Introduction to AntibioticsIntroduction to Antibiotics

Prof. Mohammad AlhumayydProf. Mohammad AlhumayydPharmacology DepartmentPharmacology Department

Definition of AntibioticsDefinition of Antibiotics

Chemical substances produced by various Chemical substances produced by various microorganisms ( bacteria, fungi, actinomyctes) microorganisms ( bacteria, fungi, actinomyctes) that have the capacity to inhibit or destroy that have the capacity to inhibit or destroy other microorganisms.other microorganisms.

Now a day they are chemically synthesized.Now a day they are chemically synthesized.

They either kill bacteria(bactericidal) or keep They either kill bacteria(bactericidal) or keep more bacteria from growing(bacteristatic).more bacteria from growing(bacteristatic).

Antibiotics will not cure infections caused by Antibiotics will not cure infections caused by viruses.viruses.

CLASSIFICATION OF ANTIBIOTICSCLASSIFICATION OF ANTIBIOTICSACCORDING TO ACCORDING TO MECHANISM OF ACTIONMECHANISM OF ACTION

INHIBITION OF CELL WALLINHIBITION OF CELL WALL SYNTHESIS SYNTHESIS e.g. e.g. Penicillins Penicillins

INHIBITION OFINHIBITION OF PROTEIN PROTEIN SYNTHESISSYNTHESIS e.g.e.g. MacrolidesMacrolides

INHIBITION OF NUCLEIC ACIDINHIBITION OF NUCLEIC ACID SYNTHESIS SYNTHESIS e.g. e.g. Quinolones.Quinolones.

According to spectrumAccording to spectrum

Narrow spectrum , e.g.:Narrow spectrum , e.g.:

penicillin G penicillin G , , aminoglycosidesaminoglycosides

Broad spectrum , e.g.:Broad spectrum , e.g.:

ampicillin ,ampicillin , amoxicillinamoxicillin

Choice of AntibioticChoice of Antibiotic

A)A)Clinical diagnosisClinical diagnosis (e.g.,syphylis)(e.g.,syphylis)

B)B)MicrobiologicalMicrobiological information information

C)C)Pharmacological Pharmacological consideration consideration

B)B)Bacteriological informationsBacteriological informations

AdvantagesAdvantages The exact antibiotic to be usedThe exact antibiotic to be used The most effective and reject the one The most effective and reject the one

with little or no activitywith little or no activity The least toxicThe least toxic The cheapestThe cheapest

DisadvantagesDisadvantages Occasionally these tests do not parallel in vivo Occasionally these tests do not parallel in vivo

sensitivity sensitivity do not take in consideration certain sites of do not take in consideration certain sites of

infectioninfection some bacteria cannot be cultivated or take time some bacteria cannot be cultivated or take time

to grow to grow ( e.g. M. Leprae, M. Tuberculosis )( e.g. M. Leprae, M. Tuberculosis ) Bacteriological services are not available at all Bacteriological services are not available at all

hospitals hospitals

Choice of Antibiotics(cont.)Choice of Antibiotics(cont.)

C)C)Pharmacological considerationPharmacological consideration 1. Site of1. Site of infection infection 2. Host factors2. Host factors a) Immune system e.g. Alcoholism, diabetes, HIV, a) Immune system e.g. Alcoholism, diabetes, HIV, malnutrition, advanced age- malnutrition, advanced age- ((higher than usual doses or higher than usual doses or longer courses are required ).longer courses are required ).

b) Genetic factorsb) Genetic factors e.g. Patients with G-6-PD deficiency treated with e.g. Patients with G-6-PD deficiency treated with sulfonamides and chloramphenicol sulfonamides and chloramphenicol (Hemolysis ) (Hemolysis )

Choice of Antibiotics ( Cont.)Choice of Antibiotics ( Cont.)

c) Pregnancy and Lactationc) Pregnancy and Lactation Aminoglycosides- Aminoglycosides- (( hearing losshearing loss)) Tetracyclines- Tetracyclines- ((bone deformity)bone deformity) d) Age of the patientd) Age of the patient e.g. Grey baby Syndrome- e.g. Grey baby Syndrome- ((chloramphenicol )chloramphenicol )

e) Renal function e) Renal function e.g. Aminoglycosides e.g. Aminoglycosides (( renal failure )renal failure )f)Liver functionf)Liver function e.g. Erythromycine.g. Erythromycin( hepatic failure ( hepatic failure ))

g) Poor perfusiong) Poor perfusion e.g. Lower limbs of diabeticse.g. Lower limbs of diabetics

Choice of Antibiotics ( Cont.)Choice of Antibiotics ( Cont.)

