Antibiotics used in

dentistry
prepared by zirgi

DEFINATION
Antibiotics are chemical substance

elaborated by various species of

micro-organism such as fungi,
actinomycetes and bacteria. They
suppress the growth of other microorganism and may ultimately destroy
them in low concentration.

History

Early history
3500 BC the Sumerian doctors would give

patients beer soup mixed with snakeskins and

turtle shells.
Babylonian doctors would heal the eyes by
using an ointment made of frog bile and sour
milk.
The Greeks used many herbs to heal
ailments.
All of these "natural" treatments contained
some sort of antibiotic.

Modern history
Louis Pasteur was one of the first recognized

physicians who observed that bacteria could

be used to kill other bacteria.
In 1929 Sir Alexander Fleming a Scottish
bacteriologist, went on a vaction and left a
petri dish of staphylococci bacteria uncovered.
When he returned, he noticed that there was
mold growing on it. Upon further examination,
he saw that the area around the mold had no
bacteria growing. He named the mold
Penicillium, and the chemical produced by the
mold was named penicillin, which is the first
substance recognized as an antibiotic.

Almost immediately after penicillin was

introduced, resistance in certain strains of

staphylococci was noticed.
In 1935, Domagkdiscovers synthetic
antimicrobial chemicals (sulfonamides).
During World War II, because of need for
antibiotic agents, penicillin was isolated and
further tested by injection into animals. It was
found to be extremely useful in curing infections,
and to have extremely low toxicity to the
animals. Because of these findings, use of
penicillin greatly increased. This also spurred a
search of other chemical agents of similar use.

the late 1940's through the early 1950's,

streptomycin, chloramphenicol, and tetracycline

were discovered and introduced as antibiotics.
In 1953, during a Shigella outbreak in Japan, a
certain strain of dysentery bacillus was found to
be resistant to chloramphenicol, tetracycline,
streptomycin, and the sulfanilamides.
By the 1950's it was apparant that tuberculosis
bacteria was rapidly developing resistance to
streptomycin, which had commonly been used
to treat it.

Classification of
antibiotids

Classification of
antibiotics
Classification based on chemical structure &
proposed mechanism of actions as fallows
1. Agents that inhibits synthesis of bacterial cell wall
these includes
a) penicillin & cephalosporin which are structurally
simillar
b) Cycloserine vancomycin bacitracine & the azole
antifungal agent ( e.g clotrimazole, fluconazole &
itraconazole which are structurally dissimilar
agent

2.Agent that act directly on the cell

membrane of the micro organism
affecting permeablity & leading to
leakage of intercelluar compound
e.G polymyxin & polyene antifungal agent
nystatin
Amphotericin B which bind to cell wall
sterolls

3 .Agent that affect the function of 30 s or 50 s

ribosomal subunit to cause or reversible
inhibition of protein synthesis
e.G chloramphenical
Tetracycline
Erythromycin
Clindamycin

4 .agent that bind to 30s ribosomal subunit

&alter protein synthesis which eventually lead
to cell death
E.g. aminoglycosides
5.agent that affect bacterial nucleic acid
metabolism such as rifamycin (e.g. rifampin )
which inhibit RNA polymerase & the quinilones
which inhibit topoisomerase

6 . agent that block essential enzymes of folate

metabolisum
E.g. trimethoprim& sulfonamide

7 . Antiviral agent which are of several classes including

Nuclic acid analog such as acyclovir or gancyclovir
that selectively inhibit viral DNA polymerase and
zidovidine which inhibit reverse transcriptase
b) Non nucleoside reverse transcriptase inhibitors such as
nevirapine
c) Inhibitor of other essential viral enzyme. E.g. inhibitors
of HIV protease or influenza neuraminidase
a)

classification
According to spectra

1.Antibiotic effective against gram positive

bacteria
a.For systemic infection, erythromycin,
lincomycin, novobiocin.
b. Those employed topically
e.g. bacitracin
2.Antibiotic mainly against gram negative bacteria
a.For sylstemic infection
e.g. strepomycin & other aminoglycosides
b.Those used locally in intestine
e.g.paromomycin

