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Dr.

Anjali Savita
Post graduate 1ST year
Dept of Conservative dentistry
and endodontics
CONTENTS
 DEFINITION OF ANTIBIOTICS
 HISTORY
 CLASSIFICATION OF ANTIBIOTICS
 MECHANISM OF ACTION
 PRINICIPLE OF ANTIBIOTIC THERAPY
 CHOICE OF AN ANTIMICROBIAL AGENTS
 COMBINED USE OF ANTIMICROBIAL AGENTS
 ANTIBIOTICS USEFUL FOR OROFACIAL INFECTIONS
 PROPHYLACTIC ANTIBIOTICS
 ANTIBIOTIC RESISTANCE
 PUBLIC HEALTH SIGNIFICANCE OF ANTIBIOTICS
 SUMMARY
 CONCLUSION
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 REFERENCES
What is
•Substances producedAntibiotic?
by microorganisms,
•Selectively suppress the growth , kill other microorganisms at very
low concentrations.

•‘Chemotherapeutic agent’ - synthetic compounds,


•Antimicrobial agent (AMA) - synthetic + naturally obtained drugs
that
attenuate microorganisms. 3
4
HISTOR
Y
Period of empirical use Ehrlich’s phase of dyes The modern era of
and organometallic chemotherapy
compounds (1890–1935)
• 16th 17th century AD
• Ehrlich tried methylene • Domagk in 1935
• Use of mouldy curd by
blue, trypan red, etc demonstrated therapeutic
Chinese on boils, • He developed the
chaulmoogra oil by the effect of Prontosil, a
Hindus on leprosy , arsenicals— atoxyl for sulfonamide dye, in
cinchona bark for fevers sleeping sickness, pyogenic infection
etc. arsphenamine in 1906 and
neoarsphenamine in 1909
for syphilis.
• He coined the term
‘chemotherapy’.
5
 1877 - Pasteur demonstrated Phenomenon of antibiosis.

1929 – Fleming - Penicillium mould - destroy Staphylococcus on


the culture plate. He named penicillin but could not purify it.

 1941 - Chain and Florey found out the clinical use of penicillin.

 1944 -Waksman and his colleagues discovered Streptomycin.


6
CLASSIFICATION OF ANTIBIOTICS

Chemical

structure Mechanism Spectrum Type of


of action of action
activity
Source
Type of organism
against which they
are active

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A. Chemical
structure
1.Sulfonamides and related drugs: Sulfadiazine, Sulfones— Dapsone
(DDS), Paraaminosalicylic acid (PAS).
2. Diaminopyrimidines: Trimethoprim, Pyrimethamine.
3. Quinolones: Nalidixic acid, Norfloxacin, Ciprofloxacin, etc.
4. β-lactam antibiotics: Penicillins, Cephalosporins, Monobactams.
5. Tetracyclines: Oxytetracycline, Doxycycline, etc.
6. Nitrobenzene derivative: Chloramphenicol.
7. Aminoglycosides: Streptomycin, Gentamicin, Neomycin, etc.

8. Macrolide antibiotics: Erythromycin, Clarithromycin, Azithromycin, etc.


8
9. Lincosamide antibiotics: Lincomycin, Clindamycin.
10. Polypeptide antibiotics: Polymyxin-B, Bacitracin.
11. Glycopeptides: Vancomycin
12. Oxazolidinone: Linezolid.
13. Nitrofuran derivatives: Nitrofurantoin.
14. Nitroimidazoles: Metronidazole, Tinidazole.
15. Nicotinic acid derivatives: Isoniazid, Pyrazinamide.
16. Polyene antibiotics: Nystatin, Amphotericin-B.
17. Azole derivatives: Miconazole, Clotrimazole, Ketoconazole, Fluconazole
18. Others: Rifampin, Viomycin, Ethambutol, Thiacetazone, Griseofulvin.
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B. Mechanism of action

1.Inhibit cell wall synthesis: Penicillins, Cephalosporins,


Vancomycin, Bacitracin.
2.Cause leakage from cell membranes: Polypeptides—Polymyxins, Bacitracin ,
Polyenes—Amphotericin B, Nystatin.
3.Inhibit protein synthesis: Tetracyclines, Chloramphenicol,
Erythromycin, Clindamycin.
4.Cause misreading of m-RNA code and affect
permeability: Aminoglycosides— Streptomycin, Gentamicin, etc.
10
5. Inhibit DNA gyrase: Fluoroquinolones— Ciprofloxacin.
6. Interfere with DNA function: Rifampicin, Metronidazole.
7.Interfere with DNA synthesis: Acyclovir, Zidovudine.
8.Interfere with intermediary metabolism: Sulfonamides, Sulfones,
Trimethoprim, Pyrimethamine, Ethambutol.

