Dr. NAFRIALDI, PhD, SpPD, SpFK

Transcription

1 Dr. NAFRIALDI, PhD, SpPD, SpFK Lahir: Bukittinggi, 30 Oktober Pendidikan Dokter Umum: FKUI, 1986 S2 Farmakologi: Universite Claude Bernard, Lyon, Perancis, 1991 S3 Farmakologi: Universite Montpellier, Perancis, 1994 Spesialis Penyakit Dalam: FKUI, 2005 Pekerjaan Staf Pengajar Departemen Farmakologi FKUI Deputy Chief Editor Medical Journal of Indonesia Editorial Board Member, Acta Medica Indonesiana Sekretaris Komite Etik Penelitian FKUI-RSCM 1

2 Principles of Rational Antibiotic Use Dr. NAFRIALDI, SpPD, PhD, SpFK Departemen Farmakologi FKUI, Jakarta 2

3 Introduction Antibiotics are the most important weapons for the treatment of many infectious diseases caused by bacteria. However, irrational use will lead to: Selection of drug resistant organism Interference of normal flora Increased incidence of side effects Increased cost 3

4 Rational Use of Medicine Patients receive medications: appropriate to their clinical needs INDICATION, in doses that meet their own individual requirements proper DOSAGE, for an adequate period of time proper DURATION, and at the lowest cost to them and their community 4

5 Rational Use of Antibiotic Proper Indication Proper dosage Proper duration Lowest cost Other considerations: Proper drug choice Proper route of administration Proper timing of administration 5

6 RATIONAL IRRATIONAL There is no clear cut between rational and irrational drug use 6

7 Exemples of Irrational AB Use Using AB without clear indication AB for viral infection (mumps, faringitis, acute diarrhea, dengue fever) Reliance of AB use on laboratory results, without adequate clinical background: AB use based on Widal test AB use for reactive leukocytosis (colic pain, MCI, stroke) 7

8 Exemples of Irrational AB use Neglecting other factors Foreign body, pus, necrotic tissue AB combinations or broad spectra as a cover for diagnostic imprecision Inappropriate AB combination Early AB treatment for FUO 8

9 Types of AB use Empirical Without microbiolgic data Definitive Based on culture and sensitivity test Prophylaxis: Surgical Non surgical 9

10 Empirical AB Use Use of AB without microbiology and sensitivity data The most commonly used The most common misused Needs local updated sensitivity pattern Important in severe condition Live saving AB combination may be needed It is important to take culture specimen before AB administration. 10

11 Considerations in Using AB 1. Is an AB really indicated? 2. What is the most appropriate AB? 3. What dose, frequency, route and duration? 4. What is the aim of AB treatment? Empirical, definitive, prophylaxis 5. When to use antibiotic combination 11

12 1. Is an AB really indicated? Antibiotic is useful only for the treatment of bacterial infections Fever is commonly use as indicator Not all fevers are due to infection Not all infections are due to bacteria Not all bacterial infections require antibiotics In patients with viral infection, there is no evidence that AB will prevent secondary infection 12

13 2. What is the most appropriate AB? Depends on: Etiologic agent Identification Sensitivity Patient factors Immune status Comorbid, organ dysfunction Drug factors PK-PD 13

14 Etiologic Agent What organism are most likely? Gram staining may give rapid clue Bacterial culture should give definitive answer What organ system involve URTI: mostly gram positive Pulmonary: H. influenzae, S. pneumoniae Skin, cellulitis: mostly gram positive Urinary and GI: usually gram negative Hospital or Community acquired? Hospital acquired: gram negative, MRSA, VRE, pseudomonas, highly resistant microbe 14

15 Etiologic Agent Importance of local resistance data Resistance patterns vary From country to country From hospital to hospital in the same country From unit to unit in the same hospital 15

16 Etiologic Agent Laboratory results Was the specimen properly collected? How to interpret the result? The isolated microbial is not necessarily the causative pathogen Is it a contaminant/coloniser or is it the causative agent? 16

17 Patient factors Physiological factors Age: Neonates, children,young adult, elderly Immune status Immuno competent Immuno compromized: DM, HIV, longterm steroid treatments Comorbid liver disease, kidney dysfunction 17

18 Other factors Local factors may affect the AB activity Pus, can bind drugs or inhibit drug action Low ph in infected sites and anaerobic condition Foreign body Prosthetic materials promotes a bacterial biofilm favor bacterial persistence frequent relapses 18

19 3. What dose, frequency, route and duration? Depends on: PK-PD of AB Killing pattern Concentration dependent Time dependent 19

20 Pharmacokinetic-Pharmacodynamic (PK-PD) Parameters CONC. Cmax Concentration-dependent killing Cmax/MIC required > 10 x Time-dependent killing Time above MIC required: > 40% Area Under the Curve MIC Time Time above MIC 20

21 Killing patterns of AB Concentration-dependent killing High Cmax/MIC ratio is important High single dose may be better than devided doses Exp: aminoglycoside, quinolones Time-dependent killing Duration of exposure (T > MIC and AUC24/MIC ratio) are important Prolonged infusion is better Exp: penicillins, cephalosporins 21

22 Antimicrobial Combination Aims: To have synergistic effect in specific infection (endocarditis, Ps aeruginosa, H influenzae). To retard the emergence of resistant microorganism (in TB, H. pylori infection) Indications Empirical therapy in severe infection HAP due to P. aeruginosa Meningitis Febrile neutropenia, sepsis Intra-abdominal abcess Polymicrobial infection 22

23 Etiologic Considerations Agent in AB combination Different mechanisms of action B-lactam + aminoglycoside B-lactam + macrolide or quinolone Different spectrum (gr+, gr -, anaerobic) Sinergistic AB combination may have additive toxicity (Vanco + aminoglycoside) Avoid long-term combination for empirical treatment Be cost sensitive 23

24 Disadvantages of AB Combination Increase risk of toxicity Selection of multiple-drug resistant microorganisms Eradication of normal host flora with subsequent superinfection Increase cost to patients Possibility of antagonistic effect 24

25 Non-surgical AB PROPHYLAXIS Streptococcal infection in patient with a history of RHD Before dental extraction in patients with implanted prosthetic devices Prophylaxis of TB, PCP, in HIV-infected patients In patients with viral infection, there is no evidence that AB will prevent secondary infection 25

26 AB prophylaxis Surgical Clean-contaminated prophylaxis Contaminated treatment Selected surgical cases (cardiac, ophtalmic, brain) prophylaxis 26

27 AB prophylaxis Use 1 st or 2 nd generation cepalosporins. If anaerobic bacteria is suspected, metronidazole may be added The use of 3 rd and 4 th generation cephalosporin, carbapenem, and quinolones, is not recomanded. 27

28 Surgical AB Prophylaxis AB must be present at wound site at the time of its closure The drug must be given IV within minutes before incision Another one dose for prolong procedure (> 3h) or if bleeding > 1500 ml. The AB must be active against the most likely contaminating microorganisms Use beyond 24 hour is unnecessary 28

29 GYSSEN CRITERIA FOR QUALITY of AB USE 29

30 Gyssen s algorythm 30

31 Gyssens category for Quality of AB Use VI. Insufficient information stop V. Unjustified Indication stop IV. Inappropriate AB choice due to availability of: More effective alternative (IV a) Less toxic alternative (IV b) Less expensive alternative (IV c) Narrower spectrumalternative (IV d) III. Inappropriate duration (too long (IIIa); too short (IIIb) II. Improper dosage (IIa), interval (IIb), route (IIc) I. Improper timing 0. Appropriate use of AB therapy/prophylaxis 31

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