Antibiotics in Endodontics

Part II
 PRINCIPLES FOR CHOOSING THE APPROPRIATE
ANTIBIOTIC

1) Identification of the causative organism

2) Determination of antibiotic sensitivity

3) Use of specific, Narrow spectrum antibiotic

i) more effective against specific groups of susceptible

microorganisms than are broad-spectrum agents.

ii) produce less alteration of the normal microflora, thereby

reducing the incidence of superinfection.
4. Use of a least toxic antibiotic

5. Use of a bactericidal rather than a bacteriostatic drug

The advantages of bactericidal drugs are :

a) Less reliance on host resistance.
b) Antibiotic itself kills the bacteria.
c) Works faster than bacteriostatic drugs
d) There is greater flexibility with dosage intervals.
6. Use of the antibiotic with a proven history of success

7. Cost of the antibiotic

 DRUG DOSAGE

‘Dose’ is the appropriate amount of a drug needed to produce

a certain degree of response in a patient.

1. Body size :

Individual dose = BW (kg) x average adult dose

70

BSA (m2)
Individual dose = x average adult dose
1.7

BSA (m2) = BW (kg)0.425 x height (cm)0.725x 0.007184

2. Age :

The dose of drug for children is often calculated from the

adults dose
Young’s formula

Age
Child dose = x adult dose
Age +12

Dilling’s formula

Age
Child dose = 20 x adult dose
 CLASSIFICATION OF ANTIMICROBIAL DRUGS
A) Mechanism of action :
1. Inhibit cell wall synthesis
• Penicillins
• Cephalosporins
• Vancomycin
• Bacitracin
2. Cause leakage from cell membranes
• Polypeptides – Polymyxins, colistin, Bacitracin
• Polyenes – Amphotericin B, Nystatin
3. Inhibit protein synthesis
• Tetracyclines
• Chloramphenicol
• Erthromycin,
• Clindamycin
• Linezolid
4. Cause misreading of m-RNA code and affect permeability
• Aminoglycosides
o Streptomycin
o Gentamicin
5. Inhibit DNA gyrase
• Fluoroquinolones – Ciprofloxacin
6. Interfere with DNA function
• Rifampin
• Metronidozole
7. Interfere with DNA synthesis
• Idoxuridine
• Acyclovir
• Zidovudine
8. Interfere with intermediary metabolism
Sulfonamides PAS
Sulfones Ethambutol
B) 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
4. -lactam antibiotics
• Penicillins
• Cephalosporins
• Monobactams
• Carbapenems
5. Tetracyclines
• Oxytetracycline
• Doxycycline etc
6. Nitrobenzene derivative
• Chloramphenicol
7. Aminoglycosides
• Streptomycin
• Gentamicin
• Neomycin
8. Macrolide antibiotics
• Erythromycin
• Roxithromycin
• Azithromycin etc
9. Polypeptide antibiotics
• Polymyxin-B
• Colistin
• Bacitracin
• Tyrothricin
10. Glycopeptides
• Vancomycin
• Teicoplanin
11. Oxazolidinone
• Linezolid
12. Nitrofuran derivatives
• Nitrofurantoin
• Furazolidone
13. Nitroimidozoles
• Metronidozole
• Tinidazole
14. Nicotinic acid derivatives
• Isoniazid
• Pyrazinamide
• Ethionamide
15. Polyene antibiotics
• Nystatin
• Amphotericin-B
• Hamycin
16. Azole derivatives
• Miconazole
• Clotrimazole
• Ketoconazole
• fluconazole
17. Others
• Rifampin
• Lincomycin
• Clindamycin
• Spectinomycin
• Sod. fusidate
• Cycloserine
• Viomycin
• Ethambutol
• Thiacetazone
• Clofazimine
• Griseofulvin
C) Type of organisms against which primarily active
1. Antibacterial
• Penicillins
• Aminoglycosides
• Erythromycin etc
2. Antifungal
• Griseofulvin
• Amphotericin B
• Ketoconazole
3. Antiviral
• Idoxuridine
• Acyclovir
• Amantadine
• Zidovudine etc
4. Antiprotozoal
• Chloroquine
• Pyrimethamine
• Metronidazole
• Diloxanide etc
5. Anthelmintic
• Mebendazole
• Pyrantel
• Niclosamide
• Diethyl carbamazine etc
D) Spectrum of activity

