M.

Djanaluddin MG
Departement of Pharmacology
Achmad Yani School of Medicine

Antiinfective agents play an important role
in dentistry because:
Infection and after pain,is the dental
problem for which drugs are most aften
prescribed.

As the knowledge about the etiology of
dental diseases is countinually increasing
and the involvement of microorganisms
becoming understood, dental health care
workers continue to better a understood
the proper place of antibiotics and their
effect on microorganisms


Another important piece of the puzzle of
infection is the immunolgic response of the host
This puzzle piece has not yet led to therapeutic
intervention strategies.
Types of Dental Infection
1.Caries
Caries produced by Streptococcus mutant
First important dental infection of the
newly erupting teeth of of the young
patient
The traditional antiinfective agents have
not useful for this problem in the
general population.

The treatment of choice involve use of
floured water, local physical removal of
bacterial plaque, on regular basis (good
oral hygiene,dental prophylaxis), and
approprietly placed scalant
2.Periodontal disease:
It is the biggest dental problem
Caused by Actinobacillus actinomycesetem
comitans
Treatment that used localized method of the
drug delivery (e.g Tetracycline fibres) hold
promise for the future management of
periodontal disease
3.Localized Dental Infection
Extensios from either periodontic or endodontic
related source
For most localized dental infections,if adequate
drainage can beobtained antiinfective agent are
not indicated unless the patient is
immunocompromised.in occusional situation in
which antibiotic are indicated the antibiotic
choice is determine by the organism likely to be
present.


4.Systemic Isnfection
Systemic infection can be identified because
they produced systemic symptons as
fever,malaise and tachycardia.Lesion
associated with infections producing these
type of symptoms shoul be drained but if
this possible,antibiotic should be given.

The duration of therapy should include the
number of day for the number of days for
the signs and symptoms to be totvally gone
plus 2 or 3 days.
If the dental infection has systemic
symptoms the use of antiinfective agents is
indicated and may even be critical
DENTAL INFECTION EVOLUlTION
Dental infection often follow similar pathway
evolution from their begining to their end.
In the beginning the dental infection are primary
caused by gram positive cocci such as Streptococcus
viridans or -hemolytic streptococi.
After a short time to include variety of gram
positive and gram negative anaerobic
organism,such as Peptostreptococcus
(Peptococcus) and Bacteriodes.
At this point is termed mixed infection.
Over time the proportion of organismsthatbare
anaerobic increases.Wit additional time and no
treatment the infection progresses until it
consist of predominantly anaerobic flora

The choice of antibiotics depend on where in its
evolution .In the beginning infection organism most
likely to be present are gram positive cocci Penicillin
is the drug of choice,Amoxicillin is most often used
because it is less irritting to the stomach and can be
taken with food or milk.
cocci penicillin gram positive
DEFINITION
Antiinfective agents
Antiimicrobial agents
Antibiotic agents
Antibacterial agents
Antiviral agents
Anti fungal agents
Bactericidal
Bacteriostatic
Blood/serum levelconcentration (MIC)
Spectrum
Infection
Minimal Inhibitory (MIC)
Super/suprainfection
Synergism
Antonism
Potentiation

INFECTION
The factors that determine the likehood of mo
causing anfection are:
Vurulence of microorganisme
Number of microorganism
Resistence of host (Immunologic response)
CULTURE AND SENSITIVITY
Idealy,all infectons requiring antimicrobial therapy
would be cultured,and sensitivity tests would be
performed.
Culture an d sensivity is the only way to be sure that a
drug will kill or inhibit the growth of infecting
microorganism in a patient specific infection
In cases of a serious infection that is not responding
to treatment,it is imperative that a culture be taken
RESISTENCE
When a culture is taken,proper collection materials
(tubes or vials with correct media) and methods must
be used to obtain reliable result.
Dental professionals need to communicate to the
laboratory personnel the nature of approviate culture
to be taken
The laboratory personnel should performed a Gram
stain so thay they may report all of the bacteria that
are present an high number
SENSITIVITY
Observing wether the organism are sensitive or
resistent to certain test antibiotic assists in
determining which antibiotic to use in difficult
infections.Antiinfective, 1 or 2 days are required before
the results of this test are available
And may be changed,after the media results are
available.
If clinical respone has been adequate,often original
antibiotic is continued despite sensivity results
RESISTANCE
Resistance related to antibiotic is natural or acquired
ability of an organism to be immune to r to resist the
effects of an antiinfective agent.
Natural resistance because of the bacterias normal
properties such as lipid structur in the cell wall.
Acquired resistance occurs when an organism that was
previously sensitive to an antimirobial agent develops
resistance.
A decrease in the use of an antibiotic drcreases the
proportion of organism resistant to that antibiotic in
that given population.
The first organism,which is resistant to one or more
antibiotics.
The second organism which was not previously
resistant,thus becomes resistant to the same antibiotic
as the first organism without ever having been exposed
to that antibiotic
The three most common mechanisms of acquired
resistance are decrease in bacterial
permeability,theproduction of bacterial enzymes and
an alteration in the target site
INDICATION FOR ANTIMICROBE
1.Therapeutic indication
2.Prophylactic indication

