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. 30% of inpatient individuals has been given antibiotics
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. AB Resistance Side effect Definition 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
HOST
ANTIBIOTICS
PHARMACOKINETICS
PHARMACODINAMICS

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

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

15. RATIONAL USE OF AB PROCEDURES STEPS TO PROCEDURES
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
Clinical diagnosis
Identification, sensitivity test of bacteria
Pharmacodynamics
Pharmacokinetics
Host factors

16. RATIONAL USE OF ANTIBIOTICS
PREVENTION IN HIGH SUSCEPTIBILITY TO GET INFECTION
THERAPY ERADICATING
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
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
Chapter 28, Fig Lippincott’s ed.2nd

23. PROPHYLAXIS SURGICAL Contaminated op. NON SURGICAL
Clean – contaminated op
Selected op  may suffer
post-op.infection
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

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