Types of B lactams:

Penicillins.
Cephalosporins.
Carbapenems.
Monobactams.
Penicillins
Mechanism of Action

 All beta-lactam antibiotics, including penicillins and

cephalosporins, are inhibitors of bacterial cell wall
synthesis.
 The antibiotic must first bind to the penicillin-
binding protein (PBP) located within the cytoplasmic
membrane of the cell wall. Once bound, the antibiotic
can cause various effects that eventually lead to cell
death, but primarily they inhibit the cross-linking of
the peptide chains and there by, prevent the
development of normal peptidoglycan structure.
Chemical Structure

 all contain the four-membered beta-lactam ring.

 The antibacterial activity of these molecules resides in
the ring itself, and cleavage of the ring by bacterial
beta-lactamases inactivates the compound.
 All penicillins are derived from the 6-
aminopenicillanic acid nucleus, which consists of:
 five-membered thiazolidine (penam) ring.
 four-membered beta-lactam ring.
 a side chain.
Manipulations in the side chain result in the
formation of other penicillins, which differ in their
spectrum of activity, beta-lactamase resistance, and
pharmacokinetic properties
Mechanisms of Resistance

Either by:
1. destruction of the antibiotic by beta-lactamases
2. decreased penetration of the antibiotic to reach the
PBP
3. and decreased affinity of the PBP to the antibiotic
Some bacteria, such as Staphylococcus
species, Haemophilus influenzae,
gonococci, and most gram-negative
enteric rods produce beta-lactamases
(penicillinases). These enzymes can
break the beta-lactam ring of the
antibiotic, rendering it ineffective .
 To overcome this resistance, some antibiotics are
combined with beta-lactamase inhibitors, such as
 Clavulanic acid to prevent the destruction of the
beta-lactam ring.
 Other penicillins, such as nafcillin, are resistant to
beta-lactamase destruction due to the positioning of
their side chain.
Bacteria differ in their number and types of
PBPs.Antibiotics differ in their affinity to bind to the
PBP. Also, mutations in the PBPs can cause an
organism once sensitive to become resistant
Classification

The penicillins have been divided into categories based

on their spectrum of activity
The natural penicillins (penicillin G) were the first
agents in the penicillin family to be used clinically to
treat infections. Shortly after the introduction of
penicillin, the emergence of penicillinase-producing
staphylococci caused the natural penicillins to be
ineffective for these organisms.
This led to the development of the penicillinase-
resistant penicillins, also known as the
antistaphylococcal penicillins. Methicillin was the
first of this group. The addition of a side chain
protected the beta-lactam ring by sterically inhibiting
the action of the penicillinase.
Examples:
 Cloxacillin
 Dicloxacillin
 Methicillin Not available
 Nafcillin
 Oxacillin
The need for penicillins with extended activity against
gram-negative microorganisms prompted further
manipulations of the side chains. This led to the
development of three new classes of penicillins:
 the aminopenicillins: Amoxicillin and Ampicillin
 Carboxypenicillins: Carbenicillin and Ticarcillin
 ureidopenicillins :Mezlocillin and Piperacillin
Antimicrobial Activity and
Therapeutic Uses
The natural penicillins have excellent gram-positive
activity and until recently were considered the drug
of choice for many infections caused by pneumococci,
streptococci, meningococci, and non-β-lactamase-
producing staphylococci and gonococci. Emerging
resistance to these drugs is changing the way these
infections are treated
The penicillinase-resistant penicillins, also known as
the antistaphylococcal penicillins, have excellent
activity against both Streptococcus and
Staphylococcus species (including those strains of
penicillinase-producing Staphylococcus aureus) but
no activity against gram negative bacteria. They
are considered the drugs of choice for the treatment
of staphylococcal infections, commonly seen in
cellulitis or other skin infections, for example
 Aminopenicillins were the first group of penicillin
antibiotics to have activity against both gram-
positive and gram-negative bacteria.
 ampicillin has more activity against enterococci, but
somewhat less activity against S.
pyogenes,Streptococcus pneumoniae, Neisseria
species, and Clostridium species. It also has some
activity against gram negative bacteria such as
Escherichia coli, Proteus mirabilis,
Salmonella,Shigella,Listeria, and non-β-lactamase-
producing strains of H. influenzae.The emergence of
resistant organisms,however, is limiting its use
clinically.
 Carboxypenicillins have the same antibacterial
spectrum of activity as ampicillin,but with greater
gram-negative activity. Carbenicillin and ticarcillin
are the two drugs in this class.
 They also have activity against indole positive
Proteus,Enterobacter,Providencia,Morganella and
Pseudomonas aeruginosa. Unlike the aminopenicillin,
ampicillin, carbenicillin and ticarcillin are not very
active against enterococci
The ureidopenicillins and piperazine penicillins have
the broadest spectrum of activity among the
penicillins, covering many gram-positive and gram-
negative bacteria. The addition of the ureido group to
the penicillin structure produces the antibiotics
azlocillin and mezlocillin,
whereas the addition of the ureido group and a
piperazine side chain produces piperacillin. Their
coverage is very similar to that of the
carboxypenicillins but with enhanced activity against
P. aeruginosa
CEPHALOSPORINS
Mechanism of Action

