Introduction to
antimicrobial agents
1. Chemotherapy,化学治疗
 Definition: Use of drugs to combat infectious
diseases and cancer.
Antimicrobial drug (抗微生物药)
Antiparasitic drug( 抗寄生虫药)
Anticancer drug (抗癌药)
Antimicrobial drug
Antimicrobial drugs either kill microbes
(microbicidal) or prevent the growth of
microbes (microbistatic).
Antibacterial
Antiviral
Antifungal
Antiparasitic
Antimicrobial Chemotherapy
Differential toxicity: based on the concept that the
drug is more toxic to the infecting organism than to
the host
Majority of antibiotics are based on naturally
occurring compounds
or may be semi-synthetic or synthetic
What is the ideal antibiotic
Have the appropriate spectrum of activity for the clinical
setting.
Have no toxicity to the host, be well tolerated.
Low propensity for development of resistance.
Not induce hypersensitivies in the host.
What is the ideal antibiotic
Have rapid and extensive tissue distribution
Have a relatively long half-life.
Be free of interactions with other drugs.
Be convenient for administration.
Be relatively inexpensive
Definitions
Spectrum of Activity:
Narrow spectrum - drug is effective against a limited
number of species
Broad spectrum - drug is effective against a wide
variety of species
Gram negative agent
Gram positive agent
Anti-anaerobic activity
Definitions
Minimum Inhibitory Concentration (MIC)
- minimum concentration of antibiotic required to inhibit the
growth of the test organism.
Minimum Bactericidal Concentration (MBC)
- minimum concentration of antibiotic required to kill the test
organism.
Bacteriostatic
Bactericidal
Definitions
Chemotherapeutic Index ( CI ): LD50/ED50 or LD5/ED95
PAE (Post antibiotic effect): the continued suppression
of antibacterial growth after the administration of
antibiotic has ceased and serum concentrations have
fallen below the minimum inhibitory concentration .
机
体
抗菌作用
抗微生物药
耐药性
病原微生物
Five modes of antimicrobial action
(i)
(ii)
(iii)
(iv)
(v)
Inhibition of cell wall synthesis
Disruption of cell membrane function
Inhibition of protein synthesis
Inhibition of nucleic acid synthesis
Action as antimetabolites
Peptidoglycan
The glycan backbone
Tetrapeptide
side chain
Peptidoglycan cross-bridges
Targets of antimicrobial drugs
——Disruption of cell membrane function—
—
Cationic and alters cytoplasmic membrane
Polymyxin
permeability by binding to a negatively
charged site in the lipopolysaccharide layer
Amphotericin B
Associates with ergosterol, the main
component of fungal cell membranes
Drugs that disrupt cell membrane
function
Inhibition of protein synthesis
Generally work at different stages of prokaryotic mRNA
translation into proteins, like initiation, elongation
(including aminoacyl tRNA entry, proofreading, peptidyl
transfer and ribosomal translocation) and termination.)
The antibiotic only affects 70S ribosomes in the bacteria
and does nothing for the 80S ribosomes in human.
Inhibition of protein synthesis
Macrolides
Lincomycin
Chloromycetin
Tetracyclines
Aminoglycosides
bind to 50s
bind to 30s
Inhibition the Synthesis of metabolites
Antibiotics that mimic the structure of the specific
substrate that the normal substrate is replaced and don’t
have contact with the enzyme which acts on a substrate
to produce a certain metabolically important metabolite
inside the cell.
Action of sulfanilamide
——
Inhibitors of nucleic acid synthesis—
—
Quinolones
Inhibit the DNA gyrase→ Interfer with DNA replication
Rifampicin
Inhibits DNA-dependent RNA polymerase →mRNA↓
Antimicrobial resistance
Resistance: the inability to kill or inhibit the organism
with clinically achievable drug concentrations
Resistance may be innate (naturally resistant)
Resistance may be acquired
- mutation
- acquisition of foreign DNA
Antimicrobial resistance
Factors which may accelerate the development of
resistance
- inadequate levels of antibiotics at the site of
infection
- duration of treatment too short
- overwhelming numbers of organisms
- overuse / misuse of antibiotics
Antimicrobial resistance
General mechanisms of resistance:
 Inactivation / destruction of antibiotic
 Altered binding site
 Altered permeability
 Efflux (pumps) mechanisms
 Bypass of metabolic pathways
Resistance gene transmission
Principles of use of antibacterial agents
Proper selection of an antibacterial agent is based on a
number of factors.
The identity of the pathogen
The site of infection
Pharmacokinetics (PK)
Pharmacodynamics (PD)
Potential toxicity
Possible drug interactions,
Cost, and convenience of administration.
Prophylaxis for infection
Prevention of Rheumatic Fever
Epidemic cerebrospinal meningitis
Infective endocarditis
Surgery