The document discusses antimicrobial drugs and antibiotics. It begins by noting that the modern era of antibiotics started with Fleming. It then defines antimicrobial drugs as chemicals that interfere with microbial growth within a host, including antibacterial, antiviral, antiparasitic and antifungal drugs. Antibiotics are natural products produced by bacteria and fungi that kill or inhibit other microorganisms. Antimicrobial drugs are further classified based on their spectrum of action, source, chemical nature and mode of action. The document also discusses mechanisms of action, resistance, and ideal properties of antimicrobial drugs.

1. Dr.Wafaa Ezz
Elarab
Antimicrobial Drugs-1Antimicrobial Drugs-1

2. Modern era in Antibiotics begins
with Fleming.

3. Chemicals used to treat microbial infections by
interfere with the growth m.o within host,
including (antibacterial, antiviral, antiparasitic
and antifungal) regardless of its origin.
AntibioticsAntibiotics
Are natural product produce by bacteria and
fungi which kill or inhibit the growth of other m.o
Antimicrobial DrugsAntimicrobial Drugs

4. ChemotherapyChemotherapy
Any chemical used in the treatment,
relief or prophylaxis of a disease.
ProphylaxisProphylaxis
Use of a drug to prevent infection of a
person (prevention of disease).

5. Antimicrobial Agents
• Disinfectant:
•antimicrobial agent used only on
inanimate objects
• Chemotherapeutic agent:
•antimicrobial agent that can be used
internally
• Bactericidal:
•agent that kills bacteria
• Bacteriostatic:
•agent that inhibits the growth of bacteria

6. Classification ofClassification of
antibioticsantibiotics ::
Antibiotics are classified several ways.
1.1. On the basis of spectrum of activityOn the basis of spectrum of activity
2.2. On the basis of the sourceOn the basis of the source
3.3. On the basis of chemical natureOn the basis of chemical nature
4.4. On the basis of mode of actionOn the basis of mode of action

7. 1. According to the spectrum of1. According to the spectrum of
actionaction
Antibacterial drugs.
Antifungal drugs.
Antiviral drugs.
Antiprotozoal drugs.
Antihelminthic drugs.

8. 2. According to the source2. According to the source
A. antibiotics produce by bacteria (bacitracin,
polymixins and gramacidins)
B. antibiotics produce by fungi
(penicillins, cephalosporins and grisofulvin)
C. antibiotics produce by actinomycetes
(chloramphenicol, streptomycin, erythromycin and
vancomycin.)
Note: Most antibiotics are isolated from soil
microorganisms

9. MicrobialMicrobial
Sources ofSources of
AntibioticsAntibiotics

10. 3. According to chemical nature3. According to chemical nature
PeptidesPeptides
GlycopeptidesGlycopeptides
AminoglycosidesAminoglycosides
B-lactamsB-lactams
MacrolidesMacrolides PolyenesPolyenes

11. 4. According to mode of action4. According to mode of action
1.1. Inhibition of cell wall synthesisInhibition of cell wall synthesis
2.2. Inhibition of nucleic acid synthesis,Inhibition of nucleic acid synthesis,
structure or functionstructure or function
3.3. Inhibition of protein synthesisInhibition of protein synthesis
4.4. Disruption of cell membrane structure orDisruption of cell membrane structure or
functionfunction
5.5. Inhibit synthesis of essential metabolitesInhibit synthesis of essential metabolites

12. Features of Antimicrobial Drugs:Features of Antimicrobial Drugs:
1. Selective Toxicity1. Selective Toxicity
 Cause greater harm to microorganisms than to host
 Chemotherapeutic index: lowest dose toxic to
patient divided by dose typically used for therapy
The larger the _______, the better the chemotherapeutic
agent.

13. Ehrlich’s Magic Bullets
• 1906: Paul
Ehrlich discovered
Salvarsan 606
• 1930s: sulfa drugs
discovered
Ehrlich developed the concept
of specific toxicity

14. Chemotherapeutic spectraChemotherapeutic spectra
• Narrow spectrum
– only against a single or a limited group of
microorganisms,
• e.g. INH is active only against mycobacteria.
• Extended spectrum
– against G+ organisms and also against a
significant number of G- bacteria
• e.g., ampicillin
• Broad spectrum
• e.g. tetracycline and chloramphenicol
– affect a wide variety of microbial species.
– !!! alter the normal bacterial flora
• precipitate a superinfection of an organism, e.g.,
candida.

15. Features of Antimicrobial Drugs:Features of Antimicrobial Drugs:
2.2. Effects of Combining Drugs
Combinations are sometimes used to fight
infections
Synergistic: action of one drug enhances the
activity of another or vice versa. e.g. 2 + 2 = 6)
e.g. ampicillin+gentamicin in entercoccal carditis
Antagonistic: activity of one drug interferes with
the action of another. e.g. 2 + 2 < 4)

16. Features of Antimicrobial Drugs:Features of Antimicrobial Drugs:
3. Adverse Effects3. Adverse Effects
1.1. Allergic ReactionsAllergic Reactions: some people develop
hypersensitivities to antimicrobials
2.2. Toxic EffectsToxic Effects: some antimicrobials toxic at high
concentrations or cause adverse effects
3.3. Suppression of normal floraSuppression of normal flora: when normal flora
killed, other pathogens may be able to grow to
high numbers

17. Features of Antimicrobial Drugs:Features of Antimicrobial Drugs:
4.4. Resistance to AntimicrobialsResistance to Antimicrobials
 Some microorganisms inherently resistant to
effects of a particular drug. (Intrinsic resistance)
 Other previously sensitive microorganisms can
develop resistance through spontaneous
mutations or acquisition of new genes (more
later). (Extrinsic resistance)

18. So, The Criteria of the Ideal Antimicrobial:So, The Criteria of the Ideal Antimicrobial:
 Selectively toxic to microbe but nontoxic to host.
 Soluble in body- tissue distribution.
 Remains in body long enough to be effective -
resists excretion and breakdown.
 Does not lead to resistance.
 Cost not excessive.
 Hypoallergenic.
 Microbiocidal rather than microbiostatic.

