Antibiotics in Oral and Maxillofacial Surgery

ANTIBIOTIC S IN
ORAL &
MAXILLOFACIAL
SURGERY
PRESENTED BY: DR HANEEF
MODERATED BY : DR SHIREEN
FATIMA

CONTENTS
 HISTORY & INTRODUCTION
 CLASSIFICATION
 PRINCIPLES OF ANTIBIOTIC
THERAPY
 ANTIBIOTIC SIDE EFFEECTS
 ANTIBIOTIC RESISTANCE
 ANTIBIOTIC FAILURES
 MISUSE OF ANTIBIOTICS
 ANTIBIOTIC PROPHYLAXIS
 INDIVIDUAL DRUGS
- Chemistry
- Mechanisms of action
- Spectrum
- Sensitive organisms
- Resistance
- Adverse effects
- Uses
 SPECIAL CONDITIONS-
Pregnancy
- Chronic renal failure
- Hepatic failure
- Diabetes mellitus
- Head and neck infections in
immunocompromised state
 NEWER ANTIBIOTICS
 ANTICANCER DRUGS
 SHOULD ANTIBIOTICS BE
USED?
 CONCLUSION
 REFERENCES

INTRODUCTION
ANTIBIOTIC TERMINOLOGY
DEFINITION: SUBSTANCES DERIVED FROM
MICROORGANISMS WHICH SUPPRESS THE GROWTH / KILL
THE MICROORGANISMS AT A VERY LOW CONCENTRATION
OR
A CHEMICAL SUBSTANCE PRODUCED BY
MICROORGANISMS HAVING THE PROPERTY OF INHIBITING
THE GROWTH OF OR DESTROYING OTHER
MICROORGANISMS IN HIGH DILUTION
CHEMOTHERAPY :TREATMENT OF SYSTEMIC INFECTIONS
WITH SPECIFIC DRUGS THAT SELECTIVELY SUPPRESS THE
INFECTING MICROORGANISM WITHOUT SIGNIFICANTLY
AFFECTING THE HOST.

TERMINOLOGY
 Antimicrobial - This term refers to both antibiotics and
synthetic agents active against microbes.
 Microcidal - (Bacteriocidal. Vincidal, Fungicidal) The
organism is lysed or killed by direct damage on
susceptible cell targets.
 Microstatic - (Bacteriostatic, Virostatic, Fungistatic)
 The organism is reversibly inhibited at specific
metabolic processes.
 action and host defense mechanisms. Multiplication
of the organism is inhibited.
 Narrow Spectrum Antimicrobial - An antimicrobial
that acts on a limited number of microbial species, e.g.
Nitroimidiazole derivatives etc
 Broad Spectrum Antimicrobial - An antimicrobial that
acts on a wide range of species, e.g., erythromycin for
Gram positive. Gram negative, Legionella,
Mycoplasma, etc.

HISTORY
 (A) The period of emperical use South American Indians used
the bark of the cinchona tree to extract quinine to control malaria
and mercury was known to cure syphilis in the late
1400's,‘mouldy curd’ by Chinese on boils, mercury by
Paracelsus (16th century) for syphilis, Cinchona bark (17th
century) for fevers.
 (B) Ehrlich’s phase of dyes & organometallic compounds (1890-
1935): methylene blue, tryptan red, etc.
He coined the term ‘Chemotherapy’
5

HISTORY
 (C) The Modern Era of chemotherapy was ushered in by
Domagk in 1935 by demonstrating the therapeutic effect of
prontosil , a sulfonamide dye in pyogenic infection.
Other pioneers in the field of antibiotics were Louis Pasteur,
Alexander Fleming, Chain Florey , Waksman.
All received Nobel prizes for their discoveries.
6

CLASSIFICATION
BASED ON TYPE OF ORGANISM THEY ACT
UPON:
1. Antibacterial – penicillin
amino glycosides
erythromycin
2. Antifungal - griseofulvin
amphotericin
ketoconazole
3. Antiviral- acyclovir
amantidine
zidovudine
4. Antiprotozoal- metronidazole
chloroquine

BASED ON MECHANISM OF ACTION:
1. Inhibit cell wall synthesis: penicillins
cephalosporins
cyclosporins
2. Leakage from cell membrane:
polypeptides-polymixin, bacitracin
polyenes- amphotericin B ,nystatin
3. Inhibits protein synthesis: tetracyclines,
chloramphenicol,
erythromycin,
clindamycin.
4. Causes misreading of m.RNA: aminoglycosides
5. Inhibits DNA gyrase: fluoroquinolones
6. Interfere with DNA function : rifampin,
metronidazole.
7. Interfere with DNA synthesis: acyclovir,
idoxuridine.

CHEMICAL STRUCTURE
Sulfonamides and related drugs :
○ Sulfones – Dapsone (DDS)
○ Para amino salicylic acid (PAS)
Diaminopyrimidines
○ Trimethoprim, pyrithamine
Quinolones
○ Nalidixic acid, Norfloxacin, Ciprofloxacin etc
 - lactam antibiotics
○ Penicillins, cephalosporins, monobactams, carbapenems
Tetracyclines
○ Oxytetracycline, Doxycycline etc
Nitrobenenzene Derivative
○ Chloramphenicol
Aminoglycosides
○ Streptomycin Gentamycin, Neomycin etc

- Macrolide antibiotics
○ Erythromycin, Roxithromycin, Azithromycin etc
 Polypeptide antibiotics
○ Polymyxin – B, colistin, Bacitracin, Tyrothricin etc
 Glycopeptides
○ Vancomycin, Teicoplamin
 Oxazolidinase
○ Linezolid
 Nitrofuran derivatives
○ Nitrofurantoin, Furazolidine
 Nitroimidazoles
○ Metronidazole, Tinidazole
 Polyene antibiotics
○ Nystatin, Amphotericin – B, Hamycin
 Azole derivatives
○ Miconazole, clotrimazole, ketoconazole, fluconazole

SPECTRUM OF ACTIVITY
 Narrow spectrum
Penicillin G, streptomycin and
erythromycin.
 Broad spectrum
Tetracyclines, chloramphenicol.
 Extended spectrum
Semi synthetic Penicillins, new
cephalosporins, aminoglycoside.

TYPE OF ORGANISMS AGAINST
WHICH PRIMARILY ACTIVE :
 Antibacterial
Penicillins, Aminoglycosides, erythromycin etc
 Antifungal
Griseofulvin, amphotericin B, ketoconazole etc
 Antiviral
Idoxuridine, Acyclovir, Amantadine, Zidovudine etc
 Antiprotozoal
Chloroquine, pyrimethamine, metronidazole etc
 Antihelminthic
Mebendazole, nicosamide, diethyl carbamazine etc

CLASSIFICATION
(v) TYPE OF ACTION:
13
Primarily Bacteriostatic Primarily
Bactericidal
Sulfonamides
Tetracyclines
Chloramphenicol
Erythromycin
Ethambutol
Penicillins , Cephalosporins,
Aminoglycosides,
Vancomycin,
Ciprofloxacin, Isoniazid ,
Rifampin, Cotrimoxazole,

SOURCE
 Fungi
 Penicillin, Cephalosporin, Griseofulvin.
 Bacteria
 Polymyxin B, Colistin, Bacitracin, Tyrothricin
Aztreonam.
 Actinomycetes
 Aminoglycosides, Tetracyclines, Chloramphenicol,
Macrolides, Polyenes.

