Antibiotics

By
Mohammed Ezz El-din
Demonstrator of Tropical Medicine & Gastroenterology
Faculty of Medicine, Assiut University
Email: [email protected]
 What is an antibiotic?

“Antibiotic” is from antibiosis, meaning against life.

Substances derived from a microorganism or

produced synthetically (Sulfonamides & Quinolones)
to kill or suppress the growth of other
microorganisms.
 Classification of Antibiotics

Antibiotics are classified by several ways:

• On the basis of mechanism of action
• On the basis of spectrum of activity
• On the basis of mode of action
Mechanism of action of antimicrobial agents

1. Inhibition of cell wall synthesis:

• Penicillins, Cephalosporins, Bacitracin & Vancomycin

2. Inhibition of functions of cellular membrane:

• Polymyxins

3. Inhibition of protein synthesis:

• Chloramphenicol, Macrolides & Clindamycin
• Tetracyclines & Aminoglycosides
4. Inhibition of nucleic acid synthesis:
• Quinolones
• Rifampin
5. Inhibition of folic acid synthesis:
• Sulfonamides & trimethoprim
On the basis of mechanism of action
 Antimicrobial Spectrum

Antimicrobial spectrum: the scope that a drug kills or

suppresses the growth of microorganisms.
Narrow-spectrum: The drugs that only act on one kind
or one strain of bacteria.(Isoniazide)

Broad-spectrum: The drugs that have a wide

antimicrobial scope.(Tetracycline &
Chloramphenicol)
On the basis of spectrum of activity
 On the basis of mode of action

• Tetracycline
Bacteriostatic • Chloramphenicol
antibiotics: • Erythromycin
• Lincomycin

• Cephalosporin
• Penicillin
Bacteriocidal • Erythromycin
antibiotics: • Aminoglycosides
• Cotrimoxazole
 Misuse of Antibiotics

Antibiotic misuse, sometimes called antibiotic abuse

or antibiotic overuse
The misuse or overuse of antibiotics, may produce
serious effects on health.
It is a contributing factor to the creation of multidrug-
resistant bacteria, informally called “super bugs”.
 Antibiotic Resistances and Cross
Resistances
Antibiotic resistance is the phenomenon that
susceptibility of pathogenic microorganisms
to antibiotic becomes lower or even loses after
the microorganisms contact with antibiotic many
times.
When the bacteria show resistance to one
antibiotic, they are also resistant to some other
antibiotics. This phenomenon is called cross
antibiotic resistance.
Mechanisms of Antibiotic Resistance

1. Alteration of the target site of the antibiotic

• One of the most problematic antibiotic resistances
worldwide, methicillin resistance among Staphylococcus
aureus

2. Enzyme inactivation of the antibiotic

• β-lactam antibiotics (Penicillins & Cephalosporins) can be
inactivated by β-lactamases.
Mechanisms of Antibiotic Resistance
Cont.
3. Active transport of the antibiotic out of the
bacterial cell
• Active transport of the antibiotic out of the bacterial cell
(efflux pumps) as removal of some antibiotics e.g.
Tetracyclines, Macrolides & Quinolones

4. Decreased permeability of the bacterial cell wall

to the antibiotic
• Alteration in the porin proteins that form channels in the cell
membrane e.g. Resistance of Pseudomonas aeruginosa to a
variety of Penicillins & Cephalosporins
 General Principles of Antimicrobial
Therapy
• Identification of the infecting organism should precede
antimicrobial therapy when possible.

• The pathogenic microorganism susceptibility to

antimicrobial agents should be determined, if a suitable
test exists.

