SCOPE OF ANTIBACTERIAL AGENTS

 In this course we shall attempt to cover

Antibiotic use in Bacterial infections.
 Attention will be paid to the uniqueness of
classes of Antibaterial Agents using the following
description
i.Introduction
ii.Chemistry of the antibacterial Agent
iii.Mechanism of Action
iv.Antibacterial Spectrum.v.Pharmacokinetic.
vi.Clinical uses.vii.Adverse reaction
Vii.Contraindication
 ANTIBACTERIAL AGENTS-Sulfonamides
Introduction:
Sulfonamides were the first effective
antibacterial agents to be used systematically in
man.
They were introduced by Domagk in 1935
 and in the next few years several of them were
synthesized and widely used.
Currently ,their role in therapeutic is limited
because of their toxicity,development of resistance
and avalability of safer drugs.
 Chemistry of sulfonamide
Sulfonamides are
structural analogs of
P-aminobenzoic
acid(PABA).They are
synthetic agents
that contain a
sulfonamide group.
Classification
 Antibacterial Spectrum
Sulfonamides inhibit many gram-positive
and some gram-negative bacteria
including.streptococci,H.influenzae .ducreyi
,
Nocardia.E.coli,salmonella,shigella,Proteus,
V.cholerae,a few strains of
staphylococci,gonococci,meningococci.They
are also effective against
chlamydiae,P.falpaciparum and Toxoplasma
gondii.
 Mechanism of Action
 Folic acid is essential for the synthesis
of nucleic acids.
 Bacteria synthesize their own folic acid
from PABA with the help of the
enzyme folic acid synthetase.
 Sulfonamides are struturally similar to
PABA and competively inhibit the
enzyme folic acid synthetase.
 This result in folic acid deficiency and
thereby inhibition of bacterial growth
as well as injury to the bacterial cell.
 Sulfonamides are Bactriostatic.
 Resistance
Bacteria acquire resistance to sulfonamides by:
1.Mutations:resulting in over
production of PABA.
2.Using alternative metabolic
pathway for folic acid synthesis
producing folate synthetase which
has a low affinity for sulfonamides.
3.Low permeability to sulfonamides.
Pharmacokinetics and Preparations
 Adverse Effects
Sulfonamide can cause:
1.Renal irritation,haematuria,albuminuria
and crystalluria.
2.Allergic reactions-hypersensitivity
reaction.
3.Anorexia,nausea,stomatitis,abdominal
pain,conjuctivitis and arthritis can occur.
4.Haemolytic anaemia
5.Kernicterus.
 USES
Because of the development of
resistance and availability of better
antimicrobial which are more
effective and less toxic,sulfonamides
are not commonly used now except
in a few cases.
They are given in combination with
other drug like trimethoprim and
pyrimethamine
 Uses cont’d
Sulfonamides are used in:
1.Urinary tract infections:Uncomplicated
acute UTI can be treated with
sulfonamide in areas where resistance
is not high.sulfisoxazole(1gQID) or
sulfamethoxazole(1gTDS).
2.Nocardiosis:High doses of
sulfonamides can be used as
alternatives.
 Uses cont’d
3.Toxoplasmosis:
sulfadoxine with pyrimethamine is the
treatment of choice in T.gondii infection.
sulfodoxine is given in the dose of 4g/day
while pyrimethamine is given as a bolus dose
of 75mg followed by 25mg daily.
The treatment is continue for 4-6 weeks .
such doses require leucovorin rescue(10mg
folinic acid daily) to prevent severe folic acid
deficiency).
 Uses cont’d
4.Trachoma,inclusion
conjuctivitis,lymphogranuloma
venereum and chancroid.
Sulfonamides are used as alternative
to tetracyclines
5.Malaria:
Sulfadoxine is used with
pyrimethamine in chloroquine-
resistant malaria.
 Uses cont’d
6.Prophylactic use:
In patient s allergic to
penicillins,sulfonamides may
be used for prophylaxis of
streptococcal pharyngitis in
rheumatic fever.
 Uses cont’d
7.Topical:
Sulfacetamide eye drops are used in
bacterial conjunctivitis
and sulfadiazine ointment are used
in burns to prevent infection.
8.Ulcerative colitis:
Sulfasalazine is useful in ulcerative
colitis and rheumatoid arthritis.
 COTRIMOXAZOLE
The combination of
trimethoprim and
sulfamethoxazole is
Cotrimoxazole.Trimeth
oprim is effective
against several gram-
positive and gram-
negative
organisms.However,
when used as a sole
agent,resistance
develops rapidly.
 Antibacterial spectrum
Cotrimoxazole is effective against
several gram-positive and gram-
negative organisms like
Staph.aureus,
streptococci,meningococci,C.diph
theriae,E.coli,pneumocystis
jiroveci.