H.M.DJAMALUDIN,DR.,Sp.FK.,M.KES
2014
INDICATION OF ANTIMICROBIAL
AGENTS
Two categories :
1. Prophylactic
2. Therapeutic

Therapeutic indication :
No simple rule to determine
Patient withouth immune deficiencies need no antibiotic to
manage their infection


SEVERAL FACTOR THAT MUST BE CONSIDERED

Patient
Best defence against patogen is host response, when these
defense lacking the need for antimicrobial is pressing.
Infection
Virulence & invasive of m.o are important in deciding the
acutness, if periodontal pocket (site) remains active despite
repeating root planing, use of antibiotic to alter flora maybe
considered. If antimicrobial agent are to be used, than
organism likely to produce the infection to antimicrobial agent
must be considered.
TABLE OF ANTIMICROBE AGENT
INFECTION SITUATION DRUG OF CHOICE ALTERNATIVE DRUGS
Periodontal disease
Acute necrotizing ulcerative ginggivitist
Abcess (perio)
LJP

Adult periodontitist

RAP

Penicillin VK
Amoxicillin
Penicillin VK
Doxycycline
Tetracycline
Not usually treated with drugs
Doxycycline
Tetracycline
Metronidazole

Metronidazole
Tetracycline
Tetracycline
Amoxicillin + metronidazole
Augmentine(Amoxicillin+Clavulanate)
Clindamycin

Amoxicillin + Metronidazole
Oral infection
Soft tissue infection
(Abcess, cellulitis, post surgical perocoronitis)


Osteomyelitis

Penicillin VK
Amoxicillin



Penicillin VK
Amoxicillin

Doxycycline
Clindamycin
Cephalosporine
Tetracycline

Clindamycin
Cephalosporine
TABLE OF ANTIMICROBE AGENT
INFECTION SITUATION DRUG OF CHOICE ALTERNATIVE DRUGS
Mixed infection insensitive to
Penicillin

Aerobes


Anaerobs & chronic infection




Amoxicillin


Metronidazole
Clindamycin



Cephalosporine
Sulfonamide
Tetracycline
Cephalosporine
Augmentine
Tetracycline
penicillin + Metronidazole

Prophylaxis for infective endocarditis
Prosthetic hearth valve



Patient with LJP


No penicillin allergy : amoxicillin


Doxycycline for 3 weeks followed by
usual regimen.



Penicillin allaergy
Clarithromycine
Azithromycin
Clindamycin

Prophylactic Indication
Few situation arise for whhich a definite indication for
indication for prophylactic (AHA and ADA):
1.History of infective endocarditis
2.Present of heart valve prosthesis
Congental heart disease
GENERAL ADVERSE REACTION
Superinfection
Overgrowth of an organism that different from the original
infecting organism and resistant to the agent being used.The
wider the spectrum of the antiinfective and the longer thebagent
is administered.

Allergic reaction
All antiinfective agent have potential to produce a variety of
allergic.Penicillin and cephalos porin are most allergenic than
other agents.Erythromycin and clindamycin have a low
allergenic potential


Drug interaction
Antiinfective can interact with other drugs and food
(minerals) e.c.:Oralcontraceptive,anticoagulant,
calcium.
Gatrointerstinal Complaints
Pregannacy Concideration

