Antibiotics in dentistry.pptx

Antibiotics
Presented by :
Dr. Stutee Beriwal
Pg 1st year
Department of Oral Medicine and Radiology

INTRODUCTION
▪ Antimicrobial drugs are the greatest contribution of the 20th
century to therapeutics.
▪ The purpose of antimicrobial chemotherapy is to aid the
host defences in controlling and eliminating microbes that
temporarily have overwhelmed the protective
host mechanisms.

HISTORY OF ANTIBIOTICS
1877 - Louis Pasteur & Robert Koch
Inhibition of some microbes by
others; anthrax (Bacillus anthracis)
named as antibiosis.
In 1942 - Waksman renamed it as
antibiotic.
1908 - Gelmo Synthesized sulfanilamide (1st sulfonamide)

1928 -Alexander Fleming
Penicillin notatum inhibits growth of
bacteria.
‘PENICILLINS’
1941 - Chain n Florey
Discovered properties of penicillin

▪ Waksman defined antibiotic as “a chemical substance
produced by micro-organisms having the property of
inhibiting the growth of or destroying other micro
organisms.
▪ Antibiotics are a naturally occurring, semisynthetic or
synthetic type of antibacterial agent that destroys or
inhibits the growth of selective microorganisms, generally
at low concentrations.

▪ Based on chemical structure
▪ Based on mechanism of action
▪ Based on type of organism against which
primarily active
▪ Based on spectrum of activity
▪ Based on type of action
▪ Based on organism susceptible

Type of organism against which is primarily active.
Antibacterial: Penicillins, Aminoglycosides, Erythromycin
Antifungal: Griseofulvin, Amphotericin B, Ketoconazole
Antiviral: Acyclovir, Amantadine, Zidovudine
Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole
▪
▪
▪
▪
▪ Antihelminthic: Mebendazole, Praziquantel, diethyl
carbamazine.

Classification Based on Spectrum of activity
• Narrow spectrum: Penicillin G, Streptomycin,
Erythromycin
▪ Broad spectrum: Tetracyclines, Chloramphenicol

Classification based on Type of Action
• Primarily bacteriostatic: Sulfonamides, Tetracyclines.
Chloramphenicol, Erythromycin, Ethambutol, clindamycin
▪ Primarily bactericidal: Penicillins, Cephalosporins,
Aminoglycosides, Cotrimoxazole, Vancomycin, Nalidixic acid,
isoniazid, ciprofloxacin, Metronidazole

Classification based on Antibiotics obtained from:
▪ Fungi: Penicillin, Cephalosporin, Griseofulvin
▪ Bacteria: Polymyxin B, Colistin, Bacitracin
▪ Actinomycetes: Aminoglycosides, Tetracyclines,
Chloramphenicol, Macrolides.

Classification According To The Organisms
Susceptible:
1. Antibiotics mainly effective against Gm+ve bacteria: for
systemic infections:
e.g., Penicillins, Macrolides
2. Antibiotics mainly effective against Gm-ve bacteria:
3. e.g., Streptomycin etc

3. Antibiotics effective against both Gm+ve and
Gm-ve bacteria:
For systemic infections: Ampicillin, Amoxicillin,
Cephalosporins .
For topical use: Neomycin, Framycetin
4. Antibiotics effective against both Gm+ve and Gm-ve bacteria,
Rickettsiae and Chlamydia: Tetracyclines, Chloramphenicol

5. Antibiotics effective against acid fast bacilli : Streptomycin,
Rifampin, Kanamycin
6. Antibiotic effective against protozoa: Tetracycline
7. Antibiotic effective against fungi: Nystatin, Amphotericin B,
Griseofulvin, Fluconazole, Micafungin.
8. Antimalignancy antibiotics: Actinomycin D,
Mitomycin

Problems that arise with the use of AMA
 Super infection:
Appearance of a new infection as a result of antimicrobial therapy
due to destruction of commensal organisms. Commonly associated
with the use of broad spectrum antibiotics e.g. tetracyclines,
chloramphenicol, ampicillin etc.
 Toxicity:
Local irritancy: Gastric irritation, thrombophlebitis.
Systemic toxicity: Based on therapeutic index.

▪ Hypersensitivity reactions:
The whole range of reactions from rash to anaphylactic shock can
occur. More commonly involved are pencillins, cephalosporins,
sulfonamides and fluoroquinolones.
▪ Drug resistance:
 Production of enzymes that inactivate the drug e.g B lactamase ( B
lactam antibiotics), acetyl transferase (chloramphenicol) kinases and
other enzymes (aminoglycosides)
 Alteration of drug binding site
 Reduction of drug uptake by the bacterium: Tetracyclines
• Nutritional deficiencies- Prolonged use of AMA may alter the flora may
result in vitamin deficiency.

Antibiotic Strategies
▪ Cardinal Rules:
1) Use the right drug.
2) Use the right dose.
3) Use the correct dosing schedule.
4) Correct duration.
▪ Use a loading dose to rapidly achieve therapeutic blood
levels.
▪ Avoid combination of bacteriostatic and bactericidal drugs.

Choice of an Antimicrobial?
 Patient factors
 Infecting organism
 Drug related

Patient factors
 Age
 Chloramphenicol in new born-grey baby syndrome
 Tetracycline are C/I in children below 6 years
 Half life of aminoglycosides is prolonged in the elderly
 Impaired host defence
Bactericidal drugs are must in immunocompromised patients.
 Pregnancy
 All antibiotics pose risk to the fetus when used in
pregnancy.
 Penicillin's, most cephalosporins and macrolides

 The United States Food and Drug Administration (FDA) has established
four levels of drug risk during Pregnancy:
(A) Without demonstrated risk to fetus:- No antibiotic corresponds to
group A.
(B) Animal reproduction studies have failed to demonstrate risk to fetus
but no adequate studies in pregnant women
cephalosporins, azithromycin, erythromycin, metronidazole and penicillins
with or without beta-lactamase inhibitors.
(C) Animal reproduction studies have shown an adverse effect on the
fetus, no adequate study on pregnant women,
Clarithromycin, the fluorquinolones and the sulfa drugs (including
dapsone).
(D) Teratogenic effects upon the fetus – use of the drug being
conditioned to the obtainment of benefit that outweighs the risks:-
Tetracyclines and Aminoglycosides.