 Cephalosporins, like other beta-lactam antibiotics,

inhibit peptidoglycan cross-linkage and therefore
bacterial cell wall synthesis. Like the penicillins, all
cephalosporins are bactericidal
Chemical Structure
 The 7-aminocephalosporanic acid nucleus of the
cephalosporin is very similar to the 6-aminopenicillanic
acid nucleus of the penicillin.
 In addition to the beta lactam ring,
 a six-membered dihydrothiazine (cephem) ring,
 two side chains.
 The six-membered cephem ring confers a relative
resistance to certain beta-lactamases compared to the
penam ring. Unlike the penicillins, manipulation of the
cephalosporin’s structure is allowed in two places versus
one, resulting in the formation of other antibiotics with
different spectrums of activity and pharmacokinetic
properties
Mechanisms of Resistance

 Like penicillins, bacterial resistance to cephalosporins

can be mediated through three major mechanisms:
1. alterations in PBPs.
2. formation of beta lactamases (cephalosporinases) that
inactivate the drug.
3. decreased ability of the antibiotics to penetrate the cell
wall and reach its PBP.
Classification

Cephalosporins have traditionally been divided into

four major groups or “generations” based on their
spectrum of activity:
First Generation
Cefadroxil
Cefazolin
Cephalexin
Cephalothin Not available
Cephapirin
Cephradine
Antimicrobial Activity and
Therapeutic Uses
First-generation cephalosporins are active against the
gram-positive cocci, staphylococci, and streptococci,
but not enterococcus species. Among the gram-
negative bacteria, E. coli, Klebsiella pneumoniae, and
P. mirabilis are usually susceptible.
Even though the first-generation cephalosporins have
a broad spectrum of activity and have few side effects,
they are rarely the drugs of choice to treat any
infection. However, when penicillins are to be
avoided, they are commonly prescribed to treat skin
infections, streptococcal pharyngitis.
Second Generation
o Cefaclor
o Cefamandole Not available
o Cefmetazole Not available
o Cefonicid
o Cefotetan
o Cefoxitin
o Cefprozil
o Cefuroxime
 In general, the second-generation cephalosporins are
less active against staphylococci and streptococci
compared to the first-generation agents but are more
active against selected gram negative bacilli.
Enterobacter, Klebsiella and indole-positive Proteus spp.
are usually sensitive, although P. aeruginosa is not.
 Cefoxitin, cefotetan, cefmetazole, and cefamandole all
have moderate activity to Bacteroides fragilis and can be
useful in mixed infections such as peritonitis or
diverticulitis. These agents are also commonly
prescribed for surgical prophylaxis, especially
intraabdominal procedures .
 Cefuroxime is active against H. influenzae,
Moraxella catarrhalis, and S. pneumoniae and
therefore useful in the treatment of bronchitis and
community-acquired pneumonia.
 First- and second-generation oral cephalosporins,
such as cefadroxil, cefaclor, and cefprozil, are
commonly prescribed in upper respiratory tract
infections, such as otitis media, pharyngitis/tonsillitis,
and sinusitis.
 Third Generation
Cefdinir.
Cefixime.
Cefoperazone.
Cefotaxime.
Cefpodoxime.
Ceftazidime.
Ceftibuten.
Ceftizoxime.
Ceftriaxone.
Most third-generation cephalosporins have less
staphylococcal and streptococcal activity than the
first- or second-generation agents, but possess even
better activity against gram-negative bacteria,