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C. Type of organisms against which primarily active :

1. Antibacterial: Penicillins, Aminoglycosides, Erythromycin, etc.


2. Antifungal: Griseofulvin, Amphotericin B, Ketoconazole, etc.
3. Antiviral: Acyclovir, Amantadine, Zidovudine, etc.
4. Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole, etc
5. Antihelmintic: Mebendazole, Niclosamide, Diethyl carbamazine, etc.

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D. Spectrum of activity

Narrow spectrum Broad spectrum


• Penicillin G •Tetracyclines
• Streptomycin •Chloramphenicol
• Erythromycin

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SULFONAMIDES
•First antimicrobial agents (AMAs)
•Effective against pyogenic bacterial infections.
•Primarily bacteriostatic - gram positive , gram negative bacteria.

•Used in combination with trimethoprim (as cotrimoxazole) or


pyrimethamine (for malaria).

Doses and Uses Adverse effects


•Sulfadiazine : 0.5 g QID to 2 g TDS- Nausea, vomiting and epigastric pain.
meningitis Crystalluria is dose related but
•Sulfadoxine: used in combination with infrequent now.
pyrimethamine for malaria. Hypersensitivity : 2–5% patients.
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COTRIMOXAZOLE
•Sulfamethoxazole + trimethoprim - 20 : 1.

•Individually-bacteriostatic
•Combination-Bacteriocidal.

•Uses: tonsillitis, pharyngitis, sinusitis, otitis media.

•Orodental infections,
•Patients allergic to β-lactam antibiotics.

•Dose : 80 mg trimethoprim 400 mg


sulfamethoxazole
+ tab BD for 2 days then 1 BD. Eg. 15

Septran.
Mechanism of action
FLUOROQUINOLONES

•Active against : gram positive cocci


, anaerobes.
• Mechanism of action :
Inhibit the enzyme bacterial
DNA
which nicks double-stranded
gyrase introduces negative supercoils
DNA,
and then reseals the nicked ends.

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CIPROFLOXACIN

Uses:
•Most potent first generation FQ.
• Urinary tract infection,
•Rapid bactericidal activity.
typhoid fever.
•β-lactam and aminoglycoside •Ciprofloxacin +

resistant bacteria. metronidazole = refractory

•Contraindicated during mixed infections like


pregnancy. periodontitis.
Eg. CIPLOX 250, 500, 750 mg tab
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Norfloxacin
•Less potent than ciprofloxacin.
•Primarily used for urinary and genital tract infections.
•NORFLOX 200, 400, 800 mg tab.

Ofloxacin
•Intermediate between ciprofloxacin and norfloxacin.
•Suited for orodental infections as it is active against certain anaerobes.
•ZANOCIN 100, 200, 400 mg tab. 18
NITROIMIDAZOLES
Pharmacokinetics
METRONIDAZOLE
•completely absorbed from the
•Broad spectrum antiprotozoal drug. small intestines.
•Selectively toxic to anaerobic microorganisms. •metabolized in liver primarily
by oxidation
Bacteriostatic
•excreted in urine

Adverse effects
•Most common : anorexia, nausea, bitter or metallic taste.
•Less frequent side effects are—headache, glossitis, dryness of mouth,
•Contraindicated in the first trimester of pregnancy.
FLAGYL, METROGYL, METRON, 200, 400 mg tab. 19
USES

•Dose : 200–400 mg TDS.

•ANUG (in combination with either penicillin V, amoxicillin, erythromycin

or tetracycline).

•Periodontitis, pericoronitis, acute apical infections and some

endodontic infections also respond well to metronidazole given for 5–7

days.
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•Amoebic infection.
Ornidazole

•Activity similar to but it is slowly metabolized for


metronidazole, amoebiasis, anaerobic
infections.
•ORNIDA 500 mg tab, 125 mg/5 ml suspension.