19. Antibiotics :Antibiotics :
Substance (such as penicillin) produce by
microorganisms that destroys or inhibits the growth
of other pathogenic microorganisms and is used in
the treatment of external or internal infections.
Anti – against
Bio – life

20. Mechanisms of action ofMechanisms of action of
Antibacterial DrugsAntibacterial Drugs
1. - Inhibit cell wall synthesis
2. - Inhibit protein synthesis
3. - Inhibit nucleic acid synthesis
4. - Injury to plasma membrane
5. - Inhibit synthesis of essential
metabolites

21. Mechanisms of antibacterial action

22. 1. Drugs that affect the bacterial cell wall1. Drugs that affect the bacterial cell wall
 ß-lactam antibioticsß-lactam antibiotics
Penicillins, cephalosporins and cephamycins,
carbapenems and monobactams, ß-lactamase inhibitor/ß-
lactam combinations
GlycopeptidesGlycopeptides
Vancomycin
PolypeptidesPolypeptides
Bacitracin
Drugs used for treatment of mycobacterial infectionsDrugs used for treatment of mycobacterial infections
Isoniazid, ethinamide, ethambutol, cycloserine

23. 1. Drugs that affect the bacterial cell1. Drugs that affect the bacterial cell
wallwall
23

24. 1. Drugs that affect the bacterial cell
wall
 Most bacterial cell walls contain a rigid girdle of
peptidoglycan.
 Penicillin and cephalosporin block synthesis of
peptidoglycan, causing the cell wall to lyse.
 Penicillins do not penetrate the outer membrane and
are less effective against gram-negative bacteria.
 Broad spectrum penicillins and cephalosporins can
cross the cell walls of gram-negative bacteria.
24

25. Bacterial cell wall of G+ (A) and G-Bacterial cell wall of G+ (A) and G-
(B) bacteria(B) bacteria

26. Historical aspect of Beta-lactam
antibiotics:
 1928 - Alexander Fleming observed the
antibacterial effects of Penicillin
• 1940 - Florey and Chain extracted
Penicillin
• Around the fungal colony is
a clear zone where no
bacteria are growing
• Zone of inhibition due to
the diffusion of a substance
with antibiotic properties
from the fungus

27. Fleming and Penicillin

28. Basic mechanisms of antibiotic act onBasic mechanisms of antibiotic act on
β−β−Lactam DrugsLactam Drugs
 β-Lactam antibiotics are analogues of D-alanyl-D-alanine—the
terminal amino acid residues on the precursor NAM/NAG-
peptide subunits of the nascent peptidoglycan layer.
 The structural similarity between β-lactam antibiotics and D-
alanyl-D-alanine facilitates their binding to the active site of
PBPs.
 The β-lactam nucleus of the molecule irreversibly binds to the
PBP active site. This irreversible inhibition of the PBPs prevents
the final crosslinking (transpeptidation) of the nascent
peptidoglycan layer, disrupting cell wall synthesis

29. Penicillin and most other β-lactam antibiotics act byPenicillin and most other β-lactam antibiotics act by
inhibiting penicillin-binding proteins, which normallyinhibiting penicillin-binding proteins, which normally

30. Antibacterial Drugs
that Inhibit
Cell Wall Synthesis

31. Mechanisms of resistanceMechanisms of resistance ofof
antibiotic act onantibiotic act on β−β−Lactam DrugsLactam Drugs
By definition, all β-lactam antibiotics have a β-
lactam ring in their structure. The effectiveness of
these antibiotics relies on their ability to reach the
PBP intact and their ability to bind to the PBP.
Hence, there are two main modes of bacterial
resistance to β-lactams:
1. Enzymatic hydrolysis of the β-lactam ring
2. Possession of altered penicillin-binding
proteins

32. Enzymatic hydrolysis of the β-lactam ring
 If the bacterium produces the enzyme β-lactamase or
the enzyme penicillinase, the enzyme
will hydrolyse the β-lactam ring of the antibiotic,
rendering the antibiotic ineffective.
The genes encoding these enzymes may be:
 inherently presentinherently present on the bacterial chromosome
 or may be acquiredacquired via plasmid transfer (plasmid
mediated resistance), and β-lactamase gene
expression may be inducedinduced by exposure to β-
lactams.

33. Penicillinase (Penicillinase (ββ LactamaseLactamase)
Figure 20.8

34.  As a response to increased efficacy of β-
lactams, some bacteria have changed the
proteins to which β-lactam antibiotics bind. β-
Lactams cannot bind as effectively to these
altered PBPs, and, as a result, the β-lactams are
less effective at disrupting cell wall synthesis.
2. Possession of altered penicillin-
binding proteins

35. Thank You