including P. aeruginosa and Enterobacter spp.
 Only cefoperazone and ceftazidime have activity
against P. aeruginosa, and the latter is commonly
prescribed in combination to treat such infections.
 Ceftazidime is also used in immunocompromised
patients to treat fever of unknown etiology.
 The third- and fourth-generation cephalosporins
are the only cephalosporins that penetrate the
central nervous system and therefore may be used
to treat meningitis, depending on the organism.
The newest generation of cephalosporins represents an
attempt to maintain good activity against gram-
positive as well as gram-negative organisms, including
P. aeruginosa, and is designated as fourth-generation
cephalosporins .To date only one antimicrobial agent,
cefepime, is considered a fourth-generation
cephalosporin.
CARBAPENEMS
Include:
 Imipenem,
 meropenem,
 and ertapenem
Like all beta-lactam antibiotics, carbapenems inhibit
bacterial cell wall synthesis. Their chemical structure
is similar to the penicillins, but with a few
modifications.
The carbapenems have the broadest antimicrobial
spectrum of activity of any beta-lactam antibiotics
available to date. They have excellent activity against
both aerobic and anaerobic gram-positive and gram-
negative bacteria.
 Among the gram-positive organisms, the
carbapenems are active against most strains of
methicillin-sensitive S.aureus (MSSA) and coagulase-
negative staphylococci, Streptococcus spp., and E.
faecalis.

 The two older carbapenems exhibit excellent activity

to the majority of gram-negative bacteria, including
troublesome nosocomial pathogens such as P.
aeruginosa.
 Ertapenem, on the other hand, has excellent activity
against most gram-negative pathogens except P.
aeruginosa. In cases of documented or suspected
infections due to Pseudomonas spp., ertapenem
should not be used.
The carbapenems are also active against most strains
of clinically significant anaerobes. Due to their broad
spectrum of activity, many clinicians think
carbapenems should be reserved for the treatment of
mixed bacterial infections and the treatment of
resistant aerobic gram-negative bacteria that are not
susceptible to other beta-lactam antibiotics
 The most frequent side effects associated with
carbapenem administration are phlebitis, nausea,
vomiting, diarrhea, and rash .

 Seizures occurred in 1% to 3% of treated patients but

occurred more commonly in patients with renal
insufficiency or underlying central nervous system
disease .
MONOBACTAMS
 Aztreonam is a monocyclic beta-lactam antibiotic
known as a monobactam.

 Its unique chemical structure is composed solely of

the four-membered beta-lactam ring and a side chain.
It lacks the five- or six-membered side ring shared by
the penicillins and cephalosporins, respectively. Like
other beta-lactam antibiotics.
 aztreonam exerts its bactericidal action by binding to
PBPs, disrupting the formation of the peptidoglycan
chain and ultimately inhibiting bacterial cell wall
synthesis
 Aztreonam binds primarily to the PBP-3 located on
Enterobacteriaceae, Pseudomonas spp., and other
gram-negative aerobic organisms, but not to the
PBPs found on gram-positive bacteria.
 As a result, aztreonam has a narrow spectrum of
activity, limited to gram-negative bacteria.
Because it is limited to the treatment of gram-negative
infections, it is commonly used in combination with
another antimicrobial for empiric therapy.
Thank you