictates a
restrictive and conservative use of systemic
antibiotics.

Summary
• Systemic antibiotic therapy in periodontics aims to
reinforce mechanical treatment and to support host
defenses in overcoming periodontal infections by
killing sub-gingival pathogens that remain after
periodontal instrumentation.
• Pathogens may escape the effect of mechanical
debridement because of their ability to invade
periodontal tissues, to reside in anatomical tooth
structures inaccessible to periodontal
instrumentation, or as a result of poor host defense.

Summary
• Systemic antibiotic therapy can provide
greatest benefit to periodontitis patients who
do not respond well to mechanical therapy or
who are experiencing fever or
lymphadenopathy.
• Single antimicrobial therapies may be able to
suppress various perio pathogens for a
prolonged period of time depending on the
effectiveness of the host defense of the
patient oral hygiene efforts.

Summary
• Combination drug therapies, which aim at
enlarging the antimicrobial spectrum and
exploiting synergy between antibiotics are
often indicated with complex mixed
periodontal infections.
• Prescription of any systemic antibiotic therapy
requires a careful analysis of patient’s medical
status and current medications.
• In severe infections, it may include antibiotic
sensitivity testing.

List of references
• Clinical periodontology- 10th edition- Newman MG, Takei HH,
Klokkevold PR, Carranza FA.
• Essentials of medical pharmacology- 4th edition- Tripathi KD.
• Position paper- systemic antibiotics in periodontics; J
Periodontol 2004;75:1553-1565.
• Ciancio S G: Systemic medications: clinical significance in
periodontics. J Clin Periodontol 2002; 29 (Suppl 2): 17–21.
• Quirynen M, Teughels W, van Steenberghe D- review article:
Microbial shifts after subgingival debridement and formation of
bacterial resistance when combined with local or systemic
antimicrobials. Oral Diseases (2003) 9 (Suppl. 1), 30–37.
• Walker C, Karpinia K: review- Rationale for use of antibiotics in
periodontics. J Periodontol 2002;73:1188-1196.

List of references
• Slots J. Selection of antimicrobial agents in periodontal
therapy. J Periodont Res 2002; 37; 389–398.
• Haffajee AD, Socransky SS, Gunsolly JC: Systemic anti-
infective periodontal therapy. A systematic review. Ann
Periodontol 2003;8:115-181.
• Powell CA, Mealy BL, Deas DE, McDonnell HT, Moritz AJ: Post
surgical infections: Prevalence associated with various
periodontal surgical procedures. J Periodontol 2005; 76: 329-
333.
• kleinefelder JW, Mueller RF, Lange DE: fluoroquinolones in
the treatment of Actinobacillus actinomycetemcomitans
associated periodontitis. J periodontol 2000;71:202-208.
• Proceedings of the 2nd european workshop on periodontology,
1996: chemicals in periodontics. Edited by: Lang NP, Karring
T, Lindhe J.

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