1. Guided & Checked By :
Shreyas Bhatt sir
Shreya M. Modi
MSc Sem- III
Roll no.- 11

2.  Introduction

3.  Antibiotics are chemical molecules or compounds
that specifically targets and kill cells. Not only
antibacterial, but also antifungal, antiviral and
also antineoplastic compounds are also classified
as antibiotics.
Antibacterial action generally follows some of the
mechanisms such as inhibition or regulation of
enzymes involved in the synthesis of cell wall,
nucleic acid synthesis and repair, or protein
biosynthesis. Antibiotics target the cell
functioning of rapidly dividing cells.

4. 1. The target of an antibiotic can be present
only in bacteria but not in the eukaryotic
host.
2. The target in bacteria is different from
the homologous target in the eukaryotic
host.
Modern genomics provide a great tool for
identifying targets of new selective antibiotics

5. Natural antibiotics are weapons that bacteria or fungi use
to compete with other microorganisms.
Selectivity is not a ‘natural’ feature of antibiotics.
Most of clinically-useful antibiotics are fortuitously
selective antibacterials.
Many antibiotics are omni-potent and inhibit growth of a
wide variety of organisms. Such antibiotics can be
developed into selective drugs through modification of
their chemical structures.

6. Bacteriostatic drugs make
Bactericidal drugs kill
bacteria dormant, but do not
bacteria (e.g.
kill them.
ciprofloxacin)
Most bacterial cells resume
growth after removal of the
antibiotic
(e.g. chloramphenicol)

7. Antibiotics with a bactericidal mode of action are
preferred, especially for treatment of
immunocompromised patients. The mode (static
vs. cidal) of antibiotic action may differ for
different pathogens and may depend on the drug
concentration.
The basis of bactericidal versus bacteriostatic
effects is poorly understood but maybe related to
the accumulation of reactive oxygen radicals in
the bacterial cells upon treatment with
bactericidal drugs.

8. sulfonamides 1920
-lactams 1942
aminoglycosides 1947
tetracycline 1949
macrolides 1952
glycopeptides 1958
streptogramins
1962
lincosamides
No
Golden era in antibiotic discovery principally new antibiotics
Growing resistance
linezolid 2000
daptomycin 2003

13.  Penicillins  Nitrofurantoin,
 Cephalosporins metronidazole,
 Carbapenems clindamycin,
vancomycin,
 Quinolones teicoplanin,
 Aminoglycosides cotrimoxazole, fusidic
 Macrolides acid, etc
 Tetracyclines  Isoniazid,
pyrazinamide,
ethambutol, rifampin,
cycloserine, etc

14.  Some of the antibacterial compounds interfere
with the cell wall synthesis by weakening the
peptidoglycan structures in bacterial cell wall,
by this integrity of bacterial cell wall structure
weakens and eventually disrupts.
 Mammalian cells only have plasma membrane
so these antibiotics specifically target only
bacterial cells. That is these antibiotics do not
induce any negative effect on the host
mammalian cells.

16.  Antibacterial compound β-lactam can be used
against both Gram-positive and Gram-negative
bacterial cells.
Vancomycin another antibacterial compound
also prevents cell wall biosynthesis in bacterial
cells by interfering with transglycosylases
enzyme activity.
 But this compound can be used effectively
against Gram-positive bacteria, as it is unable
to penetrate the outer cytoplasmic membrane
of Gram-positive bacteria.

17. Name Producer Chemical nature Site of action
organism
Penicillin P.Notatum Β lactum Transpeptidase
P.Crysogenum Antibiotic Reaction
Cephalosporine Cephalosporium Β lactum Transpeptidase
aeremonium Antibiotic Reaction
Cycloserine Streptomyces Analogue of Inhibit formation
spp. alanine of Park’s
nucleotide
Bacitracin B.Subtilis Peptide Phosphatase
reaction in lipid
cycle
Vancomycin Str.orientatis Glycopeptide Polymerization
step

18. Fosfomycin
The first
stage
Bacitracin
The second
stage
The third ß-lactam
stage antibiotics.

19. Beta-lactam antibiotics
 Penicilins
 Cephalosporins
 Carbapenems
 Monobactams
All β-lactam antibiotic agents
contain a β-lactam nucleus in its
molecular structure.
Core structure of penicillins (1) and cephalosporins (2).
Beta-lactam ring in red.

20. All beta-lactams:
 are bacteriocidal.
 have the same mechanism of antibacterial
action.
 have no activity against MRSA and atypical
bacteria (Legionella spp., Mycoplasma spp.,
Chlamidia spp.).
 have the allergic cross-reaction.
 have the same modes of bacterial resistance.