Principles of
antibiotics use
Identification of the infecting organism
Empiric therapy prior to identification of the organism
Determining antimicrobial susceptibility of infective organisms
Bacteriostaticversusbactericidaldrugs
Minimuminhibitoryconcentration
Minimumbactericidalconcentration
Patient factors
Age
Immunesystem
Renal dysfunction
Hepaticdysfunction
Pregnancyandlactation
Cost of therapy

 Genetic Factors:
Antimicrobials producing haemolysis in G6PD
deficient patients are:
• Primaquine, Chloroquine, Quinine
• Dapsone, Sulphonamides
• Chloramphenicol, Nitrofurantoin, Fluoroquinolones

Organism Related Considerations
➢Clinical Diagnosis itself directs the choice of the AMA.
➢Choice based on bacteriological examination.
➢Empirical Therapy:
 Refers to initiation of antibiotics depending upon
knowledge and experience of physician before result of
culture and sensitivity test is available
 Broad spectrum antibiotics started
 In serious infections like meningitis & septicemia

Drug related factors:
Combined Use of Antimicrobial Agents
➢To achieve synergism (supra additive effect)
e.g Penicillin/ampicillin + Streptomycin /Gentamycin- SABE
➢To reduce severity of adverse effects
➢To prevent emergence of resistance
➢To broaden the spectrum of antimicrobial action

General Principles
(1) make an accurate diagnosis
(2) use appropriate antibiotics and dosing schedules
(3)consider using narrow-spectrum antibacterial drugs in simple
infections to minimize disturbance of the normal microflora, and
preserve the use of broad-spectrum drugs for more complex
infections

(4)avoid unnecessary use of antibacterial drugs in treating viral
infections
(4)Revise treatment regimen based on patient progress or test
results
(4)obtain thorough knowledge of the side effects and drug
interactions of an antibacterial drug before prescribing it

(7) educate the patient regarding proper use of the drug and
stress the importance of completing the full course of therapy
(that is, taking all doses for the prescribed treatment time).

GUIDELINES
▪ Antibiotic therapy should be used as an adjunct to dental
treatment and never used alone as the first line of care.
▪ Antibiotics are indicated
involvement are evident.
when systemic signs of
Pain alone or localized
Swellings does not require antibiotic coverage

Guidelines….
▪ Fevers, malaise, lymphadenopathy or trismus are clinical signs
that possible spread of the infection has occurred.
A rapidly spreading infection or persistent
infections require antibiotic coverage
▪ Prescriptions written in generic names are as efficacious as
brand names, and produce cost savings.

Antibiotic prophylaxis in dentistry
Warranted for 2 distinct purposes:
 Prevention of local wound infection
 Prevention of distant infection ( e.g., bacterial
endocarditis) in predisposed patients following dental
procedure.

Prophylaxis given in patients with systemic conditions like
rheumatic heart disease, previous history of endocarditis, heart /
orthopaedic prosthesis.
In patients with any kind of immunocompromise – AIDS,
cancer, autoimmune diseases, corticosteroid therapy, cyclic
neutropenia, pancytopenia, uncontrolled diabetes etc.

Beta-Lactam Antibiotics
IncludesPenicillin,Cephalosporin,Monobactam,Carbapenem
All members of this family has a Beta lactam ring
and a carboxyl group resulting in similarities in the
pharmacokinetics and mechanism of action.
MOA :
Inhibits cell wall formation by inhibiting transpeptidase and cross
linking at the cell wall.
Peptidoglycan cell wall is unique to bacteria. No such substance is
synthesized in higher forms- hence penicillin is practically non toxic
to man.

Penicillin: First antibiotic to be used
clinically in 1941.
Types:
• Natural penicillin : Penicillin G and Penicillin V --- Narrow spectrum
primarily to gram-positive and gram-negative cocci, gram-positive
bacilli
• Anti-staphylococcal penicillins : Methicillin, nafcillin, oxacillin,
dicloxacillin
(penicillinase resistant penicillin)
• Extended-spectrum penicillins :
Ampicillin, Amoxycillin- additional action against gram negative bacilli
Antipseudomonal penicillins: Piperacillin, Ticarcillin

Natural Penicillins : They are obtained from the fungus
Penicillium chrysogenum
Penicillin G (Benzyl Penicillin)
Antibacterial spectrum
Streptococci (pyogenes & viridians)
Meningococci
C. diptheriae Acute suppurative pulpitis, abscess,
Provotella & Porphymonas pericornitis, cellulitis)
Spirochetes and fusobacteria ( ANUG)
Actinomyces
H .influenza
Pharmacokinetics:
Poor oral absorption as it is readily destroyed by gastric acids. Absorption
from i.m site is rapid and complete and has rapid renal excretion.

 Dose: 0.5- 5 MU i.m/i.v 6-12 hourly.
Available as dry powder, to be dissolved in sterile water at the
time of injection.
 Adverse effects:
Rarely can cause hypersensitivity : Rash , itching, urticaria, &
fever.
Anaphylaxis is rare but life threatening.
Penicillin G- Not preferred in dental practice due to fear of
causing anaphylaxis.
Precaution: History of penicillin allergy to be elicited
Scratch/ Intradermal test (2-10U)
Bacterial resistance: By Penicillinase which is narrow
spectrum Beta lactamases that opens the beta lactam ring make
it ineffective. Most staphylococci produce penicillinase.

Penicillin V (Phenoxymethyl penicillin)
 Narrow spectrum antibiotic
 Similar to Penicillin G in action but it is resistant
to gastric acids and can be taken orally.
 They are ineffective against Penicillinase
producing bacteria like staphylococci.
T1/2- 90-110 mins.
Dose: 250-500 mg 4 times a day.

Penicillinase resistant penicillin
(Anti-staphylococcal penicillins)
Methicillin, oxacillin, dicloxacillin
Their only indication is infections caused by penicillinase
producing Staphylococci for which they are the drugs of
choice
However their use is limited as except methicillin
resistant staph. Aureus (MRSA) have become
predominant.

