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• Antimicrobial drugs are effective in the treatment of infections because of their selective
toxicity (that is, they have the ability to kill or inhibit the growth of an invading
microorganism without harming the cells of the host). Including :
• Antibiotic
• Antiviral
• Antifungal
• Anti parasite
• Antibiotic
• Substance produced by microorganisms that inhibits the growth of (bacteriostatic) or
kills (bactericidal) other bacteria
• Antimicrobial agent: Chemical that kills or inhibits the growth of microorganisms
• The clinically useful antibacterial drugs are organized into six familles:
• Beta lactams ( penicillins, cephalosporins and Carbapenem )
• Tetarcyclines
• Aminoglycosides
• Macrolides
• Fluoroquinolones
• Glycopeptides
Classification of antibiotics
• Antibiotics are classified into 3 categories including :
• According to Activity Spectrum
• According to the Mode of action
• According to the mechanism of action
Classification of antimicrobials
Humans are not affected by these drugs because we do not have a cell wall, and we have
different ribosomes, nucleic acid enzymes, and sterols in our membranes.
Interactions between antimicrobials
• Antimicrobials used in combination may be:
• additive: combined effect equal to the sum of the individual agents
• Synergistic: combined effect greater than achieved with addition; e.g. gentamicin
plus penicillin;
• Antagonistic: drugs inhibit the action of each other
Inhibitors of bacterial cell wall synthesis
Fluoroquinolones :
Sulphonamides
Trimethoprim
Quinolones
Nitroimidazoles
Rifampicin
• Used against Enterobacteriaceae H. influenzae, Neisseria sp. Pseudomonas aeruginosa)
• Fluoroquinolones mod of action .
• It is prevent
1. Relaxation of supercoiled DNA before replication
2. DNA recombination
3. DNA repair
Inhibitors of peptidoglycan synthesis
• Glycopeptides :
i. Vancomycin
ii. Teicoplanin
• Mode of action:
• Inhibit peptidoglycan synthesis in the bacterial cell wall
• Prevents cross linkage of peptidoglycan chains
Mode of action of antibiotics
Cell wall synthesis DNA gyrase DNA-directed RNA polymerase
RNA elongation
Cycloserine Quinolones Nalidixic acid Rifampin
Vancomycin Ciprofloxacin Actinomycin
Streptovaricins
Bacitracin Novobiocin
Penicillins
Cephalosporins Protein synthesis
Monobactams
Carbapenems
(50S inhibitors)
Erythromycin (macrolides)
DNA Chloramphenicol
Clindamycin
Folic acid metabolism Lincomycin
Trimethoprim THF mRNA
Sulfonamides
Protein synthesis
Ribosomes (30S inhibitors)
DHF
50 50 50
Tetracyclines
30 30 30 Spectinomycin
Streptomycin
Gentamicin
Cytoplasmic membrane Kanamycin
structure and function Amikacin
Polymyxins Nitrofurans
Lipid
Daptomycin biosynthesis
Protein synthesis
Platensimycin (tRNA)
PABA Cytoplasmic Cell wall
membrane Mupirocin
Puromycin
Antibacterial mod of action
Bacteria synthesize modified targets against which the drug has a reduced effect,
e.g., a mutant protein in the 30S ribosomal subunit can result in resistance to
streptomycin
Resistant cells may alter the target of the drug so that the drug either cannot
attach to it or binds it less effectively. This form of resistance is often seen
against antimetabolites (such as sulfonamides) and against drugs that thwart
protein translation (such as erythromycin).
3. Restricted transport of the agent into the cell
Bacteria actively export drugs using a "multidrug resistance pump" (MDR pump,
or "efflux" pump).
Resistant cells may pump the antimicrobial out of the cell before the drug can act.
So-called efflux pumps, which are typically powered by ATP, are often able to
pump more than one type of antimicrobial from a cell. Some microbes become
multi-drug resistant (perhaps to as many as 10 or more drugs) by utilizing
resistance pumps.
5. Metabolic bypass
Resistant cells may alter their metabolic chemistry, or they may abandon
the sensitive metabolic step altogether. For example, a cell may become
resistant to a drug by producing more enzyme molecules for the affected
metabolic pathway, effectively reducing the power of the drug.
Alternatively, cells become resistant to sulfonamides by abandoning the
synthesis of folic acid, absorbing it from the environment instead.
5. Bacteria within biofilms resist antimicrobials more effectively than free-
living cells. Biofilms retard diffusion of the drugs and often slow metabolic
rates of species making up the biofilm. Lower metabolic rates reduce the
effectiveness of antimetabolic drugs.
6. Protection of the target site by a bacterial protein.
Some resistant strains of the bacterium Mycobacterium tuberculosis have a novel method of
resistance against fluoroquinolone drugs that bind to DNA gyrase. These strains synthesize
an unusual protein that forms a negatively charged, rod like helix about the width of a DNA
molecule. This protein, called MfpA protein, binds to DNA gyrase in place of DNA,
depriving fluoroquinolone of its target site. This is the first method of antibiotic resistance
that involves protecting the target of an antimicrobial drug rather than, say, changing the
target or deactivating the drug. MfpA protein probably slows down cellular division of M.
tuberculosis, but that is better for the bacterium than being killed