3. Drug Allergy3. Drug Allergy

4. Potential Side Effects 4. Potential Side Effects ((Drug safetyDrug safety))

Chloramphenicol Chloramphenicol (( a plastic anaemia)a plastic anaemia)

Fluoroquinolones in children&Preg. Fluoroquinolones in children&Preg.

(( tendon damage )tendon damage )

5.5. The cost of therapyThe cost of therapy

Bacterial ResistanceBacterial Resistance

Mechanism of Bacterial resistance:Mechanism of Bacterial resistance:

Inactivation of antibiotics by enzymes Inactivation of antibiotics by enzymes produced by bacteriaproduced by bacteriaReduced bacterial permeability to Reduced bacterial permeability to antibiotics antibioticsBacteria develops an altered receptor for Bacteria develops an altered receptor for the drug the drug Bacterial MutationBacterial Mutation

Prevention of ResistancePrevention of Resistance

*Use antibiotics only when absolutely required*Use antibiotics only when absolutely required

*Use antibiotics in adequate dosage for sufficient *Use antibiotics in adequate dosage for sufficient period of time period of time

Not too brief therapyNot too brief therapy

Not too prolonged therapyNot too prolonged therapy

( exceptions, e.g. TB )( exceptions, e.g. TB )

*Combination of antibiotics may be required to *Combination of antibiotics may be required to delay resistance ( e.g. TB ) delay resistance ( e.g. TB )

General Principles of ChemotherapyGeneral Principles of Chemotherapy

Administer drug in Administer drug in full dosefull dose, at , at proper intervalproper interval and by the and by the bbest routeest route

When apparent cure achieved , continue antibiotic for When apparent cure achieved , continue antibiotic for about 3 days further to avoid relapse about 3 days further to avoid relapse

Skipping doses may decrease effectiveness of antibiotic & Skipping doses may decrease effectiveness of antibiotic &

increase the incidence of bacterial resistance.increase the incidence of bacterial resistance.

General Principles of Chemotherapy(cont)General Principles of Chemotherapy(cont)

Two or more antimicrobials should not be used without good Two or more antimicrobials should not be used without good reason, e.g.: reason, e.g.:

Mixed bacterial (polymicrobial) infectionsMixed bacterial (polymicrobial) infections Desperately ill patient of unknown etiologyDesperately ill patient of unknown etiology To prevent emergence of resistance (e.g. TB )To prevent emergence of resistance (e.g. TB ) To achieve synergismTo achieve synergism eg.piperacillin+gentamicin(p. aeruginosae) eg.piperacillin+gentamicin(p. aeruginosae) Disadvantages of multiple antibioticsDisadvantages of multiple antibiotics Increased risk of sensitivity or toxicityIncreased risk of sensitivity or toxicity Increased risk of colonization with a resistant Increased risk of colonization with a resistant bacteriabacteria Possibility of antagonismPossibility of antagonism Higher costHigher cost

General principles ( Cont. )General principles ( Cont. )

In some infections bacteriological proof of cure isIn some infections bacteriological proof of cure is desirable ( e.g. TB, UTI )desirable ( e.g. TB, UTI ) Measurement of plasma conc. of antibiotics is seldomMeasurement of plasma conc. of antibiotics is seldom needed, except. streptomycin in renal TB; I.M needed, except. streptomycin in renal TB; I.M gentamicingentamicin

Indications for antibiotics Indications for antibiotics prophylaxisprophylaxis

Surgical prophylaxisSurgical prophylaxis bowel surgery, joint replacement, and some gynecological interventionsbowel surgery, joint replacement, and some gynecological interventions to prevent postoperative infections. to prevent postoperative infections.

Immunosuppressed PatientsImmunosuppressed Patients Very old, very young Very old, very young Diabetics, Anaemics, AIDS pts ,Cancer pts. Diabetics, Anaemics, AIDS pts ,Cancer pts.

Dental extractionsDental extractions Pts with total joint replacementsPts with total joint replacements Pts with cardiac abnormalitiesPts with cardiac abnormalities

MISUSES OF ANTIBIOTICSMISUSES OF ANTIBIOTICS

Treatment of untreatable infections ( wrong Treatment of untreatable infections ( wrong diagnosis)diagnosis)

e.g. viral infectionse.g. viral infections Improper dosage.Improper dosage. Therapy of fever of unknown origin.Therapy of fever of unknown origin. Presence of pus or necrotic tissues , or blood Presence of pus or necrotic tissues , or blood

at the surgical site at the surgical site Excessive use of prophylactic antibiotics inExcessive use of prophylactic antibiotics in

travelers.travelers. Lack of adequate bacteriological Lack of adequate bacteriological

information. information.