Methicillin
It is highly penicillinase resistant but not acid resistant must be injected.
MRSA is susceptible to Vancomycin/linezolid.
Adverse reaction- hematuria, albuminuria, reversible intestitial nephritis

Cloxacillin/ Dicloxacillin
Highly Penicillinase and Acid resistant
More active than methicillin, 5 to 10 times more active than methicillin
against resistant staphylococci.
Less active against PnG sensitive organisms: should not be used as its
substitute
Incompletely but dependably absorbed (oral route)
>90% protein bound, eliminated primarily by kidney, also partly by liver
Plasma half life is about 1hr
Given in staphylococcus infection resistant to benzyl penicillin
Active against a variety of gram-negative bacilli as well.
Amoxicillin + Cloxacillin:
NOVACLOX 250 + 250 mg cap

MRSA (Methicillin-resistant Staphylococcus aureus)
 Staphylococcus aureus that have become resistant to antibiotics
that once destroyed it like methicillin, amoxicillin, penicillin,
oxacillin, and many other common antibiotics.
 They have acquired penicillin binding protein which has low
affinity for β-lactam antibiotics.
 About 2% Staphylococcal infections are caused by MRSA
Treated by : Vancomycin -1 g 12 hourly i.v
Linezolid- 600 mg BD Oral

Extended-spectrum penicillins : Ampicillin, Amoxycillin
Antibacterial spectrum: Broad spectrum covering both gram- positive
and gram- negative aerobic and anaerobic bacteria commonly causing
dental infections.
Most preferred antibiotic for dental infections. Majority of dental cases
resolve with 250-500 mg TDS for 5 days.

Ampicillins
Active against all organisms sensitive to PnG; in addition, many gram-negative
bacilli
Pharmacokinetics:
• Acid resistant
• Oral absorption is incomplete but adequate
• Primary excretion is kidney, partly enterohepatic circulation occurs
• Plasma half life is 1hr

Medical Uses:
• UTI, RTI, Meningitis, Gonorrhoea, typhoid fever, bacillary dysentery,
Subacute bacterial endocarditis and Septicemias
Adverse effects:
• Diarrhoea(it is incompletely absorbed –the unabsorbed drug irritates the lower
intestine as well as causes marked alteration of bacterial flora)
• Rashes
• Hypersensitivity
Interactions:
• Hydrocortisone –inactivates ampicillin if mixed in the I.V solution.
• Oral contraceptive –failure of oral contraception
• Probenecid–retards renal excretion

DOSE
• Adult- 0.5-2g oral/i.m/i.v depending on severity of infection , every 6 hr
• Child-50-100 mg/kg given in equally divided doses every 6 hr
• Maximum-2-4 g/ day
AMPILIN, ROSCILLIN, BIOCILIN 250, 500mg CAP;
250mg/5ml dry syrup:
100mg/ml pediatric drops
250,500mg and 1g per vial inj.

Amoxicillin
Close congener of ampicillin
Similar in all respects except –
Oral absorption is better
Food doesn’t interfere with absorption
Higher and more sustained blood levels produced
Incidence of diarrheoa is lower due to complete absorption in the GI tract
Uses:
Most frequently used in dental infections 250-500mg for 5 days TDS
Prophylaxis for local and distant infection
AMOXILIN, NOVAMOX, SYNAMOX 250,500mg cap, 125mg/5ml dry syr.

Antipseudomonal penicillins: Carbenicillin, Piperacillin,
Ticarcillin
 Carbenicillin:
Antibacterial spectrum- Active against Pseudomonas aeruginosa and
Indole positive Proteus which are not inhibited by PnG or
aminopenicillins.
e.g Burns, urinary tract infection, septicaemia etc
Dose- Carbelin 1g, 5g, i.m/i.v per vial inj.
Adverse reactions: High dose can cause bleeding by interfering with
platelet function.
It has been replaced by Ticarcillin/ Piperacillin due to fewer side effects.

Ticarcillin
 Antibacterial spectrum- Active against Pseudomonas and Proteus
infections like carbenicillin but has fewer side effects and is more active.
 Gentamycin is often combined with it for treating serious pseudomonas
infections.
Dose- 3 g i.m/i.v 6 hourly.
Piperacillin
 Antibacterial spectrum- Active against Pseudomonas
, Proteus, Klebsiella (Pneumonia in pts with alcohol & DM) and some
Bacteroides.
 Used in serious gram negative infections in immunocompromised
patients and in burn cases.
Dose- 100-150 mg/kg/day in 3 divided doses

Beta-lactamase inhibitors
 Clavulanic acid
 Sulbactam
 Tazobactam
 Beta lactamases are a family of enzymes produce by many
gram positive and gram negative bacteria that inactivate beta
lactam antibiotics by opening the beta lactam ring.
 Therefore. 3 inhibitors of this enzyme are used in combination
with specific penicillin's or cephalosporins.

Clavulanic acid:
Obtained from Streptomyces clavuligerus, it has beta lactam ring but no
antibacterial activity of its own.
MOA: Permeates the outer layers of the cell wall of gram- negative
and inhibits the periplasmically located beta lactamases.
Adverse effects: Poor G.I tolerance, Candida stomatitis, Rashes.
Uses: Augmentin (amoxicillin +clavulanic acid) useful in the management of
refractory periodontitis, periapical abscess, cellulites, pericoronitis, Osteomyelitis.
▪ Amoxicillin 250mg +clavulanic acid 125 mg TDS
▪ Amoxicillin 500mg + clavulanic acid 125 mg TDS

Beta-lactamase inhibitors:
Sulbactam:
Semisynthetic, less potent than clavulanic acid.
Oral absorption is inconsistent, hence given parenterally
with ampicillin.
Indications:
Skin/soft tissue infections, especially acquired in hospital
Adverse effects:
Pain at injection site, Thrombophlebitis etc
• Ampicillin 1g + Sulbactam 500 mg i.v every 6 hours.