PRINCIPLES OF ANTIBIOTIC THERAPY
PRINCIPLE 1: TO DETERMINE THE SEVERITY OF
INFECTION
PRINCIPLE 2: TO EVALUATE STATE OF
PATIENT’S HOST DEFENSE MECHANISMS
PRINCIPLE 3:TO DETERMINE WHETHER
PATIENT SHOULD BE TREATED BY GENERAL
DENTIST OR SPECIALIST
PRINCIPLE 4:TO TREAT INFECTION
SURGICALLY

PRINCIPLE 5 :TO SUPPORT THE PATIENT MEDICALLY
PRINCIPLE 6 : CHOOSE AND PRESCRIBE
APPROPRIATE ANTIBIOTIC
PRINCIPLE 7 : PROPER ANTIBIOTIC
ADMINISTRATION
PRINCIPLE 8 :MONITORING THE PATIENT

DETERMINATION OF THE SEVERITY OF
INFECTION
 Complete history-Time of onset
-Duration of infection
-Rapidity of progress
 Eliciting patient’s symptom
 Physical examination

DIFFERENCES BETWEEN
CELLULITIS AND ABSCESS
CHARACTERISTIC CELLULITIS ABSCESS
Duration Acute Chronic
Pain Severe and generalized Localized
Size Large Small
Localization Diffuse borders Well circumscribed
Palpation Doughy to indurated Fluctuant
Presence of pus No Yes
Bacteria Aerobic Anaerobic

2)TO EVALUATE STATE OF
PATIENT’S HOST DEFENSE
MECHANISMS
 Uncontrolled metabolic diseases
e.g. – uremia, alcoholism, malnutrition, severe diabetes
(decreased function of leucocytes, decreased
chemotaxis, decreased phagocytosis, decreased
bacterial killing)
 2- Immuno Suppressing diseases
Interfere with host defense mechanism
e.g.- leukemias, lymphomas, malignant tumours
 3- Immuno Supressing drugs
e.g.- cancer chemotherapeutic drugs
Immunosuppressive agents

3)TO DETERMINE WHETHER PATIENT
SHOULD BE TREATED BY GENERAL
DENTIST OR SPECIALIST
 Criteria for referral to a specialist :
1.Rapid progressive infection
2.Difficulty in breathing
3.Difficulty in swallowing
4.Fascial space involvement
5.Elevated temperature(>101 degree F)
6.Severe jaw trismus(<10mm)
7.Toxic appearance

4)TO TREAT INFECTION SURGICALLY
GOALS :
1.To remove the cause of infection
2.To provide drainage of accumulated
pus and necrotic debris
MODES :
1.Endodontic treatment
2.Extraction
3.Incision and drainage
+extraction endodontic treatment
Drainage of pus
Reduction in tissue tension
Improved local blood supply and increased
delivery of host defenses

5)TO SUPPORT THE PATIENT
MEDICALLY
Odontogenic infection
Pain and swelling
No adequate fluid and nutritional
intake
Depressed host defenses
Adequate analgesics and fluid intake

6)CHOOSE AND PRESCRIBE
PRINCIPLES FOR CHOOSING
Identification of causative organism
 Scientifically determined either in the
laboratory, where the organism can be isolated
from pus, blood or tissue
or
 Empirically based upon the knowledge of the
pathogens and clinical presentation of specific
infection.

PRINCIPLES FOR CHOOSING APPROPRIATE
ANTIBIOTIC
(I) IDENTIFICATION OF THE CAUSATIVE
ORGANISM:-
 Scientifically - laboratory
 Emperically – knowledge of
the pathogenesis & clinical
presentation.
 Initial emperical therapy
instituted with a fair degree of reliability.
24

ANTIBIOTIC
 Typical odontogenic infection is caused by a mixture of aerobic
& anaerobic bacteria (70%)
 Aerobic bacteria – 5% (gm positive cocci)
 Pure anaerobic bacteria – 25% (gm positive cocci – 30% & gm
negative rods – 50%)
 All are sensitive to penicillin & penicillin like drugs, but
Fusobacterium frequently resistant to erythromycin (apprx. 50%)
25

Oral and Maxillofacial Surgery Clinics of NA
:2003
TYPE OF INFECTION MICROORGANISMS
ODONTOGENIC
CELLULITES/ABS
CESS
STREPTOCOCCUS MILLERI GROUP
PEPTOSTREPTOCOCCI
PREVOTELLAAND PORPHYROMONAS
FUSOBACTERIA
RHINOSINUSITIS ACUTE STREPTOCOCCUS PNEUMONIAE
HAEMOPHILUS INFLUENZAE
HEAD AND NECK ANAEROBES
(PEPTOSTREPTOCOCCI, PREVOTELLA
PORPHYROMONAS, FUSOBACTERIA)
GROUP A BETA-HEMOLYTIC STREPTOCOCCI
STAPHYLOCOCCUS AUREUS
MORAHELLA CATARRHALIS
VIRUSES
CHRONIC HEAD AND NECK ANAEROBES
FUNGAL ASPERGILLUS
RHIZOPUS SP. (MUCOR)
NOSOCOMIAL
(ESPECIALLY IF
INTUBATED)
ENTEROBACTERIACEAE (ESPECIALLY
PSEUDOMONAS, ACINETOBACTER,
ESCHERICHIA COLI)
S. AUREUS
YEASTS (CANDIDA SPECIES)
Major pathogens of head and neck infections

ANTIBIOTIC
Pathobiology of mixed odontogenic infection:-
27
Entry of organisms
(aerobic)
Effects underlying
tissues
Cellulitis develops Condtion resolves on
treatment
Hypoxic acidotic condition
Tissue destruction and
abscess formation
(anaerobic)
Production of
enzymes and toxins

CULTURES SHOULD BE PERFORMED:-
1. Pt. with an infection has compromised host defenses
2. Received appropriate treatment for 3 days without
improvement
3. Postoperative wound infection
4. Recurrent infection
5. Actinomycosis is suspected, or
6. Osteomyelitis is present
28

(II) DETERMINATION OF ANTIBIOTIC
SENSITIVITY:-
 Not responded to initial antibiotic therapy or a postoperative
wound infection – causative agent identified & the antibiotic
sensitivity determined.
29

DISK DIFFUSION METHOD
RATIONALE :
 Antibiotics diffuse into the agar and inhibit the growth
of sensitive bacteria in a semicircular zone around the disc.
 When the resistance to a given agent is present, the zone
radius will be reduced or these will be no zone at all.

Advantages :
 Simple to perform
 Inexpensive
 Provides data within 18 to 24 hours
Disadvantages :
 It is only semi quantitative and is not useful for
many flow growing or fastidious organisms.
 It has not been adequately standardized for
anaerobic bacteria.

ANTIBIOTIC
 The result of these studies provide the information needed to
prescribe the most appropriate antibiotic.
 Penicillin is excellent for treatment of streptococcus infection & is
good to excellent for the major anaerobes of odontogenic
infections.
 Erythromycin - Streptococcus, Peptostreptococcus & Prevotella
but is ineffective against Fusobacterium.
32

ANTIBIOTIC
 Clindamycin – streptococcus & major anaerobic groups.
 Cephalexin – moderately active against streptococcus & is good to
excellent against anaerobes.
 Metronidazole – no activity against streptococcus but has
excellent activity against anaerobes.
33

ANTIBIOTIC
(III) USE OF A SPECIFIC, NARROW SPECTRUM
ANTIBIOTIC:-
Advantages -
 less chances of developing resistant organisms.
E.g. streptococcus sensitive to penicillin , cephalosporin and
tetracycline.
 Minimizes the risk of super infections.
E.g. moniliasis and gram negative pneumonias
34

ANTIBIOTIC
(IV) USE OF THE LEAST TOXIC ANTIBIOTIC:-
 Equally effective but less toxic drugs have to be used.
E.g. bacteria causing odontogenic infection susceptible to both
penicillin and chloramphenicol.
 More toxicity present with the latter drug.
35

ANTIBIOTIC
(V) PATIENT DRUG HISTORY:-
 Previous allergic reactions
 Previous toxic reactions
 Allergy rate to penicillin - 5 %
 Cross sensitivity Penicillins and cephalosporins.
 Toxic reactions - identify the drug and precise reaction
 Likely to happen again.
36

ANTIBIOTIC
(Pharmacologic factors in antibiotic selection)
(VI) USE OF A BACTERICIDAL RATHER THAN A
BACTERIOSTATIC DRUG:-
Advantages:
1. Less reliance on the host resistance
2. killing of the bacteria by the antibiotic itself
3. Faster results
4. Greater flexibility with dosage intervals.
Used especially when the host defenses are low.
37

ANTIBIOTIC
(VII) USE OF THE ANTIBIOTIC WITH A
PROVEN H/O SUCCESS:-
Critical observation of the clinical effectiveness over a prolonged
period -----assessment of
 Frequency of treatment success and failures
Frequency of adverse reactions
Frequency of side effects
Standards for use
38

ANTIBIOTIC
(VIII) COST OF THE ANTIBIOTIC:-
 Difficult to place a price tag on health.
 In some situations, more expensive antibiotic is the drug of
choice.
 In other situations, there may be a substantial difference in price
for drugs of equal efficacy.
 Surgeon should consider the cost of the antibiotic prescribed.
39

ANTIBIOTIC
(IX) ENCOURAGE PATIENT COMPLIANCE:-
 Dosage interval that encourages compliance
OD 80%
BID 69%
TID 59%
QID 35%
 Non-compliant start feeling better
3-5 days 50%
>7 days 20%
 Antibiotic that would have the highest compliance would be the
drug given OD for 4 or 5 days.
40

Indications for use of
antibiotics
 Rapidly progressive swelling
 Diffuse swelling
 Compromised host defenses
 Involvement of facial spaces
 Severe pericoronitis
 Osteomyelitis

Use of antibiotics is not
necessary
 Chronic well localized abscess
 Minor vestibular abscess
 Dry socket
 Mild pericoronitis

INDICATIONS OF EMPIRICAL
ANTIBIOTIC THERAPY :
 The site and feature of the infection have been
well defined.
 The circumstances leading to the infection are
well known.
 Organisms that most commonly cause such
infections.

