1. بسم الله الرحمن الرحيم 1 1 1

2. Department Head of Microbiology
Antimicrobial Drugs:
Mechanism of Action
Dr. Manal El Said
Department Head of Microbiology

3. Antimicrobial Drugs: Mechanism of Action: Introduction
There are four major sites in bacterial cell that serve as basis for action of effective drugs:
Cell wall
Ribosomes
Nucleic acids
Cell membrane

4. Antimicrobial Drugs: Mechanism of Action: Introduction

5. Antimicrobial Drugs: Mechanism of Action: Introduction
Inhibition of cell wall synthesis
Inhibition of cross-linking (transpeptidation) of peptidoglycan
-Penicillins
Cephalosporins
Imipenem
Aztreonam,
Vancomycin
Inhibition of other steps in peptidoglycan synthesis
- Cycloserine
- Bacitracin
Antifungal activity inhibition of β-glucan synthesis
- Caspofungin
Inhibition of protein synthesis
Action on 50S ribosomal subunit
- Chloramphenicol
erythromycin
clindamycin
linezolid
Action on 30S ribosomal subunit
-Tetracyclines
- Aminoglycosides

6. Antimicrobial Drugs: Mechanism of Action: Introduction
Mechanism of Action of Important Antibacterial and Antifungal Drugs
Mechanism of Action
Drugs
Inhibition of nucleic acid synthesis
Inhibition of nucleotide synthesis
Sulfonamides, trimethoprim
Inhibition of DNA synthesis
Quinolones, e.g., ciprofloxacin
Inhibition of mRNA synthesis
Rifampin
Alteration of cell membrane function
Antibacterial activity
Polymyxin, daptomycin
Antifungal activity
Amphotericin B, nystatin, terbinafine, azoles, e.g., itraconazole
Other mechanisms of action
1. Antibacterial activity
Isoniazid, metronidazole, ethambutol, pyrazinamide
2. Antifungal activity
Griseofulvin, pentamidine

7. Antimicrobial Drugs: Mechanism of Action: Introduction
Selective toxicity
It is selective inhibition of growth of microorganism without damage to host.
It is achieved by exploiting differences between metabolism & structure of microorganism & human cells.
Penicillins & cephalosporins are effective antibacterial agents prevent synthesis of peptidoglycan
inhibiting growth of bacterial (not human cells).

8. Antimicrobial Drugs: Mechanism of Action: Introduction
Broad-spectrum antibiotics
Broad-spectrum antibiotics are active against several types of microorganisms
e.g., tetracyclines are active against many gram-negative rods, chlamydiae, mycoplasmas, & rickettsiae.
Narrow-spectrum antibiotics are active against one or very few types,
e.g., vancomycin is used against certain gram-positive cocci, staphylococci & enterococci.
Narrow-spectrum antibiotics

9. Antimicrobial Drugs: Mechanism of Action: Introduction
Bactericidal drug
Bactericidal drug kills bacteria
Bacteriostatic drug
Bacteriostatic drug inhibits their growth but does not kill them
- Bacteria can grow again when drug is withdrawn
- Host defense mechanisms, such as phagocytosis, are required to kill bacteria.

10. Antimicrobial Drugs: Mechanism of Action: Introduction

11. Antimicrobial Drugs Chemoprophylaxis
Antimicrobial drugs are used to prevent infectious diseases as well as to treat them.
They are given primarily in three circumstances:
to prevent surgical wound infections
to prevent opportunistic infections in immuno- compromised patients
to prevent infections in those known to be exposed to pathogens that cause serious infectious diseases.

12. Antimicrobial Drugs: Probiotics
In contrast to chemical antibiotics, probiotics are live, nonpathogenic bacteria that may be effective in treatment or prevention of certain human diseases.
The suggested basis for possible beneficial effect lies in:
providing colonization resistance by which nonpathogen excludes pathogen from binding sites on mucosa
enhancing immune response against pathogen
reducing inflammatory response against pathogen.

13. Antimicrobial Drugs: Probiotics
Oral administration of live Lactobacillus rhamnosus strain GG significantly reduces number of cases of nosocomial diarrhea in young children.
Yeast Saccharomyces boulardii reduces risk of antibiotic- associated diarrhea caused by Clostridium difficile.
Adverse effects are few; however, serious complications have arisen in highly immunosuppressed patients and in patients with indwelling vascular catheters.

