ANTIMICROBIAL AGENTS

GENERAL CONSIDERATION
NUR PERMATASARI

Antibiotics
Substances produced by various species
of microorganisms: bacteria, fungi,
actinomycetes- that suppress the growth
of other microorganisms and to destroy
them.
Today the term ATB extends to include
synthetic antibacterial agents:
sulfonamides and quinolones.

Sir Alexander Fleming

In 1928, Sir Alexander Fleming, a Scottish biologist, observed

that Penicillium notatum, a common mold, had destroyed
staphylococcus bacteria in culture.

1941 : Clinical uses of Penicillin

After War II: Identification of streptomycin,
chloramphenicol, chlor tetracyline
30% of hospitalized patients treated with
antimicrobial agents
Misused : 50% patients diagnosed with viral
resp.tract infection are prescribed ATB
The problem: ATB-resistant pathogens
physicians must be wiser and more selective
in the use of ATB

Classification and mechanism of

action

Susceptibility vs. Resistance

Dose of drug has to be sufficient to produce
effect inhibit or kill the microorganism:
However concentration of the drug must remain
below those that are toxic to human cells
If can be achieved microorganism susceptible
to the ATB
If effective concentration is higher than toxicmicroorganism is resistant

Resistance
Failure to reach the target ( absence/ mutation
of porin, anaerobic condition, efflux pump
mechanism)

The drug is inactivated (aminoglycosidemodyfing enzyme, beta lactamase)

The target is altered (reduced binding/

substitution of a new target)

Selection of the ATB

Requires clinical judgment, detailed knowledge of
pharmacological and microbiological factors.
Empirical therapy initial infecting organism not
identified single broad spectrum agent/ combination
Definitive therapy- microorganism identified a
narrow spectrum low toxicity regiment to complete
the course of treatment

Empirical and Definite Therapy

Knowledge of the most likely infecting
microorganism and its susceptibility
Simple and rapid laboratory- Gram stain
Help to narrow the list of potential pathogen and
permit rational selection of initial ATB therapy

Definite therapy (more narrow spectrum and

susceptibility test are known)

Factors Influencing The Effectiveness

(1)
Pharmacokinetic factors
Location of infection
Penetration of drug
The dose and dosis frequency
Knowledge of the status of the
patient
Route of administration

Factors Influencing The Effectiveness

(2)
Host factor
Host defence mechanism
Local factor
Age (biotransformation,distribution,
elimination)

Genetic factors (genetic & metabolic

abnormalities)

Pregnancy
Drug allergy

Factors Influencing The Effectiveness

(2)

Host defence mechanism

Immunocompetent host bacteriostatic
Impaired host bacteriocidic
(bacterial endocarditis~phagocitic cell
absent
bacterial meningitis~phagocitic
ineffective, neutropenic patients~totol
mass phagocitic cell reduced)

Factors Influencing The Effectiveness

(2)

Local factor
-pus, hemoglobin in infected
hematoma, pH, anaerobic, vascular
supply
- the presence of foreign body

Indications for the use of combinations

of antimicrobial agents
Empirical therapy of unknown
cause of infection
Treatment of polymicrobial
infections
Enhancement of antimicrobial
activity
Prevention of the emergence of
resistant microbial

Disanvantages of combinations of
antimicrobial agents
Risk of toxicity
The selection of multiple-drug
resitant
Increased cost
Antagonism effect

The prophylaxis of infection with

antimicrobial agents
Protection of healthy patients who are
in close contact with a case
Patients with structural lesions of the
heart predisposising to endocarditis
Patients undergoing organ
transplantation or cancer chemotherapy
Prevention of wound infections
In dirty and contaminated surgical
procedures

Superinfections
The appearance of bacteriological
and clinical evidence of a new
infection during the chemotherapy
of a primary one
Very dangerous
Very difficult to eradicate
Broad spectrum, prolonged
administration

Misuses of antibiotics
Treatment of untreatable infection
Therapy of fever of unknown origin
Improper dosage
Inappropriate reliance on
chemotherapy alone
Lack of adequate bacteriological
information