EMPIRIC ANTIBIOTIC TREATMENT
Early infection (first 3 days of symptoms and mildly
immunocompromised)
 Penicillin
 Clindamycin
 Cephalexin
Late infection (After 3 days of symptoms or moderately to severely
immunocompomised)
 Clindamycin
 Revicillin and metranidazole.
 Ampicillin and sulbactam.
 Cephalosporin (first or second generation).
-Mild, moderate and severe compromised based on CD4 / viral
loads, glycemic control, and the degree of alcoholic related disease.

7)PROPER ANTIBIOTIC ADMINISTRATION
 Proper dose.
 Proper time interval.
 Proper route of administration.
 Combination antibiotic therapy.
 It is indicated in few situations like in:
 Situations of life threatening situations of unknown cause.
 To increase the bactericidal effect of a specific organism.
 Prevention of the rapid emergence of resistant bacteria.
- Empiric therapy of certain odontogenic infections like when the
infection progresses to the lateral and retropharyngeal spaces and
caused by aerobes and anaerobes.

PRINCIPLES OF ANTIBIOTIC DOSING
 GOAL :
1.To aid the body’s defenses to clear the
tissues of microbial pathogen by achieving
antibiotic levels in the infected area to or greater
than the MIC

ANTIBIOTIC DOSING VARIABLES
 PHARMACOKINETIC FACTORS
Diffusion to the site of action
1.Tissue pH.
2.Lipid and water solubility
3.Plasma protein binding
 INOCULUM EFFECT- It is defined as a laboratory
phenomenon that results in significantly increased MIC
required of an antibiotic. When the number of inoculated
organisms increases. It generally occurs in case b-lactum
antibiotics and b-lactamase producing bacteria
(review of infectious diseases vol.2 number.3 may- june 1989)
 SURFACE AREA TO VOLUME RATIO

Lipophilic antibiotics
Tetracyclines,macrolides,fluoroquinolones
Pass better through tissue barriers
Effective against intracellular pathogens
Drug depot within macrophages

Hydrophilic antibiotics
Beta-lactams,vancomycin,aminoglycosides
Confined to ECF
Poor diffusion through capillaries

PLASMA PROTEIN BINDING
Limited plasma protein binding
Diffuse easily through capillary walls
and
other barriers

PRINCIPLES OF ANTIBIOTIC THERAPEUTIC DOSE
(I) PROPER DOSE:-
 Dose – 3 to 4 times the MIC
for e.g. penicillinase producing staphylococcus -
MIC 6 µg/ ml , plasma level - 18µg /ml
 Administration of doses above this level – increases the
likelihood of toxicity & is wasteful.
 Sub therapeutic levels - mask the infection ,recurrence.
51

DRUG DOSE CALCULATION
 BASED ON BODY SURFACE AREA
Individual dose = BSA[m2] x adult dose
1.7
 BASED ON BODY WEIGHT
Individual dose = BW[kg] x average
70 adult dose

IN PEDIATRICS
YOUNG’S FORMULA :
CHILD DOSE = Age x adult dose
Age + 12
DILLING’S FORMULA :
CHILD DOSE = Age x adult dose
20

NEONATES AND INFANTS
 Greater percentage of body weight
compared with body water
Greater volume of distribution
Increased serum half lives
 Reduced gastric emptying
 Reduced plasma protein binding
 Reduced GFR

ELDERLY
 Reduced host defenses
 Underlying illness
 Reduced total body water
 Lean body mass
 Reduced cardiac output
 Reduced gastric emptying time
 Decreased renal function

 LOADING DOSE; This is a single or few
quickly repeated doses given in the beginning to
attain target concentration capacity.
 MAINTAINANCE DOSE: This is the dose
repeated at specific interval after attainment of
target cycles per second

ANTIBIOTIC LOADING DOSES
 INDICATIONS :
1.The half-life of the antibiotic is longer
than 3-hours.
2. A delay of longer than 12-hours to
achieve therapeutic blood levels is unacceptable.
Because most acute orofacial infections
begin and peak rapidly

DURATION OF ANTIBIOTIC DOSING
 The ideal antibiotic duration is the shortest
time that will prevent both clinical and
microbiological relapse.
Clinical improvement of the patient
Remission of infection.

MISCONCEPTIONS IN LONGER DURATION OF
ANTIBIOTICS
 Prolonged antibiotic therapy destroys resistant
bacteria.
 Prolonged antibiotic therapy is necessary to
prevent rebound infections.
 The dosage and duration of therapy can be
extrapolated from one infection to another.
 The prescriber knows how longer the infection
will last.

(II) Proper time interval:-
 Established plasma t 1/2 – one half of the absorbed dose is
excreted.
 Usual dosage interval for therapeutic use of antibiotics - Four
times the half life.
E.g. cefazolin t 1/2 - 2 hours.
60

(III) Proper route of administration:-
In some infections , only the parenteral route produces necessary
serum level of antibiotic
For e.g. Penicillin V oral - 2 gm
Plasma level - 4 µG/ mL
Oral route - variable absorption.
Serious well established infection - parenteral route
61

(IV) Consistency in Route of Administration:-
After initial response , immediate discontinuation of parenteral
route - Recurrence
Maintenance of peak blood levels of antibiotic for an adequate
period is important – max. tissue penetration & effective
bactericidal action.
After the 5th day of parenteral administration, the blood levels
achievable with oral administration are usually sufficient.
62

(V) Combination Antibiotic therapy:-
 Life threatening sepsis of unknown cause
 Increased bactericidal effect against a specific µorg is desired.
E.g. treatment of infections caused by enterococcus
 Prevention of rapid emergence of resistant bacteria
E.g. tuberculosis
 Empiric treatment of certain odontogenic infections
E.g. Penicillin G & Metronidazole
63

COMBINATION ANTIBIOTIC THERAPY
Combination therapy with two or more antibiotics is
used in special cases:
 Prevent the emergence of resistant strains
 To treat emergency cases during the period when
an etiological diagnosis is still in progress
 To take advantage of antibiotic synergism

ADVANTAGES vs DISADVANTAGES
 Broad antibacterial
spectrum
 Reduced dose for each
agent.
 Antibiotic synergism
 Decreased adverse drug
reactions
 Greater likelihood of
adverse reactions
 Antibiotic antagonism
 Increased financial costs
 Greater microbial
resistance
 Resistance genes
 Increased risk of
superinfection

SYNERGISTIC ANTIBIOTIC
COMBINATION
 Cell wall inhibitors and aminoglycosides
 Beta-lactams with beta-lactamase inhibitors
 Beta-lactams that act on different PBPs
 Sulfonamides and trimethoprim

 Should be avoided when not specifically indicated.
 Usual result – broad spectrum exposure that leads to depression
of the normal host flora & inc opportunity for resistant bacteria
to emerge.
 For routine infections, the disadvantages of combination therapy
outweigh the advantages.
67

FACTORS INFLUENCING
 Minimal Inhibitory Concentration
 Post-antibiotic effects
 Microbial persistence and regrowth.
 Dosing and resistance
 Antibiotic loading dose
 Duration of antibiotic dosing
 Incision and Drainage
 Special conditions

MINIMAL INHIBITORY CONCENTRATION
 Is the lowest antibiotic concentration that prevents growth
of microorganism after an incubation period of 18 – 24
hours incubation period with a standard inoculum of 104
to 105 cfu/ml
MINIMAL BACTERICIDAL CONCENTRATION
 Is the lowest concentration of drug that causes the
complete destruction of the organisms or permits survival
of less than 0.1% of the inoculum

ADVANTAGES IN DETERMINING MIC
 DETERMINES:
1.The ratio of the peak drug
concentration in the serum to the MIC
2.The duration of the time the serum
drug concentration exceeds the MIC
3.The ratio of the 24-hour area under
the curve [AUC] to the MIC
The AUC is the measure of
the drug exposure to the bacteria over time

DISADVANTAGES WITH MIC
 Is only a point in time and tells nothing about the
true antibiotic activity at the locus of infection
 The concentration of organisms at the site of
infection is 108-1010 cfu/ml – greater than that
used to determine the MIC in the laboratory.
 Exponential growth in vitro
 Differing variables- temperature, inoculum Size,
pH and growth period.