Cephalosporins
Mechanism of action:
All cephalosporins have the
same mechanism of action as penicillin, i.e.
inhibition of bacterial cell wall synthesis
Spectrum of Activity: Bactericidal

Parenteral Oral
First generation Cephalothin Cephalexin
Cefazolin Cefadroxil
Second Generation Cefamandole Cefachlor
Cefuroxime Cefuroxime axetil
Third generation Cefotaxime Cefixime
Ceftrioxone cefdinir
Cefoperazone ceftibuten
Fourth generation Cefepime
cefpirome
Fifth generation Ceftaroline

1st generation 2nd generation
Predominantly act against Gram +ve
organisms
Wide coverage against Gram -ve
organism
Staphylococci, streptococci,
pneumococci
H. influenzae
Efficacy against Beta lactamase
producing organisms is POOR.
Efficacy against Beta lactamase
producing organisms is GOOD
Used for Prophylaxis of surgical
procedures. Given IM/IV
Less activity against Gram + compared
to 1st generation.
Active against Anaerobes.
• Cefalexin- In dentistry alternative to
amoxicillin
• Cefodroxil-Good tissue penetration
including alveolar bone (socket)
• Cefaclor
• Cefuroxime axetil- Effective against
anaerobes hence used in dental
infections

3rd generation 4th generation
In serious Gram negative infections,
a third generation cephalosporin is
combined with gentamicin or amikacin.
useful for serious gram -ve infections
Anti pseudomonal activity
Active against streptococci and
methicillin sensitive staphylococci
More active against Gram -ve bacilli
than 1&2nd generations
The indications for these drugs
include aminoglycoside resistant or
multi-resistant Gram negative bacillary
systemic infections. They have almost
replaced the second generation
cephalosporins for this purpose.
CNS penetration is better than 1st &
2nd generation
CNS penetration is excellent
Ceftaroline is new addition to this
group. Its active against MRSA

Plasma Half life Dose Preparations
1st Generation
Oral
Cephalexin 0.9h 0.25-1.0g 6-8h
SPORIDEX, CEPHAXIN,
250,500mg cap
Cefadroxil 1.6h 0.5-1g 12h DROXYL 0.5,1g tab
Parenteral
Cephazolin 1.8h
0.5-1g I.m/I.v
6-8h
ALCIZON,ORIZOLIN
0.25g,0.5g ,1g per vial inj
2nd Generation
Oral
Cefaclor 0.6h 0.25-0.5 6h
KEFLOR,VERCEF
250, 150 mg cap
Cefuroxime
axetil
1.3h 0.25-0.5 12h
CEFOGEN,SUPACEF,FUROXIL
250mg and 750mg
Parenteral
Cefuroxime 1.4h 0.75-1.5g IM/IV
CEFOGEN,SUPACEF
250mg and 750mg/vial inj

Plasma Half
life
Dose Preparations
3rd Generation
Oral
Cefixime 3.5h 200-400mg BD
TOPCEF, ORFIX
100,200 mg tab/cap ,
Cefpodoxime
Proxetil
2.2h
200mg BD(max
800mg/day)
CEPODEM ,100,200 mg tab,
50mg/5ml susp
Parenteral
Cefotaxime 0.9h
0.5-1g I.m/I.v
q6-8h
OMNATAX
0.25,0.5,1.0g per vial inj
Cefaperazone 1.7h
1-3g i.m/i.v
12hourly
MAGNAMYCIN 0.25g, 1,2 g inj ;
4th Generation
Oral
Cefepime 2.0h
1-2g i.v, 8-
12hourly
CEPIME- 0.5,1g inj.
5th Genration
Parenteral
Ceftaroline
600mg i.v over
60mins , 12h
TEFLARO,ZINFORO 600mg/vial inj.

Diarrhoea - due to altered gut ecology common with oral cephradine and
parenteral cefoperazone which is significantly excreted in bile
Hypersensitivity-similar to penicillin. rashes, anaphylaxis, angioedema,
and urticaria
Cross resistance between penicillin & cephalosporin reported
Nephrotoxicity – low grade. May be attenuated by existing renal disease.
reduction required even in cases of mild renal failure
Bleeding –cefoperazone, ceftriaxone due to Neutropenia and
thrombocytopenia are rare adverse effects reported with ceftazidime and
some others
A disulfiram like reaction with alcohol in cefoperazone
Adverse effects

Acquired Resistance to Cephalosporins
 Mechanism same as in penicillin.
a) Alteration in target proteins reducing affinity for antibiotic
b) Impermeability so that it does not teach its site of action
c) Elaboration of beta lactamases .

 Alternative to penicillin/amoxicillin (if pt develop resistance/allergy),
orally active 1st and 2nd gen drugs are used in orodental infections
 1st gen cephalexin.,cephadroxil used due to high activity against gram +ve
bacteria and good penetration in alveolar bone(socket)
 2nd gen cefuroxime axetil and cefaclor are the only ones which have good
activity against oral anaerobes and preferred in dentistry, eg: klebsiella
which may occurs in neutropenic patients
 Cephalexin and cephadroxil are alternatives to amoxicillin for
prophylaxis of local wound infection as well as bacterial endocarditis
following dental surgery in predisposed patients.
Dental Uses

 Disulfiram like reaction:
Inhibition of aldehyde dehydrogenase results in inhibition of
metabolism of acetaldehyde to acetate.
The increase in serum acetaldehyde results in unpleasant clinical
manifestations.
Symptoms: Palpitations, facial flushing, nausea, vertigo,
hypotension, and tachycardia. This aggregation of symptoms is
known as the disulfiram-alcohol reaction
Eg:
Metronidazole (Flagyl and other brands),
trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS)
Tinidazole,

First AMA to be effective against pyogenic bacterial infection
SULFONAMIDES
MOA: It inhibits bacterial folate synthesis. As a result, a number of
essential metabolic reactions suffer.
Not active in pus and tissue extracts as it contains purines and
thymidine that decreases the bacterial requirement of FA, thus
antagonising the action.

Pharmacokinetics
✓ Nearly completely absorbed from GIT
✓ Plasma protein binding varies (10-95%)
✓ Highly protein bound-long acting
✓ Cross placenta freely
✓ Less soluble in acidic urine – can precipitate and cause crystalluria
✓ Sulphonamides – mainly excreted by kidney

Sulfadiazine- Short acting.
Rapidly absorbed orally and rapidly excreted in urine
Good permeability – brain, CSF – preferred compound for meningitis
Dose: 0.5 g QID to 2 g TDS
Sulfamethoxazole- Intermediate acting
Slow oral and urine absorption and urinary excretion
Intermediate duration of action
T1/2 10 hrs
Combination with trimethoprim as the t1/2 of both is the same
Dose: 1g BD for 2 days ,then 0.5g BD

Sulfadoxine , Sulfamethopyrazine
✓ Ultralong acting
✓ High plasma protein binding
✓ Hence Action >1week
✓ Slow renal secretion (t1/2 : 5-9 days)
✓ Not suitable for pyogenic infections
✓ Used in combination with pyrimethamine in malaria, pneumonia in
AIDS patient.