3.Antibiotic mainly effective against gram

ve & +ve bacteria
a.Used for systemic infection
e.g. ampicillin, amoxycillin, cephalosporin
b.For topical application
e.g. neomycin
4. Effective against rickettsial & chlamydia
e.g. tetracycline & chloramphenicol
5.Effective against acid fast bacilli
e.g. steptomycin, rifampicin & viomycin

6.Effective against protozoa

e.g. paramomycin & tetracyclin
7.Effective against fungi
e.g.nystatine, amphotericin B
8.Effective against malignancy
e.g. actinomycin, mitomycin

PRINCIPLES OF
ANTIBITIC
THERAPY IN
DENTAL
INFECTIONS

Following are the points by which the clinician

can make a decision of when to use antibiotic,

which are to select, and how to use both
therapeutic and prophylactic situations. To do
this one should atleast know about the
following
1. Bacterial flora causing most
odontogenic infections
2. The basic mechanism of host defenses
3. The variety of contemporary
antibiotics and principles to choose

Bacterial flora causing

most odontogenic
The indigenous microbial flora of the mouth is
infections
bacteria, which are almost always the cause
of odontogenic infections. The usual flora is
both aerobes and anaerobes

The basic mechanism

of host defenses

Host defense mechanism is the most important factor in the

final outcome of a bacterial insult.Each patient has many

defenses against infections.
1. Physiologic depression of host defence,
Shock
Disturbances of circulation caused by advanced age
Obesity
Fluid imbalance
2. Diseases and disease state that may inhibit host defense
Malnutrition syndrome
Patient with cancer and leukemia
Poorly controlled diabetics

3 Congenital defect which causes defective

host mechanism
Agammaglobulinemia
Multiple myeloma
Total body radiation therapy
Children who have had splenectomy
4. Therapeutic drugs that impares host
defense mechanism
Cytotoxic drugs
Immunosuppressive drugs

principles to choose
Antibiotics
Once the decision has been made to use antibiotics
as an adjunct to treating infection the antibiotics
should be properly selected. The followingguide
linesare useful
1. Identification of causative
organism
2. Determination of antibiotic
sensitivity
3. Choice of antibiotics

1. Identification of causative organism

Causative organism can be isolated from
pus blood, or tissue fluids. Based upon the
knowledge of pathogenesis and clinical
presentation of specific infection,antibiotic
therapy will be either initial or definitive
depending upon whether or not the organism
is diagnosed previously.

2. Determination of antibiotic sensitivity

When treating an infection that has not
responded to initial antibiotic therapy or when
treating a postoperative wound ,the causative
agent must be previously identified and the
antibiotic sensitivity must also be determined.

3 Choice of antibiotics
Upon receipt of the culture and sensitivity report,
there may be a choice of four or five antibiotics.
Selection should be based on consideration of
several factors like
1. Patients previous history of allergy
2. Antibiotics with narrow spectrum
3. Drug that cause fewest adverse reactions.
4. Drug which is least toxic
5. The well established still effective antibiotics
6. Bactericidal rather than bacteriostatic drug
7. The less expensive still effective antibotic
8. Combination antibiotics

1. Patient`s history of allergy

Allergic reaction to drugs should be

considered first. When it exists, alternative
drugs must be used. Example erythromycin or
clindamycin is usually use if the patient is
allergic to penicillin

2. Antibiotics with narrow spectrum

The only majour indication for use of

broad spectrum antibiotics coverage is in
severe life threatening infection where
identification of causative agent is obsure.
Each time bacteria are exposed to antibiotics,
the opportunity for development of resistant
strains is present. If narrow spectrum
antibiotics is used ,fewer organisms have the
opportunity to become resistant.

3. Drug that cause fewest adverse reactions

The goal of antibiotic therapy is to

provide an effective Drug that causes least
problem to the patient
4. Drug which is least toxic
Toxicity reactions are those that occur as
a result of excessive dose or duration of
therapy, but can occur in individual patients
with normal doses.

5. The well established still effective

antibiotics
Since its initial availability, penicillin, has
been used for oral infection and it has been
very effective, with low incidence of adverse
reaction. Newer antibiotics should be used
only when they have proved advantage over
the older ones .

6. Bactericidal rather than bacteriostatic drug

Bactericidal drugs are effective during the

log phase of bacterial growth the time.If
growth is slowed or brought to stop,cidal
drugs have a greately diminished effect. As a
result, in these situations, when combination
drug therapy is to be used,cidal and static
combination should not be used in
combination.