RULE OF THUMB
 The concentration of the antibiotic in the
blood should exceed the MIC by a factor
of 2-8 times to offset the tissue barriers
that restrict access to the infected site.

CONCENTRATION DEPENDENT
Vs
TIME DEPENDENT ANTIBIOTICS
CONCENTRATION
DEPENDENT
TIME DEPENDENT
ANTIBIOTICS
1. Aminoglycosides,
metronidazole,
fluroquinolones
2. Bactericidal activity
depends on the drug
concentration
1. Beta-lactams and
vancomycin
2. Long time of exposure of
the organisms
3. Better the bactericidal
concentration
4. Require organisms in the
process of cell division

POSTANTIBIOTIC EFFECTS
 Is the persistent supression of microbial growth
after short time exposure to an antimicrobial
agent.
 MECHANISM :
Is the time necessary to recover from
sublethal structural and metabolic alterations that
prevents resumption of bacterial regrowth.

FACTORS INFLUENCING PAE
 The particular organism
 Inoculum size
 Growth medium
 Organism growth phase
 Mechanism of action of antibiotic
 Duration of exposure to the drug

MICROBIAL PERSISTENCE AND
REGROWTH.
 The subpopulation of organisms that is not inhibited
or killed during a given dose interval which can then
reestablish themselves and continue growth.
 FACTORS DETERMINING :
1.Initial inoculum size
2.Bactericidal activity
3.Organism MIC
4.Post-antibiotic effects
5.Antibiotic pharmacokinetics
6.Doubling time of the organism.

8)MONITORING THE PATIENT
1)Response to treatment.
Reasons for treatment failure:
-Inadequate surgical treatment.
-Depressed host defences.
-Presence of foreign body.
-Antibiotic problems – Drugs not reaching infection.
Dose not adequate
Wrong bacterial
diagnosis.
Wrong antibiotic.
2)Development of adverse reactions:
3)Superinfection and recurrent infection:

ANTIBIOTIC SIDE EFFECTS
Side effects are unwanted but often unavoidable
pharmacodynamic effects that occur at therapeutic doses.
1) HAEMATOLOGIC EFFECTS
a) Leucopenia and thrombocytopenia: Beta lactams
sulfonamides(Cotrimazole)
b) Anaemia: Beta lactam- Autoimmune anaemia
Cotrimazole- Folate deficiency- Megaloblastic anaemia
Chloramphenicol- Aplastic anaemia.
c) Platelet dysfunction: Anti pseudomonal penicillins- Impaired
platelet aggregation.
d) Clinical bleeding: Moxalactam- Interferes with vit.K depended
clotting factor synthesis.
Trovafloxacin- Increases prothrombin time.

2) HYPERSENSITIVITY EFFECTS
Drug fever: 10-15% of unexplained fever in hospitalized patients.
Beta lactams, Sufonamides.
Drug rashes: Itching, urticaria, maculo popular rashes.
Beta lactams, sulfonamides.
Anaphylactic reactions: Beta lactams, rare in Sulfonamides.
Serum sickness: Develops 2 weeks after exposure- Beta lactams.
Photosensitivity reactions: Tetracycline, Sparfloxacin
Rare with Doxycyclin, minocycline
Drug induced Systemic Lupus Erythematosus(SLE):
Minocyclin, Isoniazide, Nitrofurantoin, Griseiofulvin.

3) NEUROLOGIC EFFECTS
a) Encephalopathy: Trovafloxacin- Mental
confusion
Clarithromycin
b) Seizures: Ciprofloxocin, Imipenem,
Trovafloxacin.
It depends on seizure threshold of patient.
c) Neuromuscular blockade: Aminoglycosides
d) Peripheral neuropathy: Isoniazide, Griseiofulvin
e) Muscular tremors and myalgias: Trovafloxacin
f) Ototoxicity: Aminoglycisides, Parenteral
Erythromycin
g) Blindness: Ethambutol, Chloroquine.

4) PULMONARY EFFECTS
a) Acute pulmonary reactions: Rifampicin- Flu like illness.
Nitrofurantoin: Varying degrees of respiratory
Insufficiency, Pleural effusion.
b) Chronic pulmonary reaction: Nitrofurantoin-
Pulmonary fibrosis.
5) CARDIAC EFFECTS
a) Ventricular arrhythmias: Erythromycin
b) Hypotension: Trovafloxacin, Amphotericin-B

6) GASTROINTESTINAL EFFECTS
a)Nausea and vomiting
Clarithromycin,Amoxicillin/Clavulanate,Azithromycin,
Doxicycline,Minocycline.
b) Non-clostridium difficile diarrhea:
Macrolides,Ampicillin, Trovafloxacin
c)Cl. Difficile diarrhoea
Beta lactums, Quinolones
d)Anti pancreatitis
Trovafloxacin.

7)HEPATIC SIDE EFFECTS
a) drug induced hepatitis
-Isoniazide- elevates serum transaminas,
Trovafloxacin,Oxacillin
b) Cholestasis
-Erythromycin,Nitrofurantoin
c) Hepatic necrosis
-PAS, Ketoconazole or Trovafloxacin
8)NEPHROTOXIC SIDE EFFECTS
a) Nephrotoxicity
Aminoglycosides-Tubular toxicity.
Tetracyclines, Polymyxin –B
b) Interstitial nephritis
Beta lactamase therapy.

ANTIBIOTIC RESISTANCE
 The organisms continue to multiply even in the
presence of antibiotic.
 Resistance to an antimicrobial can arise
(1) Mutation in the gene that
determines sensitivity/resistance to the agent or
(2) Acquisition of
extrachromosomal DNA (plasmid) carrying a
resistance gene.
(3) Bacteriophages.
(4) Mosaic genes
Mutation: random, undirected, heritable variation caused
by an alteration in the nucleotide sequence at some
point of the DNA of the cell

CROSS RESISTANCE
Single mechanisms confers resistance to
multiple antimicrobial agents
MULTIPLE RESISTANCE
Multiple mechanisms
Cross resistance - closely related antimicrobial
agents
Multiple resistance - unrelated antimicrobial
agents.

ANTIBIOTIC RESISTANCE MECHANISMS
1.ENZYMATIC ANTIBIOTIC INACTIVATION
a.Beta-lactams - beta lactamases
b.Aminoglycosides - aminoglycosides
modifying enzymes
c.Chloramphenicol - acetyl transferases
2.MODIFICATION PROTECTION OF TARGET
SITE
a.Beta-lactams-altered PBPs
b.Fluoroquinolones:altered DNA gyrases
c.Rifampin:altered RNA polymerase
d.Sulfonamides: altered dihydropteroate
synthase

3.LIMITING ACCESS OF ANTIBIOTIC
Beta-lactams and fluoroquinolones
Altered outer membrane porins
4.ACTIVE ANTIBIOTIC EFFLUX
5.FAILURE TO ACTIVATE ANTIBIOTIC
Metronidazole - flavodoxin production

6.USE OF ALTERNATE GROWTH
REQUIREMENTS
7.OVERPRODUCTION OF TARGET SITES
a.Sulfonamides:overproduction of
PABA
b.Entericbacilli:overproduction of beta-
lactamases

ANTIBIOTIC FAILURES
Common reasons for antibiotic failure:
1.Failure to surgically eradicate - source of
infection
2.Too low - blood antibiotic concentration
3.Inability to penetrate the site of infection
4.Impaired host defenses
5.Patient failure to take the antibiotic

6.Inappropriate choice of antibiotic
7.Limited vascularity or blood flow
8.Decreased tissue ph or oxygen tension
9.Antibiotic resistance
10.Delay or incorrect diagnosis
11.Antibiotic antagonism

MISUSE OF ANTIBIOTICS
 1) Treatment of untreatable infections
 2) Therapy of fever of unknown origin
 3) Improper dosage
 4) Inappropriate reliance on
chemotherapy alone
 5) Lack of adequate bacteriological
information

DEVELOPMENT OF DRUG RESISTANCE
 Refers to unresponsiveness of a microorganism to an AMA
 Natural Resistance
 Acquired Resistance
.
92

 Single step mutation
E.g. Enterococci to Streptomycin, E.coli & Staphylococci
to rifampin
 Multistep mutation
E.g. resistance to erythromycin, tetracyclines &
chloramphenicol by many organisms.
93

 Gene Transfer:- from organism to another can occur by,
(i) Conjugation:-
E.g. Chloramphenicol – typhoid bacilli,
Streptomycin – E.coli, Penicillin – Haemophilus & Gonococci
(ii) Transduction:-
E.g. Penicillin, Erythromycin & Chloramphenicol
(iii) Transformation:-
E.g. pneumococcal resistance to Penicillin G
94

PRINCIPLES OF PROPHYLACTIC
ANTIBIOTICS
It is the use of antibiotics before, during, or after a
diagnostic, therapeutic, or surgical procedure to
prevent infectious complications.
ADVANTAGES:
1.Prevention of infection.
2.Decrease patient morbidity and mortality.
3.Decrease hospital stay.
4.Decreased medical cost.
5.Decreased total antibiotic usage.
6.Decrease numbers of resistant bacteria – because of
short term course.