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Beta-Lactam Antibiotics

•Antibiotics having a β-lactam ring.

•penicillins and cephalosporins.

•most commonly used antibiotics in dentistry.

•Mechanism of action—inhibition of synthesis of


the bacterial peptidoglycan cell wall.

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Bacterial cell wall synthesis


PENICILLINS

•First antibiotic - 1941.

•Originally obtained from the fungus


Penicillium notatum, but presently from P. chrysogenum.

•Consists of fused thiazolidine and β-lactam rings to which side chains


are attached through an amide linkage.
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a. Acid-resistant
alternative to penicillin
G:
Phenoxymethyl penicillin
(Penicillin V).

1.Natural b. Penicillinase - resistant


penicillins : penicillins : Methicillin,
Penicillin G 2.Semisynthetic Cloxacillin.
(Benzyl penicillin) penicillins:
Methicillin,
Cloxacillin c. Extended spectrum
penicillins :
i)Aminopenicillins:
Ampicillin,
Amoxicillin.
ii)Carboxypenicillins:
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iii)
Carbenicillin.
Ureidopenicillins:
PENICILLIN-G (BENZYL PENICILLIN)

•Narrow spectrum
•Activity is limited primarily to gram-positive bacteria and few others.
•Streptococci , gram-positive bacilli and spirochetes are highly
pneumococci sensitive.
•Many bacteria are
inherently insensitive to
PnG .
•Acquired resistance through
production of penicillinase. 27
Adverse effects:

•Pain at i.m. injection site, nausea


Uses:
on oral ingestion.
•Dental infections like those caused as a
•In large doses, toxicity to the
sequelae of carious lesions and are
brain may be manifested as
caused by both aerobic and anaerobic
mental confusion, muscular
bacteria.
twitchings.
•Periodontal abcess , periapical abscess
•Hypersensitivity.
, pericoronitis , acute
suppurative pulpitis , ANUG , cellulitis
etc.
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SEMISYNTHETIC PENICILLINS

•Produced by chemically combining specific side chains (in place of benzyl side chain of PnG)
or by incorporating specific precursors in the mould cultures.

•Eg. Procaine penicillin and Benzathine penicillin are salts of PnG and not
semisynthetic penicillins.

•The aim of producing semisynthetic penicillins has been to overcome the shortcomings
of PnG, which are:
1. Poor oral efficacy.
2. Susceptibility to penicillinase.
3. Narrow spectrum of activity.
4. Hypersensitivity reactions 29
Phenoxymethyl penicillin (Penicillin
V)
•Acid stable.
•Better oral absorption.
•Plasma t½ is 30–60 min.
•Antibacterial spectrum is similar to penicillin G but it is about 1/5 as active
against Neisseria, other gram-negative bacteria and anaerobes.
•Dose: 250–500 mg, children 125–250 mg; given 6 hourly.

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PENICILLINASE-RESISTANT PENICILLINS
•Have side chains that protect the β-lactam ring from attack by staphylococcal
penicillinase.

Methicillin

•It is highly penicillinase resistant but not acid resistant—must be injected.

Cloxacillin

•Highly penicillinase as well as acid resistant.


•More active than methicillin against penicillinase producing Staphylococcus.
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EXTENDED SPECTRUM PENICILLINS

Semisynthetic penicillins active against gram-negative bacilli.

Ampicillin
•Active against all organisms sensitive to PnG.

•More active than PnG for Strep. viridans and enterococci (therefore better suited
for dental infections).
•Dose: 0.5–2 g oral/i.m./i.v. depending on severity of infection, every 6
hours; children 25–50 mg/kg/day.
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USES:
1. Urinary tract infections
2. Respiratory tract infections
3. Meningitis
4. Subacute bacterial endocarditis: preferred over PnG.

Adverse effects:
Diarrhoea is frequent after oral administration of ampicillin

Interactions:
Hydrocortisone inactivates ampicillin if mixed in the i.v. solution.
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AMOXICILLIN

•Close congener of ampicillin.