 Mechanism of Action
Sulfonamides inhibit the
conversion of PABA to
dihydrofolic(DHF) acid
and trimethoprim
inhibits dihydrofolate
reductase(DHFR) and
thus prevents the
reduction of DHF to
tetrahydrofolic(THF)
acid.
 Mechanism of Action
The two drugs thus block
sequential steps in folic
acid synthesis and the
combination is
synergistic.Given
alone,both
trimethoprim and
sulfonamides are
bacteriostatic but the
combination is
bactericidal.
 Resistance
Development of resistance to
the combination is lower when
compared to either drug given
alone.
Bacteria may acquire resistance
by mutation or by acqisition of a
plasmid coding for an altered
DHFR.
Pharmacokinetics and Preparations
 Adverse Effects
• Nausea,vomiting,headaache,g
lossitis,stomatitis and allergic
skin rashes are relatively
common.
• In patient with folate
deficiency ,cotrimoxazole may
precipitate anaemia.
 Adverse Effects
• Haematological reaction like
anaemia and granulocytopenia are
rare.
• Patient with renal disease may
develop uraemia.
• Cotrimoxazole should not be given in
pregnancy as it is an antifolate drug
and could be teratogenic.
 Uses
1.Urinary tract infection:
Uncomplicated acute UTI
It is treatedd for 7-10days with
cotrimoxazole( DS,twice a day).
Both drugs attain good
cocentration in the urine.
 UTI cont’d
Chronic and recurrent UTI:
Small doses are given for
prophylaxis(1tab.single strength
thrice a week).
Bacterial prostatitis:
Trimethoprim attains high
concentration in prostatic
fluid.Cotrimoxazole DS,twice daily
 Used cont’d
2.Respiratory tract infection:
Upper and lower respiratory infections
inluding bronchitis,sinusitis and otitis
media respond.
3.Bacterial gastroenteritis:
Due to shiggella and E.coli respond to
cotrimoxazole .
4.Typhoid:
Cotrimoxazole is used as an alternative to
 Uses cont’d
5.Pneumocystis jirovecii infection:
Cotrimoxazole is used for the prophylaxis
and high doses (trimethoprim20mg/kg +
sullfamethoxazole 100mg/kg daily) for
the treatment of pneumocystis jiroveci
pneumonia in neutropenic and AIDS
patients.
it also protect against infections with
other gram-negative bacteria.
 Uses cont’d
6.Chancroid:Cotrimoxazole (DS,BD
for 7days) is the drug of choice.
7.Meliodosis:Eradication requires 3
months of cotrimoxazole-+
doxycycline.
8.Toxoplasmosis:As alternative to
pyrimethamine + sulfadiazine.
 Uses cont’d
• 9.Intravenous cotrimoxazole:
Generally cotrimoxazole is used
orally.
In serious illness and when it cannot
be taken orally as in pneumocystis
pneumonia,typhoid, and UTI caused
by susceptible
microbes,cotrimoxazole may be given
 QUINOLONES
• These are synthetic
antimicrobials having a
• quinolone structure.
The first member
Nalidixic acid
introduced
• in mid-1960s. Other
newer
• fluorinated compounds
are also available e.g
Ciprofloxacin.
Classificatios
 Nalidixic Acid
Nalidixic Acid is bactericida against various gram-
negative organisms ,
like E.coli,shigella,Enterobacter,Proteus and
Klebsiella.
The mechanism of action is by inhibition of DNA
gyrase in the bacteria.
Nalidixic acid is well absorbed orally.
However ,the plasma concentration of the free
drug is inadequate to produce systemic effects
because it is too rapidly excreted .
However it attains high concentrations in the
 Adverse Effects
Adverse effects are
uncommon,haemolytic
anaemia,particularly in G6PD
deficient individuals,allergic
reactions
and CNS effects like
headache,myalgia,drowsiness and
visual disturbances may be
encountered
 USES
1.Urinary tract infection:
Nalidixic acid is an urinary antiseptic used in
uncomplicated UTI due to E.coli,shigella and
Proteus.
2.Diarrhoea:
Nalixic acid is useful in the treatment of
diarrhoea due to proteus ,E.coli and Shigella.
Dose:0.5-1g 3-4 times a
day.GRAMONEG,URODIC 500mg tab 0.3g/ml
liquid.
 Limitation of Nalidixic Acid
The first member Nalidixic acid
introduced in mid-1960s had
usefulness limited to urinary and g.i.
tract infections
because of low potency, modest
blood and tissue levels,restricted
spectrum and high frequency of
bacterial resistance.
 FLUOROQUINOLONES
The fluorinated quinolones were
synthesized and the fluoroquinolones
have many advantages overquinolones:
1.Wider spectrum of activity
2.Fewer side effects
3.Lesser chance of resistance
4.Attain therapeutic blood levels
5.Have better tissue penetration.