Sulfasalazine
✓ Anti inflammatory activity
✓ Used in ulcerative colitis and rheumatoid arthritis
✓ Not a typical sulphonamide
✓ It is only used topically
✓ Active in pus and against pseudomonas and clostridia
✓ Mainly employed for burn dressing to prevent infection
✓ Topical – 1% cream
✓ Active against large no. of bacteria and fungi. eg - Psedomonas
✓ Slowly releases silver ions which have antimicrobial action
✓ One of the most effective drug for burnt surfaces and chronic ulcers and is well
tolerated
Mefenide
Sliver sulfadiazine

Adverse effects
✓ Nausea, vomiting, epigastric pain
✓ Crystalluria-
✓ Hypersensitivity reactions:-
✓ Hepatitis,
✓ Stevens-Johnson syndrome and other severe cutaneous reactions
especially with long acting sulfonamides
Stevens-Johnson syndrome (SJS) is a rare, serious, self limiting disorder of
the skin and mucous membranes.
It's usually a reaction to medication that starts with flu-like symptoms,
followed by a painful rash that spreads and blisters..

Interactions
✓Sulfonamides inibit the metabolism of phenytoin and warfarin-
enhance their action
✓They displace methotrexate from binding and decrease its renal
excretion- toxicity can occur
Uses:
Because of rapid emergence of bacterial resistance, currently
used only in combination with trimethoprim (Sulfadoxine +
trimethoprime) or pyrimethamine (for malaria).
Ocular sulfacetamide sod. (10-30%) is used for conjunctivitis.
Topical silver sulfadiazine (1%) or Mafenide used for preventing
infection on burn surfaces.

Use of Dapsone in Oral lesions
It’s a sulfone antibiotic. Its mechanism of action includes both
antibacterial and anti-inﬂammatory effects. It inhibits
neutrophil activation and chemotaxis.
It reduces the number and size of oral and genital ulcers
seen in Bechet's disease.
Dapsone is used for treating erosive lichen planus -
100mg/day for 3 months

Cotrimoxazole
 Fixed dose combination of trimethoprim + sulfamethoxazole is
called cotrimoxazole
 Both have the same t1/2 :- 10 hrs
 Trimethoprim:- selectively inhibits bacterial dihydrofolate reductase
(DHFR)
 Causes sequential block of folate metabolism
 Individually both are bacteriostatic but when both are combined
they become bactericidal against many organism

Uses
1. Occasional use in orodental infections only if allergic to beta lactams
2. Used in tonsillitis, pharyngitis, sinusitis, otitis media, chronic
bronchitis
3. In high doses first line of drug for pneumonia in AIDS patients
SEPTRAN, SEPMAX, BACTRIM, CIPLIN etc.
Trimethoprim + Sulfamethoxazole BD
80 mg + 400 mg tab
160 mg + 800 mg tab
20 mg + 100 mg pediatric tab.

Adverse effects
✓ All adverse effects seen with sulphonamides may be produced by
cotrimaxazoles.
✓ Folate deficiency (megaloblastic anemia) infrequent, seen only in
patients with marginal folate levels
✓ Should not be given during pregnancy , Can cause teratogenic risk
as trimethoprim is anti folate.
✓ Neonatal hemolysis and methemoglobinemia can occur if given
close to term
✓ Dose to be reduced in moderately severe renal impairment
✓ Diuretics given with cotrimoxazoles have produced higher
incidence of thrombocytopenia.

Quinolones
✓ Bactericidal
✓ Active primarily against gram –ve
✓ First member of quinolones is Nalidixic acid
✓ Newer members inhibit gram +ve as well
✓ Fluorination of quinolone structure resulted in the derivative called
fluoroquinolones, this as;
1. High potency
2. Expanded spectrum
3. Slow development of resistance
4. Better tissue penetration & Good tolerability

Nalidixic acid
✓Resistance developing is rapid
✓Absorbed orally ,highly plasma protein bound and partly metabolized in
liver
✓Plasma t1/2- 8 hrs
✓Excreted in urine. High concentration is lethal to normal urinary
pathogens

Nalidixic acid
✓Active against Gram –ve
✓Inhibits bacterial DNA gyrase & is bactericidal
Uses:
 Primarily used as urinary antiseptic, has practically no utility in
dentistry.
 Given in diarrhea caused due to proteus ,E coli, shigella or
salmonella.
Adverse effects
✓GI upset and rashes
✓Most important toxicity is neurological – headache, drowsiness,
vertigo , visual disturbances , occasionally seizures (especially in
children
Dose :0.5-1g TDS/ QID

Fluoroquinolones
✓ Extended antimicrobial activity to gram positive cocci and anaerobes . (2nd
generation)
✓ Longer t1/2
 MOA:
Inhibits bacterial DNA gyrase which results in relaxation of
supercoiled DNA, promoting DNA strand breakage.

Fluoroquinolones
First generation fluoroquinolones
• Norfloxacin
• Ciprofloxacin
• Ofloxacin
• Pefloxacin
Second generation fluoroquinolones
• Lomefloxacin
• Sparfloxacin
• Levofloxacin
• Gatifloxacin
• moxifloxacin
*3rd generation
Gemifloxacin Prulifloxacin

Mechanism of action
✓Inhibits enzyme bacterial DNA gyrase which nicks double
stranded DNA.
Antibacterial spectrum:
 Aerobic Gram –ve bacilli are the most susceptible ones, especially the
Enterobacteriaceae and Neisseria

Ciprofloxacin (prototype)
Most potent 1st gen FQ.
Remarkable microbiological features of ciprofloxacin are:
✓Rapid bactericidal
✓High potency
✓Long post antibiotic effect on ,Enterobacteriaceae, pseudomonas
and staph. Post-antibiotic effect (PAE) is the continued suppression of
bacterial growth following a limited exposure to an antimicrobial agent
✓Low frequency of mutational resistance
✓Protective intestinal streptococci and anaerobes are spared

Pharmacokinetics
✓Rapidly absorbed orally
✓T1/2 : 3-5hrs
✓Food delays absorption
✓High tissue penetrability
✓CSF levels are low
✓Excreted in urine