DISADVANTAGES
 No reduction of infection.
 Development of increased number of
resistant bacteria.
 Delay in onset of infection.
 Adverse effect on surgical technique

THE PRINCIPLES FOR
PROPHYLACTIC ANTIBIOTICS
 Increased risk of significant bacterial contamination
and a high incidence of infection.
 Organism must be known.
 Antibiotic susceptibility must be known.
 To be effective and to minimize adverse effects the
antibiotic must be in the tissue at the time of
contamination (operation) and it must be continued
for not more than 4 hours after cessation of
contamination.
 Four times the MIC of the causative organisms.
 Timing the antibiotic correctly.
 Shortest effective antibiotic exposure.

PRINCIPLE 1: PROCEDURE SHOULD HAVE
A SIGNIFICANT RISK OF INFECTION
1.Bacterial inoculum of sufficient size
2.Extensive and prolonged surgery
3.Insertion or presence of foreign body
4.Depressed host resistance

Type I. Clean wounds (no opening of mucosa in the oral cavity): Confirmed
infection rate of 1 to 4%. Antibiotic prophylaxis not required.
Type II. Clean-contaminated wounds (opening of mucosa in the oral cavity,
insertion of dental implants or intervention on inflammatory pathology):
Confirmed infection rate of 5 to 15%. These require antibiotic prophylaxis
with drugs covering Gram positive and anaerobic micro-organisms.
Type III. Contaminated wounds (oncological pathology in which there is
simultaneous action on the oral cavity and the neck): Confirmed infection
rate of 16 to 25%. Antibiotic prophylaxis must be carried out to cover
Gram negative organisms whose coverage in clean and cleancontaminated
surgeries is disputed.
Type IV. Dirty and infected wounds. Confirmed infection rate of above 26%.
These always need adequate antibiotic treatment.
CLASSIFICATION OF SURGICAL WOUNDS

PRINCIPLE 2: TO CHOOSE CORRECT
ANTIBIOTIC
1.Effective against the most likely organism
2.Narrow spectrum antibiotic
3.Least toxic antibiotic
4.Bactericidal antibiotic

PRINCIPLE 3: ANTIBIOTIC
PLASMA LEVEL MUST BE HIGH
 To ensure diffusion of antibiotic into all fluid and
tissue components
 USUAL RECCOMENDED DOSE: Two times
the usual therapeutic dose

PRINCIPLE 4: TO TIME ANTIBIOTIC
ADMINISTRATION CORRECTLY
 Antibiotic must be administered before the
surgery begins
Prolonged surgery
Additional antibiotic is required
Intraoperative dose intervals should be one half
the usual therapeutic dose interval

PRINCIPLE 5: USE OF SHORTEST EFFECTIVE
ANTIBIOTIC EXPOSURE
 Continued antibiotic administration - no benefit once the
surgical procedure is complete
 Hence the final dose of the antibiotic - after surgical
operation
Procedure lasts for Short procedure
more than two hours
2nd dose of antibiotic is Single preop dose is
required adequate

ANTIBIOTIC PROPHYLAXIS AGAINST
INFECTIVE ENDOCARDITIS
 GOALS :
1.To reduce the intensity of bacteremia.
2.Assist the RES in killing the bacteria.
3.Decrease the bacterial adherence to the
damaged heart valves and vegetations.

CONDITIONS CONSIDERD FOR ANTIBIOTIC
PROPHYLAXIS
 Antibiotic prophylaxis recommended :
High risk condition
1.Prosthetic cardiac valves
2.Bioprosthetic valves
3.Previous bacterial endocarditis
4.Complex congenital CHD
Moderate risk condition
1.Acquired valvular dysfunction
2.Hypertrophic cardiomyopathy
3.Other congenital cardiac malformation

ANTIBIOTIC PROPHYLAXIS NOT
RECOMMENDED
 LOW RISK CONDITION:
1.Isolated atrial septal defect
2.Previous coronary artery bypass
graft surgery.
3.Mitral valve prolapse without
valvular regurgitation
4.Cardiac pacemakers and
defibrillators
5.Previous rheumatic fever without
valvular regurgitation

AHA RECOMMENDATIONS
 PROPHYLAXIS RECOMMENDED :
1.Extractions
2.Periodontal surgery
3.Implants placement
4.Endodontic surgery
5.Subgingival antibiotic fiber strips
6.Intraligamentary LA injections.
 NOT RECOMMENDED :
1.Restorative dentistry
2.LA injections
3.Intracanal endodontic treatment
4.post-op suture removal
5.Oral radiographs

ANTIBIOTICS USEFUL FOR OROFACIAL
INFECTIONS:
 Penicillins.
 Cephalosporins.
 Erythromycins.
 Clindamycin and Lincomycin.
 Metronidazole.
 Aminoglycosides.
 Fluoro quinolones – ciprofloxacin.
 Sulfonamides and trimethoprim

PENICILLINS
 Discovered in 1929, it was first antibiotic drug to
be used.
 The drug of choice for the initial empirical
management of odontogenic infections remains
penicillin
 Bactericidal
 Narrow but appropriate spectrum
 Little or no toxicity

CLASSIFICATION OF PENICILLIN
I) Natural penicillins :
Penicillin G (Benzyl penicillin)
II) Acid resistant penicillins :
Phenoxymethyl penicillin (penicillin V)
III) Penicillinase – resistant penicillins :
Acid labile : Methicillin, nafillin, cloxacillin, dicloxacillin
IV) Penicillins effective against gram +ve and some gram –ve
organisms :
Ampicillin
V) Extended spectrum penicillins :
Carboxypenicillins : Carbenicillin, tiocillin

PENICILLIN-G ( Benzyl Penicillin )
-Narrow spectrum activity
Spectrum of activity- Streptococci except enterococci,
Staph. aureus, N. gonorrhoea, N. meningitides, Anthracis,
C.diphtheriae, Clostridia, Listeria.
PHARMACOKINETICS: PnG is acid liable destroyed by gastric
acid.
-Absorption of sodium PnG from i.m. site is rapid and
complete.
-Distributed extracellularly, penetration into serous cavity and
CSF is poor.
-Plasma T1/2 is 30 min.
-Extreted through kidneys by glomerular filtration.

 PREPARATION AND DOSE: 1) Sod. PnG or Crystallin
penicillin injection: 0.5-5 MU i.m. 6-12 hrly
 Repository PnG injections: These are insoluble salts must
be given deep i.m. never given i.v. Drug is released slowly
from the injection site.
 Procaine PnG: 0.5-1MU i.m.12hrly
 Fortified Procaine PnG : Contains 3lakhU
 Procaine PnG and 1lakhU Sod. PnG
 Benzathine PnG : 0.6-2.4MU i.m. every 2-4 weeks. It
releases drug very slowly and effective for prophylactic
purposes.

AMPICILLIN
Semi synthetic penicillin belongs to aminopenicillins.
Spectrum: Active against all organisms sensitive to PnG,
H.Influenza, E.Coli, Proteus, Salmonella, Shigella,
Strepto.
Viridans, Enterococci, Pseudomonas, Klebsiella.
Kinetics : Not degraded by gastric acid.
Oral absorption is incomplete but adequate.
Food interferes with absorption.
Plasma T1/2 is 1 hr, excreted through kidneys.
Dose: 0.5-2g oral /i.m. /i.v. every 6th hrly.
Children 25-50mg /kg /day.