• Factors that influence the choice of an antimicrobial agent

or its dosage for a patient include the age, renal & hepatic
function, pregnancy status and the site of infection, etc.
 Selection of Antimicrobial Agent

• Empiric therapy - prior to identification of Organism

- critically ill patients
• Organism’s susceptibility to the antibiotic
• Patient factors - immune system, renal/hepatic
function
• Effect of site of infection on therapy - blood brain
barrier
• Safety of the agent
• Cost of therapy
 Ideal Antimicrobial Agent

• Have highly selective toxicity to the pathogenic

microorganisms in host body
• Have no or less toxicity to the host
• Low propensity for development of resistance
• Not induce hypersensitive reactions in the host
• Have rapid and extensive tissue distribution
• Be free of interactions with other drugs
• Be relatively inexpensive
 Complications of Antibiotic Therapy

• Resistance due to inappropriate use of antibiotics

• Hypersensitivity (Penicillin)
• Direct toxicity (Aminoglycosides = ototoxicity)
• Super infections (broad spectrum antimicrobials
cause alteration of the normal flora; often difficult
to treat)
 Antimicrobial Combination
Results of Combination Therapy:
• Additive (indifferent) effect: the activity of two
drugs in combination is equal to the sum (or a
partial sum) of their independent activity when
studied separately.
• Synergistic effect: the activity of two drugs in
combination is greater to the sum of their
independent activity when studied separately.
• Antagonistic effect: the activity of two drugs in
combination is less to the sum (or a partial sum) of
their independent activity when studied separately.
Indications for the Clinical Use of
Antimicrobial Combinations

• Prevention of the emergence of resistant

organisms
• Polymicrobial infection
• Initial therapy
• Decreased toxicity
• Synergism
 Prevention of the Emergence of
Resistant Organisms

• Decreased resistant mycobacterium

tuberculosis with combination
• Reduction of -lactamase induction with
combination -lactam agents and
Aminoglycosides
 Polymicrobial Infection

• Intra-abdominal infection
• Pelvic infection
• Mixed aerobic and anaerobic organism
 Initial Therapy

• Neutropenic patients
• In patients where the nature of infection is not
clear yet
 Decreased Toxicity

• Decrease the toxic drug required for

treatment and thus reduce the dose related
toxicity
 Synergism

Enhanced Uptake of Aminoglycosides when Combined

with -lactam agents
• Treatment of enterococcal endocarditis: ampicillin &
gentamicin
• Viridans streptococcal endocarditis: penicillin &
gentamicin
• Staphylococcal bacteremia: vancomycin &
gentamicin
• Treatment of pseudomonas infections: -lactam
agent & Aminoglycosides
Inhibition of Sequential Steps
• Sulfonamide with trimethoprim
• Treatment and prevention of chronic urinary
tract infection, typhoid fever, shigellosis
caused by organisms resistant to ampicillin

Inhibition of enzymatic activation

 Disadvantages of the Inappropriate
Use of Antimicrobial Combination

• Antagonism
• Increased cost
• Adverse effects
• Super infections (alteration of the normal
flora; often difficult to treat)
 Classes of Antibiotics

The main classes of antibiotics are:

• Beta-Lactams • Macrolides & Ketolides
Penicillins • Aminoglycosides
Cephalosporins • Fluoroquinolones
Carbapenems • Tetracyclines, Amphenicols
Monobactams
 Penicillins

• The penicillins are the oldest class of antibiotics. Penicillins

have a common chemical structure which they share with
the Cephalosporins.

• Penicillins are generally bactericidal, inhibiting formation of

the cell wall. Penicillins are used to treat skin infections,
dental infections, ear infections, respiratory tract infections,
urinary tract infections, gonorrhea.
 Types of penicillins

• The natural penicillins

Penicillin G

• Penicillinase-resistant penicillins
Methicillin & Oxacillin

• Aminopenicillins
Ampicillin & Amoxicillin
 Penicillins side effects

• Diarrhea, nausea, vomiting, and upset stomach

• In rare cases Penicillins can cause immediate and
delayed allergic reactions - specifically skin rashes,
fever & anaphylactic shock.
• Penicillins are classed as category B during
pregnancy.
 Cephalosporins

• Cephalosporins have a mechanism of action

identical to that of the Penicillins.
• Interferes with synthesis of the bacterial cell wall
and so are bactericidal.
• Cephalosporins are used to treat pneumonia, strept
throat, staph infections, tonsillitis, bronchitis, otitis
media, various types of skin infections, gonorrhea,
urinary tract infections.