•Oral absorption is better.
•Incidence of diarrhoea is lower.
•One of the most frequently used antibiotics for treatment of dental infections
250–500 mg TDS given for 5 days.
•Prophylaxis of local wound infection , distant infection (endocarditis)
following dental surgery in susceptible patients.
•Dose: 0.25–1 g TDS oral/i.m. 34
BETA-LACTAMASE INHIBITORS

•Family of enzymes produced by many gram-positive and gram-negative


bacteria that inactivate β-lactam antibiotics by opening the β-lactam ring.
•Eg.: clavulanic acid, sulbactam and tazobactam.

Clavulanic acid

•Obtained from Streptomyces clavuligerus.


•Permeates the outer layers of the cell wall of gram negative
bacteria and inhibits the periplasmically located β-lactamase. 35
USES:

•Addition of clavulanic acid re-establishes the activity


of amoxicillin against β-lactamase producing resistant Staph.
Aureus.
•Skin and soft tissue infections, dental infections.
•Eg. AUGMENTIN, Amoxicillin 250 mg + clavulanic acid 125 mg
tab; 1–2 tab TDS, severe infections 4 tabs 6 hourly.
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CEPHALOSPORINS

•Group of semisynthetic antibiotics.


•Obtained from a fungus Cephalosporium.
•Mechanism of action : Bactericidal action.

•Chemically related to penicillins; the nucleus consists of a β-lactam ring fused to


a dihydrothiazine ring.

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Classification of Cephalosporins
First generation Second generation Third generation Fourth generation

More active against More selective against Highly active against Similar antibacterial
gram positive gram positive and gram negative activity as that of
organism gram negative organisms third generation but
organisms highly resistent to
beta lactamases

Parenteral- Parenteral- Parenteral- Parenteral


Cephalothin Cefuroxim Cefotaxim - Cefepime
Ceftizoxime
Cefazolin Cefoxitin Ceftraxone
Cephaloridine Oral- Cefiperome
Cefoperazone
Oral- Cefaclor Oral-
Cephalexin Cefuroxim axetal Cefexime
Cephadine 38

Cefadroxil
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FIRST GENERATION CEPHALOSPORINS
•1960 , high activity against gram-positive but weaker against gram-negative
bacteria.

Cefazolin

•PnG sensitive organisms, i.e. streptococci , meningococci, C.


diphtheriae, H.influenzae etc.
•Preferred parenteral first generation cephalosporin, especially for
surgical prophylaxis.
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•Dose: 0.25 g 8 hourly (mild cases), 1 g 6 hourly (severe cases) i.m. or i.v.
Cephalexin
•Orally effective.
•Used in dentistry as an alternative to amoxicillin.
•Dose: 0.25–1 g 6–8 hourly (children 25–100 mg/kg/day).

Cefadroxil
•Close congener of cephalexin.
•Good tissue penetration including that in alveolar bone (tooth socket)
•Exerts more sustained action at the site of infection.
•Dose: 0.5–1 g BD. DROXYL 0.5, 1 g tab, 41
Third generation Cephalosporins

Activity against gram-negative Enterobacteriaceae; some inhibit Pseudomonas


as well.

Cefotaxime:
• 3rd generation
• anaerobic & some gram positive bacteria
• meningitis (gram negative bacilli),
• life threatning /hospital aquired infections.
• septicaemias and infections in immunocompromised patients.
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BROAD SPECTRUM ANTIBIOTICS

TETRACYCLINE
• Broad spectrum antibiotic.
ADMINISTRATION
• Primarily bacteriostatic. •Orally taken ½ hr before or 2 hr after food
• Inhibit protein synthesis by binding •Not recommended by i.m. route.

to 30S ribosomes in susceptible organism.


• Tetracyclines have chelating property.

PRECAUTIONS:

1. Should not be used during pregnancy, lactation and in children.


2. Should be avoided in patients on diuretics.
3. Should be used cautiously in renal or hepatic insufficiency.
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4. Should not mix injectable tetracyclines with penicillin.


ADVERSE EFFECTS:
•Epigastric pain, nausea, vomiting and diarrhoea.
•Acute hepatic necrosis in pregnant women.
•Risk of kidney damage.
•Brown discolouration, ill-formed teeth, more susceptible to caries.

•Tetracyclines given between 3 months and 6 years of age affect the crown of
permanent anterior dentition.
•Given during late pregnancy or childhood, tetracyclines can cause temporary
suppression of bone growth.