 Introduction and chemistry
 A breakthrough was achieved in
the early 1980s by fluorination
of the quinolone structure at
position 6 and introduction of a
piperazine substitution at
position 7 resulting in
derivatives
 called fluoroquinolones with
high potency, expanded
spectrum, slow development of
resistance, better tissue
penetration and good
tolerability.
 Cont.
• Note: The fluoroquinolones(FQs)
include:
• 1.First generation agents:
• Norfloxacin,ciprofloxacin,pefloxacin,
ofloxacin.
• 2.Second generation:
• levofloxacin,lomefloxacin,sparfloxacin,ga
tifloxacin,moxifloxacin ,gemifloxacin.
 Mechanism of Action
 Fluoroquinolones are bactericidal.
 They inhibit the bacterial enzymes DNA gyrase
and topoisomerase IV which are required for
DNA replication and transcription.
 By inhibiting the enzyme DNA gyrase
fluoroquinolones inhibit DNA replication.
 Fluoroquinolones also inhibit topoisomerase IV
and block the separation of the daughter cells.
 Bacteria with damaged DNA are formed which
are degraded by nuclease enzymes.
 Thus FQs are bactericidal.
Mechanism of Action Cont.
 Resistance
Resistance to FQs could be due to:
1.Mutations in the target enzyme-the
drug loses affinity for it.
2.Achange in the permeability of the
organism to the drug.
3.Production of DNA gyrase by some
protein-plasmid mediated.
 Uses
1.Urinary tract infections:FQs are very
effective in UTI even those caused by multi-
drug resistant bacteria.Norfloxacin is
generall used (400mg BD for 5-10days).
2.Thyphoid:Ciprofloxacin is the drug of
choice(500mg BD-10days).It also eradicate
the carrier state.
3.diarrhoea:Due to shigella,salmonella,E.coli
and campylobacter respond.
 Uses cont’d
4.Gonorrhoea:single dose 250mg
ciprofloxacin is curative but
resistance in many countries has
now emerged and ciprofloxacin is
now not the first-line treatment Of
gonorrhoea.
5.Chancroid:As an alternative to
cotrimoxazole ,ciprofloxacin iss used
for 3days .
 Uses cont’d
6.Respiratory tract infections:
due to H.influenzae,Legionella and
Mycoplasma can be treated with
fluoroquinolones.
Gemifloxacin moxifloxacin,gatifloxacin and
levofloxacin are called respiratory
fluoroquinolones as they are effective
against most respiratory pathogens
including gram-posituve bacteria as well as
Legionell,Chlamydia and Mycoplasma.
 Uses cont’d
7.Bone,joint,soft tissue and intra-
abdominal infection:
Osteomyelitis and joint
infections require prolonged
treatment .
Soft tissue infections due to
ssensitive bacteria can be
treated with fluoroquinolones.
8.Tuberculosis:
Ciprofloxacin is one of the
drugs in multi-drug
regimens used for resistant
tuberculosis.
It is also useful in atypical
mycobacteria infections
 Uses cont’d
9.Bacterial prostatitis and
cervicitis:
FQs are usseful.Chlamydial
urethritis and cervicitis also
respond-ciprofloxacin
or sparfloxacin can be used
as alternatives to tetracycline
 Uses cont’d
10.Eye infections:
Ciprofloxacin and ofloxacin may
be used topically in the
treatment of eyes infections.
11.Anthrax:
Ciprofloxacin is the DOC for
anthrax.It is also useful for
 Uses cont’d
12.Neutropenic patient:
FQs may be used for prophylaxix of infection
in neutropenic patients.
13.Gram-negative septicaemia:
FQs may be combined with a III generation
cephalosporin/aminoglycosides in the
treatment of gram-negative septicaemia.
14.Meningococcal carrier state:
FQs eradicate carrier state,they are also used
in meningitis.
 Contraindications
1. FQs are contraindicated in
pregnancy.
2. To be avoided in boys and girls less
than 18yeaes of age because FQs
damage the growing cartilages and
cause arthropathy.However,since
the effect is rversible,FQs are being
used in some selected infections
even in children.
 Contraindication cont’d
3.To be avoided in patients with prolonged
QTc interval,in those receiving other
drugs that prolong QTc interval
(mefloquine,erythromycin and class I
and II antiarrhythmics.
4.Toxicity due to theophyline(and other
epileptogenic drugs) may be precipitated
by FQs due to microsomal enzyme
inhibition.
 Cont’d
5.Calcium,iron and other
preparations containing divalent
cations should be avoided as they
reduce FQ absorption.
6.Dose adjustment should be done
in renal failure(except for
moxifloxacin.
 Adverse Reactions
Fluoroquinolones are well-
tolerated,nausea,vomiting,
abdominal
discomfort,diarrhoea and
skin rashes may be seen.
Beta-Lactam Antibiotics
These are antibiotics having a β-
lactam ring in their structure.