1. Narrow spectrum

• Penicillin G

• Streptomycin

• Erythromycin

2. Broad spectrum

• Tetracyclines

• Chloramphenicol
E) Type of action
1. Primarily bacteriostatic 2. Primarily bactericidal
• Sulfonamides
• Tetracyclines
• Chloramphenicol
• Erythromycin
• Ethambutol
• Penicillins
• Aminoglycosides
• Polypeptides
• Rifampin
• Cotrimoxazole
• Cephalosporins
• Vancomycin
• Nalidixic acid
• Ciprofloxacin
F) Antibiotics are obtained from
1. Fungi 3. Actinomycetes
• Pencillin • Aminoglycosides
• Cephalosporin • Tetracyclines
• Griseofulvin • Chloramphenicol
2. Bacteria • Macrolides
• Polymyxin B • Polyenes
• Colistin
• Bacitracin
• Tyrothricin
• Aztreonam
 BETA LACTAM ANTIBIOTICS

Pencillins

Most important antibiotics first extracted from the mould

PENICILLIUM NOTATUM

First used in 1941 clinically and was a miracle drug with a

least toxic effect.

CLASSIFICATION OF PENICILLINS
1. Natural penicillin
• Penicillin G (benzyl penicillin)
• Procaine penicillin G
• Benzathine penicillin G
2. Acid resistant penicillin
• Phenoxymethyl penicillin (pencillin V)
• Phenoxyethylpenicillin (phenethecillin)
3. Penicillianse – resistant penicillins
• Acid labile – methecillin, nafcillin, cloxacillin, dicloxacillin
• Acid resistant – flucloxacillin
4. Penicillins effective against gram positive and some gram-
negative organisms
• Ampicillin
• Amoxycillin
• Talampicillin
5. Extended spectrum penicillins
• Carboxypenicillins – carbenicillin, ticarcillin
• Ureidopencillins – piperacillin, mezlocillin
• Amidino pencillins – mecillinam, pivmecillinam
6. Penicillins with betalactamase inhibitors
• Amoxycillin – clavulanic acid (Augmentin)
• Ticarcillin – clavulanic acid (Timentin)
 BENZYL PENICILLIN (PENCILLIN G)

• Narrow spectrum antibiotic; activity is limited primarily to gram

positive bacteria

Preparation and dose :

• PnG inj 0.5-5 MU i.m or i.v 6-12 hours
• Procaine pencillin inj 0.5, 1 MU dry powder in vial
• Penidure 0.6, 1.2, 2.4 MU as dry powder in vial
• Fortifide PP inj 3+1 lac U vial
The major drawbacks of benzyl pencillin are :
1. Inactivation by the gastric hydrochloric acid
2. Short duration of action
3. Poor penetration into CSF
4. Activity mainly against gram +ve organism
5. Possibility of anaphylaxis
SEMI SYNTHETIC PENICILLINS

I) Acid resistant penicillins :

1. Potassium phenoxymethyl penicillin (penicillin V)
Dose : infants 60 mg, children 125-250 mg given 6 hourly
CRYSTAPEN-V, KAYPEN, PENIVORAL 65, 130, 125, 250 mg
tablets

2. Potassium phenoxyethyl penicillin and

3. Azidocillin
Both have similar properties to penicillin V and no difference in
the antibacterial effect
II) Penicillinase resistant penicillins :
1. Methicillin
1. It is given IM or IV (slow) in the dose of 1 gm every 4-6
hours.
2. Haematuria, albuminuria and reversible interstitial nephritis
are the special adverse effect of methicillin.
2. Cloxacillin
1. Weaker antibacterial activity.
2. Oral dose for adults 2-4 gm divided into 4 portions children
50-100mg/kg/day.
3. IM adults 2-12 gm/day, children 100-300 mg/kg/day every
4-6 hours.
BIOCLOX, KLOX, CLOCILIN 0.25, 0.5 gm cap, 0.5 gm/vial.

3. Nafcillin : More active than methicillin and cloxacillin but less

active than PnG
III) Extended spectrum pencillins :
1. Amino penicillins
1. Ampicillin –
• Antibacterial activity is similar to that of PnG that is more
effective than PnG against a variety of gram-ve bacteria
• Drug is effective against H.influenzae strep.viridans,
N.gonorrhea, Salmonella, shigellae, Klebsilla and
enterococci.
Dose : 0.5-2 gm oral/IM or IV depending on severity of infection
every 6 hours
Children : 25-50 mg/kg/day
AMPILIN, ROSCILLIAN, BIOCILIN – 250, 500 mg cap
100mg/ml ped drops, 1 gm/vial inj.
AMOXYCILLIN :
• (amino-p-hydroxy-benzylpencillin)
Dose : 0.25-1 g TDS oral;
AMOXYLIN, NOVAMOX, SYNAMOX, AMOXIL 250, 500 mg
cap, 500 mg/vial inj.
Carboxy penciillins :
The Carboxypenicillins, the Ureidopenicillins and the Amidino
penicillins are considered extended spectrum penicillins,
because they inhibit a wide variety of aerobic gram-ve bacilli
They are ineffective against most strains of staph. Aureus
They have following properties :
1. Highly active against anaerobes
2. Most useful in infections caused by other gram-ve rods
3. Much less active than penicillin G against gram+ve organisms
BETA LACTAMASE INHIBITORS