ORAL CONTRACEPTIVE
Some antibiotic have been found to decrease oral
contraceptive efficacy by increasing clearance
from the body.(Ampicillin and tetracyclines).
Antituberculosis;ripamficine induce metabolism
of oral contraceptives
ORAL ANTICOAGULANTS
Antiinfective agents can potetiate the effect of
oral anticoagulant.Oral anticoagulant are vitamin
K inhibitors,so interfering wih the production of
vitamin K could increase the anticoagulant effect.
Tetracyclines reduce the bacterial flora that
produce most of the vitamin K in human bodies.
Erythromycin inhibits the enzymes that
metabolize warfarin,leading to increase in
warfarin level.
GIT COMPLAIN
Allantiinfective agents can produce a variety of git
complains
The complain include:stomach pain ,increased
motility,and diarrhea.
.
The incidence depending on the particular
agent,the dose of the agent and wether the patient
takes the drug with food.Erythromycin is the
highest incidence of git complain
PREGNANCY CONSIDERATION
The antimicrobial agents that can be used during
pregnanct are limited
Penicillin and erythromycin have not been
associated with teratogenicity
Clindamycin is probably also acceptable
Metronidazole is not usually used during
pregnancy but exception exist
Tetracyclines are contraindicated because of their
efffect on teeth and skleton

DOSE FORM
Adult dose of antibiotics are commonly tablets
and capsules.
Childrens dose form,including liqui and
chewable antibiotic dose forms,contain sugar as
their sweetening agent
After the use of these agents,the parent or child
mush brush the teeth.
COST
Important factor in choosing antibiotic for a
patient.
Interfere the successful of medication
The best inexpensive antibiotic that can be taken
will be more effective than expensive one that
cannot be purchased.
PENICILLIN
Divided into four major groups
1.Penicillin G and V
2.Penicillinase resistant penicillin
3.Amoxicillin
4.Extended-spectrum penicillin
Source: The mold Penicillium notatum
Pharmacokinetic:
Penicillin can be administered either orally or
parenterally but should be applied topically.
Mechanism of Action:
Penicillin is a very potent bactericidal agent that
attaches in penicillin-binding proteins (PBPs) on the
bacterial cell membrane.PBPs involved in the synthesis
of the cell wall and the maintenance of the cells
structural integraty

SPECTRUM
Penicillin is a narrow spectrum antibiotic
RESISTANCE
It can occur by several different mechanism
Staphylococci produce penicillinase that
nactivate the penicillin moiety by cleaving the B-
lactam ring.