• Cephalosporins antibiotics are also commonly used

for surgical prophylaxis. Cephalexin can also be used
to treat bone infections.
 The first generation Cephalosporins

• They possess generally excellent coverage against most

Gram-positive pathogens and variable to poor coverage
against most Gram-negative pathogens.

• The first generation includes:

Cephradine (Velosef)
Cephalexin (Ceporex)
Cefadroxil (Biodroxil, Duricef)
 The second generation Cephalosporins

• In addition to the Gram-positive spectrum of the first

generation Cephalosporins, these agents have expanded
Gram-negative spectrum.
• Cefoxitin and Cefotetan also have good activity against
Bacteroides fragilis.

• The second generation includes:

Cefaclor (Bacticlor)
Cefuroxime (Zinnat)
 The third generation Cephalosporins

• They have much expanded gram negative activity. However,

some members of this group have decreased activity against
gram-positive organisms. They have the advantage of
convenient administration, but they are expensive.
• The third generation includes:
Ceftazidime (Fortum)
Cefixime (Suprax)
Cefoperazone (Cefobid)
Cefotaxime (Claforan, Cefotax)
Ceftriaxone (Ceftriaxone, Rociphen)
Cefdinir (Omnicef)
 The fourth generation Cephalosporins

• They are extended-spectrum agents with similar activity

against Gram-positive organisms as first-generation
cephalosporins. They also have a greater resistance to beta-
lactamases than the third generation cephalosporins.
• Many fourth generation cephalosporins can cross blood
brain barrier and are effective in meningitis.

• The fourth generation includes:

Cefepime (Maxipime)
 The Fifth generation Cephalosporins

• Used to treat MRSA (methicillin-resistant Staphylococcus

aureus), penicillin-resistant Streptococcus pneumoniae,
Pseudomonas aeruginosa, and enterococci.

• The fifth generation includes:

Ceftaroline (Teflaro)
Ceftobiprole (Zeftera)
 Cephalosporins side effects

• Diarrhea, nausea, mild stomach upset

• Approximately 5–10% of patients with allergic
hypersensitivity to penicillins will also have cross-
reactivity with cephalosporins.
• Cephalosporin antibiotics are classed as pregnancy
category B.
 Carbapenems
• A class of β-Lactam antibiotics with a broad spectrum of
antibacterial activity.
• Highly resistant to most β-lactamases.
• Active against both Gram-positive and Gram-
negative bacteria, and anaerobes, with the exception of
intracellular bacteria (atypical), such as the Chlamydia.

• Agents:
Imipenem/Cilastatin (Tienem)
Meropenem (Meronem)
• Adverse effects to Carbapenems include headache, rash, GI
upset, phlebitis, hypotension, seizures in patients with
renal dysfunction.
 Monobactams

• They are β-lactam compounds.

• They work only against aerobic Gram negative
bacteria (Neisseria, Pseudomonas).
• The only commercially available Monobactams antibiotic
is Aztreonam (Azactam).
• Adverse effects to Monobactams can include skin rash and
occasional abnormal liver functions.
 Macrolides
• Macrolides are bacteriostatic, binding with bacterial
ribosomes to inhibit protein synthesis.
• Macrolides antibiotics are used to treat respiratory tract
infections (such as pharyngitis, sinusitis, and bronchitis),
genital, gastrointestinal tract & skin infections.