14. Antimicrobial Drugs:
Probiotics

15. Antimicrobial Drugs:
Probiotics

16. Department Head of Microbiology
Antimicrobial Drugs:
Mechanism of Action
Dr. Manal El Said
Department Head of Microbiology

17. Antimicrobial Drugs: Resistance
Four main mechanisms of antibiotic resistance are:
(1) enzymatic degradation of drug
(2) modification of drug's target
(3) reduced permeability of drug
(4) active export of drug.
Most drug resistance is result of genetic change in organism, caused either by:
- Chromosomal mutation
- Acquisition of plasmid or transposon.

18. Major Mechanisms of Bacterial Resistance
Antimicrobial Drugs:
Major Mechanisms of Bacterial Resistance

19. Antimicrobial Drugs: Enzyme destroy or inactivate antibiotic
Resistance: Specific Mechanisms of Resistance
Enzyme destroy or inactivate antibiotic
Bacterial resistance to antibiotics—producing an enzyme to destroy or inactivate the antibiotic. This animation can be found at The Grapes of Staph: Doc Kaiser's Microbiology Website,

20. Resistance: Specific Mechanisms of Resistance
Antimicrobial Drugs:
Resistance: Specific Mechanisms of Resistance
Altered Enzyme
Bacterial resistance to antibiotics—producing an altered enzyme to which the antibiotic no longer binds. This animation can be found at The Grapes of Staph: Doc Kaiser's Microbiology Website,

21. Altered ribosomal subunit
Antimicrobial Drugs:
Resistance: Specific Mechanisms of Resistance
Altered ribosomal subunit
Bacterial resistance to antibiotics—producing an altered ribosomal subunit to which the antibiotic no longer binds. This animation can be found at The Grapes of Staph: Doc Kaiser's Microbiology Website,

22. Altered porins block passage of antibiotic
Antimicrobial Drugs:
Resistance: Specific Mechanisms of Resistance
Altered porins block passage of antibiotic
A bacterium producing altered porins that block passage of the antibiotic through the outer membrane of a gram-negative bacterium.

23. Altered transport (carrier) protein
Antimicrobial Drugs:
Resistance: Specific Mechanisms of Resistance
Altered transport (carrier) protein
A bacterium producing an altered transport (carrier) protein that prevents transport of the antibiotic through the cytoplasmic membrane.

24. Resistance: Specific Mechanisms of Resistance Transporter molecules
Antimicrobial Drugs:
Resistance: Specific Mechanisms of Resistance
Transporter molecules
A bacterium producing transporter molecules that pump the antibiotic out of the bacterium.

25. Greater amounts of the limited enzyme
Antimicrobial Drugs:
Resistance: Specific Mechanisms of Resistance
Greater amounts of the limited enzyme
A bacterium producing greater amounts of the limited enzyme being tied up or inactivated by the antimicrobial agent. Although some enzyme is tied up by the drug, there is still enzyme available to react with its substrate and produce end products.

26. Resistance: Genetic Basis of Resistance Chromosomal mutations
Antimicrobial Drugs:
Resistance: Genetic Basis of Resistance
Chromosomal mutations
Chromosomal mutations typically:
- Change target of drug drug does not bind
- Change membrane drug does not penetrate into cell.
It occurs at low frequency (1 in 10 million organisms).
It affect only one drug or one family of drugs.

27. Resistance: Genetic Basis of Resistance
Antimicrobial Drugs:
Resistance: Genetic Basis of Resistance
Plasmids
Plasmids encoding enzymes that degrade or modify drugs.
It occurs at higher frequency
it affects multiple drugs or families of drugs.
Resistance plasmids (R plasmids, R factors) carry two sets of genes:
- One set encodes enzymes that degrade or modify drugs
- Other encodes proteins that mediate conjugation

28. Resistance: Genetic Basis of Resistance
Antimicrobial Drugs:
Resistance: Genetic Basis of Resistance
Transposons
Transposons are small pieces of DNA that move:
- from one site on bacterial chromosome to another or,
- from bacterial chromosome to plasmid DNA.
Transposons often carry drug resistance genes.
Many R plasmids carry one or more transposons.

29. Resistance: Genetic Basis of Resistance
Antimicrobial Drugs:
Resistance: Genetic Basis of Resistance

30. Nongenetic Basis of Resistance Nongenetic Basis of Resistance
Antimicrobial Drugs:
Nongenetic Basis of Resistance
Nongenetic Basis of Resistance
Drugs may not reach bacteria located in center of abscess
Certain drugs, such as penicillins, will not affect bacteria that are not growing.
Presence of foreign bodies makes antibiotic treatment difficult.

31. Selection of Resistant Bacteria by Overuse & Misuse of Antibiotics
Antimicrobial Drugs
Selection of Resistant Bacteria by Overuse & Misuse of Antibiotics
Overuse & misuse of antibiotics increase the occurrence of gram-negative rods resistant to multiple antibiotics by enhancing selection of resistant mutants:
Some physicians :
-Use multiple antibiotics when one would be sufficient
-Prescribe unnecessarily long courses of antibiotic therapy
-Use antibiotics in self-limited infections.
-Overuse antibiotics for prophylaxis before & after surgery.