The two major groups are
penicillins and
cephalosporins.Monobactams
and carbapenems are relatively
later additions.
 Penicillins
Sir Alexander Fleming discovered
penicillin in 1928 from penicillium
notatum.
In 1941 penicillin became available
for therapeutic use.
Though sevral antibiotics have been
introduced since then,
penicillins are one of the most
important groups of antibiotics.
 Chemistry of Penicillins
The structure of penicillin
consists of a thiazolidine
ring(A) attached to a beta-
lactam ring (B) to which a
side chain(R) is attached.
A and B together is called
6-aminopenicillanic acid
nucleus or penicillin
nucleus which is essetial
for the antibacterial
 Chemical structure of penicillins. (1) Thiazolidine
ring; (2) β-lactam ring; (X) Bond which is broken by penicillinase
Mechanism of Action
All β-lactam antibiotics interfere
with the synthesis of bacterial cell
wall .
By inhibiting the synthesis of
peptidoglycans resulting in the
formation of cell wall deficient
bacteria.
These undergo lysis .
Thus penicillins are bactericidal.
 Resistance to Beta-lactams
Bacteria develop resistance to penicillins by
one of the following mechanisms:
1.Many organisms like staphylococci produce
an enzyme. the penicillanase which is a
beta-lactamase-it opens the Beta-lactam
ring and inactivates penicillins-most
common mecchanism of resistance to
penicillins.
2.Altered target proteins(PBPs) on the
bacterial cell which reduce affinity for
penicillins.
 Cont.
3.Poor penetration of the drug into
the bacteria as in gram-negative
bacteria.
4.Efflux of penicillin from the gram-
negative bacteria by an efflux
pump.
Penicillin can be classified as:
 Natural PENICILLINS
Penicillin G(Benzyl penicillin).
Antibacterial Spectrum:
Penicllin G has a narrow
antibacterial spectrum and is
effective against gram-
positive cocci and bacilli and
a few gram-negative cocci.
 Cont’d
Thus
streptococci,B.anthracis
C.diphtheriae,clostridia.Lis
teria and spirochetes are
highly sensitive.Penicillins
are also effective against
 Preparations and Dose
 Penicillin G is mainly
given parentrally
 though orally effective
form of Penicillin G is also
available.Im
 inj of benzyl penicillin is
painful as it an irritant
 and is therefore,given
intravenously.
 Benzyl penicillin is given
IV,procaine penicillin IM
and benzathine penicillin
 Adverse Effects
Penicllins are highly safe
drugs with high therapeutic
index,most adverse effects
are not serious in
therapeutic doses except
hypersensitivity reaction.
Penicillin G is the
USES
5.Syphilis
antibiotic of choice for
several infections unless 6.Diphtheria
patient is allergy to it. 7.Anaerobic
1.Pneumococcal infections infections
2.Streptococcal infections 8.Actinomycosis
3.Meningococcal
9.Tetanus and gas
infections
gangrene
4.Staphylcoccal infections
10.Other infections
11.Prophylactic uses
1.Pneumococcal infections:
For infections like pneumonia,meningitis
and osteomyelitis due to penillin-sensitive
pneumococci,PnG is the drug of choice.
2.Streptococcal infections:
Pharyngitis,sinusitis,pneumonia,meningiti
s and endocarditis are alltreated with
Penicillin.
Infection endocarditis due to streptococci
viridans is treated with high dose PnG in
combination with an aminoglycoside.
3.Meningococcal infections:
PnG is the drug of choice for all
meningococal infections.
4.Staphylcoccal infections:
Since most of the staphylococci
produce penicillinase,a
penicillinase-resistant penicillin
should be used.
5.Syphilis:
Is treated with procaine
penicillin for 10days or with
benzathine penicillin.
6.Diphtheria:
Antitoxin is the only effective
treatment.PnG eliminate carrier
state given for 10-12 days.
7.Anaerobic infections:
Pulmonary,periodontal and brain
abscesses due to anaerobes
respond to PnG.
8.Actinomycosis:
PnG is the drug of choice for all
forms of actinomycosis.12 to
20MU sholud be given for
9.Tetanus and gas gangrene:
Antitoxinis the treatment for tetanus-
but PnG has adjuvant value.
Gas gangrene-PnG is the drug of
choice.
10.Other infections:
PnG is the agent of choice for
infections like anthrax,trench
mouth,rat bite fever and listeria
 Disadvantages of Natural Penicillins
Natural penicillins have the
following disadvantages
1.Narrow spectrum of activity
2.Not effective orally-acid labile
3.Susceptible to penicillinase
4.Risk of hypersentivity.
 SEMISYNTHETIC PENICILLINS
1.Acid-resistant penicillins.
PenicillinV(Phenoxymethyl penicillin) is
acid stable and can be given orally
it is used only in mind infection as it has a
low bioavailability,short action(6hrly
dosing) and a narrow spectrum of acitivity.