• Macrolides antibiotics are:

Erythromycin (Erythrocin)
Clarithromycin (Klacid)
Azithromycin (Zithromax)
Roxithromycin (Roxicin)
 Macrolides side effects

• Nausea, vomiting, diarrhea; infrequently, there may be

temporary auditory impairment.
• Oral Erythromycin may be highly irritating to the stomach
and when given by injection may cause severe phlebitis.
• Macrolides antibiotics should be used with caution in
patients with liver dysfunction.
• Pregnancy category B: Azithromycin, Erythromycin.
Pregnancy category C: Clarithromycin
 Ketolides

• Antibiotics belonging to the Macrolides group.

• Much broad spectrum than other Macrolides.
• Ketolides are effective against Macrolides-resistant
bacteria, due to their ability to bind at two sites at the
bacterial ribosome as well as having a structural
modification that makes them poor substrates for efflux-
pump mediated resistance.
• The only Ketolide on the market at this moment
is telithromycin, which is sold under the brand name
of Ketek.
 Lincosamides (e.g. lincomycin, clindamycin)

• Lincosamides prevent bacteria replicating by interfering

with the synthesis of proteins.

• They are normally used to treat staphylococci and

streptococci, and have proved useful in treating
Bacteroides fragilis and some other anaerobes.
• They are used in the treatment of Toxic Shock Syndrome.

• Lincosamides antibiotics are one of the classes of

antibiotics most associated with pseudomembranous colitis
caused by C. difficile.
 Aminoglycosides

• The Aminoglycosides are bactericidal and work by stopping

bacteria from making proteins.
• Aminoglycosides antibiotics are used to treat infections
caused by Gram-negative bacteria.
• Aminoglycosides may be used along with penicillins or
cephalosporins to give a two-pronged attack on the
bacteria.
• Since Aminoglycosides are broken down easily in the
stomach, they can't be given by mouth and must be
injected.
• Generally, Aminoglycosides are given for short time
periods.

• Aminoglycosides group includes:

Amikacin (Amikin)
Gentamicin (Garamycin)
Neomycin (Neomycin)
Streptomycin (Streptomycin)
Tobramycin (Nebcin)
 Aminoglycosides side effects

• Ototoxicity
• Nephrotoxicity
• Aminoglycosides are classed as pregnancy category D.
 Fluoroquinolones
• They are synthetic antibiotics, not derived from bacteria.

• Fluoroquinolones are broad-spectrum bactericidal drugs

that are chemically unrelated to the penicillins or the
cephalosporins.

• Fluoroquinolones inhibit bacteria by interfering with their

ability to make DNA. This effect is bactericidal.

• Because of their excellent absorption Fluoroquinolones can

be administered not only by intravenous but orally as well.
• Fluoroquinolones are used to treat most common urinary
tract infections, skin infections, and respiratory infections
(such as sinusitis, pneumonia, bronchitis).

• Fluoroquinolones group includes:

Ciprofloxacin (Ciprobay, Ciprocin)
Levofloxacin (Tavanic, Alfacef)
Norfloxacin (Noracin)
Ofloxacin (Tarivid)
Moxifloxacin (Avalox)
 Fluoroquinolones side effects

• Nausea, vomiting, diarrhea, abdominal pain

• Irreversible damage to central nervous system (uncommon)
• Tendinosis (rare)
• Fluoroquinolones are classed as pregnancy category C.
 Trimethoprim/sulfamethoxazole or Co-trimoxazole

• An antibiotic used in the treatment of a variety of bacterial,

fungal and protozoal infections.

• Co-trimoxazole is generally considered bactericidal,

although its components are individually bacteriostatic.

• Its actions are antifolate in nature, inhibiting both de

novo folate biosynthesis and metabolism.
 Co-trimoxazole side effects

• Nausea, vomiting
• An allergic reaction and infection with Clostridium difficile,
a type of diarrhea
• Co-trimoxazole is classed as pregnancy category C.
• Some state it should not be used during breastfeeding
while others say it is okay.
 Tetracyclines

• Broad-spectrum bacteriostatic agents and work by

inhibiting the bacterial protein synthesis.