Uses
✓Wide spectrum bactericidal activity ,oral efficacy, good tolerability-
it is extensively used as blind therapy for many infections.
✓Caution: Should not be used for minor cases or where gram positive
organisms are primarily causative
✓Primarily used for serious infections like septicemia and meningitis.
✓Ciprofloxacin + Metronidazole – often used for mixed refractory
periodontitis.
✓Ofloxacin, gatifloxacin, moxifloxacin are more active against gram
+ve bacteria and anaerobics and have potential use in dentistry
✓Combination chemotherapy for multidrug resistant tuberculosis

Adverse effects
✓ Gastrointestinal: nausea, vomiting, bad taste , anorexia. (gut anaerobes
not affected so diarrhea is less common)
✓ CNS- dizziness, headache , restlessness , anxiety , insomnia ,
impairment of concentration , tremor. Seizures are rare occur only at high
doses
✓ Skin/hypersensitivity: rash , pruritus, photosensitivity, urticaria,
swelling of lips etc
✓ Contraindicated in pregnancy
✓ In children require caution due to damage to weight bearing joints

Interactions
Plasma concentration of theophyline and warfarin increased by
ciprofloxacin due to inhibition of metabolism :toxicity of these drugs can
occur
NSAIDS may enhance the CNS toxicity of FQs ; seizures have been
reported
Antacids, sucralfate and iron salts given concurrently reduce absorption
of FQs
CIFRAN, CIPLOX,
250,500,750 mg tab
200 mg/100ml i.v. infusion , 3mg/ml eye drops

Norfloxacin
✓Less potent than ciprofloxacin
✓Psuedomonas and many gram +ve are not inhibited at clinical
concentrations
✓Metabolized as well as excreted in urine
✓Used in urinary and genital tract infections
✓NORBACTIN, NORFLOX 200,400,800MG tab, 3mg/ml eye drops;
✓UROFLOX, NORILET 200,400mg tab .

Ofloxacin
✓Intermediate between ciprofloxacin and norfloxacin in activity
against gram –ve bacteria
✓More potent than ciprofloxacin for gram +ve organisms.
✓Better suited for orodental infections
✓Excreted largely in urine
✓Dose to be reduced in renal failure
✓ZANOCIN,TARIVID, 100,200,400mg tab;

Levofloxacin- 2nd gen FQ
✓ Improved activity against Gram +ve and gram –ve bacteria
✓ Anearobes moderately susceptible
✓ Oral bioavilability -100%
✓ Excreted unchanged and single dose daily is enough
✓ Used in community acquired pneumonias and exacerbations of chronic
bronchitis
✓ High cure rates for Sinusitis, skin and soft tissue infections
✓ TAVANIC ,GLEVO 500mg tab OD

Gatifloxacin
✓2nd gen FQ
✓Improved activity against Gram +ve bacteria
✓Used in upper and lower respiratory tract infections , community
acquired pneumonia, chronic bronchitis.
✓Significant activity against gram +ve cocci and anerobes prompted
its use in dental infections
✓Dose :400mg on 1st day ,followed by 200-400mg OD, oral or i,.v.

Moxifloxacin
Long acting 2nd gen FQ
Used in pneumonia, bronchitis, sinusitis, otitis media etc
Not to be given in pts predisposed to seizures
Phototoxicity is rare
Dose: 400 mg OD

M etronidazole
MOA: Nitro group reacts with bacterial DNA, causing inhibition of
DNA replication, fragmentation of existing DNA
Antimicrobial spectrum: Narrow spectrum .Effective against Gram-
negative anaerobes such as P. intermedia, Porphyomonas gingivalis,
Bacteroides , Fusobacterium etc
Does not affect aerobic bacteria
Used in :
-Necrotizing ulcerative gingivitis
-Aggressive periodontitis
-Abscesses
-Orofacial infection along with Penicillins

Phramacokinetics
✓ T ½:- 8 hrs
✓ Almost completely absorbed by small intestines
✓ Little unabsorbed drug reaches colon
✓ Widely distributed in body
✓ Attaining therapeutic concentration in saliva, CSF, vaginal secretion, semen
✓ Metabolised in liver by primarily oxidation and glucuronide conjugation
✓ Then excreted in urine

Ingestion of alcohol when taking metronidazole could cause
Disulfiram like reaction i.e hallucinations and confusion,
abdominal cramps, nausea, facial flushing and headache can
occur.
Also avoid alcohol containing mouth rinses.
Decreases the metabolism of Warfarin resulting in bleeding
Dose: [Metron, Flagyl]
200-400 mg 8 hourly
Adverse effects:
Anorexia, nausea, bitter, metallic taste and abdominal cramps.
Diarrhoea less common
Prolonged administration may cause peripheral neuropathy
and CNS effects - seizures are seen in very high doses

Contraindication
✓ Neurological disease
✓ Blood dyscrasias
✓ Chronic alcoholism
Interaction
✓Disulfiram intolerance to alcohol occurs among some patients
✓Enzyme inducers (rifampin )may reduce its therapeutic effect
✓Cimetidine (Antihistaminic- peptic ulcers) can reduce metronidazole
metabolism :its dose may need to be decreased
✓Enhances warfarin action by inhibiting its metabolism
✓Prothrombin time of patients taking warfarin should be monitored

Tinidazole
✓ Similar to metronidazole except that,
✓ t ½ is 12 hours slow metabolism
✓ Longer duration of action
✓ Thus single dose or once daily therapy
✓ Lower side effects metallic taste (2%)
✓ Nausea (1%)
✓ Rash (0.2%)
✓ TINIBA 300,500,1000 mg tabs
✓ 800mg/400ml i.v. infusion;
✓ In orodental infection it is used in a dose of 500 mg BD for 5 days

Ornidazole
✓ Similar activity to metronidazole
✓ Slow metabolism
✓ t1/2 12-14hr
✓ Side effect similar to tinidazole
✓ Used in amoebiasis, giardiasis,etc
✓ DAZOLIC 500mg tb,500mg/100ml vial for i.v. infusion.