7. The less expensive still effective antibotic

Most effective but less expensive drug

should be considered first.
8. Combination antibiotics
There are situations in which the use of
antibiotic combination is clearly indicated.
Example is when it is necessary to increase
the antibacterial spectrum in patients with life
threatening sepsis of unknown cause.

Bacterial resistance to
antibiotic
1. When the drug does not reach its
target
2. The drug is not active
3. Target is altered.

Selection of antibiotics
When an antibiotic is indicated the goal is

to choose a drug that is selectivley active

for the most likely infecting micro-org.&
that has least potential to cause toxicity or
allergic reaction in individual being treated.
Antibiotic are used in three general ways
as empirical therapy
as definative therapy
As prophylactic or preventive therapy

Pharamacokinetic factor
that
affect
the
selection
Location of the infection
of
antibiotic
access
of antibiotic to sites of
infection
e.g. if the infection in the CSF the drug
must pass the blood brain barrier

Host factors
Host factor for the selection of antibiotics
1. Host defense mechanisms
a. action in the immunocompetant host can be

cure mearly by halting multiplication of

micro organism { bacteriostatic effect}
b. if host defense are impaired bacteriostatic
activity may be inadequate and a
berteriocidal agent may be required for cure
e.g. pt with bacterial endocarditis
pt with AIDS

Local factors
Antimicrobial activity may be significantly reduces

in pus
Large accumulation of Hb in infected hematomous
cab bind penecillin and tetracycline & thus may
reduce the effectiveness of other drug
Penetration of antibiotic into infected areas such
abscess is imparied because vascular supply is
reduce
Presence of the foreign bodies reduces the
effectiveness of antibiotic

Genetic factors
A no. of drug (e.g. sulfanamides,

chloramphenicol and nalidixic

acid ) may produces acute
hemolysis in pt with glucose 6phosphate dehydrogenase
deficiency

pregnancy
Pregnancy may impose an increased risk of

reaction to antibiotic for both mother & fetus

Hearing loss in child with administration of
streptomycin to the mother during
pregnancy
Tetracycline can affect bones & teeth of
fetus , may develop fatal acute fatty necrosis
of liver pancreatitis & associated renal
damage.

Drug allergy
A antibiotics especially- B-lactum are

notorious or provoking allergic reaction

Sulfonamides trimethoprim
nitrofurapterin and erythromycin also
has been associated with
hypersentitivity reaction especially rash.
Antimicrobial agent like othe drugs can
caused drug fever

Therapy with combined

antimicrobial
agent
Indication
Empirical therapy of severe infections in

which a cause is unknown

Treatment of polymicrobial infection
Enhancement of antibacterial activity in the
treatment of specific infection.

Disadvantage of
combination
of
Risk of toxicity from two or more
agent
antimicrobial
agents
The selection of multiple drug

resistance
micro organism
Increased cost to the patient

Some commonly used

antibiotics
Penicillin
It is the extract from mould

penicilium notatum
Belonging to group called
beta lactum antibiotics

Classification

1. natural penicillin

E.g.

penicillin g benzyl penicillin

Procaine penicillin

Benzedrine penicillin

2.acid resistant penicillin

Phenoxymethyl penicillin

3.penicillinase resistant penicillin

Methicillin

Oxacillin
cloxacilline

Flucloxacilline

nafcillin

4.penicillin effective against gram +ve

&some gram -ve organism

Ampicillin
Amoxicillin
Talampicin

5.extended spectram penicillin

a.carboxypenicilin
Carbenicillins
b.amidinopenicillin
Mecillinam
pivmecilliam

Mechanism of action
Act by inhibiting cell walll synthesis

in bacteria. they prevent sythesis &

crosslinkage of peptidoglycans which
is the integral part of bacterial cell
wall.

Antibacterial spectrum of
penicillin
Effective mainly against gram +ve &
gram ve cocci &and some gram +ve
bacilli.