It may be given in
streptococcal,pharyngitis,sinusitis and
trench month
 Cont.
2.Penicillinase-resistant
penicillins:
Penicillinase-resistant
penicillins are resistant to
hydrolysis by penicillinase
produced by bactria.
 Cont’d
3.Aminopenicillins:
Aminopenicillins are extended
spectrum penicillins-cover a
wider antibacterial spectrum
including many gram-negative
bacilli.
they are orally effective,,but are
sensitive to beta-lactamases.
 Cont.

4.Antipseudomonal
Penicillins
 BETA-LACTAMASE INHIBITORS

Beta-lactamases are
enzymes produced by
bacteria that open up the
Beta-lactam ring and
inactivate the Beta-
lactam antibiotic .
 Cont’d
Beta-lactamases inhibitors
bind to and inactivate
Beta-lactamases
thereby preventing the
destruction of the Beta-
lactam antibiotics.
 Cont’d
They broaden the
antibacterial spectrum of
penicillins to inlude
penicillanase producing
staphylococci,gonococci,E.
coli H.influenzae and
 Cont’d
• Three Beta-lactamase
inhibitors are available
(i).Clavulanic acid
(ii).sulbactam
(ii).tazobactam
 CEPHALOSPORINS
Cephalosporins are
semisynthetic antibiotics with a
Beta-lactam ring related to
penicillins.
They are derived from
cephalosporin-C and have a wider
spectrum of activity than
pencillins.
 Chemistry of cephalosporins
 The beta-lactam ring is fused
to a dihydrothiazine ring.
 Modification of the side
chain at position 7 of beta-
lactam ring alters
antibacterial activity
 while modification at
position 3 of dihydrothiazine
ring alters the
pharmacokinetic properties.
 Mechanism of Action & Resistance
Mechanism of Action:
 Cephalosporins inhibit the
bacterial cell wall synthesis
similar to penicillins.
 They are bactericidal.
Resistance:
 As in the case of
penicillins,beta-lactamases
or cephalosporinases and
altered target proteins.
 i.e altered PBPs determine
resistance to cephalosporins.
 The antibiotic may be unable
to penetrate the bacteria.
 Adverse Reactions
Cephalosporins are generally well-
tolerated.
1.Hypersensitivity
2.Nephrotoxicity
3.Diarrhoea
4.Bleeding
5.Low WBC count
6.Pain
7.Didsulfiram-like reaction
 BROAD-SPECTRUM ANTIBIOTIC
A.Tetracyclines:
 Tetracyclines are antibiotics with
four cyclic rings(hence the name)
in their structure obtained from
the soil actinomycetes.
 Chlortetracycline was the first
tetracycline to be obtained from
Streptomyces aureofacient in
1948
 and was named so because the
colonies appear golden yellow.
 Several semisynthetic derivative
were then produced.
Mechanism of Action
 Mechanism of Action
Tetracyclines are taken up by
susceptible microorganism by active
transport.
Since mammalian cell lack this active
transport,therefore Tetracyclines are
selectively toxic to microorgansms.
Teracyclines also inhibit protein
synthesis.
tetracyclines are bacteriostatic.
 Antibacteria spectrum
 Tetracyclines have a broad antibacterial spectrum.
 The spectrum includes gram-positive and gram-
negative bacteria including
streptococci,staphylococci,gonococci,meningococc
i,clostridia,Bacillus
anthracis,Listeria,corynebacteria,propini bacteriu
acnes,H.influenzae,Vibrio cholerae,Yersinia
pestis,H.ducreyi,Campylobacter,Brucella,Bordatell
a,Pasturella and Spirochaetes,Rickettsiae,
chlamydiae,Mycoplasma,actinomycetes and
plasmodia are inhibite by tetracyclines
 Resistance
Resistance to tetracyclines is transmitted by
plasmids that contain the genes coding for
resistance.
Resistance is exhited as:
1.Decreased uptake or efflux of the antibiotic from
the bacterium.
2. Displacing tetracyclines from the binding
site,i.e.the target ribosome.
3.Elaborating enzymes that inactivate tetracyclines
Note:Cross-resistance among different tetracycline
is also noted.
 Pharmacokinetic
 Older tetracycline are incompletely absorbed from
the gut,
 food interferes with their
absorption,bioavailability of chlortetracycline is
30% and that of tetracycline,oxytetracycline.
 demeclocycline and methacycline range between
60 and 70%.
 Doxycycline 95% and minocycline is 100%
absorbed and food does not affect the absorption
of these two agents.
 Cont.
 Tetracycline chelate calcium and other metals which
reduce their absorption.
 Hence tetracycline should not be given with milk and
milk products,iron preparations,zinc supplements and
antacid.