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Uses in Orodental conditions :

a) Periodontal inflammation
b) Chronic periodontitis General medical uses:
c) Juvenile periodontitis The drug of first choice in:
(a) Atypical pneumonia due to
Mycoplasma pneumoniae
(b) Cholera
(c) Brucellosis.
(d)Relapsing fever due to Borrelia
recurrentis.
(g) Rickettsial infections: typhus , Q fever,
etc.
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CHLORAMPHENICOL
•Broad-spectrum antibiotic.
•Gram-positive and negative bacteria, rickettsiae, chlamydia, mycoplasma etc.
•Inhibits bacterial protein synthesis.

•Attaches to the 50S ribosome and hinder the access of aminoacyl-tRNA to the
acceptor site for amino acid incorporation.
•Primarily bacteriostatic , high concentrations - cidal effect.
•Rapidly and completely absorbed after oral ingestion.
•Oral administration —as capsules; 250–500 mg 6 hourly
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Adverse effects USES
•No indication in dentistry despite
1. Bone marrow depression its broad-spectrum antimicrobial
2.Hypersensitivity reactions action.
•Enteric fever
Rashes, fever etc
•Meningitis
3.Irritative effects Nausea,
•As second choice drug
vomiting, diarrhoea, pain on
injection. (a)to tetracyclines for brucellosis,
4. Superinfections cholera,
5.Gray baby syndrome : at rickettsial and chlamydial infections.
high doses (~100 mg/kg) (b)to erythromycin for
whooping cough
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MACROLIDE
•ANTIBIOTICS
Antibiotics having a macrocyclic lactone ring with attached sugars.

ERYTHROMYCIN
•Isolated from Streptomyces erythreus.
•Widely employed, mainly as an alternative to penicillin.
•Narrow spectrum.
•Active against gram-positive and a few gram-negative organisms.

Mechanism of Action
Erythromycin is bacteriostatic at low concentration but cidal at
high concentrations. Erythromycin acts by inhibiting bacterial
combines with 50S ribosomeprotein
subunit and interferesItwith ‘translocation’.
synthesis. 48
Uses :
 Second choice drug to penicillins for:
•Periodontal/ periapical abscesses
•Necrotizing ulcerative gingivitis
•Postextraction infections
•Cellulitis, etc.
In patients allergic to penicillins, or those with penicillin resistant
infections.

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NEWER MACROLIDES
AZITHROMYCIN
•Has an expanded spectrum.
•Improved pharmacokinetics.
•Better tolerability and drug interaction profiles.
•More active than other macrolides against H. influenzae, certain
and anaerobes like Peptostreptococcus, few Clostridia.
•Better activity against oral spirochetes and gram negative anaerobes.
•Can be used in orodental infections in place of erythromycin.
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•Dose: 500 mg once daily 1 hour before or 2 hours after food.
CLINDAMYCIN

•Dental infections - anaerobic bacteria.


•Patients resistant to penicilin.
•Dentoalveolar abscesses , bone caused by Staphylococci or
infections
Bacteroides.
•Alternative antibiotic for prophylaxis of endocarditis due to
postextraction bacteraemia in patients with damaged heart valves or other risk
factors.
•Dose: 150–300 mg QID oral; 200–600 mg i.v. 8 hourly.
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AMINOGLYCOSIDES
USES
 Broad spectrum of action
 Rapid bactericidal effect •Gram-positives, except Streptococus and
 Inhibitors of Protein Synthesis Enterococcus.
Systemic aminoglycosides • Combine with aminoglycoside
•Streptomycin (Gentamicin or
•Amikacin Streptomycin) & penicillin, ampicillin or
•Gentamicin
•Kanamycin vancomycin produces a synergistic bactericidal
•Tobramycin effect.