Uses: Urinary tract infections, Respiratory tract infections, Meningitis,
Gonorrhoea, Typhoid fever, Bacillary dysentery, Cholecystitis,
SABE.
Adverse effects: Diarrhea is frequent after oral administration, rashes
Avoided in patients with a H/O hypersensitivity to PnG.
AMOXICILLIN
It is a close congener of Ampicillin, similar to it
except
- Oral absorption is better food does not interferes
- Incidence of diarrhea is less.
- Less active against Shigella, H.Influenza.
Dose: 0.25-1g orally /i.m /i.v. TDS.

BROAD SPECTRUM EFFECT
WITH CLAVULANIC ACID
 Clavulanic acid- streptomycet clavuligerous-
inhibiting β lactamase enzymes
 Broaden antibacterial spectrum of amoxicillins

SULBACTAM
 Semisnythetic betalactamase inhibitor
 Related chemically in activity to clavulanic acid
 Progressive inhibitor ,highly active against betalactamase
 2-3 times < potent
 Oral absorption- inconsistent,preferably im/iv
 Sulbactam+ ampicillin=Dicapen
 SULBACIN, AMPITUM
1g+ 0.5g per vial im/iv 6-8hourly
1g+500mg tab

 ADVERSE EFFECTS :
a) Local irritancy and direct toxicity
b)Jarisch-Herxheimer reaction
c) Hypersensitivity or drug allergy(1-10%)
Defn: An allergic drug reaction is defined as any noxious, unintended, and
undesired effect of a drug that occurs at doses used in humans for prevention,
diagnosis, or treatment.
2types predictable
unpredictable
PENICILLIN ALLERGY SKIN TESTING
Reagents: Concentration
-Penicilloate 0.01 mol/L
-Penilloate 0.01 mol/L
-Penicillin G 10,000U/ml
-Ampicillin/Amoxicillin 1-20mg/ml
PROCEDURE:
1) Epcutaneous or (scratch or prick)
2) Intradermal test

DESENSITIZATION IN PENCILLIN
ALLERGIC PATIENTS
 Administration of a penicillin to a allergic
patient, who requires penicillin for clearly
defined medical reasons.
Ex; Endocarditis, meningitis.
-Done in Intensive care setting…
-Penicillin doses of 1,5,10,100 and 1000U
administered intradermally ,60 mints
interval b/n doses.
-well tolerated- 10000U-50,000U given s.c.

Therapeutic Uses :
 Streptococcal infections
 Pneumococcal infections
 Meningococcal infections
 Staphylococcal infections
 Gonorrhoea
 Syphilis
 Diphtheria
 Tetanus and gas gangrene
 Antibiotic prophylaxis

CEPHALOSPORINS
 These are a group of semisynthetic
antibiotics derived from "cephalosporin – C"
obtained from a fungus cephalosporium.
 They are chemically related to penicillins,
the nucleus consists of a -lactam ring fused
to a dihydrothiazine ring.

CEPHALOSPORINS
1ST GENERATION CEPHALOSPORINS
Good against methicillin sensitive S. aureus,
streptococci and many Enterobacteriaceae.
Members include: Cephalexin (Keflex), Cefazolin
(Ancef), Cephapirin (Cefadyl) and Cephalothin (Keflin)
Cefadroxil.
2ND GENERATION CEPHALOSPORINS
More stable to Gram negative b-lactamase and less
active against S. aureus.
Members include: Cefuroxime (Ceftin [oral] and
Zinocef), Cefotetan (Cefotan), and Cefoxitin (Mefoxin).

3RD GENERATION CEPHALOSPORINS
Broader activity against Gram negatives.
Members include: Cefdinir (Omnicef),
Cefoperazone (Cefobid), Ceftazidime (Fortaz), and
Ceftriaxone (Rocephin), and Cefotaxime (Claforan).
4TH GENERATION CEPHALOSPORINS
More resistant to destruction by chromosomal b-
lactamases, but not completely resistant to the b-lactamases of
Serratia, Enterobacter and Pseudomonas.
Cefepime (Maxipime).

Adverse effects :
 Pain
 Diarrhoea
 Hypersensitivity
 Nephrotoxicity
 Neutropenia
 Thrombocytopenia

USES :
 As alternatives to PnG in patients developing rashes or other allergic
reactions with PnG.
 Respiratory, urinary and soft tissue infections caused by gram negative
organisms.
 Penicillinase producing staphylococcal infection.
 Septicaermias caused by gram negative organisms : an aminoglycotide
may be combined with a cephalosporin.
 Surgical prophylaxis; surgical prosthesis such as artificial heart valves,
artificial joints etc. The first generation drugs are used.
 Meningitis caused by H.influenzae, enterobacteriaceae.
 Gonorrhoea caused by penicillinase producing organisms.
 Typhoid : as alternative to fluoroquinolones (specially in children)
 Mixed aerobic – anaerobic infections seen in cancer patients those
undergoing colorectal surgery, obstetric complications.
 Prophylaxis and treatment of infections in neutropenic patients.

MACROLIDES (ERYTHROMYCIN), LONG ACTING MACROLIDES
(AZITHROMYCIN), LINCOSAMIDES (CLINDAMYCIN) AND
STREPTOGRAMINS (SYNERCID)
 Bind to the 50s ribosomal subunit.
 Block chain elongation.
 Bacteriocidal or bacteriostatic depending upon
the organism.

ERYTHROMYCIN
USES
Gram positive organisms.
Used to treat Legionella, Mycoplasma,
syphilis, diphtheria carriers and pertussis.
Safe in pregnancy.
SIDE EFFECTS
Erythromycin estolate - cholestatic
hepatitis (1/1000).
Ototoxic in high doses.

CLARITHROMYCIN
A.Uses
Spectrum is similar erythromycin and
respiratory Gram-negative pathogens
Clarithromycin can be used - H. pylori and
atypical mycobacteria infections.
B.Side Effects
Teratogenic.
Ototoxic in high doses.

CLINDAMYCIN
 A.USES
Used against Gram positive cocci and
anaerobes, both Gram-positive and Gram-
negative rods.
 B.SIDE EFFECTS
Significant risk of pseudo-
membranous colitis due to the overgrowth of
C. difficile.

AMINOGLYCOSIDES
 MECHANISM :
Works by binding to a specific protein,
S12, on the 30s ribosomal subunit.
Blocks normal activation of the initiation
complex.
At low concentrations - the mRNA is misread
and the wrong amino acid is inserted.
At higher concentrations - inhibit translation.

METABOLISM
 Excreted by glomerular filtration.
 Aminoglycosides have a low toxic to therapeutic
ratio. Blood levels need to be monitored to
insure safety and efficacy.
 If the GFR falls below 70mL/min, the daily dose
must be reduced to prevent toxicity.

SIDE EFFECTS
 Ototoxicity
 Nephrotoxicity
 Very high concentrations - neuromuscular
blockade.

GENTAMICIN
 It is effective against gram positive and negative bacteria including
penicillinase resistant staphylococci.
 Gentamicin and ampicillin should be administered separately because
gentamicin gets destroyed.
 It is indicated in severe anaerobic infections.
 Dose – Adult – 3-7mg/kg/day in 2-3 divided dose.
Child – 1-3mg/kg/day in 2-3 divided dose.
 Toxicity – It causes ototoxicity (vestibular and cochlear). If serum
concentrations exceeds 10mg/ml transient tinnitus may occur.
 When used over a weak, nephrotoxicity occurs.
 Allergic reactions – not recommended in lactating mothers.

QUINOLONES
CLASSIFICATION
First generation: Cinoxacin, Oxalinic acid,
Nalidixic acid.
Second generation: Ciprofloxacin,
Ofloxacin, Norfloxacin, Levofloxacin
Third generation: Gatifloxacin,
Sparfloxacin, Tosulfioxacin
Fourth generation: Gemifloxacin,
Moxifloxcin, Torvafloxacin.

QUINOLONES
 Mechanism
Interfere with the activity of DNA
gyrase.
Prevent winding of the DNA helix
into the supercoiled form.
Actions are bacteriocidal.

THERAPEUTIC USES
 Used against Enterobacteriaceae.
 Ciprofloxacin most active against
Pseudomonas.
 Fluoroquinolones used for
UTIs
Pneumonia
Atypical pneumonia and
Bacterial gastroenteritis.