Adverse effect of
penicillin
Intolerance
Thrombophlebitis
Allergy with manifestation like
1.skin rash
2.serum sickness like syndrome
3.renal disturabane
4.haemopoitic disturabance
5.anaphylaxis

Jarish herxiheimer reaction on

syphilitic pt treated with penicillin

Superinfection e.g. candida
hypermia

Classification

Usual adult
resgimen
Natural penicillin 250-500mg
vk
QID

Activity against oral

pathogens
Gm+ve
gm+ve
gmve
Arobes anarobes anarobes
+ve

+ve

+ -ve

Penicillinase

resistance
Dicloxacillin
Nafcillin

250mg 6 hrly
500mg QID

stap &

-ve

-ve

-ve

-ve

strepto

Amoxicilline
Amox/

potassium
clavulanate
(augmantin)
Ampicillin

stap.only

250-500mg
8hrly
250-500mg
8hrly

+ve
+ve

+ve

+ve
+ve

-ve

-ve
-ve

-ve

AMINOGLYCOSIDES
These are group of natural &

semisynthetic drugs having polybasic

amino groups & linked glycosidically
to two or more amino sugars.

Mechanism of action
The drugs combine with the bacterial

ribosomes & interfares with m-RNA

ribisomes combination which
ultimately prevents protien synthesis.

Absorbtion fate and

excreation
It is excreted mainly by glomerular
filtration &asmall portion in bile

spectrum
Vibrio comma
Proteus
E-colli
Enterobacteria
Klebsiella
H- influenza

This group includes drug like

Streptomycine
Gentamycine
Kanamycine

Tetracycline
They are naphthalene derivatives
its nucleus is made up by the fusion

of foci partialy unsaturated

cyclohexiane radius and hence
named tetracycline

Mechanism of action
Interfer with protein synthesis by

blocking the attachment of amino

acyl transfer rna to acceptor site on
m-RNA ribosome complex.

Absorption fate &

excretion
Tetracycline form insoluble
complexes by chelation with
calcium ,magnesium &
aluminium
Iron interferes with absorption
excreted mainly in urine

Spectrum
Includes both gram +ve

& -ve orgamism

Dose
orally-250-500mg

TDS
Parantally- 1-2gms in two equal doses
12hrly interval.
Newer drug areDoxycycline
Demeclocycline
Methacycline
Minocycline
lymecycline

Disadvantages
GI system
Diahrroea
Nausea
Vomiting

Suprinfection
Candida

infectionis comman
Fetal hepatic disfuction
Azotemia may be agrevated to renal
impairment
Chelating effect in teeth & bone

Cephalosporins
1st generation
They are highly effective against gram

+ve but weaker against gram _ve bacteria

These are
cephalexim
Cephalethin
Cephaloridine
Cephradine
cefadroxil

Cephalexin
Only orally active first generation cephalosporin

with spectrum
Strptococcus
Staphylococci
Gonococci
Closridia
C. diptheria
Actinomyces
Klebshiella
Protease
Salmonella
shingella

Dose
Adult 25mg to 1gm 6 to 8 hrly.
children 25mg to

100mg/kg/day

Cefadroxil
A it is close congener of

cephalexim& has good tissue

penetration
B can be given 12 hrly
C spectrum is same as cephalexim
Dose 0.5gm -1gm BD.

SECOND GENARATION
They are newer to first genaration.
They have more activity against

gram ve organisms.
E.g. cefuroxime it is higher
activity against penicilliase
producing organisms and all
ampicillin resistant H-influenzae.

Other spectrum
More active against klebsiella, E-coli,

enterobacter, indole positive protiens.

Dose a. 0.75 1.5 gms/ IM or IV/9
hrly
b.30- 100mg/kg/day.
Available as- supacef.

Third generation
These were developed in end of 1980s.
They have augmentation activity against

ve Endobactericeae.
They are resistant to lactamase.
These areCefotaxamine
Ceffizoxime
Ceftriaxone
Moxalactum
ceftazidium

Cefotoxamine
Potent action on gram-ve as well as gram+ve
It is not so active against anaerobic like bact.