Topical aminoglycosides •In serious infection, with beta-lactams or


•Neomycin fluoroquinolones.
•Framycetin
• Gram-negative nosocomial infections
TOXICITIES

•Ototoxicity
-Cochlear damage
-Vestibulaar damage
•Nephrotoxicity
•Neuromuscular blockade

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ANTIFUNGAL DRUGS
Polyenes: Amphotericin B (AMB), Nystatin,

AMPHOTERICIN B (AMB)
•Combine with ergosterol present in fungal cell membrane, and create micropores
through which ions, amino acids and other water-soluble substances move out.
•Candida albicans, Histoplasma capsulatum,, aspergillus etc.
•Not absorbed orally, excretion occurs slowly both in urine and bile.
•Uses: can be used topically for oral, vaginal and cutaneous candidiasis
52
NYSTATI
N
•Used only locally.
•In dentistry, topically applied nystatin is the 2nd choice drug to clotrimazole for oral thrush,
denture stomatitis, antibiotic associated stomatitis, corticosteroid associated oral
candidiasis and mucocutaneous candidiasis of lips, etc

•1 mg tablet is placed in the mouth to dissolve slowly 4 times a day, or it can be crushed and
suspended in glycerine for application on the lesions.
•Bitter foul taste and nausea are the side effects.

53
PRINCIPLES OF ANTIBIOTIC THERAPY

•To determine the severity of infection.


•To evaluate state of patient’s host defense mechanisms.
•To determine whether patient should treated by general dentist or
be specialist.
•To treat infection surgically.
•To support the patient medically.
•Choose and prescribe appropriate antibiotic.
•Proper antibiotic administration.
•Monitoring the patient.
54
CHOICE OF AN ANTIMICROBIAL
AGENT • Age
• Renal and hepatic function
• Local factors
1.Patient factors • Drug allergy
• Impaired host defence
• Pregnancy

2.Organism related
considerations
• Spectrum of activity
• Type of activity
• Sensitivity of the organism
3.Drug factors • Relative toxicity
• Pharmacokinetic profile 55
Age :
•Larger doses of chloramphenicol - grey baby syndrome.

•Sulfonamides displace bilirubin from protein binding sites—can cause


kernicterus in the neonate.
•The t½ of aminoglycosides is prolonged in the elderly and they are more
prone to develop VIII nerve toxicity.
•Tetracyclines accumulate in the developing teeth and bone —discolour and
weaken them— are contraindicated below the age of 6 years.

56
Renal and hepatic function

57
Local factors :
(a) Presence of pus and secretions
(b)Presence of necrotic material or foreign body
(c)Haematomas foster bacterial growth
(d)Lowering of pH at site of infection

Drug allergy :

•Erythromycin or Clindamycin are the alternative drugs for


dental infection in patients allergic to penicillin
60
Impaired host defence :

•Pyogenic infections occur readily in neutropenic patients; while if cell-


mediated immunity is impaired (e.g. AIDS), infections by low-grade pathogens
and intracellular organisms abound.

•In an individual with normal host defence, a bacteriostatic AMA may achieve
cure; while intensive therapy with cidal drugs is imperative in those with
impaired host defence.
59
Pregnancy

Safe drugs Contraindicated


> Penicillins > Tetracyclines
> Cephalosporins > Aminoglycosides
> Erythromycin > Fluoroquinolones
> Cotrimoxazole
> Chloramphenicol
> Sulfonamides

60
Genetic factors:
•Sulfonamides, chloramphenicol and fluoroquinolones are likely to produce
haemolysis in G-6PD deficient patient.

Organism-related considerations
Antibiotic susceptibility test

Disc diffusion test

61
Minimum inhibitory concentration (MIC)

•The lowest concentration of an antibiotic which prevents visible growth of a


bacterium determined.

•Done in microwell culture plates using serial dilutions of the antibiotic.

•For treatment purposes, the dosage of antibiotic given should yield a peak
body fluid concentration 3-5 times higher than the MIC or MIC x 4 = dosage to
obtain peak achievable concentration.
62
Minimum bactericidal concentration (MBC)

•MBC is the concentration of the antibiotic which kills 99.9% of the bacteria.

65

Broth dilution methods showing MIC and MBC


DRUG FACTORS

1. Spectrum of activity:

•For definitive therapy → a narrow spectrum drug is preferred.

•For empirical therapy → often a broad-spectrum drug is preferred.

2. Type of activity:

•A bactericidal antibiotic may be preferred over bacteriostatic.

•Acute infections generally resolve faster with bactericidal than with


bacteriostatic drugs 66
3. Relative toxicity:

•Obviously, a less toxic antibiotic is preferred, e.g. a β-lactam over an


aminoglycoside or erythromycin over clindamycin.

