Antibiotics

1. Ahmed Osman Gasim
MSC in microbiology

2. Antimicrobial drugs
 Definition
 mode of actions
 classification types
 and bacterial resistance.

3.  Antimicrobial drugs or agents:
Definition :
medical intervention in an infection primarily
involve attempts to eradicate the infecting pathogen
using substances actively inhibit or kill it, this substance s
is Antibiotics or Chemotherapeutic agents.
Depending on the type of organisms targeted , these
substances are also known as antibacterial , anti fungal ,
or antiviral agent.

4.  Definition s:
1-Antibiotics:
 Natural: substances produce by an organism to kill or
inhibit the growth of another organism. Their
effectiveness as therapeutic agents is limited by their
toxicity for human cells.
 Semi-synthetic: are synthetic derivative of naturally
occurring antibiotics.
2- Chemotherapeutic agents:
Are chemical that are used for treating infectious
diseases.

5.  Bacteristatic agent:
Antimicrobial the usual dosage prevent active
multiplication of bacteria.
Bactericidal agent:
Antimicrobial the usual dosage kill bacteria.
 Some bacteristatic agents become bactericidal when
used at higher concentrations
 Broad spectrum antibiotic:
Antimicrobial with activity against a wide range of
bacteria.

6.  Efficacy of antimicrobial agents:
products of qualities that make it useful in treatment
of infectious disease, include:
o Rate of absorption.
o Rate of elimination.
o Ability to penetrate the infected site
Selective toxicity is the most important single attribute
of an antimicrobial agent.
Selective Toxicity: means that the drug is harmful to
a pathogen without being harmful to the host.

7. Sir Alexander Fleming discovered penicillin in 1928

8. Microbial
Sources of
Antibiotics

10. All antibiotics have the common property of interfering in
some way with a normal, critical function of the target
bacterial cell.
The most commonly used antibiotics exert their effect
by one of the following methods:
A) Inhibition of cell wall synthesis
B) Disruption of cell membranes
C) Interference with protein synthesis
D) Interference with nucleic acid synthesis

12. A) Inhibition of cell wall synthesis
1.Penicillins (Beta-lactam agents)
 Benzylpenicillin Cloxacillin ,(Penicillin G) Carbenicillin ,
Phenoxymethyl Ticarcillin , penicillin (V) Azlocillin , Ampicillin
Piperacillin , Amoxycillin Mecillinam , Flucloxacillin
2. Cephalosporins (Beta-lactam agents)
Cephradine* Ceftazidime*** , Cefuroxime**
Cefotaxime****1st generation, **2nd generation, ***
3rd generation
3. Glycopeptides
Vancomycin , Teicoplanin
4. Carbapenems
Imipenem , Meropenem

13. 1. Penicillins (beta lactum agents):
o The first β-lactam antibiotic to be discovered was
benzylpenicillin, or penicillin-G.
o whose action is restricted to Gram-positive bacteria,
when administered intramuscularly, but cannot be
taken by mouth because it is broken down in the acid
conditions of the stomach.
 Another naturally occurring penicillin, penicillin-V,
represented an advance in asmuch as it is less acid-
labile and can therefore be taken orally.
o extensive research has led to the development of many
variants of this, the so-called semisynthetic penicillins.

14. o Ampicillin is a semi-synthetic penicillin that has a
broader specificity than Penicillin G; it is appreciably
more effective against Gram-negative bacteria , its
hydrophobic nature making it better able to penetrate
their outer membrane. It has the additional benefit of
being acid-stable and can therefore be taken orally.
 Another drawback to natural penicillins is that they
are susceptible to naturally occurring bacterial β-
lactamases (also called penicillinases), which breaks a
bond in the β-lactam core of the penicillin molecule.

15. o Penicillin is not an appropriate treatment for the
estimated 1–5 per cent of adults who show an allergic
reaction to it; in extreme cases, death from
anaphylactic shock can result.
o Hypersensitivity include anaphylaxis (IgE mediated)
delayed hypersensitivity (IgG mediated), erythemia
and skin rash.

16. A. Benzylpenecillin (Penicillin G) (IV & IM) and
Phenoxymethyl penecillin (Penicillin V) (oral):
are drugs of choice of infections caused by
streptococci, pneumococci, meningococci ,Spirocaehte
& Closteridia
B. Ampicillins and oxacillins:
(can be administrated orally) Semi-synthetic
penicillins, broad spectrum, useful in treating gram +ve
bacteria including enterococci, H. influenzae & many
coliform.

17. 2. Cephalosporins (beta-lactum agents):
o Produced by fungus Acremonium cephalosporium.
o Broad spectrum & structurally similar to penicillin.
o Inhibit cell wall synthesis of gram –ve & gram +ve.
o Can be given to people with allergies to penicillin.
o Use to treat severe infection caused by gram –ve bacteria
o Expensive and cause kidney damage.