21. Penicillin-binding proteins (PBPs), enzymes
that catalyze the last steps of peptidoglycan
synthesis (cross-linking).
β-Lactam antibiotics are analogues of D-
alanyl-D-alanine amino acid residues
irreversible binding to the active site of
penecillin-binding proteins (PBPs)

22. Inhibition of the PBPs prevents the final
crosslinking of the nascent peptidoglycan layer
disrupting bacterial cell (bactericidal effect)

23. Generation Example Clinical use
Natural penicillins Penicillin G Syphilis, rheumatic fever
meningitis, tonsillitis,
scarlet fever, endocarditis
Antistaphylococcal Methicillin Mild and moderate
penicillins staphylococcal infections
Extended-spectrum Ampicillin Noncomplicated
penicillins Amoxicillin community-acquired
infections (lower and upper
respiratory tract infections,
UTIs, skin and soft tissues)
Antipseudomonal Carbenicillin P.aeruginosa infections
penicillins

24.  Some antibiotics inhibit the action of enzyme
RNA polymerase, hence interfere with RNA
(ribonucleic acid) synthesis in the cells.
Antibiotics such as asdoxorubicin
andactinomycin D interfere with RNA
biosynthesis in both bacterial cells as well as in
mammalian cells. These compounds are used
in treating rapidly growing tumor cells in
cancer patients.
Some of the examples are Doxorubicin
hydrochloride, Levofloxacin, Irinotecan
hydrochloride, Rifampcin

25.  Penicillin G
 Still useful for a number of diseases (e.g. meningitis,
syphilis)
 Cloxacillin
 For MSSA infections
 Ampicillin, amoxicillin
 Active vs. Gram-positive (not MSSA), Gram-
negative organisms
 Augmentin, Unasyn
 Broad spectrum, covers Gram-positive, Gram-
negative and anaerobes
 Piperacillin, Tazocin, Timentin
 Are active vs. Pseudomonas

26. Generation Example Spectrum
First Cefazolin Most active against gram-positive
Generation bacteria (staphylococci). Have no
activity against gram-negative
bacteria.
Second Cefuroxim Enhanced activity against gram-
Generation positive and some gram-negative
bacteria.
Third Cefotaxime Broad-spectrum (gram-positive and
Generation gram-negative). Resistant to most
type of beta-lactamases.
Fourth Cefepime Most active against gram-negative
Generation bacteria. Very active against
P.aeruginosa. Resistant to beta-
lactamases. Have little gram-positive
activity.

27.  Imipenem
 Broad spectrum, covers Gram-positive, Gram-
negative (including ESBL-producing strains),
Pseudomonas and anaerobes
 Meropenem
 Less seizure-inducing potential, can be used to
treat CNS infections
 Ertapenem
 Lacks activity vs. Acinetobacter and
Pseudomonas
 Has limited activity against penicillin-resistant
pneumococci

28.  Is not absorbed from the
gut.
 IV administration.
 Excreted unchanged by the
kidneys.

29. Forms a complex with the C-terminal D-alanine of
peptidoglycan precursors
Prevents the following addition of new units to the
peptidoglycan
Inhibition of peptidoglycan synthesis
Bactericidal effect

31.  Do not penetrates the membrane of gram-negative
organisms.
 Gram positive organisms only
 Staphylococcus spp. including Methicillin-
resistant Staphylococcus aureus (MRSA)
 Streptococcus spp.
 Enterococcus faecalis and E. faecium
 Clostridium difficile and other Clostridia (cause
pseudomembranous colitis)

32.  Serious, life-threatening gram-positive
infections
 MRSA infections
 Pseudomembranous colitis caused by
Clostridium difficile (oral administration of
vancomycin)

33.  Nephrotoxity: mostly in
combinations with
aminoglycosides
 Ototoxicity
 Red man syndrome (or red neck
syndrome):
 within 4–10 minutes after the start
of infusion
 flushing and an erythematous
rash at the face, neck and upper
body.
 is due to non-specific mast cell
degranulation. It is not allergic
reaction.

34.  Ciprofloxacin
 Active vs. MSSA, Gram-negative and Pseudomonas
 Levofloxacin
 Has activity vs. Streptococcus pneumoniae, but
slightly less active towards Pseudomonas compared
to ciprofloxacin
 Moxifloxacin
 Has activity vs. anaerobes but less active towards
Pseudomonas

35.  Active vs. some Gram-positive and Gram-negative
organisms
 Gentamicin
 Active vs. Pseudomonas
 Tobramycin
 More active vs. Pseudomonas than gentamicin
 Shows less activity against certain other Gram-negative bacteria
 Amikacin
 More stable to enzymes, used in severe infections by
gentamicin-resistant organisms
 Streptomycin
 Used for tuberculosis

36.  Erythromycin
 Active vs. Gram-positive organisms, atypicals
 GI side effects
 Clarithromycin
 Slightly greater activity than erythromycin
 Azithromycin
 Slightly less active than erythromycin vs. Gram-
positive but enhanced activity vs. some Gram-
negative organisms

37.  Drug of choice in infections caused by
Chlamydia, Rickettsia, Brucella and Lyme
disease
 Value has decreased due to increasing bacterial
resistance
 Tetracycline
 Role in Helicobacter pylori eradication (less
frequently used than other antibiotics)
 Doxycycline
 Once daily
 Minocycline
 Broader spectrum

