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
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
1. Most selective, most effective to infectied
microorganisms
2. More bactericidal effect in the site of
action
3. Antibacterial effect is not interfered by
body fluid, exudate, plasma protein or
enzymes and persist for a long duration
in the blood
4. Minimal toxicity
5. Resistance develops slowly
6. Given by any route
7. 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
1. ALLERGIC REACTION
2. TOXIC REACTION
Direct effects in unproper dose e.g. :
aminoglycosides
3. 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
1. Stop the giving antibiotics
2. 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
ANTIBIOTICS HOST
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
THERAPY ERADICATING
M.O
DEFINITIVE THERAPY
EMPIRIC THERAPY
PROPHYLAXIS
IN NON SURGICAL CONDITIONS
IN SURGICAL CONDITIONS
PREVENTION IN HIGH
SUSCEPTIBILITY TO
GET INFECTION
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. PROPHYLAXIS
SURGICAL
1. Contaminated op.
2. Clean –
contaminated op
3. Selected op may
suffer
post-op.infection
NON SURGICAL
PREVENT :
1. Streptococcal infection in
patient with a history of
RHD
2. In pre-dental extraction
who have implanted
prosthetic devices
3. TB/meningitis in close
contact individual
4. Protect fetus from
infection in HIV-infected
pregnant woman
24. Common Error in AB prophylaxis
1. Selection of wrong AB
2. The initial therapy too early or too
late
3. Excessive duration
4. Inappropriate use of BSAB
25. DISADVANTAGES TO PROPHYLACTIC
AB
1. Toxic/allergic reaction
2. Superinfection with more resistant
flora
3. The infection may be temporarily
masked
4. 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
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)