TETRACYCLINES
These are class of antibiotics having a nucleus of four cyclic rings.
All are obtained from soil actinomycetes.
The first to be introduced was chlortetracycline in 1948.
Clinically relevant tetracyclines and glycycline are:
Tetracycline Demeclocycline
Oxytetracycline Doxycycline
Minocycline
Glycycline: Tigecycline.
Mechanism of action: The tetracyclines are primarily
bacteriostatic; inhibit protein synthesis by binding to 30S ribosomes
in susceptible organism.
Antibacterial spectrum: Broad-spectrum antibiotic.
Inactive against Enterobacteriaceae i.e E.coli, Klebsiella,
Pseudomonas.

✓ Tetracylines except Doxycycline and minocycline are incompletely
absorbed from g.i.t : absorption is better if taken in an empty
stomach
✓ Tetracyclines have chelating property – form insoluble and
unabsorbable complexes with calcium and other metals – Teeth
discoloration.
✓ Milk , iron preparations , non systemic antacids and sucralfate
reduce their absorption
 Excreted in urine by glomerular filtration- dose to be reduced in
renal failure. Exception is doxycycline as it is primarily eliminated
via the bile into the feces.
Pharmacokinetics

Adverse effects
Teeth and bones: due to chelating property of tetracyclines, calcium-tetracycline chelate get
deposited in bones and teeth
Irritative effects: nausea, epigastric pain, vomiting and diarrhea
Dose related toxicity
Liver damage. Oxytetracycline & tetracyclines are safer in this regards.
Tetracyclines are risky in pregnant women, can precipitate acute hepatic necrosis
Kidney damage
Phototoxicity
Increased intracranial pressure is noted in infants
Vestibular toxicity-Minocycline.

Superinfection
✓Most common drug which is responsible for superinfection, because they
cause marked suspension of normal residential flora
Precautions :
✓Not used in pregnancy, lactation and in children under 8 yrs.
✓Patients on diuretics as blood urea may rise in such patients.
✓Used cautiously in renal or hepatic patient
✓Do not mix injectable tetracyclines with penicillin's –inactivation occurs

Uses in Oro dental conditions
• They benefit certain periodontal condition due to their broad spectrum
antimicrobial action as well as by suppressing the activity of collagenases that
contribute to gingival inflammation.
• It can be used in chronic periodontitis, juvenile periodontitis
• Dose: 2-weeks tetracycline(1g/day) or doxycycline (0.1-0.2g/day ) therapy
controls
• 2-4 week tetracycline therapy & surgery halts the progression of juvenile
periodontitis

Tigecycline
 New class of synthetic tetracycline analogue which is active
against bacteria that has developed resistance to
tetracyclines
e.g Enterobacteriaceae.
 Approved only for treatment of serious infections in
hospitalized patients like pneumonia, complicated skin/
intra abdominal infections etc.
Dose: 100 mg loading dose followed by 50 mg 12 hourly iv

Chloramphenicol
It was initially obtained from the Streptomyces venezuelae.
Antibacterial spectrum
Broad spectrum like tetracycline.
Mechanism of action
—
Chloramphenicol is a bacteriostatic drug that stops bacterial growth
by inhibiting protein synthesis by attaching at 50S ribosome subunit.

Adverse effects
— Major adverse effect -Bone marrow depression
— Gray baby syndrome:
It occurred when high doses (~100 mg/kg) were given
prophylactically to neonates, especially premature. The baby stopped
feeding, with irregular respiration ; an ashen gray cyanosis
developed, followed by cardiovascular collapse and death. It occurs
because of inability of the newborn to adequately metabolize and
excrete chloramphenicol.

Uses- Due to risk of bone marrow aplasia
Never use it for minor infections or infections that can be
treated by safer antimicrobials.
Daily dose should not exceed 2-3 g, duration less than 2-3
weeks, total dose less than 28 g
There is no indication in dentistry that warrants use of
chloramphenicol despite its broad-spectrum antimicrobial
action

Streptomycin was the first member discovered in 1944 by Waksman.
They are extensively used in medical, surgical, gynecological and other
systemic infections but seldom employed in dentistry.
All aminoglycosides are obtained from soil actinomycetes and have many
common properties.
 They ionize in solution are not absorbed orally, distribute only
extracellularly,
 Excreted unchanged in urine. (Dose to be reduced even in mild renal
failure)
 Bactericidal
 All exhibit ototoxicity and nephrotoxicity

Classification
Systemic aminoglycosides
Streptomycin
Gentamicin
Kanamycin
Tobramycin
Amikacin
Sisomycin
netimicin
Topical aminoglycosides
Neomycin
framycetin

 Antibacterial spectrum:
All are active primarily against aerobic gram negative bacilli;
do not inhibit anaerobes.
e.g. E.coli, klebsiella pneumonia, Enterobacter, H. influenza,
Proteus, Pseudomonas.
 MOA:
They act by interfering with bacterial protein synthesis by
binding to several sites on 30S and 50S subunits that freezes
initiation of protein formation and caused misreading of the
code.

SHARED TOXICITY:-
 Ototoxicity- Drug gets concentrated in the labyrinthine fluid
and slowly gets removed once plasma concentration falls-
concentration dependent destructive changes.
 Cochlear damage- Permanent deafness , tinnitus often
disappears on stopping the drug.
 Vestibular Damage- Headache, vomiting, nystagmus, vertigo,
ataxia. Recovery occurs in 1-2 years.
 Nephrotoxicity- More in elderly patients with pre-existing renal
disease. Totally reversible.
 Neuromuscular Blockade- Rare. However, effects happens due
to reduce Ach release from motor nerve endings.

PRECAUTIONS & INTERACTIONS:
 Avoid during pregnancy: risk of fetal ototoxicity( crosses
placenta)
 Avoid concurrent use of other Nephrotoxic drugs eg: NSAIDs,
amphotericin B, vancomycin, cyclosporine.
 Cautious use in elderly patients and those with Kidney damage.
 Do not mix amino glycoside with any drug in the same
syringe/infusion bottle.

Dosing regime
 Because of low safety margin, the daily dose must be
precisely calculated according to body weight and level of
renal function.
 Normal renal function: CLcr > 70 ml/min.
 Gentamycin/tobramycin: 3-5 mg/kg/day ( i.m)
 Streptomycin/kanamycin/amikacin: 7.5-15 mg/kg/day

STREPTOMYCIN:
Practically restricted to treatment of Tuberculosis.
Streptomycin is not used in dentistry.
Lowest nephrotoxicity.
GENTAMICIN:
The only application in dentistry is to give gentamicin 2 mg/kg
i.m./i.v. (single dose) to supplement amoxicillin or vancomycin
for prophylaxis of bacterial endocarditis following dental surgery
in patients with prosthetic heart valves or past history of BE.
TOBRAMYCIN:
Identical to gentamicin, but it is 2–4 times more active.
It should be used only as a reserve alternative to gentamicin.
Ototoxicity and nephrotoxicity is probably lower than
gentamicin.