18. Cephalosporins generations:
o 1st cephalexin and cephradine.
o 2nd cefoxitin and cefuroxime.
o 3rd cetriaxone and ceftoxime.
o 4th cefepime.

19. 3- Bactericin:
o Peptide antibiotics produce by Bacillus subtitles.
o It prevents peptidoglycan synthesis.
o Toxic for human cells.
o Topical application.
o Since , its use internally can cause kidney damage.
o Act against gram-positives bacteria.
.

20.  4. Carbapenems:
(Imipenem and Meropenem)
o Carbapenems are β-lactam antibiotics produced
naturally by a species of Streptomyces.
o A semisynthetic form, imipenem, is active against a
wide range of Gram-positive and -negative bacteria,
and is used when resistance to other β-lactams has
developed.
 Beta-lactam agent, Potent, Broad spectrum, expensive,
resistant to hydrolysis by beta lactamases.

21. 5. Glycopeptides (IV)
e.g. Vancomycin and Teicoplanin.
o Are produce by Streptomyces orientalis
o Vancomycin is used to treat serious infection
(endocarditis and septicaemia) caused by gram +ve
bacteria.
o Important "last line" against multidrug resistant
MRSA.
o Expensive & cause ototoxicity & nephrotoxicity
6.Cycloserine:
o Produce by Streptomyces species.

22. B- Antibiotics acting on cell membrane
1.Polymexin:
o produced by Bacillus ploymyxa
o Inhibit the normal function of bacterial cells
membrane.
o Too toxic for internal use (topical treatment).
2. Nystatin:
Used as topical antifungal agents

23. 3. Amphotericin B:
o Is used to treat systemic mycosis
o Its highly nephrotoxic (bind to cholesterol in
mammalian cells)
4.The imidaole:
topical antifungal agent (Ketocanazole, miconazole)

24. C. Antibiotics Inhibit protein synthesis
1. Aminoglycosides (bactricidal):
o Inhibits proteins synthesis in bacteria by binding to
ribosome.
o Show synergy with beta-lactam agents
o Used to treat severe sepsis due to coliforms.
o Cause hypersensitivity, oto- and nephrotoxicicty
o e.g. Streptomycin, Amikacin, kanamycin, neomycin,
gentamicin, and tobramycin.

25. 2. Tetracycline (bacteristatic):
o Include tetracycline and doxycycline
o broad-spectrum, produce by streptomyces
o It prevents the interaction of new amino acids into the
polypeptide chains.
o Side effects include gastrointestinal disturbances,
kidney damage, and stainig of teeth in children.
o It should not be used in pregnancy.

26. 3. Chloramphincol:
o prevents peptide bond formation by blocking the
action of peptidtransferase
o Bacteristatic and broad spectrum
o Rabidly absorbed from GIT
o Used for many types of infections.
o May cause A plastic anaemia and is toxic in neonates.

27. 4.Macrolides (Erythromycin):
o Produced by streptomyces erythrus.
o bacteristatic agent
o Active against gram +ve bacteria
o Side effects include gastrointestinal upsets and rashes.
5.lincosamides:
o Useful in treating staphylococcal bone and joint
infections, associated with with pseudomembrane
colitis.

28. D. Antibiotics inhibt transcription of
nucleic acid synthesis
1- Quinlones:
Nalidixic
Fluroquinlones (Ciprofloxacin & Norfloxacin)
o Bacteristatic or bactericidal.
o Active against gram -ve & gram +ve bacteria.
o Have grater antibiotic activity & low toxicity.

29. 2.Sulphanomides and trimethoprim:
o Include: Co-trimoxazole, Trimethoprim,
Sulphadimine, and Sulphadoxine
o Bacteristatic.
o Active against gram - ve & gram +ve bacteria.
o Side effects include nausea, vomiting, mouth
ulceration, rashes, and occasionally thrombocytopenia
and leucopenia.

30. 3. Metronidazole:
o Used to treat anaeobic infection, Vincent,s angina,
and protozoal infection.
o Bactericidal.

31.  Anti - Mycobacterial agents:
1- Rifamicin:
o Semi-synthetic derivative of rifamycin.
o Active against some G -ve & G +ve, Mycobacteria &
Chlamydia
2. Ethambutol.
3. Isonizid.

32. Antimicrobial resistance
o Most of the antimicrobial resistance which is now
making it difficult to treat some infectious diseases is
due to the extensive use and misuse of antimicrobial
drugs which have favoured the emergence and survival
of resistant strains of micro-organisms.

33. Bacteria become resistant to antimicrobial agents
by a number of mechanisms, the commonest being:
1) production of enzymes which inactivate or modify
antibiotics,(Production of beta-lactamase enzymes
that destroy the beta-lactam ring of penicillins and
cephalosporins (commonest form of resistance).
2) changes in the bacterial cell membrane, preventing the
uptake of an antimicrobial,
3) modification of the target so that it no longer interacts
with the antimicrobial.
4) development of metabolic pathways by bacteria which
enable the site of antimicrobial action to be bypassed.

34. Any questions??