SIDE EFFECTS
 High drug levels are neurotoxic.
 Prolonged use leads to tendon damage (rupture of
Achilles tendon).
 Not approved for children causes cartilage
damage.
 Safety in pregnancy is not established

METRONIDAZOLE
Belongs to Nitroimidazole group.
Mechanism
-In a reducing environment, metronidazole is
reduced to a substance - inhibits bacterial
DNA synthesis.
-Its action is broadspectrum bacteriocidal
-Its use is limited to anaerobic organisms.
* Plasma t1/2 is 8hrs.

SIDE EFFECTS
 Anorexia nausea and abdominal cramps.
 Produces metallic taste in the mouth.
 Peripheral neuropathy, seizures and ataxia have
been seen with prolonged use.
 Thromboflebitis of injected vein occurs if the
solution is not well diluted.

CONTRAINDICATIONS
-Neurological disease.
-Blood dyscrasias.
-First trimister of pregnancy.
-Chronic alcoholism.
Preparations: Tab Metrogyl 200mg 400mg
200mg/5ml susp
500mg/100ml i.v. infustion

USES
 Amoebiasis
 Giardiasis
 Trichomonas vaginitis
 Anaerobic bacterial infections
 Pseudomembranous enterocolitis
 Ulcerative gingivitis, trench mouth
 Helicobacter pylori gastritis/peptic ulcer

SULFONAMIDES AND TRIMETHOPRIM:
 These are bacteriostatic agents.
 inactivated by presence of pus.
 They act by inhibition of bacterial synthesis of
folic acid from para amino benzoic acid
(PABA).
 The concentration of sulfonamides in the urine
is greater than in blood this leads to formation
of crystals of sulfonamides termed as
crystalluria and leads to renal damage.

Toxic effects:
 Allergic reactions
 Prolonged therapy can lead to macrocytic
anemia
 Also cause kernicterus by displacing
bilirubin from plasma albumin in babies during
intrauterine life. They may also cause foetal
malformation.
 Sulfadizine: It penetrates blood brains
barrier. It is commonly used in traumatic
meningitis.

COTRIMOXAZOLE (SULFAMETHOXAZOLE
AND TRIMETHOPRIM)
 This agent inhibits the conversion of folic acid to folinic
acid which is important for bacterial synthesis of DNA and
RNA.
 It is active against strep pyogens and most staphylococci
and haemophili.
 It is indicated in acute exacerbations in post irradiation
osteomyelitis secondary to osteoradionecrosis. It is also used
in mixed actinomycotic infections along with penicillin.
 Dose 80 mg of Trimethoprim + 400 mg of sulfamethoxazole
2 tablets 12 hourly
Child : 20 mg + 100 mg

USES :
Cotrimoxazole is widely used
 Urinary tract infections
 Respiratory tract infections
 Typhoid
 Bacterial diarrhoeas and dysentery
 Chancroid
 Granuloma inguinale
 It is an effeictive alternative to penicillin for protecting
agranulocytosis patients and treating respiratory and
other infections in them.
 Pneumocystitis carinii.

TOPICAL ANTIBIOTICS
These are the antibiotics used for external application of drugs to the surface
for local action.
POLYPEPTIDE ANTIBIOTICS
 Low molecular weight cationic drugs.
 Powerful bactericidal
 Toxic when used systemically.
 They are: Polymyxin-B, Colstin, Bacitran, Tyrothricin.
POLYMYXIN-B & COLISTIN
 Active against g-ve bacteria.
 They have a detergent like action on cell membrane causing leak in
cell constituents. No cross resistance with other drugs.
 Adverse effects: No systemic absorption after oral or topical
administration.
 Given orally causes G.I.T. disturbances.
 Systemic effects are flushing, paraesthesia, renal and CNS
disturbance.

Uses: 1. Topically used in combination with other anti microbials for
skin infections, burns, otitis externa, conjunctivitis, corneal ulcers.
2. Orally for g-ve bacillary dysentery, diarrhea in children and
infants.
Preparation and dose: 1. Neosporin powder: 5000u polymyxin with
neomycin sulphate 3400u and bacitracin 400u per g.
 Neosporin eye drops.
 Neosporin-H ear drops.
BACITRACIN
 Discovered from Bacillus Subtilis.
 Active against g+ve organisms like Neisseria, H.Influenza,
Staph, Strepto, Clostridium, Corynebacterium.
 Not absorbed orally and does not penetrate the intact skin.
 Commonly combined with Neomycin and Polymyxin-B.

NEOMYCIN
It is an aminoglyciside, obtained from Steptomyces Fradiaea.
Binds to ribosomal 30S subunit to inactivate DNA polymerase cause
misreading of genetic code.
Spectrum: Active against g+ve and g-ve bacteria less active against
Pseudomonas, Strepto. Pyogens.
It is not used systemically because of nephro and ototoxicity.
No systemic absorption from topical and oral administration.
Uses: a) Topical: Combined with Polymyxin-B & Bacitracin for infected
wound, ulcers, burns, external ear infection, conjunctivitis.
 Oral: -For preparation of bowel before surgery to decrease post
operative infection.
In hepatic coma to reduce nitrogen producing bacteria in G.I.T.

FOUR CATEGORIES BASED ON HOW SAFE OR RISKY IT IS
TO USE ANTIBIOTICS DURING PREGNANCY.
Category A – No evidence of foetal harm.
Eg : Nystatin
Category B – No known association with birth defects
Eg : Amoxicillin, Augmentin, Metronidazole
Category C – Information only from animal studies
Eg : Bactrim, isoniazid, rifampin
Category D – Clear - cut problems
Eg : Tetracyclines, minocycline, sulfa drugs.
SPECIAL CONDITIONS-PREGNANCY

DRUG ADMINISTRATION DURING PREGNANCY
AND BREAST FEEDING :
Drug Use during
pregnancy
Risk Use during
Breast feeding
Antibiotics
Pencillins YES - YES
Erythromycin YES - Avoid
estolate form
- YES
Cephalosporins YES - YES
Tetracylines AVOID Tooth discoloration
inhibits bone
formation
Avoid
Metronidazole YES - YES
Clindamycin YES - YES

RENAL FAILURE
 Concentration-dependent antibiotics
Dosage interval should be increased
 Time-dependent antibiotics
Dose is decreased

ANTIMICROBIALS NEED DOSE
REDUCTION IN RENAL FAILURE
- Aminoglycosides
- Cotrimoxazole
- Cephalexin
- Carbenicillin
- Ethambutol
- Cefotaxime
- Vancomycin
- Norfloxacin
- Amphotenicin –B
- Metronidazole

DRUGS TO BE AVOIDED IN
CHRONIC RENAL FAILURE :
 Cephalothin
 Cephaloridine
 Talampicillin
 Tetracycline (except doxycline).

LIVER
 ATTENTION IN LIVER DISEASE :
 Antimicrobials to be avoided or used at lower dose in
liver disease are :
 Drugs to be avoided Dose reduction
needed
 Erythromycin estolate Chloramphenicol
Pyrazinamide Metronidazole Talampicillin
Clindamycin Tetracycline Isoniazid
Nalidixic acid Rifampin
Pefloxacin
 The biliary concentration of ampicillin may be significantly
reduced in patients with hepatic disease, rendering the
antibiotic less effective.

THE DIABETIC PATIENT
 Antibiotic prophylaxis.
 Amoxicillin is better choice.
 Uncontrolled diabetes.
 PRECAUTION;Gatifloxacilin- causes both
hypoglycemia and hyperglycemia.
 Compared with macrolides- Gatifloxacilin
4.3 times higher risk hypoglycemia
16.7times higher risk hyperglycemia

MANAGEMENT OF HEAD AND NECK
INFECTIONS IN THE IMMUNOCOMPROMISED
PATIENT :
 The immunocompromised host has a potential
risk for severe head and neck infections that
usually require aggressive antimicrobial therapy
and prolonged hospitalization.

Management steps
 Airway monitoring and possible surgical airway
establishment.
 Comprehensive history and physical examination.
 Obtaining appropriate laboratory and imaging studies.
 Empiric antimicrobial therapy.
 Surgical debridement and irrigation, as needed.
 Culture and antibiotic sensitivity testing of infectious
organisms to appropriately adjust antibiotic therapy.
 Close follow-up to monitor for resolution and
recurrence.

NEWER ANTIBIOTICS
1. MEROPENEN
 It is a beta-lactam, belongs to the subgroup of
carbapenem.
 Ultra broad spectrum injectable antibiotic.
 Inhibits bacterial cell wall synthesis.
 Action against gram positive and gram negative
bacteria and some anaerobic bacteria.
 Administered intravenously.