32. Selection of Resistant Bacteria by Overuse & Misuse of Antibiotics
Antimicrobial Drugs
Selection of Resistant Bacteria by Overuse & Misuse of Antibiotics
In many countries, antibiotics are sold over the counter to general public encourages inappropriate & indiscriminate use of the drugs.
3. Antibiotics are used in animal feed to prevent infections and promote growth selects for resistant organisms in animals contribute to pool of resistant organisms in humans.

33. The minimal inhibitory concentration (MIC)
Antimicrobial Drugs:
Antibiotic Sensitivity Testing
The minimal inhibitory concentration (MIC)
It is lowest concentration of drug that inhibits growth of bacteria isolated from patient
NB: it is not known whether inhibited bacteria have been killed or just have stopped growing.
The minimal bactericidal concentration (MBC)
It is lowest concentration of drug that kills bacteria isolated from patient.

34. Use of Antibiotic Combinations Use of Antibiotic Combinations
Antimicrobial Drugs:
Use of Antibiotic Combinations
Use of Antibiotic Combinations
Two or more antibiotics are used to:
- treat life-threatening infections before cause has been identified,
- prevent emergence of resistant bacteria during prolonged treatment regimens
- achieve synergistic (augmented) effect.

35. Use of Antibiotic Combinations Use of Antibiotic Combinations
Antimicrobial Drugs:
Use of Antibiotic Combinations
Use of Antibiotic Combinations
Synergistic
Synergistic effect is : effect of two drugs given together is much greater than sum of effect of two drugs given individually.
e.g. marked killing effect of combination of penicillin & aminoglycoside on enterococci compared to minor effect of either drug given alone.

36. Use of Antibiotic Combinations
Antimicrobial Drugs:
Use of Antibiotic Combinations
Rarely, the effect of the two drugs together is antagonistic, in which the result is significantly lower activity than the sum of the activities of the two drugs alone.

37. Antimicrobial Drugs

38. Bacterial Vaccines

39. Bacterial Vaccines
Immunity to certain bacterial diseases can be induced by:
Immunization with bacterial antigens (active immunity)
Administration of preformed antibodies (passive immunity).

40. Bacterial Vaccines Active immunity
Active immunity can be achieved by vaccines consisting of:
bacterial capsular polysaccharides, toxoids, whole bacteria (either killed or live, attenuated)
purified proteins isolated from bacteria.

41. Bacterial Vaccines
Active immunity

42. Bacterial Vaccines Active immunity
Vaccines containing capsular polysaccharide as immunogen are directed against :
Streptococcus pneumoniae
Haemophilus influenzae
Neisseria meningitidis
Salmonella typhi.
Capsular polysaccharide is conjugated to carrier protein to enhance antibody response.

43. Bacterial Vaccines Active immunity
Two vaccines contain toxoids as immunogen:
- Diphtheria
- Tetanus.
Toxoid is inactivated toxin that has lost its ability to cause disease but has retained its immunogenicity.

44. Bacterial Vaccines Active immunity
Two vaccines contain purified bacterial proteins as immunogen:
1-Acellular pertussis vaccine:
Combination with diphtheria & tetanus toxoids
It is recommended for all children.
2-Anthrax vaccine:
 Contains purified proteins
It is recommended only for individuals who are likely to be exposed to organism.

45. Bacterial Vaccines Active immunity
BCG vaccine against tuberculosis contains live, attenuated Mycobacterium bovis & is used in countries where the disease is endemic.
One of vaccines against typhoid fever contains live, attenuated Sal. typhi.
Vaccines against cholera, plague, typhus, & Q fever contain whole killed bacteria.
These vaccines are used only to protect those likely to be exposed.

46. Bacterial Vaccines Passive Immunity
Antitoxins for prevention & treatment of :
- Tetanus
- Botulism
- Diphtheria.
These three diseases are caused by exotoxins.
Antitoxins (antibodies against exotoxins) bind to exotoxins & prevent their toxic effects, i.e., they neutralize toxins.

47. Passive–Active Immunity
Bacterial Vaccines
Passive–Active Immunity
This involves providing both immediate (but short-term) protection in form of antibodies & long-term protection in form of active immunization.
e.g. prevention of tetanus in unimmunized person who has sustained contaminated wound.
- Both tetanus antitoxin & tetanus toxoid should be given.
-They should be given at different sites so that antibodies in antitoxin do not neutralize toxoid.