PRESENTATION LAYOUT
 Introduction to antimicrobial drugs
 Classification of antimicrobial drugs
 Antibacterial drugs:
- Classification
- Indications
- Side effects
 Antibacterial Resistance
 Antimicrobial drugs are chemotherapeutic drugs
 Two categories:
– Antibiotics : Antimicrobial drugs produced by
microorganisms
– Synthetic drugs : Antimicrobial drugs
synthesized in the lab
Ideal antimicrobial drug
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 hypersensitivies in the host
Have rapid and extensive tissue distribution
Be free of interactions with other drugs
Be relatively inexpensive
Where do antibiotics come from
 Several species of fungi including Penicillium and
Cephalosporium
E.g. penicillin, cephalosporin
 Species of actinomycetes, Gram +ve filamentous
bacteria
 Many from species of Streptomyces
 Also from Bacillus, Gram +ve spore formers
 A few from myxobacteria, Gram -ve bacteria
 New source explored : plants, fish
Sources of some common antibiotics and semisynthetics
History of Antimicrobial Therapy
 Ehrlich (1854–1915) coined the term
chemotherapy
 1929 Penicillin discovered by Alexander Fleming
 1940 Florey and Chain mass produced penicillin
 becomes
Alexander Fleming
was firstto
tothe
characterize
for war time use,
available
public
penicillin’s activity. He found mold
 1935 Sulfa drugs discovered
contaminating his culture plates, with clearing of
 1944 Streptomycin
discovered
by Waksman
staphylococcal
colonies
all around thefrom
mold.
Fleming then isolated penicillin from the mold
Streptomyces griseus
 Thanks to work by Alexander Fleming
Classification of antimicrobial agent
Chemical
structure
Type of
organism to
be killed
Antimicrobial
agent
Based on chemical structure
Group
Examples
Sulfonamide
sulfadiazine, dapsone, paraminosalicylic acid
B-lactam
penicillins, cephalosporins, monobactams
tetracycline
oxytetracycline, doxycycline
aminoglycoside
streptomycin, gentamycin, neomycin
Macrolide
erythromycin, azithromycin, clarithromycin
polypeptide
polymyxin-B, bacitracin
glycopeptide
vancomycin
Quinolones
ciprofloxacin, ofloxacin, moxifloxacin, gatifloxacin
Azole derivative
miconazole, clotrimazole, ketoconazole, fluconazole
nitroimidazole
Metronidazole, tinidazole
Antibacterial drugs
 Drugs active against bacteria
 Natural or synthetic
 Naturally, obtained from microorganisms which
suppress the growth or kill other microorganisms
are k/a antibiotics
 Synthetics are made in lab by bioengineering
 The term antibiotic was first used in 1942
by Selman Waksman
classification
Spectrum of activity
Type of action
Mechanism of action
Type of action
Bacteriostatic
Bactericidal
Sulphonamides
Penicillins
Tetracycline
Aminoglycosides
Chloramphenicol
Cephalosporins
Macrolides
Vancomycin
Spectrum of activity
Broad spectrum
Narrow spectrum
Tetracyclin
Penicillin G
Chloramphenicol
Streptomycin
Cephalosporins
Erythromycin
Mechanism of action
• Inhibit cell wall synthesis
• Cause leakage from cell membranes
• Inhibit protein synthesis
• Inhibit DNA gyrase
• Action as antimetabolite
Mechanism of action
Inhibit cell wall synthesis
 These are the drugs that interfere with the cell
wall synthesis process
 These drugs consist β-Lactam rings so called
β-lactam antibiotics
 Bactericidal in nature
Inhibitor of cell wall synthesis
Penicillin
Cephalosporin
Vancomycin
Penicillin
First antibiotic to be used clinically
Obtained from fungus Penicillium notatum
Structure
β-lactam is responsible for antimicrobial activity
Properties like antimicrobial spectrum, stability to
stomach acid and susceptibility to bacterial degradative
enzymes (β-lactamases) depends upon the side chain
Also, differ in structure by the side chain
Working of penicillin
NAM-NAG-NAM-NAG
Penicillin
Binds to PBPs
Pep
Pep
Pep
Pep
NAM-NAG-NAM-NAG
Inhibition of cross linkage
Blockage of peptidoglycan
synthesis
Pep side chains are cross linked as the
final step in synthesis of peptidoglycan in
the presence of penicillin binding protein
(PBPs).Penicillin drugs inhibit this
process after binding with PBPS.