 Tetracycline undergo enterohepatic circulation
because of which they remain in the body for a long
time.
 Tetracycline like oxytetracycline and doxycycline can
be given intravenously but they cause irritation and
thrombophlebitis.
 Intramuscular injectionare painful due to local
irritation and should,therefore be avoided.
 Cont.
 Tetracyclines are widely distributed in the body.
 They accumulate in the liver,spleen bone
marrow ,bone and teeth and attain a good
concentration in most secretions including
CSF,sinuses,synovial fluid ,urine,prostate and
milk.
 They also cross the placenta barrier.
 All tetracycline except doxycycline and
minocycline are excreted through th gut even
when given parenterally and are therefore,safe in
renal insufficiency.
 Administration
 Tetracyclines are available for oral,parenteral and
topic al use
 Tetracyclines may be given with food to reduce
the severity of gastrointestinal irritant effect.
 Milk,dairy products,antacids,iron and
sucrlfate(contain aluminium) can interfere with
the absorption of tetrcyclines and should
therefore,not be given concurrently
 Intramuscular injection of tetracyclines should be
avoided because.
(i).They can cause irritation.(ii).Absorption is poor
and unreliable
 Adverse Effects
1.GIT 7.Phototoxicity
2.Hepatotoxicity 8.Effect on teeth and
3.Renal toxicity bones.
4.Antianabolic 9.Suprainfections
effect 10.Hypersensitivity
5.Long term 11.Local
6.Pseudotumor 12.Nephrogenic
cerebri disbete insipidus
 Clinical Uses
Tetracycline are drugs 8.Traveler’s diarrhoea
of choice in:
1.Rickettsial 9.Sexually transmitted
infections diseases
2.Chlamydial 10.Acne
infections
11.Tularaemia
3.Atypical pneumonia
4.Granuloma 12.Other infections
inguinale 13.Protozoal
5.Cholera infections.
6.Brucellosis
 Contraindications

1.Tetracyclines are contraindicated in

pregnancy,lactation and in children up to
8years of age for the following reasons
• Their effects on teeth and bones.
• Risk of acute hepatic necrosis in pregnant
women
• Risk of pseudotumor cerebri in infants.
2.Should be used cautiously in renal and
hepatic impairement.
 CHLORAMPHENICOL
Chloramphenicol is a broad-
spectrum antibiotic first
obtained from streptomyces
venezuelae in 1947.
Mechanism of Action
Chloramphenicol is
bacteriostatic but to some
organism it is bactericidal.It
binds to 50S ribosomal
subunit and inhibits protein
synthesis-by inhibiting
transpeptidation.
 Antibacterial Spectrum
Antibacterial spectrum is broad
and includes gram-negative
organisms,some gram-positive
organisms,anaerobic
bacteria,rickettsiae and
mycoplama.
 RESISTANCE
Resistance is plasmid-mediated and may
be due to:
1.Inactivating enzymes(chlorampheniclo
acetyltransferase which inactivates
chloramphenicol)
2.Reduced permeability of the
microorganism to the antibiotic
3.Ribosomal insensitivity.
 Pharmacokinetic
Chloramphenicol is rapidly absorbed
from the gut ,penetration into the
tissues is excellent,attains high
concentration in CSF-almost as much
as in plasma.
It is metabolized in the liver by
reduction and glucuronide
conjugation.
The metabolites are excreted in the
urine.
 Adverse Effects
1.Gatrointestinal disturbances
2.Bone marrow depression
3.Gray baby syndrome
4.Hypersensitivity reaction
 Clinical Uses
1.Typhoid fever
2.Bacterial meningitis
3.Anaerobic infections
4.Rickettsiae infections
5.Eyes and Ear infections
6.Brain abscess.
 Aminoglycosides
 Aminoglycosides are
antibiotics with amino sugars
joined by glycosidic linkages.
 They are derived from soil
actinomycetes of the genus
streptomyces(Septromycin,ka
namycin,tobramycin,
neomycin)
 and the genus
Micromonospora(gentamicin
and sisomicin)
 Common properties of Aminoglycosides
1.Aminoglycosides are polycationic carbohydrates
containing amino sugars in glycosidic linkages.
2.They are highly water-soluble,polar compounds.
3.Aminoglcosides are not absorbed orally (as they
ionize in solution)-therefore they are all given
parenterally.
4.They remain extracellularly and penetration into
CSF is very poor.
5.They are more active at alkaline pH.
6.They are excreted unchanged by the kidneys.
 Cont.
7.They are all Note:Aminoglycosides
bactericidal. include:
8.They act by inhibiting • Streptomycin,gentamic
bacterial protein in,tobramycin,kanamyc
synthesis in,paromomycin
9.They are mainly • Newer one are
effective against gram- amikacin,sisomicin,neti
negative organism. lmicin
10.They produce variable • Topical-
degree ototoxicity and neomycin,framycetin.
neprotoxicity.