• Tetracyclines may be effective against a wide variety of

microorganisms, including Rickettsia and Amoebic
parasites.

• Tetracyclines are used in the treatment of infections of the

respiratory tract, sinuses, middle ear, urinary tract, skin,
intestines.
• Tetracyclines also are used to treat Gonorrhea, Rocky
Mountain spotted fever, Lyme Disease, Typhus.
• Their most common current use is in the treatment of
moderately severe acne and rosacea.
• Tetracycline antibiotics are:
Tetracycline
Doxycycline (Vibramycin)
Minocycline
Oxytetracycline (Oxytetracid)
 Tetracyclines side effects
• Cramps or burning of the stomach, diarrhea, sore mouth or
tongue
• Skin photosensitivity
• Allergic reactions
• Tetracycline antibiotics should not be used in children
under the age of 8 and specifically during periods of tooth
development.
• Tetracyclines are classed as pregnancy category D. Use
during pregnancy may cause alterations in bone
development.
 Chloramphenicol
• It is a bacteriostatic.

• It is considered a prototypical broad-spectrum antibiotic,

alongside the tetracyclines, and as it is both cheap and easy
to manufacture, it is frequently an antibiotic of choice in
the developing world.

• Effective against a wide variety of Gram-positive and Gram-

negative bacteria, including most anaerobic organisms.
• Due to resistance and safety concerns, it is no longer a first-
line agent for any infection in developed nations, with the
notable exception of topical treatment of
bacterial conjunctivitis.
 Chloramphenicol side effects

• The most serious adverse effect associated with

chloramphenicol treatment is bone marrow toxicity.
• Use of intravenous chloramphenicol has also been
associated with gray baby syndrome.
• Other less serious reactions include fever, rashes,
headache, confusion.
 Glycopeptides (e.g. vancomycin, teicoplanin)

• These antibiotics are effective principally against Gram-

positive cocci.

• This class of drugs inhibit the synthesis of cell walls in

susceptible microbes by inhibiting peptidoglycan synthesis.

• Vancomycin is used if infection with methicillin-

resistant Staphylococcus aureus (MRSA) is suspected.
• Due to their toxicity, use of glycopeptides antibiotics is
restricted to patients who are critically ill, who have a
demonstrated hypersensitivity to the β-lactams, or who are
infected with β-lactam-resistant species.

• They exhibit a narrow spectrum of action, and are

bactericidal only against the enterococci.
• Oral preparations of vancomycin are available, however
they are not absorbed from the lumen of the gut,
formulated for the treatment of infections within the
gastrointestinal tract, Clostridium difficile, for example.
 Vancomycin side effects

• Vancomycin is usually given intravenously, as an infusion,

and can cause tissue necrosis and phlebitis at the injection
site.
• Red man syndrome, an idiosyncratic reaction to bolus dose
caused by histamine release
• Nephrotoxicity including renal failure and interstitial
nephritis
• Blood disorders including neutropenia, and deafness, which
is reversible once therapy has stopped
• Risk of accumulation in patients with renal impairment
 Streptogramins

• Effective in the treatment of vancomycin-

resistant Staphylococcus aureus (VRSA) and vancomycin-
resistant Enterococcus (VRE), two of the most rapidly
growing strains of multidrug-resistant bacteria.

• Members include:
Quinupristin/dalfopristin
Pristinamycin
Virginiamycin
Adverse effects include:
Related to administration via peripheral vein
Inflammation, pain, edema, infusion site reaction,
thrombophlebitis
Non-venous adverse effects
• Nausea, vomiting, diarrhea
• Rash
• Headache
• Pain, ill-defined focal or generalized discomfort
• Pruritus
• Arthralgia, myalgia
• Asthenia
• Conjugated hyperbilirubinaemia
 Oxazolidinones (e.g. linezolid)

• Linezolid inhibits ribosomal protein synthesis by inhibiting

formation of the initiation complex.