Pep=peptide linkage
Cell dies
NAM &NAG =N-acetyl muramic acid and Nacety glucosamine
Types
Penicillin G
-Have side chain of benzyl group
-Active against Gram +ve
bacteria than Gram -ve
Penicillinase resistant
penicillins
-Resistant against
penicillinase/β-lactamase
producing bacteria
eg. Methicillin, Cloxacillin
Extended spectrum
penicillins
-Sensitive against wide range of
bacteria(Gram +ve/-ve)
eg. Ampicillin, Amoxicillin
 The latter two are semisynthetic in nature
Coverage of Penicillins
Penicillin G
Gram Positive cocci:
Streptococcus pneumonia
Streptococcus pyogens
Gram Positive bacilli:
Bacillus anthracis
Corynebacterium
Clostridia, Listeria
Spirochetes
Gram Negative cocci:
Neisseria gonorrhoeae
Neisseria meningitidis
Penicillinase resistant
penicillins
Penicillinase producing
Staphylococcus
Extended spectrum
penicillins
Sensitive against all Gram
positive as well following
Gram negative bacteria
- E.coli
- Haemophilus
- Salmonella
- Proteus
Indications
Penicillin G
o
o
o
o
o
o
o
Pneumococcal infection
Streptococcal infection
Meningococcal infection
Tetanus
Gas gangrene
Syphilis
Gonorrhea
Extended spectrum
penicillins
o Respiratory tract infection
o
o
o
o
o
o
Sinusitis
UTI
Bacillary dysentery
Gonorrhea
Enteric fever
Preseptal cellulitis
Side Effects
 Hypersensitivity reaction (rash, itching, urticarial,
fever)
 Pain at i.m. injection site, thrombophlebitis of
injected vein
 Oral penicillin can cause nausea, vomiting or diarrhea
 Toxicity to the brain: mental confusion, convulsions &
coma
Beta-lactamase inhibitors
 Some of the bacteria produces β-lactamase enzyme. This
enzyme causes hydrolysis of β-lactam ring so that the
antibiotic activity of penicillin/ β-lactam drug is destroyed
 This can be prevented by two inhibitors i.e. clavulanic acid
and sulbactam
 These are the enzyme with β-lactam ring but has no
antibacterial activity. It combines with the lactamase
enzyme and thus prevent the destruction of lactam ring of
antibiotic making it potent to show action
Cephalosporins
Have similar action to penicillin (bactericidal)
Semisynthetic antibiotics derived from
cephalosporin-C obtained from fungus
Cephalosporium
Classification
Cephalosporins
First Generation
 Exhibits good activity against Gram positive
cocci like Staph.sps, Strep. sps & Gram –ve
rods like E.coli, Klebseilla
Includes
Cefazolin
Cephalexin
Cephradine
Cephadroxil
Second Generation
 Shows somewhat enhanced activity towards Gram –ve
bacteria compared to 1st generation
Coverage:
 Coverage of 1st generation &
 Additional -ve cocci like Neisseria gonorrhoea & -ve
rod H.influenza
Includes
Cefuroxime
Cefoxitin
Cefaclor
Cefuroxime Axetil
Third Generation
 More potent than 2nd generation
 Shows augmented activity against:
 Enterobacteria
 β-lactamases producing bacteria
 Pseudomonas
Includes
Cefotaxime
Ceftriaxone
Ceftizoxime
Cefixime
Fourth Generation
 Similar to 3rd generation
 Shows increased resistance to β-lactamase
producing bacteria
Includes
Cefepime
Cefpirome
Indications
 Alternative to penicillin allergic patient
 Respiratory , urinary and soft tissue infection
caused by Gram –ve organism
 Septicaemia by Gram –ve bacterai
 Surgical prophylaxis
 Gonorrhoea
 Typhoid
 Preseptal cellulitis & endophthalmitis
Side effect
 Pain on intramuscular injection
 Diarrhoea due to alteration of gut ecology