4. Pharmacokinetic profile:

•A drug, which penetrates better and attains higher concentration, is likely


to be more effective.
65
COMBINED USE OF
ANTIMICROBIALS
More than one AMAs are frequently used concurrently. The objectives of using
antimicrobial combinations are:

1. To achieve synergism:
Eg.:
1. combination of a β-lactamase inhibitor clavulanic acid or sulbactam with amoxicillin or ampicillin for β-
lactamase producing H. influenzae.

2. Penicillin/ampicillin + streptomycin/gentamicin for enterococcal SABE.

3. Penicillin + sulfonamide for actinomycosis

66
2. To reduce severity or incidence of adverse effects.

3. To prevent emergence of resistance.

4. To broaden the spectrum of antimicrobial action.

a) Treatment of mixed infection

b) Initial treatment of severe infections

67
Disadvantages of antimicrobial combinations

1. They foster a casual rather than rational outlook in the diagnosis of


infections and choice of AMA.
2. Increased incidence and variety of adverse effects.
• Toxicity of one agent may be enhanced by another, e.g. vancomycin
tobramycin and gentamicin + cephalothin produce exaggerated kidney
failure.

3. Increased chances of superinfections.


70

4. Higher cost of therapy.


PROPHYLACTIC USE OF ANTIMICROBIALS

Refers to the use of AMAs for preventing the setting in of an infection or


suppressing contacted infection before it becomes clinically manifest.

Antimicrobial prophylaxis in dentistry

This is warranted for two distinct purposes viz.


(a) prevention of local wound infection
(b) prevention of distant infection (e.g. bacterial endocarditis) in predisposed patients
following dental procedures.
69
Prophylaxis of dental wound infection
•Clear risk of wound infection.

•Simple extractions and minor periodontal procedures does not require.

•Incidence of postoperative infection is higher when oral surgery had lasted 2 hours or more
eg. prosthesis insertion into the bone or soft tissue, such as dental implants and extensive
reconstructive surgeries.

•All orodental procedures which disturb/ damage mucosa including extractions, scaling, etc.
need to be covered by prophylaxis in diabetics, corticosteroid recipients and other
immunocompromised subjects
70
71
PROPHYLAXIS OF DISTANT INFECTION

•Gentamicin 120 mg (2 mg/kg) i.m./i.v. may be given just before the dental
procedure in addition to amoxicillin (or its substitute) and another dose of
amoxicillin 500 mg (12.5 mg/kg) be repeated 6 hours after the procedure.

• If patient is allergic to penicillin :

vancomycin 1 g (20 mg/kg) i.v. over 2 hours + gentamicin 120 mg (2


mg/kg) i.m./i.v. just before the procedure.
72
FAILURE OF ANTIMICROBIAL THERAPY

1. Improper selection of drug, dose, route or duration of treatment.


2. Treatment begun too late.
3.Failure to take necessary adjuvant measures, e.g. drainage of abscesses.
4.Poor host defence—as in leukaemias, neutropenia and other causes; especially
if bacteriostatic AMA is used.
5. Infecting organism present behind barriers, such as vegetation on heart valves
(in SABE), inside the eyeball, blood-brain barrier.
73
ANTIBIOTICS USEFUL FOR OROFACIAL INFECTIONS:

1. Penicillins.
2. Cephalosporins.
3. Erythromycins.
4. Clindamycin and Lincomycin.
5. Metronidazole.
6. Aminoglycosides.
7. Fluoro quinolones – ciprofloxacin.
8. Sulfonamides and trimethoprim
74
AHA RECOMMENDATIONS

NOT RECOMMENDED: PROPHYLAXIS


RECOMMENDED:
1.Extractions
1.Restorative dentistry
2.Periodontal surgery
2.LA injections
3.Implants
3.Intracanal endodontic
placement
treatment
4.Endodontic surgery
4.post-op suture removal
5.Subgingival antibiotic fiber
5.Oral radiographs
strips
6. Intraligamentary LA
injections. 77
Odontogenic infection, oral and maxillofacial implications

•Initial stage- Aerobic bacteria invade.


•Severe infection- Aerobic and anaerobic bacteria invade.
•Advanced stage- anaerobic infection.