Fragillis, Staphylococcous aureus,

Pseudomonas aerugemosa.
It is very important drug in teratment of
meningitis, hospital acquired diseases
septicaemia and infection in immuno
compromised pt.
Dose
A.1-2gms/Imor IV/6- 12hrly
50-100mg/kg/day

Available as Omnatax
claforan

Ceftizaxone
Long acing cephalosporin
One daily dose is good enough and it has

good CSF penetration

Dose
Adult - 1-2gms/IM or IV /day
Child- 75-100mg/kg/day

Ceftazidime
Most prominent feature is high activity againt

pseudomonas.
It is used in febrile pt including pt with burns.
It is less effective to staphylococcus aureus.
Dose
Adult-0.5-2gms/IM or IV/ every 8 hours
Child- 30mg/ kg/day

Forth generation
cephalosporine
E.g. cefepime(maxipime) and cefpirome
It is new cephalosporine with properties like

those of 3rd generation cephalosporine but

more resistance to some beta-lactumase.
It is active against streptococci and
methyciline sensetive staphylococci but not
against methyciline resistance staphylococci.

Spectrum
Its main use is in serious gram ve infection

(H-influenza, Neisseria- gonorrhoae and

Neissera meningities) including infection of
CNS inti which it has exelent penetration.
Half life is of 2hrs.
Dose -2gm I.V. every 12hrs

Fifth generation
cephalosporine
Ceftobiprole has been described as "fifth
generation",though acceptance for this
terminology is not universal.
Ceftobiprole (and the soluble prodrug
medocaril) are on the FDA fast-track.
Ceftobiprole has powerful antipseudomonal
characteristics and appears to be less
susceptible to development of resistance.

These cephems have progressed far enough

to be named, but have not been assigned to a

particular generation.
Cefaclomezine
Cefaloram
Cefaparol
Cefcanel
Cefedrolor
Cefempidone
Cefetrizole
Cefivitril

Cefmatilen
Cefmepidium
Cefovecin
Cefoxazole
Cefrotil
Cefsumide
Ceftaroline
Ceftioxide
Cefuracetim

Adverse effect
Pain after injection.
Diarrhoea due disturbance in Gut ecology
Hypersensitivity reaction- anaphylaxis,

angiodema, asthma, urticaria.

Nephrotoxicity
Neutropenia or thrombocytopenia
Hyperprothombinemia
A flase +ve cmbs test may occur in as
many as 60%of pt or cephalathin therapy.

Macrolides
They are antibiotics having a

macrocyclic lactone ring with

attached sugars
They are bacteriostatic drug

Erythromycin
Used as aternative in penicillin sensitive

individuals
CONTRAINDICATIONS
Hypersensiivity
Liver dieases- ester salt is avoided
Available as tablet & syrup
Dose ADULT- 250-500mgQID
CHILDREN-30-50mg kg/day
in form of divided doses.

Adverse reaction
Nausea
Vomiting
Diahrroea
Hypertention
Cardiac arrythmias
Revesible hearing loss
ONSET OF ACTION- 2to4hrs

Azithromycin
This new azalide longer of

erytromicin has an expanded

spectrum, hyper, Pharmacokinetics,
better tolerability and drugs
interation profile however it is not
effective against erythromycin
resistant bacteria.

Indications
Respiratory track infection
Urenary track infection.
Otitis media

Contraindications
Hypersensitivity
Hepatic impairment

DOSE- ADULT-500mg OD for 3days OR 500mg OD

on days one followed by 250mg OD for 4 days.
CHILDREN- 10mg/kg/ day for 3 days OR
10mg/kg/day followed by 5mg/kg/day OD for
5day.
ONSET OF ACTION- one to two hrs

Adverse effect
Mild gastric upset
Abdominal pain
Headache
Dizziness

Imidazoles
Metronidazole
Prototype netroimidazole
Active against anarobes

Mode of action
In anarobic micro-organisms

metronidazole is converted into an

active form by reduction of its nitro
group.
This binds to DNA and prevents
formation of nuclic acid.

Absoption fate and

excretion
The drug is well absorbed after oral
or rectal administration.
It is elimanated urine, partly
unchanged & party metabolized

Contraindications
Neurogenic diseases
Blood dyscrasias
first trimester of pregnancy

Uses
Acute ulcerative gingivitis
Dental infections
Amoebiasis
Giardiasis
Trichomoniasis

Dose
Orally 400mg 8hrly
IV infusion 0.5gms/8hrs.
Treatment should be continue for 7

days.