 Hypersensitivity reaction( rashes, asthma,
angioedema and urticaria)
 Nephrotoxicity
Vancomycin
 Highly effective against Gram +ve cocci
 Uses : used for serious infections
 Drug of choice for treating:
 Methicillin resistant staphylococci
 Penicillin resistant S. pneumoniae
 Recommended for topical, intravitreal &
subconjunctival therapy for bacterial
endophthalmitis
Side effect
 If used with other ototoxic or nephrotoxic drugs
can cause impaired renal function and lead to
permanent deafness
 Contraindicated in hypersensitivity reaction
Tetracycline
Chloremphenicol
Drugs
inhibiting
Protein
synthesis
Macrolide
Aminoglycoside
Mechanism of action
Tetracycline
 Broad spectrum antibiotics
 Have nucleus of four cyclic rings, so named
tetracycline
 1st tetracycline to be obtained was
chlortetracycline
 Bacteriostatic in nature
Division of Tetracycline
Class I
Class II
Class III
• Tetracycline
• Oxytetracycline
• Methacycline
• Doxycycline
• Minocycline
Coverage of Tetracycline
Gram -ve
Gram +ve
Rickettsiae
Spirochaetes
Entamoeba
Chlamydiae
Mycoplasm
Indications
Drug of first choice
Drug of second choice
Atypical pneumonia due to
mycoplasma
To penicillin for tetanus,
actinomyces
Cholera
To ciprofloxan for gonorrhoea
Brucellosis
To ceftriaxone for syphilis
Plague
Rickettsial infection
To azithromycin for chlamydial
infection
Ocular Use
Trachoma
Conjunctivitis
Ophthalmia
neonatorum

Preferred over silver nitrate because it does not cause
chemical conjunctivitis.
Side effects
 Epigastric pain, nausea, vomiting and diarrhoea (irritation
from mucosa )
 Liver toxicity
 Renal toxicity
 Vestibular toxicity (due to drug accumulation in
endolymph)
 Affect teeth and bone: tetracycline get deposited in
developing teeth and bone hence cause discoloration and
ill formation. so contraindicated
 Contraindicated in pregnant, lactating woman and
child<8yrs
 Also contraindicated in pt. with renal dysfunction
Chloramphenicol
 Broad spectrum
 Nitrobenzene substitute
 Bacteriostatic in nature
 Initially obtained from Streptomyces, now
synthesized chemically
Coverage of chloramphenicol
Though static in nature, its high concn can be
cidal too
Active against
Gram +ve cocci & bacilli
Gram –ve cocci & bacilli
Chlamydia
Indications
 Because of serious bone marrow toxicity use of this drug
has been reduced much
 Not used for infection that can be treated by other
antibiotics. However, some of its use are:
- Enteric fever
- H. Influenza meningitis
- Anaerobic infection by fragillis
 Has extended ocular use as the topical application is less
hazardous than systemic use
 Primarily used in oint. as well gtt. form for conjunctivitis,
blepharitis etc.
Indications
 Chloramphenicol available in ointment and
eye drop form
 Ointment
1%
 Eyedrop
0.5%
Side effects
 Bone marrow depression
 Aplastic anaemia, thrombocytopenia
 Hypersensitivity reaction
 Rashes, fever, angioedema
Gray baby syndrome
 Occurs when high doses=1oomg/kg to neonate as
prophylactic
 Baby stops feeding, vomit, abdomen distended,
hypothermic, irregular respiration
 An ashen gray cyanosis appear with complication of
cardiovascular collapse
 It occurs due to poor renal development in neonate
which results in accumulation of drug
Aminoglycosides
 Bactericidal in nature
 Includes neomycin, gentamicin, tobramycin,
amikacin, streptomycin
 good coverage for Gram –ve bacilli like P.
