2. DEFINITION Chemical substances produced by various microorganisms ( bacteria, fungi, actinomycetes ) that have the capacity to inhibit or destroy other microorganisms. They either kill bacteria(bactericidal) or keep more bacteria from growing(bacteriostatic). Antibiotics will not cure infections caused by viruses.

3. HISTORICAL BACKGROUND Discovery of sulfonamides in 1935 by Domagk Clinical use of sulfonamides in 1936 Discovery of penicillin in 1928 by A. Fleming Purification of penicillin by H.Flory&E.chain(1940) Production of penicillin in 1941 Antibiotics are the 2nd most commonly used drugs They cost approx. $15 billion /year ( U.S. ). 25%-40% of hospitalized pts receive one or more courses of antibiotics ( China 79% ) In the west, 30% of drug prescription for out-pts are for antibiotics, more than 70% in China. They become among the most misused drugs.

4. Misuses of Antibiotics 50% of antibiotic use is inappropriate 7 out of 10 Americans receive antibiotics for common cold >90% of Antibiotics are available w/out prescriptions in 3rd world countries Some types of bacteria in Asia no longer respond to 1st line drugs (WHO). Resistance rates in several Asian countries are the highest in the world (WHO). Some physicians are given financial incentives to prescribe Antibiotics are used as growth promoters in animals.

5. MISUSES OF ANTIBIOTICS A consequence of many factors: 1- Availability of a very wide selection 2- Limitation of physician’s time 3- Physician shortage and expenses 4- Availability without prescription in pharmacies 3- Public demand ( pressure to prescribe ) 4- Pts do not take them according to their doctor’s instructions. 5- Some pts save unused antibiotics for another illness, or pass to others.

6. MISUSES OF ANTIBIOTICS 1- Treatment of untreatable infections e.g. viral infections 2- Improper dosage 3- Therapy of fever of unknown origin 4- Reliance on chemotherapy with omission of surgical drainage 5- Lack of adequate bacteriological informations

8. Antibiotic Prescription Clinical situation Microbiological information Pharmacological consideration

9. Bacteriological informations Advantages 1- The exact antibiotic to be used 2- The most effective and reject the one with little or no activity 3- The least toxic 4- The cheapest

10. Disadvantages 1- Occasionally these tests do not parallel invivo sensitivity 2- do not take in consideration certain sites of infection 3- some bacteria cannot be cultivated or take time to grow ( e.g. M.Leprae, M. Tuberculosis ) 4. Bacteriological services are not available at all hospitals

11. BACTERIAL RESISTANCE Definition Conc of drug required to inhibit or kill the bacteria is greater than the conc that can safely be achieved in the plasma. Examples

12. Mechanism of Antibiotic Resistance Mechanism of Antibiotic Resistance 1. Inactivation by enzyme produced by bacteria 2. Reduced bacterial permeability to antibiotic 3. Bacteria develops an altered receptor for the drug 4. Bacteria develops an altered metabolic pathway 5. Bacteria develops an altered enzyme

13. Prevention of Resistance *Use antibiotics only when absolutely required *Use only in adequate dosage for sufficient period of time Not too brief therapy Not too brief therapy Not too prolonged therapy Not too prolonged therapy ( exceptions, eg. TB ) ( exceptions, eg. TB ) *Combination of antibiotics may be required to delay resistance ( eg. TB )

14. Choice of Antimicrobial Drugs 1. Clinical diagnosis eg. Syphilis 2. Bacteriological identification a) infecting organism is not identified.eg.bronchopneumonia, UTIs,meningitis. b) infecting organism is identified but sensitivity to antibiotic isn’t known e.g. T.B 3. Site of infection

15. Choice of Antimicrobials ( Cont.) 4. Host factors a) Genetic factors eg. Patients with G-6-PD deficiency treated with sulf. and chloramphenicol--- Hemolysis b) Pregnancy and Lactation Aminoglycosides- hearing loss in the child Tetracyclines- injury to the developing teeth( child ) Fatal acute fatty necrosis of the liver ( preg. Mother ) c) Age of the patient eg. Grey baby Syndrome-chloramphenicol Discolouration of teeth-tetracycline d) Renal function eg. Aminoglycosides, Vancomycin in renal failure e)Liver function eg. Erythromycin, Chloramphenicol in hepatic failure

16. Choice of Antimicrobials ( Cont.) 5. Drug Allergy 6. Potential Side Effects Chloramphenicol ( a plastic anaemia) Tetracyclines in children (dental discol.) Flouroquinolone in children &pregnancy ( tendon dammage )

17. General Principles of Chemotherapy 1. Administer drug in full dose, at proper interval and by the best route 2. Apparent cure achieved-continue for about 3 days further to avoid relapse ( exception TB and bacterial endocarditis ) 3. Skipping doses may decrease effectiveness of treatment & increase the likelihood of bacterial resistance. 4. Two or more antimicrobials should not be used without good reason, eg.: Mixed bacterial infections Desperately ill patient of unknown etiology To delay emergence of resistance (eg. TB ) To achieve synergism eg.piperacillin+gentamicin(p.aeruginosae)

18. General principles ( Cont. ) Disadvantages of multiple antibiotics Increased risk sensitivity or toxicity Increased risk of colonization with a resistant bacteria Possibility of antagonism Higher costs 4. In some infections bacteriological proof of cure is desirable ( eg. TB, UTI ) 5. Measurement of plasma conc. of antibiotics is seldom needed, except.streptomycin in renal TB; I.M gentamicin

19. Indications for antibiotics prophylaxis Surgical prophylaxis To prevent postoperative infections To prevent postoperative infections Immunosuppressed Patients Very old, very young Very old, very young Diabetics Diabetics Anaemics Anaemics AIDS pts AIDS pts Cancer pts Cancer pts Dental procedures Pts with total joint replacements Pts with total joint replacements Pts with cardiac abnormalities Pts with cardiac abnormalities To prevent bacterial endocarditis To prevent bacterial endocarditis

20. Reasons for failure of chemotherapy 1. Wrong diagnosis 2. Wrong choice of drug 3. Wrong dose 4. Development of resistance 5. Infection with more than one organism 6. Presence of pus