 Antibacterial Spectrum
Aminoglycosides have narrow
spectrum and are effective
mainly against aerobic gram-
negative bacilli like
E.coli,proteus,Y.pestis,Nocardia.V
.choleral,pseudomonas,Brucella,
salmonella,shigella and
Klebsiella.
 Mechanism of Action
 Aminoglycosides,being water-soluble,penetrate
the bacterial cell membrane through aqueous
pores and reach the periplasmic spaces.
 They are taken up and transported across the cell
membrane into the cytoplas by an oxygen –
dependent active transport process.
 It is observed that aminoglycosides distrupt the
bacterial cell membrane and this also allows
penetration of the drug into the bacterium from
the periplasmic space.
 Mechanism of Action
Inside the cell,Aminoglycosides bind to 30S
ribosomes and inhibit bacterial protein
synthesis-block initiation of protein synthesis
,cause termination of protein synthesis and
cause addition of incorrect amino acid
resulting in the synthesis of abnormal
protein.
Note:Aminoglycosides are bactericidal.The
higher the concentration,the greater is the
bactericidal effect(dose-dependent killing)
 Resistance to Amino glycoside
Resistance to aminoglycosides is acquired by:
1.Aminglycoside inactivating enzymes:On
binding to aminiglcosides,the enzyme
inactivates aminoglycosides which fail to
bind to the target ribosomes
2.Low affinity of ribosomes-acquired by
mutation
3.Decrease in permeability to the antibiotic
Note:There is partial Cross-resistance among
various aminoglycosides.
 Pharmacokinetics
 Aminoglycoside are not absorbed from the gut but
when instilled into body cavities or applied
overlarge wounds,they may get rapidly absorbed.
 Following IM injection, peak levels are seen in
60minutes.
 They are not bound to plasma proteins and do not
enter the cells or cross barriers –mostly remain in
vasculature.
 Aminoglycoside are excreted almost completely
through the kidneys.Half-life is 2-3hr but gets
prolonged to 24-48hrs
 in renal impairment-dose should be reduced.
 Adverse Effects
1.Ototoxicity:Is the most important
toxicity.Both vesticular and auditory
dysfunction can occur depending on the
dose and duration.
2.Nephrotoxicity:Aminoglycosides attain high
concentration in the renal cortex and cause
damage to the renal tubules.
3.Neuromuscular blockade.:Aminoglycosides
have curare-like effects and block
neuromuscular transmission.
 Precaution in using Aminoglycosides
1.Avoid concurrent use of other ototoxic drug like
loop diuretics.
2.Avoid concurrent use of other nephrotoxic drugs
like amphotericin B,cephalothin and cisplatin
3.Avoid concurrent use of curarimimetic drugs
4.To be used cautiously in elderly,in renal
dysfunction and in combination with skeletal
muscle relaxants.
5.Contraindication in pregnancy because of the risk
of deafness in the child.
 Cont.
6.Do not mix aminoglycosides with any
other drug in the same syringe
7.Determination of plasma levels of
aminoglycosides may be needed in
severe infection and in patients with
renal dysfunction.
 Uses
1.Aminoglycosides are used in the treatment of
infections due to gram-negative bacterial.
2.Aminoglycosides are also used in streptococcocal
and entrococcal endocarditis in combination with
a penicillin.The combinationis synergistic due to
the following reasons
• Both are bactericidal
• Low pH and anaerobiasis reduce the uptake of
aminoglycosides by active transport.This negative
effect is reversed by penicillins.
• Penicillin improve penetration of aminoglycosides
by inhibiting cell wall synthesis in the bacterial.
 Cont.
3.Some Aminoglycosides
(strptomycin,kanamycin,amikacin) are also
used in tuberculosis.:Streptomycin is the
second line drug in tuberculosis.
4.Urinary tract infection:Gentamicin is
effective in uncomplicated UTI as it is
released fro a long time from the renal
cortex.
5.Pneumonia due to gram-negative orgarnisms
may be treated with gentamicin+penicillin
 Cont.
6.Osteomyelitis,peritonitis,septicaemi
a,abscess,burns cause by gram-
negative
organisms(psedomonas,proteus and
klesiella) can be treated with
gentamicin.
 Macrolides
Macrolides are antibiotics with a large
(macro-cyclic) lactone ring to which sugars
are attached.
Erythromycin and its semisynthetic
derivatives roxithromycin,clarithromycin
and azithromycin are the macrolides
currently used.
Dirithromycin,oleandomycin,troleandomyci
n and spiramyccin are other macrolide
antibiotics
 ERYTHROMYCIN
Erythromycin is obtained from
streptomyces erythreus
 Antibactrial Spectrum
Erythromycin has a narrow spectrum
and is effective against aerobic gram-
positive bacterial and a few gram-
negative organism.