• Amoxicillin+clavulanic acid (augmentin)

• Ticarcillin+clavulanic acid (timentin)

AUGMENTIN, AMONATE, ENHANCIN

• 250+125mg tab 1-2tab TDS

• 250+50mg vial im/iv 6-8 hourly

SULBACTAM

• Sulbactam+ ampicillin=Dicapen

• SULBACIN, AMPITUM

• 1g+ 0.5g per vial im/iv 6-8hourly

• 1g+500mg tab

Uses :

• Mixed aerobic-anaerobic infections

• Gonorrhoea

• Skin/soft tissue infections

 CEPHALOSPORINS
Cephalosporium acremonium was the first source.
They contain 7 amino cephalosporonic acid nucleus.
Structurally they contain betalactam and dihydrothiazine rings.
Mechanism of action :
Act by inhibiting bacterial cell wall synthesis and are
bactericidal.
Classification

Classified according to its antibacterial activity.

First generation cephalosporin

•Good activity against gram +ve bacteria. (except enterococci).

•Most oral cavity anaerobes are sensitive.

Parental Oral

CEPHALOTHIN CEPHALEXIN

CEFAZOLIN CEPHRADINE

CEFADROXIL
Cefazolin :
•For antimicrobial prophylaxis in most surgical procedures.
•Given only IM / IV.
•Dose: Oral 0.25 - 1g 6-8 hrly
Children : 25-100mg/kg/day
IM – 0.25g 8 hrly (mild cases) 1g 6 hrly (severe cases).
Drops – cephaxin 125mg/5ml syrup.
100mg /ml ped. drops.
SPORIDEX, CEPHAXIN, CEPHACILLIN, CEFADROX,
DROXYL
Second generation cephalosporins :
Increased activity against gram –ve organism.
More active against anaerobes.
Parenteral Oral
CEFUROXIME CEFACLOR
CEFOXITIN CEFUROXIME AXETIL
Dose : 250mg, 125mg, 125mg/5ml syr. and
50 mg /ml ped. drops.
KEFLOR, CEFTUM, CEFOGEN, FUROXIL.
Third generation cephalosporin :
•They highly augmented against gram –ve enterobacter and
pseudomonas.
•Less active on gram +ve cocci
Parenteral Oral
CEFOTAXIME CEFIXIME
CEFTIZOXIME CEFDINIR
CEFTRIAXONE CEFTIBUTEN
CEFTAZIDIME
CEFOPERAZONE
Dose : 100, 200 mg tab/cap.
100mg/5ml syr., 50mg/ml susp. CESPAN, CEFOPROX,
PROCADAX, CEPODEM, ORFIX.
Fourth generation cephalosporins :
Developed in 1990 similar to that of 3rd generation.
It has high potency and extended spectrum.
Effective in many serious infections.
Parenteral
CEFEPINE, CEFPIROME
USES :
Serious and resistant hospital acquired infections.
Septicaemia,
Lower respiratory tract infection.
Dose : 1-2g IM / IV 12 hrly.
CEFROM, CEFORTH – 1g inj.
Uses :
• Alternatives to pencicillins.
• RTI, UTI and soft tissue infection
• Penicillinase producing staph infection.
• Septicaemias.
• Surgical prophylaxis
• Meningitis, gonorrhoea
• Typhoid
• Mixed aerobic and anaerobic infections
• Infection by odd organism or hospital infections
• Prophylactic treatment in neutropenic patients.
.
NORFLOXACIN
 It is less potent than ciprofloxin
 It attains lower concentration in tissues.
 It is metabolized as well as excreted unchanged in urine.
 NORBACTIN, NORFLOX, UROFLOX
 200, 400, 800 mg tab
 OFLOXACIN
Intermediate between Cipro and Nor in activity against Gr-ve
bacteria
 More potent for Gr +ve organisms
 Good activity against chlamydia

 ZENFLOX, OFLOX

 100, 200, 400 mg tab, 200 mg/100IV infusion 5mg/5ml susp.