38.  Clindamycin
 Vs. Gram-positive cocci and anaerobes
 Metronidazole
 Vs. anaerobes
 Preferred therapy in antibiotic associated diarrhoea
(Clostridium difficile) than oral vancomycin,
although unlicenced
 Vancomycin, teicoplanin
 For Gram-positive organisms (including MRSA)

39.  Cotrimoxazole
 Role in uncomplicated UTI, UTI prophylaxis, acute
exacerbations of chronic bronchitis
 Pneumocystis carinii (now jiroveci) infections
 Nitrofurantoin
 For UTI, prophylaxis vs. UTI
 Fusidic acid, rifampin
 For penicillin-resistant staphylococci
 Not for monotherapy due to risk of emergence of
resistance

40.  Inhibition of protein synthesis
 Structure of prokaryotic ribosome acts as target for
many antimicrobials of this class
 Differences in prokaryotic and eukaryotic ribosomes
responsible for selective toxicity
 Drugs of this class include
 Aminoglycosides
 Tetracyclins
 Macrolids
 Chloramphenicol
 Lincosamides
 Oxazolidinones
 Streptogramins

42.  RNA, which participate in the protein
biosynthesis.
 DNA, which carries the entire genetic
information for the characters to be expressed
by the organisms, by acting as hereditary
material.

43.  Certain antibiotics are able to bind with the key
enzyme involved in RNA synthesis like-
RNA polymerese.
 Binding of antibiotics to this enzyme interferes
with the functioning of this enzyme and
prevent RNA synthesis.

44.  Certain other antibiotics bind with GC pair of
DNA and prevent unfolding of DNA, required
for transcription. thus, they inhibit RNA
synthesis.
 E.g.- Mitomycin C
Actinomycin D

45. Antibiotic Mode of action
Actinomycin Binds to GC pair of DNA and interferes with
D transcription
And replication process.
Mitomycin C Binds to GC pair of DNA and interferes with
transcription
And replication process.
Rifampicin Binds with β- subunit of bacterial RNA polymerese
and
Interferes with transcriptional process.
Rifamycin Binds with β- subunit of bacterial RNA polymerese
and
Interferes with transcriptional process.
Griseofulvin Binds to DNA polymerese
Anthramycin Binds to DNA and damage its structure and

46.  Protein synthesis is a multi-step process. Majority
of antibiotics inhibit the process s that occurs in the
30S 0r 50S subunit of 70S bacterial ribosome, this in
turn inhibits the protein biosynthesis.
Most of the antibiotics inhibits the formation of 30S
initiation complex or altogether inhibits the
formation of 70S ribosome by the 30S and 50S
ribosome subunits or they inhibit assembling of
amino acids into a polypeptide chain.

47.  Tetracyclines, includingdoxycycline, block protein
synthesis by preventing the binding of aminoacyl- tRNA
in 30S ribosome subunit. These compounds block protein
synthesis in both prokaryotic and eukaryotic system.
Streptomycin interferes with the formation of 30S
initiation complex hence inhibits the protein biosynthesis.
Erythromycin interferes with the assembly of 50S subunit
of ribosome hence inhibit the protein synthesis.
Antibiotics lincomycin and clindamycin inhibits enzyme
peptidyl transferase, hence prevent the protein synthesis.

48.  Whereas antibiotic puramycin does not inhibits
the enzymatic process, but they act as an
analoge of 3'-terminal end of aminoacyl-tRNA,
hence disrupts protein synthesis and causes
premature polypeptide chain termination. In
other words this antibiotic produces non
functional proteins in the cell.
 Some of the examples for this category of
antibiotics are Doxocycline hyclate,
Erythromycin, Hygromycin B, Kanamycin
disulfate salt and much more.

49. Name Chemical nature Target site of action
Puromycin Structural analogue Compete with binding of
tRNA aminoacyl tRNA at a
side on ribosome.
Streptomycin Aminoglycoside Binds to 30s ribosomal subunit
and cause misreading of
codons.
Tetracycline Naphthalene ring Binds to 30s ribosomal subunit
structure and prevent binding of
aminoacyl tRNA to ribosome
Chloramphenicol Nitrobenzene Binds to 50s ribosomal subunit
Ring and interferes with peptide
bond formation.
Erythromycin Macrolide ring Binds to 50s ribosomal subunit
and interferes with peptide
bond formation as well as
block translocation step.

50.  Good news
 A few novel antibiotics have shown promising
results / are undergoing clinical studies
 Bad news
 As immunosuppressive diseases and use of
immunosuppressive agents become more prevalent,
opportunistic infections becomes more common, esp.
by organisms rarely encountered previously
 Diseases: e.g. HIV, leukemia
 Drugs: e.g. in solid organ transplants, bone marrow
transplants, rheumatoid disorders
 Development of bacterial resistance to antibiotics is
much faster than research and development of new
antibiotics

51. Antibiotics inhibits the growth of infectious
agents such as bacteria, virus, fungus or other
types of microorganisms by inhibiting cell wall
formation or nucleic acid synthesis or protein
synthesis.