Introduction to Antibiotics 1 st yr( Respiratory block) Prof. Azza Elmedany

Definition of Antibiotics Chemical substances produced by various microorganisms that have the capacity to inhibit or destroy other microorganisms Nowaday they are chemically synthesized drugs. Antibiotics will not cure infections caused by viruses.

CLASSIFICATION OF ANTIBIOTICS ACCORDING TO MECHANISM OF ACTION INHIBITION OF CELL WALL SYNTHESIS e.g. β -lactam : Penicillins, cephalosporins, carbapenems INHIBITION OF CELL WALL SYNTHESIS e.g. β -lactam : Penicillins, cephalosporins, carbapenems Others : Vancomycin, cycloserine Others : Vancomycin, cycloserine INHIBITION OF PROTEIN SYNTHESIS e.g. Mcrolides, Tetracyclines INHIBITION OF PROTEIN SYNTHESIS e.g. Mcrolides, Tetracyclines INHIBITION OF NUCLEIC ACID SYNTHESIS e.g. Quinolones. INHIBITION OF NUCLEIC ACID SYNTHESIS e.g. Quinolones.

Classification of antimicrobial agents ( Cont.) Inhibition of essential enzymes of folate metabolism e.g. : Trimethoprim, sulfonamides Inhibition of essential enzymes of folate metabolism e.g. : Trimethoprim, sulfonamides Inhibition of nucleic acid metabolism by inhibiting RNA polymerase e.g. : Rifampin Inhibition of nucleic acid metabolism by inhibiting RNA polymerase e.g. : Rifampin

Classification According to spectrum Narrow spectrum, e.g.: Narrow spectrum, e.g.: penicillin G, aminoglycosides penicillin G, aminoglycosides Broad spectrum, e.g.: Broad spectrum, e.g.: ampicillin, amoxicillin ampicillin, amoxicillin

Choice of Antibiotics A) Clinical diagnosis ( e.g. syphils) B) Microbiological information C) Pharmacological consideration

B) Bacteriological information Advantages Advantages 1) The exact antibiotic to be used, through studying the sensitivity of the infecting organisms to antibiotics 2) The most effective & reject the one with little or no activity 3) The least toxic 4) The cheapest

Disadvantages 1) Occasionally these tests do not parallel in vivo sensitivity 2) Do not take in consideration certain sites of infection 3) Some bacteria can not be cultivated or take time to grow ( M. leprae, M. tuberculosis ) 4) Bacteriological services are not available at all hospitals

C) Pharmacological consideration 1) Patient factors 1) Patient factors a)Immune status ( Alcoholism, diabetes, HIV) a)Immune status ( Alcoholism, diabetes, HIV) b)Genetic factors b)Genetic factors Patients with G-6-PD deficiency with Patients with G-6-PD deficiency with sulfonamides or chloramphenicol

Choice of Antimicrobials ( Cont.) c) Pregnancy and Lactation ( contraindicated) Aminoglycosides ( hearing loss ) Tetracyclines ( bone deformity ) d) Age Old patients tend to have decreased renal functions; infants have poorly detoxification mechanisms e) Renal Disease ( contraindicated) e.g. Aminoglycosides ( renal failure ) f) Hepatic disease ( contraindicated) e.g. Erythromycin ( hepatic failure )

( Cont.) ( Cont.) 2- Drug Factors a - Site of infection b - Mode of administration c - Potential Side Effects (Drug safety) Chloramphenicol ( a plastic anaemia) Flouroquinolones ( cartilage damage ) d - The cost of therapy

MISUSES OF ANTIBIOTICS  T T T Treatment of untreatable infections e.g. viral infections  I I I Improper dosage.  T T T Therapy of fever of unknown origin.  P P P Presence of pus or necrotic tissues, or blood at the surgical site  E E E Excessive use of prophylactic antibiotics in travelers.  L L L Lack of adequate bacteriological information.

Mechanisms of Acquired Antibiotic Resistance Inactivation of the drug Inactivation of the drug Bacterial β-lactamase inactivates penicillins & cephalosporins by cleaving the β-lactam ring of the drug. Bacterial β-lactamase inactivates penicillins & cephalosporins by cleaving the β-lactam ring of the drug.  Mutation of the target Bacteria synthesize modified targets against which the drug has no effect ( B- Streptococcus can develop resistance to erythromycin) Bacteria synthesize modified targets against which the drug has no effect ( B- Streptococcus can develop resistance to erythromycin)

Continue Prevention of the drug from entering the cell by decreasing permeability of the cell Prevention of the drug from entering the cell by decreasing permeability of the cell Actively transporting the drug out of the cell Actively transporting the drug out of the cell

Prevention of bacterial resistance Use antibiotic only when absolutely required Use antibiotics in adequate dosage for sufficient period of time Combination of antibiotics may be required to delay resistance

General Principles of Chemotherapy  A A A Administer drug in full dose, at proper interval and by the best route  W W W When apparent cure achieved-continue for about 3 days further to avoid relapse SSSSkipping doses may decrease effectiveness of antibiotics & increase the incidence of bacterial resistance

Cont.  T T T Two or more antimicrobials should not be used without good reason, e.g.: Ill patient of unknown etiology To prevent emergence of resistance (e.g. TB ) To achieve synergism e.g. piperacillin+ gentamicin (p. aeruginosae)

Cont.  In some infections bacteriological proof of cure is desirable  Measurement of plasma conc. Of antibiotics is seldom needed, except in some conditions such as streptomycin in renal TB.

Indications for antibiotics prophylaxis Is recommended for patients undergoing procedures that will cause bacteremia : a- Surgical prophylaxis bowel surgery, joint replacement, gynecological intervention bowel surgery, joint replacement, gynecological intervention b- Dental extraction In patient with joint replacement or with prosthetic heart valves or history of bacterial endocarditis In patient with joint replacement or with prosthetic heart valves or history of bacterial endocarditis

Continue “Indications for antibiotics prophylaxis “ Immunosuppressed patients very old, very young, diabetic, cancer very old, very young, diabetic, cancer