RATIONAL USE OF

ANTIBIOTICS
dr. Siti Suparti
Medical School Padjadjaran University
Department of Pharmacology & Therapy

References :
1. Lippincotts 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

Resistance

Side effect

Definition

In vitro

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, chlolamph,
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 to day available
antibiotics.

AVOIDING SUPERINFECTION

1. Stop the giving antibiotics

2. Culturing the microorganism that
causes superinfection
3. Treatment according to bacterial
identification and sensitivity test

The specimen was taken from feces

and secretion of upper resoiratory
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
Patients 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 Lippincotts 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

DISANVANTAGES 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 : 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

Cont.
- Pathogen

drug resistence
superinfection
dual infection initially

- Laboratory :
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)