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Antibiotics
By: Noor Hisham Al-Atraqchi
M.Sc. pharmacognosy
Definition
• Antibiotics
are
chemical
substances
produced
by
a
microorganism, that has the capacity, in low concentration, to
inhibit or kill, selectively, other microorganisms.
• The term antibiotic is now used to include anti-infective
produced from synthetic or semi synthetic compounds.
• The term antibiotic may be used interchangeably with term
antibacterial .
• However, it is incorrect to use the term antibiotic when
referring to antiviral, antifungal and antiprotozoal agents.
History of Antibiotics
• The first antibiotic to be discovered was penicillin, a natural
product of Penicillinum mold .
• Alexander Fleming 1928 observed inhibition of Staphylococci
on an ager plate contaminated by a Penicillinum mold , there was
a halo of inhibited bacterial growth around the mold.
• Fleming concluded that the mold was releasing a substance that
was suppressing the growth & lysing the bacteria.
• The antibiotic substance, named penicillin, was not purified
until the 1940s (by Florey and Chain), just in time to be used at
the end of the second world war.
Penicilium notatum
Criteria that determine the effectiveness of
antimicrobial agents
 Selective destruction of the microorganism.
 Antimicrobial substances should have a specific action
against molecules or enzymes or metabolism of the
microorganism only.
 No or rare side effects on the host
Natural sources of antibiotics
Most antibiotics in clinical use are of bacterial or fungal
origin.
• Among the bacteria, the genus Streptomyces is the
largest source of antibiotics, they produce antibiotics like
streptomycin, chloramphenicol, chlortetracycline ,
erythromycin and neomycin
• Cyanobacteria: mostly produce toxins that kill higher
organisms.
• Fungi:
e.g:
penicillin produced by the genera
“penicillium notatum and P. chrysogenum .
Cyanobacteria
Sources of antibiotics
How the microorganisms
produce antibiotics ?
 Primary metabolism is the metabolism of energy
production for the cell, the primary metabolites are
produced during active growth ,e.g: alcohol, lactic acid
 Secondary metabolism regards the production of
metabolites that are not used in energy production .The
metabolite is being utilized as a defense mechanism
against other microorganisms in the environment.
• Natural antibiotics made by microbes as products of
their secondary metabolic pathways .
• Secondary metabolites are not essential for growth and
reproduction.
• The pathways for synthesis of antibiotics are turned off
during growth phase (lag phase) when there is
abundance of nutrients .
• Secondary metabolites are produced
in stationary
phase, they are only produced in times of stress when
resources are low and the organism must produce these
compounds to kill off its competitors to allow it to
survive, e.g: penicillin, streptomycin.
• These information are important for the industrial
preparation of antibiotics from the natural sources.
Non microbial sources of antibiotics
• Lichens: Many of these appear to owe their bacteriostatic
and antifungal properties to usnic acid or vulpinic acid.
• Order Coniferae. Various essential oils from Pinus spp.
• Marine organisms
• Plants/insects
• Monocotyledons,e.g:
 Fresh garlic owes its antibiotic action to alliine. A sulphurcontaining amino acid;
 ginger has antibacterial properties
 aloe vera gel.
Non microbial sources of antibiotics
• Dicotyledons. examples o f this group are:
 the sesquiterpen
ketones of hops (humulene and
lupulene)
 Mastic gum is effective in the treatment of gastric ulcers
and has been shown to be active in low doses against
Helicobactor pylori .
 Cinnamon extracts have been shown to inhibit the
growth and urease activity of the same organisim.
(Helicobactor pylori).
Types of Antibiotics according to
the source
 Natural antibiotic agents: metabolic products produced by
microorganisms ,e.g:
• Penicillium notatum-penicillin
• Streptomyces spp.-streptomycin
 Semi-synthetic antibiotic agents: chemically modified
natural agents (large group of modern antibiotics).
 Synthetic antibiotic agents: chemically related to the
natural
antibiotics
but
completely
industrially
manufactured.
Classification of antibiotics
Based on chemical structure :
 Beta lactam antibiotics - penicillins, cephalosporins
 Aminoglycosides: streptomycin, gentamycin, amikacin.
 Macrolides : erythromycin, azithromycin
 Tetracyclines - oxytetracycline, doxycycline
 Sulfonamides : Sulfadiazine, paraaminosalicylic acid (PAS)
 Quinolones: Norfloxacin, Ciprofloxacin
 Diaminopyrimidines: Trimethoprim, Pyrimethamine
 Nitrobenzene : chloramphenicol.
Classification of antibiotics
Antibiotics can be classified according to their Spectrum of
activity:
A. Narrow-spectrum antibiotics: chemotherapeutic agents
acting only on a single or a limited group of
microorganisms, For example, penicillin G is active
against gram positive bacteria.
A. Broad-spectrum antibiotics: drugs that affect a wide
variety of microbial species and are referred to as
broad-spectrum antibiotics, such as tetracycline which
is active against gram negative and gram positive
bacteria.
Classification of antibiotics
• Antibiotics can be classified according to their mechanism
of action :
bacteriostatic vs bacteriocidal
• Bacteriostatic antibiotics: arrest the growth and
replication of bacteria, thus limiting the spread of
infection until the immune system attacks, immobilizes,
and eliminates the pathogen.
• Bactericidal antibiotics : kill bacteria at drug serum
levels achievable in the patient. Because of their more
aggressive antibiotic action, bactericidal agents are often
the drugs of choice in seriously ill and
immunocompromised patients.
Complications of antibiotics therapy
• Hypersensitivity:
the penicillins, despite their almost
absolute selective microbial toxicity, can cause serious
hypersensitivity problems, ranging from urticaria (hives) to
anaphylactic shock.
•
Direct toxicity :High serum levels of certain antibiotics may
cause toxicity by directly affecting cellular processes in the
host. For example, aminoglycosides can cause ototoxicity.
• Superinfections: antibiotic therapy, particularly with broadspectrum antimicrobials or combinations of agents, can lead
to alterations of the normal microbial flora of the upper
respiratory, oral, intestinal, and genitourinary tracts,
permitting the overgrowth of opportunistic organisms,
especially fungi or resistant bacteria.
Resistance to Antibiotic Therapy:
 The widespread and indiscriminate used of antibiotics
together with poor hygiene resulted in that many
pathogenic organisms have acquired resistance to
specific antibiotic and these strains particularley
evident in the hospital environments .
 Development of resistant strains :
• Production of enzymes that can destroy antibiotics.
• Rsistance genes e.g: in plasmids, transferred from one
bacterial cell to the other.
• Modifications of the target.