Streptococci,pneumococci,staphylococci
,gonococci,legionella,C.diphtheriae,B.pe
rtussis,T.pallidum,C.jejuni,Mycoplasma,C
hlamydiae
and some atypical mycobacteria are
sensitive.
 Mechanism of Action
 Erythromycin is bactriostatic at low and cidal at high
concentrations.
 It is more effective in the alkaline pH.
 It binds to 50S ribosomes and inhibits bacterial
protein synthesis.
 Macrolide inhibit the translocation of the growing
peptide chain from A site to P site
 hence ,A site is not available for binding of the next
amino acid (brought by tRNA)
 and protein synthesis stops.
Note:Chloramphenicol and clindamycin also bind to 50S ribosomes and
the three may antagonise each others activity because they compete
for the same binding site.Henc,the combination should be avoided.
Mechanism of Action
 Resistance
 Resistance to macrolides is acquired through
plasmids.
 The mechanism of expression of resistance may
be:
• Low permeability of the bacteria to the antibiotic
• Production of inactivating enzymes that hydrolyze
macrolides.
• Low affinity of ribosomes to macrolides-such
organisms are also resistant to other drugs which
binds 50S ribosomes-lincosamides and
strepgramins called macrolidelincosamide-
streptogramin or MLS-type resistance.
 Pharmacokinetics
 Food interferes with absorption.
 Among the different salts,erythromycin estolate is
the best absorbed,but not prefered due to the risk
of adverse effects.
 Erythromycin is destroyed by gastric acid and is
therefore given as enteric coated tablets.
 Plasma t1/2 is 1.5hr.Good concentration is
attained in most fluids except brain and CSF.
 It is also crosses the placenta.
 Erythromycin is a microsomal enzyme inhibitor.
 It is mainly excreted through the bile,dose
 Adverse Effect
1.Hepatitis with cholestatic jaundice starts after 2-
3weeks of treatment and incidence is more with
the estolate salt.
2.Epigastric distress,nausea,vomiting and diarrhoea
are often reported
3.Allergic reactions including fever and skin rashes
can occur.
4.Cardiac arrhythmias are reported in patient with
cardiac diseases or on other arrhymogenic drugs.
5.Erythromycin can also cause rversible hearing
impairement in some patients.
 Drug Interaction
Erythromycin and clarithromycin are
microsomal enzyme(cytochroP450)
inhibitors.
They inhibit the hepatic metabolism and
thereby enhance the plasma level of
other drug like,
carbamazepine,terfenadine,
theophyline,valproate,digoxin and
warfarin resulting in toxicity due to
these drugs.
 USES
Erythromycin can be used as an alternative to
penicillin in patients allergic to penicillin.
1.Atypical pneumonia
2.Legionnaires’ pneumonia
3.Whooping cough
4.Stretococcal infections
5.Staphylococcal infections
6.Diphtheria
7.Syphilis and gonorrhoea
8.Campylobacter gastroenteritis
 Cont.
9.Tetanus
10.Anthrax
11.Prophylaxis
12.Topical:Erythromycin ointment(2-
4%) is used for skin infections and
boils,lotion for acne vulgaris.
 KETOLIDES
Ketolides are modified macrolides that resemble
newer macrolides and are effective against
macrolide-resistant pneumococci
Telithromycin:
A ketolide,is a semisynthetic derivative of
erythromycin.
It is effective against Staphylococcus
aureus,streptococcuu pyogenes S. pneumonia
H.influenzae,H.pylori
M.catarrhalis,Mycoplama,Chlamydia
T.gondii,Legionella,B.fragilis and some
 Mechanism of Action
Mechanis m of action of ketolides is similar
to macrolides but may be effective even
against organisms that are resistant to
macrolides.
This is because the structure of ketolides is
such that they are not destroyed by the
inactivating enzymes and also bind to the
50S ribosomes with greater affinity than
macrolide.
The mechanism that confers resistance to
 Pharmacokinetics
Telithromycin is well absorbed on
oral administration
with bioavalabilty 60%
and has a t1/2 of 9-10hrs given
once a daily.
Its penetration into tissues is
good,metabolized by the liver.
 Adverse effects
Telithromycin is well
tolerated,however,it can cause
nausea,vomiting,diarrhoea and
pseudomembranous colitis.
Raised liver enzymes and hepatic
failture have been reported.
 Uses
Telithromycin can be used in mild
to moderate community-acquired
bacterial
pneumonia,Streptococcal
pharyngitis and sinusitis.
 About the lecturer:Prof.Sola Omodamiro
Prof.Sola Omodamiro,(B.Th,Bmls-AIMLS,M.Sc,Ph.D)
is a professor of Biochemical
Pharmacology &
Chemotherapy @ Micheal
Okpara University
Umudike,Abia State Nigeria
and A visiting Professor at
Kampala International
University western campus
Uganda