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ORAL &
MAXILLOFACIAL
SURGERY
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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.
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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:
Primarily Bacteriostatic Primarily
Bactericidal
Sulfonamides Penicillins , Cephalosporins,
Tetracyclines Aminoglycosides,
Chloramphenicol Vancomycin,
Erythromycin Ciprofloxacin, Isoniazid ,
Ethambutol Rifampin, Cotrimoxazole,
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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
Physical examination
DIFFERENCES BETWEEN
CELLULITIS AND ABSCESS
CHARACTERISTIC CELLULITIS ABSCESS
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
Scientifically - laboratory
Emperically – knowledge of
the pathogenesis & clinical
presentation.
Initial emperical therapy
instituted with a fair degree of reliability.
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PRINCIPLES FOR CHOOSING APPROPRIATE
ANTIBIOTIC
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Major pathogens of head and neck infections
TYPE OF INFECTION MICROORGANISMS
:2003
GROUP A BETA-HEMOLYTIC STREPTOCOCCI
STAPHYLOCOCCUS AUREUS
MORAHELLA CATARRHALIS
VIRUSES
FUNGAL ASPERGILLUS
RHIZOPUS SP. (MUCOR)
NOSOCOMIAL ENTEROBACTERIACEAE (ESPECIALLY
(ESPECIALLY IF PSEUDOMONAS, ACINETOBACTER,
INTUBATED) ESCHERICHIA COLI)
S. AUREUS
YEASTS (CANDIDA SPECIES)
PRINCIPLES FOR CHOOSING APPROPRIATE
ANTIBIOTIC
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PRINCIPLES FOR CHOOSING
APPROPRIATE ANTIBIOTIC
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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.
PRINCIPLES FOR CHOOSING APPROPRIATE
ANTIBIOTIC
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PRINCIPLES FOR CHOOSING APPROPRIATE
ANTIBIOTIC
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PRINCIPLES FOR CHOOSING APPROPRIATE
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
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PRINCIPLES FOR CHOOSING APPROPRIATE
ANTIBIOTIC
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PRINCIPLES FOR CHOOSING APPROPRIATE
ANTIBIOTIC
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PRINCIPLES FOR CHOOSING APPROPRIATE
ANTIBIOTIC
3. Faster results
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PRINCIPLES FOR CHOOSING APPROPRIATE
ANTIBIOTIC
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PRINCIPLES FOR CHOOSING APPROPRIATE
ANTIBIOTIC
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PRINCIPLES FOR CHOOSING APPROPRIATE
ANTIBIOTIC
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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
Dry socket
Mild pericoronitis
INDICATIONS OF EMPIRICAL
ANTIBIOTIC THERAPY :
The site and feature of the infection have been
well defined.
Proper dose.
Proper time interval.
Proper route of administration.
Combination antibiotic therapy.
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
Beta-lactams,vancomycin,aminoglycosides
Confined to ECF
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DRUG DOSE CALCULATION
BASED ON BODY SURFACE AREA
YOUNG’S FORMULA :
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.
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PRINCIPLES OF ANTIBIOTIC THERAPEUTIC DOSE
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PRINCIPLES OF ANTIBIOTIC THERAPEUTIC DOSE
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PRINCIPLES OF ANTIBIOTIC THERAPEUTIC DOSE
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COMBINATION ANTIBIOTIC THERAPY
Antibiotic antagonism
Reduced dose for each
agent. Increased financial costs
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FACTORS INFLUENCING
MECHANISM :
Is the time necessary to recover from
sublethal structural and metabolic alterations that
prevents resumption of bacterial regrowth.
FACTORS INFLUENCING PAE
5) CARDIAC EFFECTS
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
9.Antibiotic resistance
11.Antibiotic antagonism
MISUSE OF ANTIBIOTICS
Natural Resistance
Acquired Resistance
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DEVELOPMENT OF DRUG RESISTANCE
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DEVELOPMENT OF DRUG RESISTANCE
(ii) Transduction:-
(iii) Transformation:-
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.
Type IV. Dirty and infected wounds. Confirmed infection rate of above 26%.
These always need adequate antibiotic treatment.
PRINCIPLE 2: TO CHOOSE CORRECT
ANTIBIOTIC
4.Bactericidal antibiotic
PRINCIPLE 3: ANTIBIOTIC
PLASMA LEVEL MUST BE HIGH
GOALS :
1.To reduce the intensity of bacteremia.
Bactericidal
Little or no toxicity
CLASSIFICATION OF PENICILLIN
I) Natural penicillins :
Penicillin G (Benzyl penicillin)
IV) Penicillins effective against gram +ve and some gram –ve
organisms :
Ampicillin
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
b)Jarisch-Herxheimer reaction
PROCEDURE:
1) Epcutaneous or (scratch or prick)
2) Intradermal test
DESENSITIZATION IN PENCILLIN
ALLERGIC PATIENTS
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.
Ototoxicity
Nephrotoxicity
Mechanism
Interfere with the activity of DNA
gyrase.
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.
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.
Concentration-dependent antibiotics
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 :
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)
Administration – intravenously.
USES
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
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
ANTIBIOTICS
WHAT TO DO
WHAT TO GIVE
PROBLEMS OF HOW TO DO
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 ]
MANAGEMENT
Medical pharmacology.
- K.D. Tripathi.