RATIONAL USE OF ANTIBIOTICS

1. RATIONAL USE OF ANTIBIOTICS R. Anita Indriyanti Pharmacological Department Bandung Islamic University

2. References : 1. Lippincott’s Illustrated Reviews : Pharmacology, 2nd ed (Chapter 28) 2. Buku Pedoman Kuliah Farmakoklinik Farmakologi III Jilid 1 edisi 2 Prof. DR. Herri S. Sastramihardja, dr., SpFK

3. A medical doctor has to know the definite clinical pharmacology of antibiotics, how to select and use them rationally. 30% of inpatient individuals has been given antibiotics

4. Resistance Side effect Definition AB Ideal antibiotics In vitro Spectra Classification Chemical structures Mechanism of action

5. DEFINITION AB are chemical substances obtained from microbes/microorganisms (bacteria, fungi, actinomycetes) that able to inhibit or eradicate the growth of the other microorganisms. Antimicrobial all antiinfections semisynthetic synthetic nature  antibiotics

6. IDEAL ANTIBIOTICS CRITERIA • Most selective, most effective to infectied microorganisms • More bactericidal effect in the site of action • Antibacterial effect is not interfered by body fluid, exudate, plasma protein or enzymes and persist for a long duration in the blood • Minimal toxicity • Resistance develops slowly • Given by any route • Reachable cost

7. In vitro 1. Primary bacteriostatic effect  inhibit the growth of m.o Sulfonamide, tetrac, chloramph, erythromycin (low concentration), lincomycin, clindamycin and fusidic acid 2. Primary Bactericidal Effects  Eradicate/kill Pen, cef, aminoglic, erythromycin (high concentration), cotrimazol. Rifampisin and vankomycin. Those classification is not absolute but relative

8. SPECTRUM OF AB EFFECTS 1. Narrow spectrum antibiotics (NSAB) Main effect : sensitive for gram positive bacteria and bacil e.g. : Pen. G, Pen. Resistent penicillinase semisynthetics, bacitracin, macrolides, lincomycin, vancomycin 2. Broad Spectrum Antibiotics (BSAB) Main effect : sensitive for gram positive and gram negative bacteriae e.g. : Pen. (ampicillin and amoxycillin), cefalosporins, tetracyclins, chloramphenicol, trimetroprim and sulfonamides

9. Widely used of BSAB  an umbrella in treating the unidentified bacterial infection  resistance  RESISTANCE and MECHANISM OF ACTION recall in microbiology

10. SIDE EFFECTS • ALLERGIC REACTION • TOXIC REACTION Direct effects in unproper dose e.g. : aminoglycosides • SUPERINFECTION : new infection caused by pathogen microbes or fungi during AB therapy to primary infection. SUPERINFECTION : frequent potentially harmed risk Causa : Enterobacter, Pseudomonas, Candida and other fungi. Those agents are difficult to be eradicated by today available antibiotics.

11. AVOIDING SUPERINFECTION • Stop the giving antibiotics • Treatment according to bacterial identification and sensitivity test The specimen was taken from feces and secretion of upper respiratory tract, to be analyzed

12. RATIONAL THERAPY OF ANTIBIOTICS PHARMACOKINETICS PHARMACODINAMICS HOST ANTIBIOTICS

13. CHARACTERISTIC OF ANTIBIOTICS HOST ASPECTS BIOCHEMICAL & PHYSIOLOGICAL & PATHOLOGICAL CONDITIONS

14. DEFINITION OF RATIONAL USE OF ANTIBIOTICS (WHO) PROPER INDICATION PROPER DRUG PROPER DOSAGE SE MONITORING

15. Define the patient problems specify the therapeutic objectives Verify the suitable of your personal treatment Start the treatment Give information, instruction and warning Monitoring and stop treatment RATIONAL USE OF AB PROCEDURES STEPS TO PROCEDURES Clinical diagnosis Identification, sensitivity test of bacteria Pharmacodynamics Pharmacokinetics Host factors

16. RATIONAL USE OF ANTIBIOTICS PREVENTION IN HIGH SUSCEPTIBILITY TO GET INFECTION THERAPYERADICATING M.O DEFINITIVE THERAPY EMPIRIC THERAPY PROPHYLAXIS IN NON SURGICAL CONDITIONS IN SURGICAL CONDITIONS