ADVERSE REACTION
Toxic,allergic or hypersensitivity
Penicillins toxicity is almost nonexist,large doses
have been tolerated without adverse because
penicillin have margin of safety.
With m ssive IV doses direct CNS irritation can
result convulsion
Penicillin G renal damage (fever,eosinophilia,
albuminuria and BUN)
ALLERGY and HYPERSENSITIVITY
Incidence:5%-10% of patients receiving penicillin
Oral penicillin are less common than with parenteral
penicillin
The types of reaction:
Anaphylactic reaction
Rash
Delay serum sickness
Oral lesions
Other reaction (Intertitial nephritis,hemolytic
anemia,and eosinophilia)
USES
Penicillin ios mportant antibiotic in medical and
dental practice.Its use in dentistry results ffrom
its bactericidal potency,lack toxicity,and
spectrum of action.
Penicillin effectiveness in the treatment of dental
infection is explained by effectiveness against
many aerobic and anaerobic bacteria.
Specific Penicillins
Penicillin G
Is available as sodium,potassium,procaine or
benzafhine salts.
These salts differ in their onset ofv action and
duration of action.
Caution:Sodium salts should not be avoided in
patients with a limited sodium intake such as CV
patients.Renal patients should not be given potassium
salts.Patients may be allergic to the procaine in
penicillin procaine
Penicillin V
Spectrum is similar to Penicillin G
The potassium salts of penicillin is more soluble
than the free acid and therefore is better
absorbed when takken orally.
PENICILLINAS PENICILLINS
Used only for penicillinase-producing
staphylococci.
EXP:Cloxacillin and Dicloxacillin
EXTENDED-SPECTRUM PENICILLINS
Carbenicillin:
Wider spectrum of action than penicillin G
MACROLIDES
The macrolides antibiotics consist of erythromycin
,clarythromycin and azithromycin
ERYTHROMYCIN:
Usually bacteriostatic
Interferes with protein synthesis by inhibiting the enzyme
peptidyl transferase at the 50S ribosomal subunit
The spectrum against gram-positive bacteria.
(Bordetella,Legonella,and
Actinomycesorganism,Mycoplasma
pneumoniae,E.hystolytica)
PHARMACOKINETICS
Route of administration
Orally as tablets and capsules,IV and IM suspension
and topical preparations.
ADVERSE REACTIONS
Git effects (Stomatitis,abdominal
cramps,nausea,vomiting and diarrhea)
Cholestatic jaundice
USES:
Aerobic and anaerobic bacteria infection.
Such as Bacteroide species implicated in dental
infections
AZITHROMYCIN and CLARITHROMYCIN
The newer macrolide antibiotics like erythromycin
Are indicated as alternative antibiotics in the
treatment of common orofacial infection caused by
aerobic gram-positive cocci and susceptible anaerobs
Doses: Azithromycin for 5 days of therapy:First day 250
mg twice a day,and then 250 mg/day for 4 days.
Clarithromycin:500 mg twice a day for 7 days.
DRUG INTERACTION:
Azithromycin can increase the level of
Astemizole,loratadine,carbamazepine,digoxjn,and
triazolam
Clarithromycin increase level of drugs metabolized in
liver such as:
Theophylline,carbamazepine,digoxin,omeprazole,and
astemizole
CLINDAMYCIN
Clindamycin is bacteriostatic antibiotic
Effective primarilyvagainst gram-positive orgganisms
and anaerobic Bacteriodes species.
ROA:
Orally,topically,iM,IV,and vaginally.
Oral clindamycin is well absorbed.
Excreted as inactive metabolit in the urine and fece
(via bile)
Adverse Reaction
GIT Effects
Superinction
Allergy
Other Effects
USES
METRONIDAZOLE
Metronidazole has antiinfective and antiinflamatory
effects.
Effective for Trichomonas vaginalis,Entamoeba
hystolitica and anaerobic Bacteriode species.
PHARMACOKINETICS.
Taken orally,metronidazole is well absorbed in 1 and 2
hours after administration.
Half life 8 hours.
Distributed into LCS fluid,saliva,and breast milk
Concentrated in the ginggival crevicular fluid
producing concentrations that are bactericidal to
pathogenic periodontal organism
Spectrum
The spectrum of metronidazole includes protozoa and
Bacteriodes,Fusobacterium,Veillonella,Treponema,Clo
stridium,Peptococcus,Camptlobacter,and
Peptostreptococcus.
Adverse Reactions
Gastrointestinal Effects: Stomach distress is
common
(Nausea,anorexia,diarrhea)
CNS
(Headache,dizziness,vertigo,ataxia,confusion,depressi
on,weakness,insomnia and serious convulsive seizure
are rarely associated with metronidazole)
ORAL EFFECTS
Xerostomia,unpleasant metalic taste
RENAL TOXICITY
Cystitis,polyuria,dysuria,darkning urine (rarely)

DRUG INTERACTION
No alcohol with metronidazoledisulfiram effect


CEPHALOSPORINS
A group of antibiotics is structurely related to the
penicillin.
Cephalosporins iare active against a wide variety of
both gram-positive and negative organisms.
The source of cephalosporins was Cephalosporium
acremonium near Sardinia in Italy
GENERATION OF CEPHALOSPORINS
First Generation:
Cephalexin
Cephradine
Cefadroxil
Second Generation
Cefador
Cefuroxime
Cefrozil
Third-Generation
Cefime
Cefpodoxime
Cefdinir

Fourth Generation
Cefepime
Spectrum
Bactericidal
Effective for Gram-positive and Gram-negative
organism
MOA
Cephalosporins inhibit of cell wall synthesiss

Adverse Reactions
GIT Effects
Nephrotoxicity
Superinfection
Local Irritation
Hemostasis and Disulfiram-Like Reaction
Allergy
RATIONAL USE OF ANTIINFECTIVE AGENTS IN
DENTISTRY
Stage 1
Acute abscess and cellulitis are primarily the result of
gram-positive organism
DOC Penicillin 500 mg, 4 times for 5-7 days
Stage 2
During stage 2,the infecttion in micxed
This can be handled by attacking gram-positive and
gram-negative
DOC Clindamycin
Stage 3
The organisms have coalesced one area and are almost
solely anaerobic.Most often incision and drainage is
sufficient.In fact,the patient is cured.
If chronic infection persist or if the patient is
immunocompromised use of an antibotic with
anaerobic coverage is warranted.

TETRACYCLINES
Spectrum
Adverse Reaction
GIT Effects
Effects on Teeth and Bones
Hepatotoxicity

Nephrotoxicity
Hematogenic Effects
Superinfection
Pphootosensitivity
Allergy
Refference
Elena Bablenis Haveles,BS Pharm,PharmD
in Applied Pharmacology for the Denttal
Hygienist