• It is used for the treatment of serious infections caused

by Gram-positive bacteria that are resistant to several other
antibiotics.

• Linezolid is active against most Gram-positive bacteria that

cause disease, including streptococci, vancomycin-resistant
enterococci (VRE), and methicillin-resistant Staphylococcus
aureus (MRSA).
• The main indications of linezolid are infections of the skin &
soft tissues and pneumonia (particularly hospital-acquired
pneumonia).
• Common adverse effects of short-term use
include headache, diarrhea & nausea. Long-term use,
however, has been associated with serious adverse effects;
linezolid can cause bone marrow suppression and low
platelet counts, particularly when used for more than two
weeks. If used for longer periods still, it may cause
sometimes irreversible chemotherapy-induced peripheral
neuropathy and optic nerve damage, and lactic acidosis.
 Ansamycins

• A family of secondary metabolites that

show antimicrobial activity against many Gram-positive and
some Gram-negative bacteria and includes various
compounds, among which: streptovaricins and rifamycins.

• Rifamycins are a subclass of ansamycins with high potency

against mycobacteria. This resulted in their widespread use
in the treatment of tuberculosis, leprosy, and AIDS-related
mycobacterial infections.
• The antibacterial activity of rifamycins relies on the inhibition of
bacterial DNA-dependent RNA synthesis. This is due to the high
affinity of rifamycins for the prokaryotic RNA polymerase.

Adverse effects include:

• Hepatotoxic - hepatitis, liver failure in severe cases
• Respiratory - breathlessness
• Cutaneous - flushing, pruritus, rash, redness and watering of
eyes
• Abdominal - nausea, vomiting, abdominal cramps with or
without diarrhea
• Flu-like symptoms - with chills, fever, headache, arthralgia,
and malaise, rifampin has good penetration into the brain, and
this may directly explain some malaise and dysphoria in a
minority of users.
Rifaximin is a semisynthetic antibiotic based on rifamycin. It
has poor oral bioavailability, meaning that very little of the
drug will be absorbed into the blood stream when it is
taken orally. Rifaximin is used in the treatment of traveler's
diarrhea and hepatic encephalopathy, for which it
received orphan drug status* from the U.S. Food and Drug
Administration in 1998.
Rifaximin interferes with transcription by binding to the β-
subunit of bacterial RNA polymerase.

* An orphan drug is a pharmaceutical agent that has been

developed specifically to treat a rare medical condition.
 Metronidazole
• A nitroimidazole antibiotic medication used particularly
for anaerobic bacteria and protozoa.

• It is antibacterial against anaerobic organisms,

an amoebicide and an antiprotozoal.

• It inhibits nucleic acid synthesis by disrupting the DNA of

microbial cells. This function only occurs when
Metronidazole is partially reduced, and because this
reduction usually happens only in anaerobic cells, it has
relatively little effect upon human cells or aerobic bacteria.
• Metronidazole is primarily used to treat: bacterial
vaginosis, pelvic inflammatory disease (along with other
antibacterials like ceftriaxone), pseudomembranous
colitis, aspiration pneumonia, rosacea (topical), fungating
wounds (topical), intra-abdominal infections, lung
abscess, gingivitis, amoebiasis, giardiasis, trichomoniasis,
and infections caused by susceptible anaerobic organisms
such as Bacteroides.
• It is also often used to eradicate Helicobacter pylori along
with other drugs and to prevent infection in people
recovering from surgery.

• Adverse effects include:

Discolored urine, headache, metallic taste , nausea
Metronidazole is classed as pregnancy category B.
For more information:
http://www.emedexpert.com/classes/antibiotics.shtml
http://en.wikipedia.org/wiki/List_of_antibiotics
http://www.orthobullets.com/basic-
science/9059/antibiotic-classification-and-mechanism
http://www.nlm.nih.gov/medlineplus/antibiotics.html
https://www.youtube.com/channel/UCvl8mk9dKfhidf8oVh
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