17. DEFINITIVE THERAPY It is the most effective, least toxicity and the narrowest selection Based on : * identification of bacteria * sensitivity test * interpretation in the content of the overall clinical picture * the AB of choice directed to M.O

18. EMPIRIC AB THERAPY Giving AB directly without identification and sensitivity test of bacteria, but…… obtaining specimen for lab. analysis before giving AB. Empiric AB therapy based on local epidemiological data : • What is the pathogen M.O potentially infected • AB given based on susceptibility pattern • Initiated after obtaining specimen • Started with AM combination or single BSAB

19. SELECTING AB IN EMPIRIC THERAPY • The site of infection There are barriers inside the body : brain, prostate, bone Other : foreign bodies local factors • Patient’s history :

20. PATIENT HISTORY • Age  baby, child, adult, old age ! • Immune system  immunocompromised! Who? • Renal dysfunction  accumulation! How ? • Hepatic dysfunction metabolism! How ? • Genetic factors  G6-PD. Attention, contraindication ! • Pregnancy  teratogenic, embryogenic • Lactation  vulnerable AB for new born

21. INDICATION IN EMPIRIC THERAPY • Infection of unknown origin • Neutropenic patients • Characteristic symptoms of meningitis MISUSE of AB : • Treatment of untreatable infection • Therapy of fever of unknown origin • Improper dosage • Inappropiate reliance on AB alone • Lack of adequate bacterial information

22. STRATEGIC FOR EMPIRIC THERAPY Empiric therapy : Coverage by a combination of antibiotics such as Clindamycin plus gentamycin Effective against gram positive, gram negatives and anaerobes Or A single broad spectrum AB Such as imipenem/cilastatin Receive culture report With sensitivities If gram positive only if mixed ↓ ↓ Continue gram pos. continue therapy Coverage, discontinue as initiated Gram neg. and anaerobic Coverage If gram negative only If anaerobic only ↓ ↓ Continue gram neg. continue anaerobic coverage, coverage, discontinue discontinue gram positive Gram pos. and anaerobic and gram negative coverage Coverage Chapter 28, Fig.28.1 Lippincott’s ed.2nd

23. NON SURGICAL • PREVENT : • Streptococcal infection in patient with a history of RHD • In pre-dental extraction who have implanted prosthetic devices • TB/meningitis in close contact individual • Protect fetus from infection in HIV-infected pregnant woman PROPHYLAXIS SURGICAL • Contaminated op. • Clean – contaminated op • Selected op  may suffer post-op.infection

24. Common Error in AB prophylaxis • Selection of wrong AB • The initial therapy too early or too late • Excessive duration • Inappropriate use of BSAB

25. DISADVANTAGES TO PROPHYLACTIC AB • Toxic/allergic reaction • Superinfection with more resistant flora • The infection may be temporarily masked • Ecology of the hospital flora may be altered

26. COMMON CAUSES OF FAILURE OF AB THERAPY DRUGS : ө inappropriate drug ө inadequate dose ө improper route of administration ө accelerated inactivation ө poor penetration HOST : ө poor host defence ө undrained pus ө retained infected foreign bodies ө crusta/necrotic tissues

27. Cont. - Pathogen ө drug resistence ө superinfection ө dual infection initially - Laboratory : ө erroneous report of susceptible pathogen

28. AB – COMBINATION Synergisme (3) : 1) Blockade of sequential steps in a metabolit sequence - Trimethoprim - sulfamethoxazol 2) Inhibition of enzymatic inactivation - Amoxycillin - clavulanat 3) Enhancement - Aminoglycosides - Penicillins - Aminoglycosides

29. Antagonism (2) : 1. Inhibition of cidal activity by static agent - Tetracyclines – Betalactam AB 2. Induction of enzymatic inactivation - Ampicillin - Piperacillin

30. CLINICAL INDICATION OF AB COMBINATION : ► Mixed infection ► Synergism effect ► Risk of developing resistant organism < ► Increase AB coverage or ► Infection of unknown origin

31. DISADVANTAGES OF AB COMBINATION - Increase risk of toxicity - Increase MDR-pathogens - Increase cost - Increase antagonism (bacteriostatic + bactericide)

32. Thank You