 LEVOFLOXACIN

 It is levoisomer of ofloxacin having improved activity against

strep pneumoniae and some other gram +ve and –ve bacteria.

 Anaerobes are moderately susceptible.

 Oral bioavailability is nearly 100%

 Excreted unchanged and single daily dose is sufficient

 Oral and IV doses are similar.

 Theophylline, Warfarin, Cyclosporine has been found to remain

unchanged during levofloxacin treatment.

TAVANIC, GIEVO, 500mg tab, 500 mg/100 ml inj.

 GATIFLOXACIN

Another 2nd generation FQ has excellent activity against strep.

Pneumonia and many atypical respiratory pathogens including
chlamydia pneumonia and other anaerobes.

Dose :

 400 mg on 1 day followed by 200-400 mg OD.

 MYGAT, GATIQIN, GAITY

 200, 400 mg tab, 400 mg/200 ml inj

MOXIFLOXACIN :

 It is long acting 2nd generation FQ having high activity

against strep pneumonia, other Gr +ve bacteria.

 MOXIF 400 mg tab OD

 ANTIAMOEBIC AND OTHER ANTIPROTOZOAL
DRUGS
METRONIDAZOLE :
 It is the prototype nitroimidazole and found to be highly
active amoebicide.
Antiprotozoal activity :
 Broad spectrum cidal activity against protozoa and
anaerobic bacteria such as B fragilis, Fusobacterium.
 Metronidazole is selectively toxic to anaerobic
microorganisms.
 Metronidazole has been found to inhibit cell mediated
immunity and cause radiosensitization.
Pharmacokinetics :

 Completely absorbed from the small intestine.

 Widely distributed in the body

 It is metabolized in liver primarily by oxidation and

glucuronide conjugation, and

 Excreted in urine.

Adverse effects :

Side effects relatively frequent but mostly not serious,

 Anorexia, nausea, metallic taste and abdominal cramps are the

most common.
 Looseness of stool is occasional,

 Headache, glossitis, dryness of mouth, dizziness, rashes and

transient neutropenia.

 Prolonged administration may cause peripheral neuropathy and

CNS effects

 Seizures have followed by high doses.

 Thrombophebitis of injected vein.

Contraindications :

 In neurological disease, blood dyscrasias, first trimester of

pregnancy, chronic alcoholism.
Uses :
 Amoebiasis
 Giardiasis
 Trichomonas vaginitis.
 Anaerobic bacterial infections
 Pseudomembranous enterocolits.
 Ulcerative gingivitis
 Helicobacter pylori gastritis/peptic ulcer
 Guinea worm infestation.
 FLAGYL, METROGYL, METRON, ALDEZOLE 200, 400
mg tab, 200 mg/5ml susp.
 TINIDAZOLE

 It is an equally efficacious congener of metronidazole, similar

to it in every way except.

 Metabolism is slower.

 Incidence of side effects is lower.

 Metallic taste, nausea, rashes

 TINIBA, TRIDAZOLE, 300, 500, 1000 mg tab, 800 mg/400 ml

I.V.
 Prophylaxis
regimen for
subacute bacterial
endocarditis
 Prophylaxis
regimen in
patients with
prosthetic valve
endocarditis
Pediatric dosages of commonly used antibiotics
Maximum dosage for life-threatening infections
 Antibiotic prophylatic regimen
Situation Antibiotic Regimen
Standard Amoxicillin Adult – 2gm children 50mg/kg
prophylaxis PO, 1 hr before
Cannot use oral Ampicillin Adult – 2gm children 50 mg/kg
medication IM/IV. 30 min before
Allergic to Clindamycin Adult – 600mg children 20
pencillin mg/kg PO, 1 hr before
Cephalexin / Adult – 2gm children 50 mg/kg
cefadroxil PO, 1 hr before
Azithromycin or Adult – 500mg children 15
clarithromycin mg/kg PO, 1 hr before
Allergic Pn, Clindamycin Adult – 600mg children 15
cannot use oral mg/kg IV 1 hr before
medication Cefazolin Adult 1 gm, children 25 mg/kg
IM / IV30 min before
 REFERENCE
1) Essentials of medical pharmacology – K.D. Tripathi
2) Pharmacology and pharmacotherapeutics – R.S. Sathoskar
3) Clinical pharmacology – Laurence and Bennett
4) OOO 2004 ; 139-46
5) JADA 2001 ; 451-56
6) Quint Int 2001 ; 365-371
7) OMCNA 2003 ; 15: 155-160.