aeruginosa, Proteus, Klebseilla, E. coli
Neomycin
 Broad spectrum among all the aminoglycoside
 But, cannot show effectivity against P. aeruginosa
 Widely used in ophthalmology in the form of drop
and ointment
 Ointment
0.5%
 Eyedrop
0.5%
Gentamicin
 Mainstay in the treatment of serious Gram –ve
bacilli infection
 Frequently used for empiric therapy in presumed
Gram –ve bacilli infection
 Choice of drug for EOD like corneal ulcer
 Ointment
0.3%
 Eyedrop
0.3%
Tobramycin
 Same coverage as gentamicin
 Also effective against Staphylococci
 Potent to P.aeruginosa
 In ophthalmology preferred for paediatric use
 Ointment
0.3%
 Eyedrop
0.3%
Amikacin
 It is semisynthetic
 Preferred in Gram –ve infection resistant
to gentamycin and tobramycin
Indications
 Gram –ve bacillary infection
 Septicaemia, abdominal and pelvic sepsis
 Bacterial endocarditis
 TB
 Plague
Side effects
 Ototoxicity: these drugs get accumulated in the
endolymph and perilymph of inner ear and destroy
the hair cell in organ of corti
 Nephrotoxicity: retention of these drugs in proximal
tubular cells disrupts Ca mediated transport system
and cause renal damage
 Neuromuscular paralysis: these drugs cause decrease
in release of Ach
 Allergic reaction: Contact dermatitis
Macrolides
 Bacteriostatic in nature
 Protein synthesis inhibitor
 Are compounds having a macrocyclic lactone ring to
which deoxy sugars are attached
 Includes erythromycin, clarithromycin and
azithromycin
Erythromycin
 First member of this group
 Effective against many of the same organism as
penicillin G
 So, used in patient allergic to penicillin
 For ocular use  Ointment 0.5%
 oral erythromycin are preferred in treatment of
chlamydia infection in children where tetracycline is
contraindicated
 Also used in treatment of trachoma
250mg X PO X QID X 3-4 weeks
Azithromycin
 Far more active against respiratory infections
due to H.influenza and Moraxella catarrhalis
 Nowadays preferred in Chlamydial infection too
 For trachoma single dose of 1 gm
Clarithromycin
 Same effectivity as erythromycin
 But effective against Haemophilus influenza and
chlamydia too
Side effects
 Epigastric distress
 Ototoxicity
 Cholestatic jaundice
Contraindications
 In patient with hepatic dysfunction because of their
accumulation in liver as well compromised renal
function because their metabolite are excreted from
renal
Drug interfering with DNA
Fluoroquinolones
Fluoroquinolones
 Inhibit bacterial DNA
synthesis
 Are synthetic fluorinated
analogs of quinolones
(Nalidixic acid)
 Bactericidal in nature
Mechanism of action
 Fluoroquinolones block the bacterial DNA
synthesis by inhibiting bacterial topoisomerase II
(DNA gyrase) and topoisomerase IV
 Inhibition of DNA gyrase prevents the relaxation
of positively supercoiled DNA that is required for
normal transcription and replication
 Inhibition of topoisomerase IV interferes with
separation of replicated chromosomal DNA into
the respective daughter cells during cell division
Classification
2nd Generation
1st Generation
Norfloxacin
Ciprofloxacin
Ofloxacin
Pefloxacin
Cinafloxacin
Lomefloxacin
4th Generation
3rd Generation
Levofloxacin
Moxifloxacin
Gatifloxacin
Trovafloxacin
Ciprofloxacin
 Broad spectrum( most susceptible are aerobic
Gram –ve bacilli)
Widen use due to




Rapid in action
Relatively long post-antibiotic effect
Low frequency of mutational resistance
Active against many β-lactam and aminoglycoside
resistant bacteria
Ofloxacin
 Active against gram negative
 Also shows more potency against gram +ve cocci +
chlamydia, mycoplasma too
Moxifloxacin