Adverse effects
Anorexia
Nausea
Metalic taste
Headache
Glossitis
Dryness of mouth
Thromphlebitis of injected veins

Indication for antibiotic

used
A. Systemic indications
1. Congnital or acquired heart

a. Rheumatic heart disease

b. Valvular diseases
c. Pt with ventricular defects
2. Severe kidney diseaes
a. chronic glumerulonephritis
b. pt undergoing dialysis

Active leukemia, agranulocytosis,

aplasia , anemia
4. Metabolic disturbances diabetes
5. Pt on chemotherapeutic drugs
6. Pt with vascular graft
3.

B. Maxillo- facial trauma

1.Hard tissue trauma-the consensus is that
antibiotic convert should be used for any
mandibular or maxillar fracture compented
into mouth or paranasal sinus through
mouth.
2.Soft tissue trauma
3.Orthognathic & recontructive maxillo- facial
surgery.
4.Odontogenig infection
5.Pericoronities
6.Osteomylitis

contraindication
Minor chronic localised abscess.
Well localised vesibular abscess .
Localised ostitis
For sterilizing root canal
Pt with mild pericoronitis, minor

gingival oedema & mild pain which

do not required antibiotcs

Prophylactic antibiotic
Standard recommendation
therapy
A cephalosporin cefadroxil preferred
1preoperatively

500 mg orally 1hr before surgery

2 post operatively 250 mg orally 6hr after initial
dose

or
Clindamycin in penicillin allergic pt
1 pre operatively 300 mg orally 1 hr before surgery
2 post operatively 150 mg orally 6hr after initial
dose

Principles of antibiotic
prophylaxis
1 antimicrobial agent t is chosen on

basis of most likely micro organisum to

cause infection
2 an antibiotic loading dose should be
employed
3 antibiotic should present in sufficient
concentration in blood and targate
tissue prior to dissemination of
offending micro organisum

4 antibiotics should be continued

only as long as microbial

contamination from operative site
persist
5 patient benefits from prophylaxis
should out high risk of antibiotic
included allergy , toxicity ,
superinfection.

Dental procedure that

require
endocardititis
Tooth extraction
prophylaxis
Periodontal suergery
Subgingival dental prophylaxis
Endodontic surgery
Incision & Drainage of infection

Supragingival prophylaxis
Restorative tooth preparation

Dental
procedures
that
Placement of orthodontic appliances
do
not require
Conserative
endodontic theraphy
endocardiatis prophylaxis

REASONS FOR
ANTIBIOTIC
FAILURE
INAPPROPIATE choice of antibiotics
Too low blood concentration
Poor penetration to infected site
Limited or decreased vascularity
Impaired host defence
Unfavourable local factors

Increased plasma protein binding

Antibiotic antagonism
Slow microbial growth
Antibiotic resistant organisms
Patient failure to take antibiotics
Failure to eradicate sorce of infection

Myths &misconception in
antibiotic
th
erapy
Myth- antibiotics cure pt
1

except in immunocompramised
pt antibiotics are not curative but
rather function to provide time for
normal host defence initially
overwhelmed by micro organisum to
gain and control &eventually
eliminate the in fectious process

2 .Antibiotics

are substitute for

surgical drainage - never are
antibiotics a substituted for
eradication of the source of infection
( extraction, incision, drainage )
unless the infection is too diffuse
(pericoronitis)

3 culture and sensitivity test are required

- orofacial infection are characteristically

acute in nature, polymicrobial in cause,
short in duration with proper treatment.
These infection require immediate
attention and a dealy of 18 to 36 hrs for
result of culture & sensitivity tests prior
to initiation of antibiotics therapy is
usually not appropriate because the
microbial cause Is commly such that
common antibiotics are effective, incision
&drainage are relatively easy.

Myth antibiotics
The followoing condition appear valid at present
incresed
host defence to
1 antibiotic that can peenetrate into the
mammelion cell (tetracycline , eryt hromycin)
infection
are more likely to affect host defence than
those that can not (beta lactum)
2 tetracycline may supress white cell
chemotaxis where as betta lactum do not
3 most antibiotics (except tetracycline) do not
depress phagocytosis
Tnb lymphocyte transformation may be
depressed by trtracyclines

Multiple antibiotics are

superior
to as
single
It is often assume
that antbiotic
combination are superior to single
antibiotics.
antibiotic such as not commonly the case.
The primary clilical indication for antibiotic

conbination therapy is severe infection in

which ofending organism is unknown and
major conciquences may ensue if antibiotic
therapy is not instituted immediatey before
culture and sensetivity test are available.