Pericoronitis :
•Acute pericoronitis, if severe, may require antibiotic therapy.
•Treatment - debridement, drainage of the site,
penicillin 500 mg qid,
amoxacillin 500mg qid,
clindamycin 300mg
qid
Dento Alveolar Abscess: 78

Penicillin is the drug of choice


Soft tissue wounds :
•open for six hours or more, (considered infected,)
•if primary closure is elected, a delayed primary closure is preffered.
•delayed technique cannot be utilized,-antibiotic support is helpful.

•early primary closure -amoxicillin with clavulanic

acid Chronic inflammatory periodontal diseases :


•TOPICAL MEASURES - Tetracyclins, metronidazole 250mg tid, , penicillins500mg qid,

cephalosporins.
ANUG
Topical measures with systemic antibiotic penicillin, metronidazle 400mg qid, 79
Antibiotic regimen for osteomyelitis
For hospitalalized/ when inta-venous therapy is indicated-
Aqueous penicillin, 2 million Units IV Q6h, metronidazole 500mg q6h for 4 - 6 weeks
OR
Ampicillin/sulbactum 1.5 to 3.0 gm IV q6h for 2 days then amoxacillin/clavulanate
(augmentin)875, 125.mg PO bd for 4 to 6 weeks.

For out patient treatment

penicillin V 2gm + metronidazole 500mg q8h for 2 to 4 weeks after last sequestrum removal
and patient with out symptons.
OR
cefoxitin 1 gm q8h IV OR IM
cephalexin 500mg q6h PO for 2 to 4 weeks
OR
clindamycin 600, 900mg q6h IV then clindamycin 300, 450 mg PO. 80
Regimen for fracture
•therapeutic doses for 10 to 14 days.

•should begin as early as possible after diagnosis.

Pre-operatively
penicillin 2 million units or cefazolin 0.5 gm-1.5 gm 12 hr [25- 50 mg/kg].

Post-operatively

Penicillin 500mg 6 hr [30-40 mg /kg]


Cephalexin 500mg 6 hr [25- 50 mg/kg]

In suspected intra-cranial contamination-


Pre-operatively- naficillin 2-6 gm 6hr+ gentamycin 3-5mg/kg 8
hr Post-operatrively- cephalexin 500mg 6 hr[25-50 mg/kg] 81
80
81
ANTIBIOTIC RESISTANCE Resistance arises through one of three mechanisms:

 natural resistance in certain types of bacteria,


genetic mutation,
one species acquiring resistance from another.

82
PUBLC HEALTH IMPORTANCE OF THE ANTIBIOTICS

Increased prevalence of resistant and multi-resistant bacterial strains

Limited supportive care provided by health


professionals.

 Difficulty in treating various infections

Antibiotic Resistance – Economic burden to the


healthcare system.

85

An overview of antimicrobial resistance and its public health significance, Brazilian journal of Microbiology 45, 1, 1-
DEFINITION OF ANTIBIOTICS

S HISTORY

U CLASSIFICATION OF ANTIBIOTICS

M COMBINED USE OF ANTIMICROBIAL AGENTS

ANTIBIOTICS USEFUL FOR OROFACIAL INFECTIONS


M
PROPHYLACTIC ANTIBIOTICS

A ANTIBIOTIC RESISTANCE

R
86
PUBLIC HEALTH SIGNIFICANCE OF ANTIBIOTICS
CONCLUSIONS

Antibiotics are used to treat infections and are also responsible for making
them more difficult to treat because of their misuses and development of
resistance.
The only way to keep antibiotics useful is to use them appropriately and
judiciously.

85
REFERENCES
 THE PHARMACOLOGIC BASIS OF THERAPEUTICS GOODMAN & GILMAN 11THED

 ESSENTIALS OF MEDICAL
PHARMACOLOGY K.D.TRIPATHI 5TH ED

 TEXTBOOK OF PHARMACOLOGY -
TOPAZIAN

 TEXTBOOK OF MUCROBIOLOGY- C. P.
BAVEJA 3RD ED.

 BURKET’S ORAL MEDICINE, 12TH ED

 SYMPOSIUM ON ANTIMICROBIAL THERAPY, GENERAL PRINCIPLES OF ANTIMICROBIAL


THERAPY
 AN OVERVIEW OF ANTIMICROBIAL RESISTANCE AND ITS PUBLIC 86
HEALTH
SIGNIFICANCE, BRAZILIAN JOURNAL OF MICROBIOLOGY 45, 1, 1-5(2014)

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