Antibiotic and Its Resistance

Eddy Bagus Wasito

• Definition
• Classification
• Desirable properties
• Mechanism of bacterial resistance
 Definition
• Chemical substance
• Produced by microorganism
• Small concentration inhibit microorganism
• Wholly / partially synthesis
• A chemical substance derived from or
produced by various species of
microorganisms which is capable in small
concentrations inhibits the growth of other
microorganisms
• Wholly / partially synthesis
 Mechanism(s) of action
• Affect the cell wall synthesis
• Affect the cytoplasmic membrane function
• Inhibit the protein synthesis
• Interfere the DNA function
• Metabolic antagonism
 Interfere with Cell Wall Synthesis
• Beta lactam antibiotic (Penicillin, Cephalosporin,
Monobactam, Carbapenem, Oxacephem, Clavam)
• Cycloserin
• Fosfomycin
• Vancomycin
• Bacitracin
 Cell Membrane Inhibitor
• Polymyxin (A – E)
• Polyene (Azole)
 Inhibitor of Protein Synthesis
• Inhibitor of transcription (Actinomycin D,
Rifampin)
• Inhibitor of translation
– 30S ribosomal unit (Aminoglycoside, Tetracyclin,
Nitrofurans)
– 50S ribosomal subunit (Chloramphenicol,
Erythromycin, Lincomycin, Clindamycin, Puromycin,
Fusidic acid)
 Metabolite Analoque
• Inhibitor of tetrahydrofolate synthesis
(Sulfonamide, Sulfone, PAS)
• Inhibitor of Dihydrofolate Reduktase
(Trimethoprim)
• Others (Isoniazid, Flucytosine)
 Desirable properties of
an antibiotic
• Selective toxicity
• Bactericidal
• Does not cause resistancy
• Should not be allergenic
• Should not cause adverse side effects
• Remain active in plasma, body fluids,
exudates
 Continued …….
• Water soluble and stable
• Bactericidal level in the body be rapidly
reach and maintain for prolonged period
• Broad spectrum
 Resistance may be attributed
• Inactivation of the drug
• Alteration of the target site
• Blocking transport of the drug into the cell
• Resistance of cycloserine :
• Loss of the alanine transport
• Elevated of alanine racemase & D-alanyl-
D-alanyl synthetase
• Resistance of fosfomycin :
• Altered transport system
• Altered target enzym - decrease affinity
• Resistane of aminoglycoside :
• Acetylation of amino group (3 enzym)
• Phosphorylation of hydroxyl group (5 enzym)
• Adenylation of hydroxyl group (4 enzym)
• Resistance of chloramphenicol :
• Chloramphenicol acetyl transferase
• Resistance of erythromycin :
• Altered L4 & L12 of 50S subunit ribosome
(E.coli)
• Resistance of sulfonamid :
• Altered dihydropteroate synthetase

• Resistane of trimethoprim :
• Dihydrofolate reductase