Antimicrobial

drug and their

therapeutics uses

Dr Rashidah Iberahim
Lecture content

 History
 General Properties
 Resistance of Microorganism
 Determining Microbial Activity
Terms and definition

– Chemotherapeutic agent
– Antibiosis
– Synthetic drugs
– Semisynthetic drugs
– Broad spectrum vs narrow spectrum
– Bacteriostatic vs bactericidal
 History

Egyptian – Gerhard Alexander

Paul Ehrlich -
moldy bread Domagk – Fleming -
chemotherapy
treat wound sulfa drug penicilium
Selective toxicity

 Selective toxicity – AB should harm microbe but not the host cell
 Toxic dosage level vs therapeutic dosage level
 Chemotherapeutic index – maximum tolerable dose per kg of body weight
minimum dose per kg of body weight
• The higher the value, the better effect of AB agent
 Modes of action
 Inhibition of cell wall synthesis
 Disruption of cell membrane function
 Inhibition of protein synthesis
 Inhibition of nucleic acid synthesis
 Action as antimetabolites
Modes of action
Inhibition of cell wall synthesis
– Attack bacterial and fungal CW
– Contain ß lactam ring which
attaches to the enzymes that cross-
link peptidoglycans – prevent CW
synthesis
– Eg: penicillin, bacitracin,
vancomycin
– Less effective for fungi and archaea
with CW lack peptidoglycan
Disruption of cell membrane
function
– Polymixin - distort bacterial cell
membrane by binding to
phospholipid (gram negative
bacteria)
– Amphotericin B – bind with sterol
(fungal)
 Inhibition of nucleic acid
Inhibition of protein synthesis synthesis
– The structure of ribosome in bacteria – Attack the types of enzyme used by
(70S) are different from animal cell bacterial to synthesize nucleic acid
(80) – Eg. Rifamycin, quinolones,
– Allow the AB agent to attack metronidazole
bacterial cells without damaging
animal cell
– Eg. Tetracycline, erythromycin,
streptomycin, chloramphenicol
– Act on 50S of bacterial ribosome
– Act on 30S of bacterial ribosome
Action as antimetabolites

– Metabolites are essential for growth

and survival
– Func: by competitively inhibiting
exzymes
: by being erroneously
incorporated into important molecules
such as nucleic acid
– Molecular mimicry to normal
molecule
– Eg. Sulphanilamide, trimethoprim
 Side effects

 Toxicity
 Allergy
 Disruption of Normal Microflora
Toxicity Disruption of normal
Mental confusion and microflora
hallucination Kill normal flora which act as
Seizure, brain 1st defence line
problems sometimes Superinfection – rapidly
permanent but Allergy inhabit unoccupied areas
sometimes temporary Condition where the body
immune respond to foreign
substance (Protein)
As mild as skin rashes up to
life-threatening
(anaphylactic shock)
 Resistance of
Microorganisms

• Alteration of Targets
• Alteration of membrane permeability
• Development of enzyme
• Alteration of an enzyme
How resistance is Acquired?
– Genetic vs non genetic resistance
– Non-genetic resistance – evasion..keep out of AB agent reachable areas.
Progeny still susceptible. *Change form from not producing CW to producing
CW.
– Genetic resistance – mutation..due to rapid and rigorously replication, mutation
happen and leads to a new generation of resistance org
– Relate wt chromosomal resistance or extrachromosomal resistance
Mechanism of resistance
Alter the target
– Affects in bacterial ribosome
– So protein produced and target is
modified
– Eg. Erythromycin, rifamycin and
antimetabolites AB
Alteration of membrane
permeability
– Changes in new genetic
information that will change the
nature in the membrane
– AB no longer able to cross the cell
membrane
– Eg tetracycline, quinolones and
some aminoglycosides
Mechanism of resistance

Development of enzymes Alteration of enzymes

– Destroy or inactivate AB – Formerly inhibited reaction to
– Enzyme type = ß lactamase occur

– Breaking ß lactam ring in AB – Eg. sulfonamide

– Mostly gram negative

– Eg. Penicillin, chloramphenicol,
aminoglycosides
Mechanism of Resistance

Alteration of a metabolic
pathway
– Bypasses a reaction inhibited by an
antimicrobial agent
– Org. acquired the ability to use
ready made folic acid from
environment , not from PABA
Homework revision

– Cross-resistance?
– Limiting drug resistance
– Quorum sensing to block resistance
– 1st line, 2nd line and 3rd line drugs
Test to detect presence of
AB resistance
Disk Diffusion Method

– Kirby-Bauer method
– Appear zone of inhibition – presence of resistance
– Using disk (filter paper)
– Latest version known as Epsilometer test
The Dilution Method

– Observing minimum inhibitory concentration (MIC)- concentration of particular

agent affecting special org
– Minimum bactericidal concentration (MBC) – for 2nd subculture inhibition..the
same method as MIC
Other test

Serum Killing Power Automated method

– Using serum of pt that uptake
antibiotics against bacteria