Antibiotic prophylaxis
usually
effective
It is commonly assume that
antibiotics administered prior to
invasive surgical procedure remain
post operative infection.
The reality based on laboratoru
studies is that antibiotic prophalaxis
is only some time effective.

Bacteriocidal agents are

always
superior
to
Bacteriocidal antimicrobials are
bacteriostatic
required in pt withagent
impaier host
defenses (nutropenia, meningitis)
but bacteriostatic agent are
uaually satisfactory, if host
defence against infection are
adequqte.

Antimicrobials are
effective
in
chronic
Antimicrobials are never been
infectious
successful indisease
the eradication of
a chronic infection because the
prolong exposure of microorganism to chemical leads to
eventual dominance of drug
resistance organism

Antibiotics are safe and

non
toxic
Most antimicrobials are among safest
drug yet all are associated with
allergy, ecological damage to human
and microbial environment.

Infection require a
complete
of
There is no such course
things as predetermine
complete course of antibiotic therapy.
therapy
The only guide for determining the
effectiveness of antibiotic therapy and hence
duration of treatment is related to clinical
improvement of pt.

Misconceptions
Prolong therapy destroy resistant micro-

organism.
Prolong therapy is necessary for rebound
infection that recur as organism is suppresed
but not eliminated (orofacial infections do
not rebound if the sourse of infection is
properly eliminated)
Antibiotic doseges and duration of therapy
can be extra polated from one infection to
another

REFERENCE
GOODMAN & GILLMAN
TEXTBOOK OF PHARMACOLOGY
BY TRIPATHI
BY SATOSKAR

A New Concept of
Antibiotic Loaded
HAP/TCP Bone
Substitute for

INTRODUCTION:
Infections and their consequences are a considerable problem inorthopedic

surgery.
Despite systemic prophylaxis, infection rates after orthopedic surgery are
above1%.
Antibiotic loaded PMMA bone cements have been shown to enhance the
efficiency of intravenous prophylactic treatments for total hipreplacement1.
However, less than 10% of the load is released during the first 5-10 days
ofimplantation2: the remaining antibiotic is released at low levels over many
months3 and could select antibiotic-resistant strains2.
The recommendations for the use of antibiotic in prophylactic applications
are to obtain high levels, with treatment duration inferior to 48 hours.
A new HAP/TCP bone substitute loaded with 125 mg of Gentamicin was
designed for prophylactic use in bone filling applications.
Its aim was to enhance the efficacy of systemic prophylactic treatments by
increasing the local antibiotic concentration without selecting resistant
strains.

Methods
A commercial bone substitute composed of 70%

Hydroxyapatite and 30% - Tricalcium Phosphate4

containing 125 mg of Gentamicin (ATLANTIK Genta,
Medical Biomat, France) was used in this study.
The release rate of Gentamicin from the bone
substitute was investigated after implantation in
the femoral condyle of 5 sheep. In order to
investigate the local and systemic Gentamicin
concentrations, synovial fluids and blood samples
were assessed by immunoassay over a 5 day
period.

There were differences in local Gentamicin

concentrations between individuals but for all

animals, the local Gentamicin concentrations
measured during the first 8 hours were higher
than the minimal bactericidal concentration of
the majority of the germs responsible for
infections in orthopedic surgery, i.e. 6-12
g/ml. After 48 hours, the concentration in
blood and synovial fluids was less than 0.5
g/ml.

The mean Gentamicin concentration peak

obtained in blood was 4.2 g/ml and then

mean local Gentamicin concentration
obtained in synovial fluids during the first 8
hours was305 g/ml
The Gentamicin amount remaining in the
implant explanted at day 8 was less than
0.003% of the initial amount

New era of
antimicrobial
therapeutics

It is a fact that selection of multi-drug-

resistant bacteria has occurred throughout

history. Unfortunately, however, drug-resistant
bacteria have been met with antibiotics that
are nothing more than recapitulations of
earlier drugs. There has been an urgent need
for new avenues of therapeutic treatment,
and a new era of prophalytic (preventative)
treatment has begun. Here the most plausible
approaches are described:
bacterial interference

bacteriophage therapy
bacterial vaccines
cationic peptides
cyclic D,L-a-peptides

Bacterial
interference

One
way
is
to
Bacterial
interference, also known as
bacteriotherapy, is the practice of deliberately
inoculate
hosts
with
inoculating hosts with nonpathogenic
(commensal) bacteria to prevent infection by
nonpathogenic
pathogenic strains. To establish an infection
and propagate disease, pathogenic bacteria
bacteria.
must find nutrients and attachment sites
(adhesion receptors).
.