 Active against gram –ve bacilli, gram +ve cocci, βlactam and macrolide resistant ones and anaerobic
bacteria
From first to fourth generation
-ve
+ve coverage
Indications







Prophylaxis and treatment of urinary tract infection
Bacillary desentry
Enteric fever
Diarrhoea due to E.coli
Gonorrhoea
Septicaemia
Respiratory infection
Ophthalmic use
Generic name
Trade name
indication
Ciprofloxacin(0.3
%)
Ciloxan
Conjuctivitis,
keratitis
Ofloxacin (0.3%)
Exocin
Conjuctivitis,
keratitis
Levofloxacin
Quixin
Conjuctivitis
Topical ophthalmic drops can be used for children from one
year old
Side effects
GI upset most common
nausea, vomiting, diarrhoea
Hypersensitivity reaction
rash, photosensitivity
CNS disturbances
dizziness, headache, confusion
 Tendinitis in children (damage growing cartilage). Ophthalmic
drops do not show such toxicity. Hence is safer to use
 Contraindicated in patient with known hypersensitivity to
these drugs
Metabolic inhibitors
Sulfonamides
 Bacteriostatic
 Binds and blocks enzymes mainly pteridine
synthetase, dihydrofolate reductase responsible for
folic acid synthesis
 Folic acid enzymes are nessary for the synthesis of
amino acids, hence necessary for bacterial protein
Mode of action - These antimicrobials are analogues of paraaminobenzoic acid (PABA) and competitively inhibit formation
of dihydropteroic acid
Spectrum of activity - Broad range activity against Gram +ve
and Gram -ve bacteria; used primarily in urinary tract and
Nocardia infections
Combination therapy - The sulfonamides are used in
combination with trimethoprim; this combination blocks two
distinct steps in folic acid metabolism and prevents the
emergence of resistant strains
p-aminobenzoic acid + Pteridine
Pteridine
synthetase
Sulfonamides
Dihydropteroic acid
Dihydrofolate
synthetase
Dihydrofolic acid
Dihydrofolate
reductase
Trimethoprim
Tetrahydrofolic acid
Methionine
Thymidine
Purines
Antibacterial Drugs of choice for initial treatment of
ocular infection
Ocular infections
Antibacterial drugs
Route of
administration
Blepharitis
chloramphenicol,
Topical
Meibomianitis
Tetracycline
Oral
Gentamycin ,ciprofloxacin,
ofloxacin,tobramycin
cefriaxone
tetracycline ,erythromycin
Topical
Hordeolum
cloxacillin, dicloxacillin
Topical
Dacryocystitis
Amoxicillin ,erythromycin
Oral , topical
Keratitis
Gentamycin & cepazolin
,ciprofloxacin
Topical
Endopthalmitis
Vanomycin & amikacin
Intravitreal
Preseptal cellulitis
Ampicillin, cloxacillin, cefaclor
oral
Conjunctivitis :
Acute mucopurulent
Hyper acute
Chlamydial
Parenteral
Oral
Antibiotic Resistance
A variety of mutations can lead to antibiotic resistance
Mechanisms of antibiotic resistance
 Enzymatic destruction of drug
 Prevention of penetration of drug
 Alteration of drug's target site
 Rapid ejection of the drug
Resistance genes are often on plasmids or transposons
that can be transferred between bacteria
Mechanism of Resistance
In cell wall synthesis
inhibitor
Penicillinases: break the beta
lactam ring structure
( staphylococci)
Structural changes in PBP:
S.aureus, S. pneumococci
Change in porin structure:
concerns the Gram Negative
organism
In protein synthesis inhibitor
 A mutation of ribosomal binding site
 Enzymatic modification of antibiotic
 An active efflux of antibiotic out of cell
In nucleic acid synthesis inhibitor
 An alteration of alpha subunit of DNA
gyrase (chromosomal)
 Beta subunit of RNA polymerase
(chromosomal) is altered
References
oTextbook of microbiology by Ananthanarayan & Paniker
o Essentials of Medical Pharmacology KD Tripathi
o Basic & Clinical Pharmacology by Bertram G. Katzung
o Ophthalmic Drugs by Graham Hopkins and Richard Pearson
o Internet