Antibiotics are drugs that kill or inhibit the growth of bacteria. They work by either killing bacteria or preventing them from growing and dividing. The most common class of antibiotics are beta-lactam antibiotics, which include penicillins, cephalosporins, monobactams, and carbapenems. Beta-lactam antibiotics work by inhibiting the synthesis of peptidoglycan in bacterial cell walls. Bacteria can develop resistance through producing beta-lactamase enzymes or by altering penicillin-binding proteins. Different classes of beta-lactam antibiotics are named based on the ring structure they are fused to.

1. Antibiotics
• Antibiotics, also called antibacterials, are a type
of antimicrobial drug used in the treatment and
prevention of bacterial infections.
• They may either kill or inhibit the growth of
bacteria.
• A limited number of antibiotics also possess
antiprotozoal activity.
• Antibiotics are not effective against viruses such
as the common cold or influenza; drugs which
inhibit viruses are termed antiviral drugs or
antivirals rather than antibiotics.

2. • Term antibiotic (which means
"opposing life") is used to refer to
any substance used against
microbes,synonymous with
antimicrobial.
• Antibacterials are used in soaps and
disinfectants, while antibiotics are
used as medicine.

3. Historical background of
antibiotics
• The term antibiotic was first used
in 1942 by Selman Waksman and
his collaborators in journal articles
to describe any substance
produced by a microorganism that
is antagonistic to the growth of
other microorganisms in high
dilution.

4. Staphylococcus aureus

5. Nomenclature of antibiotics
• β-lactam antibiotic
• are a class of broad-spectrum antibiotics,
consisting of all antibiotic agents that contain a
beta-lactam ring in their molecular structures.
• This includes penicillin derivatives (penams),
cephalosporins (cephems), monobactams, and
carbapenems.
• Most β-lactam antibiotics work by inhibiting
cell wall biosynthesis in the bacterial organism
and are the most widely used group of
antibiotics.

6. Core structure of penicillins (top) and
cephalosporins (bottom). β-lactam ring
in red.

7. • Bacteria often develop resistance
to β-lactam antibiotics by
synthesizing a β-lactamase, an
enzyme that attacks the β-lactam
ring.
• To overcome this resistance, β-
lactam antibiotics are often given
with β-lactamase inhibitors such
as clavulanic acid.

8. Medical use
• β-lactam antibiotics are indicated for the
prevention and treatment of bacterial
infections caused by susceptible
organisms.
• At first, β-lactam antibiotics were mainly
active only against Gram-positive
bacteria, yet the recent development of
broad-spectrum β-lactam antibiotics
active against various Gram-negative
organisms has increased their usefulness.

9. Adverse effects
• Common adverse drug reactions for
the β-lactam antibiotics include
• diarrhea,
• nausea,
• rash,
• urticaria,
• superinfection (including candidiasis).

10. Infrequent adverse effects
include
• fever,
• vomiting,
• erythema,
• dermatitis,
• angioedema,
• pseudomembranous colitis.

11. Allergy/hypersensitivity
• A Jarisch–Herxheimer reaction may occur after
initial treatment of a spirochetal infection such
as syphilis with a β-lactam antibiotic.
• the risk of cross-reactivity is sufficient to
warrant the contraindication of all β-lactam
antibiotics in patients with a history of severe
allergic reactions (urticaria, anaphylaxis,
interstitial nephritis) to any β-lactam
antibiotic.

12. In the absence of
β-lactam
antibiotics, the
bacterial cell wall
plays an
important role in
bacterial
reproduction.
β-lactam antibiotics are bacteriocidal, and act by
inhibiting the synthesis of the peptidoglycan layer
of bacterial cell walls.
Mode of action

13. Adding β-lactam
antibiotics to the
cell medium while
bacteria are dividing
will cause them to
shed their cell walls
and fail to divide,
forming large,
fragile spheroplasts.

14. Penicillin and most
other β-lactam
antibiotics act by
inhibiting penicillin-
binding proteins,
which normally
catalyze cross-linking
of bacterial cell walls.

15. Potency
• The first is known as "Woodward's parameter",
h, and is the height (in angstroms) of the
pyramid formed by the nitrogen atom of the β-
lactam as the apex and the three adjacent
carbon atoms as the base.
• The second is called "Cohen's parameter", c, and
is the distance between the carbon atom of the
carboxylate and the oxygen atom of the β-
lactam carbonyl.
• The best antibiotics are those with higher h
values (more reactive to hydrolysis) and lower c
values (better binding to PBPs).

16. Modes of resistance
• Enzymatic hydrolysis of the β-lactam ring
• If the bacterium produces the enzyme β-
lactamase or the enzyme penicillinase, the
enzyme will hydrolyse the β-lactam ring of the
antibiotic, rendering the antibiotic ineffective.
• The genes encoding these enzymes may be
inherently present on the bacterial chromosome
or may be acquired via plasmid transfer
(plasmid-mediated resistance), and β-lactamase
gene expression may be induced by exposure to
β-lactams.

17. Clavulanic acid

18. Amoxicillin

19. •The production of a β-
lactamase by a
bacterium does not
necessarily rule out all
treatment options with
β-lactam antibiotics.

20. Possession of altered penicillin-binding
proteins
• As a response to the use of β-lactams to control
bacterial infections, some bacteria have evolved
penicillin binding proteins with novel structures.
• β-lactam antibiotics cannot bind as effectively to
these altered PBPs, and, as a result, the β-lactams are
less effective at disrupting cell wall synthesis.
• examples of this mode of resistance include
• methicillin-resistant Staphylococcus aureus
(MRSA)
• and penicillin-resistant Streptococcus
pneumoniae.

21. Nomenclature
• β-Lactams fused to saturated five-membered
rings:
• β-Lactams containing thiazolidine rings are
named penams.
Benzylpenicillin, an example of a penam

22. β-Lactams containing pyrrolidine rings
are named carbapenams.
Structure of (3S,5R)-carbapenam-3-carboxylic acid

23. β-Lactams fused to oxazolidine rings
are named oxapenams or clavams.
Clavulanic acidoxapenams

24. β-Lactams fused to unsaturated five-
membered rings:
• β-Lactams containing 2,3-dihydrothiazole rings
are named penems.

25. β-Lactams containing 2,3-dihydro-1H-
pyrrole rings are named carbapenems.
Core structure of the carbapenem molecule

26. β-Lactams fused to unsaturated six-
membered rings:
Core structure of the cephalosporins.
•β-Lactams containing 3,6-dihydro-2H-1,3-thiazine rings
are named cephems.

27. β-Lactams containing 1,2,3,4-
tetrahydropyridine rings are named
carbacephems.
Loracarbef, a carbacephem

28. β-Lactams containing 3,6-dihydro-2H-1,3-
oxazine rings are named oxacephems.
Latamoxef

29. β-Lactams not fused to any other ring
are named monobactams.
Aztreonam.

30. • The bicyclic β-lactams are numbered starting with the
position occupied by sulfur in the penams and
cephems, regardless of which atom it is in a given
class.
• That is, position 1 is always adjacent to the β-carbon
of β-lactam ring.
• The numbering continues clockwise from position one
until the β-carbon of β-lactam is reached, at which
point numbering continues counterclockwise around
the lactam ring to number the remaining to carbons.
• For example,
• the nitrogen atom of all bicyclic β-lactams fused to
five-membered rings is labelled position 4, as it is in
penams, while in cephems, the nitrogen is position 5.

31. The numbering of monolactams
follows that of the IUPAC;
•the nitrogen atom is
position 1,
•the carbonyl carbon is 2,
• the α-carbon is 3,
•and the β-carbon 4.