Infection by pathogenic bacteria is prevented

by commensal bacteria, which compete with

pathogenic bacteria for nutrients and
adhesion receptors or spur attack through
secretion of antimicrobial compounds

This treatment has had promising results in

infections of the gut, urogenital tract, and

wound sites. The major advantage of using
bacteria in a positive way to benefit health,
known as probiotic usage, is that infection is
avoided without stimulating the hosts immune
system and decreases selection for antibiotic
resistance. Understanding how bacterial species
compete, an essential criterion for research, has
been known for at least 20 years but its
practical application has yet to be realized.

Bacteriophage
therapy

Bacteriophages (commonly called phages)

are viruses that infect bacteria and were

recognized as early as 1896 as natural killers
of bacteria. Bacteriophages take over the
hosts protein-making machinery, directing
the host bacteria to make viral proteins of
their own. Therapeutically, bacteriophages
were used as a prophylaxis against cholera,
typhoid fever, and dysentery from the 1920s
to the early 1940s.

The practice was abruptly stopped when

synthetic antibiotics were introduced after

World War II. Now that there is a plethora of
multi-drug-resistant bacteria, bacteriophage
therapy once again has become of keen
interest.

Pathogens may be
Bacteriophage therapy is quite attractive for
targeted
through
the following reasons:
phage particles are narrow spectrum agents,
manipulation
phage
which means they posses an of
inherent
mechanism to not only infect bacteria but
DNA.
specific strains

Other pathogens may be targeted through

manipulation of phage DNA

exponential growth and natural mutational
ability make bacteriophages great candidates
for thwarting bacterial resistance.
Development of bacterial vaccines has
become an increasingly popular idea with the
advent of complete genomic sequencing and
the understanding of virulence regulatory
mechanisms.

Bacterial vaccines

Bacterial genomics allows scientists to scan an

entire bacterial genome for specific sequences

that may be used to stimulate a protective
immune response against specific bacterial
strains. This approach expedites the drug
discovery process and, more importantly,
provides a more rational, target-based approach.
The best targets are essential bacterial genes
that are common to many species of bacteria,
which code for proteins with the ability to gain
accesses through lipid membranes, and possess
no homology to human genes.

Regulatory genes that control virulence

protein production are excellent vaccine

candidates for priming the human immune
system or inhibiting virulence production.
Bacterial genomics can also detect conserved
sequences from bacterial species and strains
worldwide. This technology will inevitably
yield superior clinical vaccine candidates.

Cationic peptides

These diverse peptides are natural

compounds that posses both hydrophobic and

hydrophilic characteristics, which means
portions of the molecule are water avoiding or
water loving. Cationic peptides are found
throughout nature in the immune systems of
bacteria, plants, invertebrates, and
vertebrates

Other Peptides are

These peptides are not the usual synthetic
synthetic,
aredrug
drugs encountered in and
pharmaceutical
design; however, they do exhibit antibacterial
engineered
effects. Cationic peptidesto
havekill
several
mechanisms of action, all of which involve
bacterial
interaction with thecells.
bacterial cell membrane

leading to cell death. From a therapeutic

standpoint, these proteins have great promise,
as they have coevolved with commensal
bacteria yet have maintained the ability to

Other peptides are

Unlike cationic peptides,
synthetic,
or cyclic D,L-a-peptides
are synthetic and amphipathic (molecules
engineered,
killhating
having both water lovingto
and water
characteristics) cell membrane disruptors. As
bacterial
the name implies cells.
these peptides are cyclic in
nature and are composed of alternating D and
L amino acids. Cyclic D,L-a-peptides are
engineered to target gram-positive and
negative membranes (not mammalian cell
membranes).

In contrast to any other known class of

peptides, these peptides can self-assemble

into flat ring shaped conformations forming
structures known as nanotubes, which
specifically target and puncture bacterial cell
membranes resulting in rapid cell death