NEOMYCIN:
Uses
1. Topically (often in combination with polymyxin, bacitracin,
etc.) for infected wound, ulcers, burn, external ear infections,
conjunctivitis.
ADVERSE EFFECTS:
Oral neomycin has a damaging effect on intestinal villi—
prolonged treatment can induce malabsorption syndrome with
diarrhea and steatorrhea.
Superinfection by Candida can also occur.

Macrolides
These are group of antibiotics that have in common
macrocyclic lactone ring linked with amino sugars.
Natural: Erythromycin
Semisynthetic: Developed to overcome the limitations of
erythromycin
• Narrow spectrum of activity
• Gastric irritation on oral ingestion
• Gastric acid liability
• Lower oral bioavailability
Azithromycin, Clarithromycin, Telithromycin

Erythromycin
Antibacterial spectrum:
Overlaps with Penicillin G and hence widely used as an alterative to the
beta
lactam antibiotics.
Provide good coverage against Gram positive organisms.
e.g. Str. Pyogenes, Str. Pneumonia. N. gonorrhea, Clostridia etc.
MOA
Bacteriostatic & interfere with bacterial protein synthesis by binding to
the 50s ribosomal subunits
This interfere with the translocation step of protein synthesis
Erythromycin is bacteriostatic at low but cidal at high concentrations
Renal excretion is minor, hence dose need not to be altered in renal
failure.

Adverse effects – Remarkably safe drug
Mild GI symptoms
Hepatotoxicity- Hepatitis can occur after 1-3 weeks. Incidence
higher in pregnant women. Should be used cautiously in
patients with hepatic dysfunction
Drugs are excreted in human breast milk so should be
cautious when prescribing the drug to nursing mother
Very high doses have caused reversible hearing impairment.
Interference with the metabolism of drugs, such as
theophylline, statins, antiepileptics, digoxin

Dental uses : Because erythromycin is orally
administered, safe and active against both aerobic and
anaerobic gram-positive bacteria commonly infecting
dental structures and mouth.
It is the second choice drug to penicillin’s (pts
allergic to penicillin ) for periodontal/ periapical
abscesses, necrotizing ulcerative gingivitis, post
extraction infections, gingival cellulitis, etc.
Dosage :
Erythromycin – orally 250-500 mg QID, in children
30-60 mg/kg/day
It is acid labile. To protect it from gastric acid, it is given
as enteric coated tablets
Medical uses:
Pharyngitis, Tonsilitis, First line of drug- Mycoplasma
pneumonia, chancroid.

Newer macrolides
Roxithromycin-
Used as an Alternate to erythromycin.
Better gastric tolerance, t half of 12 hrs.
Dose: 150-300 mg BD 30 min before meals, children 2.5-5 mg/kg BD
Clarithromycin –
Additional antibacterial spectrum
First line against Mycobacterium avium complex
Second line drug against Mycobact. Leprae.
Dose: 250 mg BD for 7 days (Mild cases)
500 mg BD for 14 days
Azithromycin –
Extended spectrum against H. influenza
Dose: 500 mg once daily 1 hr before or 2 hr after food- 3 days

LINCOSAMIDE
CLINDAMYCIN
MOA : similar to macrolides
significant activity against many gram-positive and gram negative
anaerobic and aerobic microorganisms, including Bacteroides,
Prevotella, Porphyromonas, Veillonella,
Better bone penetration due to relatively small molecular size. So
used in treatment of Osteomyelitis, Dentoalveolar abscess.
Most common adverse effect is diarrhea, due to
pseudomembranous enterocolitis caused by overgrowth of C.
difficile.
( Treatment- Stop the drug and start
Metronidazole/Vancomycin)
Dose : 150-300 mg QID

Glycopeptide
Vancomycin:
Vancomycin was discovered in 1956 as penicillin
substitute.
Antibacterial spectrum: Active particularly against MRSA.
MOA: It inhibits cell wall synthesis.
Pharmacokinetics:
Vancomycin is poorly absorbed orally.
90% of the drug is excreted by glomerular filtration- Dose
reduction in renal insufficiency.

Clinical uses:
Parenteral:
Indicated for serious MRSA infections.
Dose: 500 mg 6 hourly or 1 g 12 hourly i.v
Oral:
2nd choice of drug to metronidazole for antibiotic associated
pseudomembranous enterocolitis.
Dose: 125- 500 mg QID
Adverse effects
Concentration dependent nerve deafness & kidney damage.
Rapid i.v injection can cause chills, fever, urticaria, and
intense flushing- Red man syndrome.

 Bacitracin
 Bacitracin is active against gram-positive microorganisms.
 It inhibits cell wall formation.
 It is markedly nephrotoxic if administered systemically,
thus limited to topical use in burns from getting infected.
 Cycloserine
 Cycloserine is used almost exclusively to treat tuberculosis
caused by strains of M tuberculosis resistant to first-line
agents.
 Most of the drug is excreted in active form into the urine.
 Cycloserine causes serious dose-related central nervous
system toxicity with headaches, tremors, acute psychosis,
and convulsions.

 Atridox:(doxycycline hyclate) ®
Available as a tray or pouch containing a doxycycline hyclate syringe
(50 mg).Use in the treatment of chronic adult periodontitis for a gain in
clinical attachment, reduction in probing depth, and reduction in
bleeding on probing.
 ARESTIN
ARESTIN (minocycline HCl) Microspheres, 1 mg is a concentrated,
locally applied antibiotic that remains active in the pocket for an
extended period of time to reduce pocket depth.

PerioChip
 Its a Orange-brown, rectangular chip (rounded at one end) for insertion
into periodontal pockets as a part of maintenance therapy
 Contains 2.5 mg of chlorhexidine gluconate
Others:
Actisite
Elyzol

Handle antibiotics with care to prevent
resistance!

Antibiotics in dentistry.pptx

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