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ANTIMICROBIAL

AGENTS
Suryadi Nattadiputra
Department of Pharmacology
Medical Faculty
Sriwijaya University
LEARNING OBJECTIVES
To know the definition of antibiotic
To know classification & mechanism of action of antimicrobial
To know factors that determine the susceptibility & resistance of
microorganisms to antibiotics
To know how bacterial can be resistant to antimicrobial agents
To know how to select an antibacterial agent
To know susceptibility test (disk diffusion test)
To know host factors that determine selection of antimicrobial agents
To understand therapy with combined antimicrobial agents
To know the prophylaxis of infection with antibiotics
To understand superinfection
To understand antibiotics misused
Definition: Antibiotics are substances produced
by various species of microorganisms (bacteria,
fungi, actinomyecetes) that suppress the
growth of other microorganisms and eventually
may destroy them.

However, common usage often extended the


term antibiotics to include synthetic
antibacterial agent, such as sulfonamides and
quinolone
Classification and Mechanism of Action
1. Agents that inhibit synthesis of bacterial cell
walls.
a. Structurally similar : penicillin &
cephalosporin
b. Structurally dissimilar : cycloserine,
vancomycin, bacitracin and imidazole
antifungal : miconazole, ketokonazole and
clotrimazole.
2. Agents that act directly on the cell membrane
of the microorganisms, affecting permeability
and leading to leakage of intracellular
compounds.
- detergents
- polymyxin
- colistimethate
- polyene antifungal agents that bind to cell
wall sterol :
- nystatin
- amphothericyn B
3. Agents that affect the function of 30S or 50S
ribosomal subunits to cause a reversible
inhibition of protein synthesis, these
bacteriosatic drugs include:
- chloramphenicol,
- the tetracycline,
- erythromycin, and
- clindamycin
4. Agents that bind to the 30S ribosomal subunit
and alter protein synthesis, which eventually
leads to cell death.
- aminoglycosides

5. Agents that affect nucleic acid metabolism :


- rifamycins : inhibit DNA dependent RNA
polymerase
- quinolones : inhibit gyrase
6. Antimetabolites :
Block specific metabolic steps that are
essential to microorganisms
- trimethoprim
- sulfonamides

7. Nucleic acid analogs , inhibit viral enzymes


that are essential for DNA synthesis, thus
halting viral replication.
- zidovudin , ganciclovir , vidarabine
acyclovir
Factors that Determine the Susceptibility and
Resistance of Microorganisms to Antimicrobial
Agents
1. Host defenses
2. Dosage
3. Drug concentration at the site of infection
4. The ability of microorganisms to inhibit drugs
effect
5. The pH
6. Osmolality
Resistance to Antimicrobial Agents
Bacteria can be resistant to an antimicrobial
agents because :
1. the drug fails to reach its target
2. the drug is inactivated
3. the target is altered
The ways microorganisms become resistance:
1. Mutation
2. Transduction
3. Transformation
4. Conjugation
Selection of an Antimicrobial Agent
- Requires : - Clinical judgment
- Knowledge of pharmacology &
- Microbiology
- Antibiotics are used in two general ways:
- empirical (initial therapy) :
- combination
- single broad spectrum agent
- definitive therapy :
- a narrow spectrum
- low toxicity or allergic reactions
Whenever the clinician is faced with initiating
therapy on a presumptive bacteriological
diagnosis, cultures of blood and certain other
body fluid should be taken prior to the
institution of drug therapy.

Immediate identification of bacteria : Grams stain

Testing for microbial sensitivity to antibiotics:


- disk-diffusion technique
- dilution test
Pharmacokinetic Factors:
- Location of infection
- Acces of antibiotics to sites of infection
- Penetration of drugs into infected loci
- Status of patients mechanisms for
metabolism & elimination of drugs

Route of Administration :
- oral
- parenteral
Host factors :
- Host defense mechanisms
- Local factors
- Age
- Genetic factors
- Pregnancy
- Drug allergy
- Disorders of the nervous system
Therapy with combined antimicrobial agents
- For specifically defined situation

Indications for use :


- Treatment of mixed bacterial infections
- Severe infection which unknown etiology
- Enhancement of antibacterial activity in the
treatment of specific infections
- Prevention of the emergence of resistant
microorganism
Disadvantages of combination of antimicrobial
agents:
- The risk of toxicity
- Resistance
- Antagonism (bacteriostatic + bactericidal)
- Increase cost to the patient
The prophylaxis of infections with antibiotics.
1. To protect healthy persons from acquisition
of or invasion by specific microorganisms
to which they are exposed.
2. To prevent endocarditis in patients with
valvular or other structural leision of the
heart who are undergoing surgical pro-
cedures that produce a high incidence of
bacteremia.
3. To prevent wound infection after various
surgical procedures
Superinfections.
The appearance of bacteriological and clinical
evidence of a new infection during the chemo-
therapy of a primary one.

Misuse of antibiotics.
- Treatment of untreatable infections
- Therapy of fever of undetermined origin
- Improper dosage
- Inappropriate reliance on chemotherapy alone
- Lack of adequate bacteriological information

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