Transcript RATIONAL USE OF ANTIBIOTICS

RATIONAL USE OF
ANTIBIOTICS
R. Anita Indriyanti
Pharmacological Department
Bandung Islamic University
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
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
Side effect
Definition
In vitro
Resistance
Ideal antibiotics
AB
Classification
Spectra
Chemical structures
Mechanism of action
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
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
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
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
Widely used of BSAB  an umbrella in
treating the unidentified bacterial
infection
 resistance 
RESISTANCE and
MECHANISM OF ACTION
recall in
microbiology
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.
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
RATIONAL THERAPY OF ANTIBIOTICS
ANTIBIOTICS
HOST
PHARMACOKINETICS
PHARMACODINAMICS
CHARACTERISTIC
OF ANTIBIOTICS
HOST ASPECTS
BIOCHEMICAL &
PHYSIOLOGICAL &
PATHOLOGICAL
CONDITIONS
DEFINITION OF RATIONAL USE OF
ANTIBIOTICS (WHO)
PROPER INDICATION
PROPER DRUG
PROPER DOSAGE
SE MONITORING
RATIONAL USE OF AB
Define the patient problems specify the
therapeutic objectives
PROCEDURES
Verify the suitable of your personal
treatment
Start the treatment
Give information, instruction and warning
Monitoring and stop treatment
Clinical diagnosis
STEPS TO PROCEDURES
Identification, sensitivity test of
bacteria
Pharmacodynamics
Pharmacokinetics
Host factors
RATIONAL USE OF ANTIBIOTICS
PREVENTION IN HIGH
SUSCEPTIBILITY TO
GET INFECTION
THERAPY
M.O
ERADICATING
DEFINITIVE THERAPY
EMPIRIC THERAPY
PROPHYLAXIS
IN NON SURGICAL CONDITIONS
IN SURGICAL CONDITIONS
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
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
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 :
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
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
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
↓
Continue gram pos.
Coverage, discontinue
Gram neg. and anaerobic
Coverage
If gram negative only
↓
Continue gram neg.
coverage, discontinue
Gram pos. and anaerobic
Coverage
if mixed
↓
continue therapy
as initiated
If anaerobic only
↓
continue anaerobic coverage,
discontinue gram positive
and gram negative coverage
Chapter 28, Fig.28.1 Lippincott’s ed.2nd
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
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
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
COMMON CAUSES OF FAILURE OF AB
THERAPY
DRUGS : ө
ө
ө
ө
ө
inappropriate drug
inadequate dose
improper route of administration
accelerated inactivation
poor penetration
HOST :
poor host defence
undrained pus
retained infected foreign bodies
crusta/necrotic tissues
ө
ө
ө
ө
Cont.
- Pathogen
ө drug resistence
ө superinfection
ө dual infection initially
- Laboratory :
ө erroneous report of susceptible
pathogen
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
Antagonism (2) :
1. Inhibition of cidal activity by static
agent
- Tetracyclines – Betalactam AB
2. Induction of enzymatic inactivation
- Ampicillin - Piperacillin
CLINICAL INDICATION OF AB
COMBINATION :
► Mixed infection
► Synergism effect
► Risk of developing resistant
organism <
► Increase AB coverage or
► Infection of unknown origin
DISADVANTAGES OF AB COMBINATION
-
Increase risk of toxicity
Increase MDR-pathogens
Increase cost
Increase antagonism (bacteriostatic
+ bactericide)