CLINICAL USES
 Cystic fibrosis
 Infections in immunocompromised patients.
 Intra abdominal infections.
 Urinary tract infections.
 Septicaemia.
 Skin infections
 ADVERSE EFFECTS :
Diarrhoea, Nausea, Vomiting, headache, rash,
thrombophlebitis.

2. CEFEPIME
 Fourth generation cephalosporin.
 Extended spectrum of activity against gram +ve and gram –ve
microbes compared to third generation cephalosporins.
 Administrated intramuscularly or intravenously dose – 1
gm to 2 gm every 12 hourly.
PHARMACOKINETICS :
 Peak plasma concentration after i.m. administration is 1.0 to
1.6 hour.
 It is distributed throughout the body tissues and fluids.
 Primarily excreted unchanged in urine.

USES
 Lower respiratory tact infections.
 Urinary tract infections.
 Skin and skin structure infections.
 Sepsis and bacteremia
 Febrile neutropenia
 Meningitis.
ADVERSE EFFECTS :
 Headache, nausea, vomiting, rash, diarrhoea,
dizziness.

3. QUINUPRISTIN /
DALFOPRISITIN (SYNERCID)
 Synercid is the brand name of combination of quinupristin and
dalfopristin antibiotics.
 These are semisynthetic pistinamycin derivatives.
 Active against methicillius sensitive staphylococcus aureus,
group A streptococci, Enterococcus faecium.
 500 mg strength of synercid contains 150 mg of quinupristin and 350
mg of Dalfopristin.
 Administration – intravenously.

USES
 In life threatening infections and certain skin
infections.
 Adverse effects :
 Pain, swelling and irritation at the injection site.
 Muscle and joint pain, nausea, vomiting, rash,
diarrhoea, headache, itching.

4. LINEZOLID
 New antibacterial drug belongs to class
oxazolidones.
 Inhibits protein synthesis – 70s ribosomes.
 Active against methicillin resistant and sensitive
staphylococci, and streptococci enterobacteria
faecalis.
 400 – 600 mg orally twice daily (12 hrly) parenteral
route for severely ill patients. Dosage is same as that
of oral route
 Metabolized by oxidation and hence can safely
used in renal failure.

5. MOXIFLOXACIN
 It is a synthetic fluoroquinolone agent.
 Inhibits topoisomerase II and IV, there by
affects the replication and repair of bacterial DNA.
 It is active against following organisms :
 Step. aureus, staph Epidermides, strepto
pneumonias, H. influenzae, Klebsiella,
Enterobacilus, mycobacterium, Bacillus anthracis.
 Administrated both oral and intravenous route.
 Dose : 400 mg daily orally or i.v. infusion.

USES
 Acute sinusitis.
 Acute exacerbation of chronic bronchitis.
 Pneumonia.
 Skin and skin structure infections.
 Second – line agent in T.B.
CONTRAINDICATIONS :
 Known hypersensitivity, in QT prolongation.
 Pregnancy and lactation.
SIDE EFFECTS :
 G.I. disturbances – Nausea vomiting anorexia, bloating.

6. GATIFLOXACIN
 It is a fourth generation fluro-quinolone
agent.
 Greater affinity for topoisomerase IV.
 Active against gram +ve cocci.
 Oral and intravenous route.
 Dose – 200 to 400 mg orally or i.v. once daily
(+½ shown)
 Active against – Streptococcus pneumonias.
 Chlamydia pneumonias.

INTERCALATING AGENTS
 The reversible inclusion of a molecule between two other
groups, most commonly seen in DNA
 Inhibits DNA replication in rapidly growing cells

ANTHRACYCLINES
 First anthracycline antibiotics were isolated
from Streptomyces peucetius in 1958
 Interact with DNA by intercalcation and
inhibit topsoimerase
 Some of the most effective cancer drugs
available
 Very wide spectrum

Common Anthracyclines
 Daunorubicin (Cerubidine)
 Doxorubicin (Adriamycin, Rubex)
 Epirubicin (Ellence, Pharmorubicin)
 Idarubicin (Idamycin)

DOX vs. DNR
 Daunomycin (DNR) for acute lymphocytic and myeloid
leukenmia
 Doxorubicin (DOX) for chemotherapy for solid tumors
including breast cancer, soft tissue sarcomes, and aggressive
lymphomas

MECHANISMS OF ACTION
 Disrupt DNA
 Intercalate into the base pairs in DNA minor grooves
 Inhibits topoiosomerase II enzyme, preventing the relaxing of
supercoiled DNA, thus blocking DNA transcription and replication
 Cause free radical damage of ribose in the DNA

Negative Effects
 Causes cardiotoxicity due to free radical
formation
 Interference with ryanodine receptors of the
sarcoplasmic reticulum in the heart muscle cells
 Free-radical formation in the heart
 Leads to forms of congestive heart failure, often
years after treatment
 Counteract with dexrazoxane

Bleomycins (BLM)
 Natural glycopeptidic antibiotics produced
by Streptomyces verticillus
 Efficacy against tumors
 Mainly used in therapy in a combination
with radiotherapy or chemotherapy
 Commonly administered as Blenoxane, a
drug that includes both bleomycin A2 and
B2.

History of Bleomycins
 First discovered in 1966 by Hamao Umerzawa
from Japan when screening cultures of S.
verticullus
 Launched in Japan by Nippon kayaku in 1969
 Initially marketed by Bristol-Myers Squibb
under brand name-Blenoxance

Mechanism
 Induction of DNA strand breaks
 Medicate DNA strand scission of single and
double strand breaks dependent on metal
ions and oxygen

Side effects
 Pulmonary fibrosis and impaired lung
function
 Age and dose related
 Capillary changes, atypical epithelial cells

Resistance to Anticancer
Agents
 Resistance mechanisms can operate to
 Prevent agents from entering cells, as in loss of
plasma membrane carriers for nucleoside analogs
 Enhance their extrusion, as exemplified by
energy-dependent pumps such as ABC
transporters

ANTIBIOTICS
NEEDED,NOT
NEEDED
WHAT TO DO
WHAT TO GIVE
HOW TO DOPROBLEMS OF
MISUSE

WHEN THE QUESTION OF USING ANTI
BIOTICS ARISES IN MAXILLOFACIAL
SURGERY????
 SURGICAL EXTRACTIONS
 SURGIAL MANAGEMENT OF LESIONS
 SPACE INFECTIONS
 TRAUMA
 ORTHOGNATHIC SURGERY
 OSTEOMYELITIS

[ ASIAN J OMFS : VOL 18 : NO. 4 : 272-278 ]
MOST ORAL INFECTIONS ARE ODONTOGENIC IN
ORIGIN
SEQUELAE OF DEEP CARIOUS LESION /
PERIODONTAL / PERICORONAL INFECTIONS
MANAGEMENT
EXTRACTION / ENDO TREATMENT
/ SURGICAL DRAINAGE
WITHOUT ANTIBIOTICS

CONCLUSION
UNCOMPLICATED EXTRACTION,SURGERIES
+
OTHERWISE HEALTHY
LOW INFECTION RATE
ANTIBIOTICS NOT NEEDED
[ JIDA VOL.69 : SEPT-DEC 1998 : 274 – 277]

CONCLUSION
 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.

 NEVER ACCEPT CONCEPT OF ANTIBIOTICS ON DEMAND
 NEVER USE A BROAD SPECTRUM ANTIBIOTICS WHEN NARROW
SPECTRUM IS INDICATED
 NO LONG COURSE OF ANTIBIOTICS
 NO NEED OF ANTIBIOTIC PROPHYLAXIS FOR SIMPLE SURGICAL
PROCEDURES or WHEN THERE IS LESS CHANCE OF POST
SURGICAL INFECTION
 WHEN NO SIGNS OF INFECTIONS SUCH AS
SWELLING,LYMPHADENOPATHY, ELEVATED TEMPERATURE
 ALWAYS MAKE SURE THE SOURCE OF INFECTION IS ELIMINATED-
EXTRACTION OF TOOTH
INCISION AND DRAINAGE

REFERENCES
 Medical pharmacology
- Satoskar
 Medical pharmacology.
- K.D. Tripathi.
 Contemporary oral and maxillofacial surgery.
- Lary J. Peterson 4th Edition.
 Pharmacology and therapeutics and dentistry.
- Yogiela Dowd Neidle
 OMFS Clin N Am -2003
 Oral and maxillofacial infections
Topazian
 Internet

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