This document discusses various types of beta-lactam antibiotics including penicillins. It describes semisynthetic penicillins which were developed to overcome limitations of penicillin G, including poor oral efficacy and susceptibility to penicillinase. Examples mentioned include phenoxymethylpenicillin, methicillin, and extended spectrum penicillins. It also discusses beta-lactamase inhibitors like clavulanic acid which are used in combination with antibiotics to overcome bacterial resistance.

1. Beta Lactam
Antibiotics

2. SEMI-SYNTHETIC
PENICILLINS

3. Semisynthetic penicillins are produced by chemically
combining specific side chains
(in place of benzyl side chain of PnG) or
by incorporating specific precursors in the mould
cultures.
Thus, procaine penicillin and benzathine penicillin are
salts of PnG and not semisynthetic penicillins.

4. The aim of producing semisynthetic penicillins has
been to overcome the shortcomings of PnG, which
are:
I. Poor oral efficacy
2. Susceptibility to penicillinase
3. Narrow spectrum of activity.
4. Hypersensitivity reactions
(this has not been overcome in any preparation).
In addition, some B-lactamase inhibitors have
been developed which themselves are not
antibacterial, but augment the activity of penicillins

5. Semi Synthetic
Penicillin`
Acid Resistant
Penicillin
Phenoxymethy
Penicillin
(Penicillin V)
Penicillinase
Resistant Penicillin
Mithicillin
Cloxacillin
Dicloxacillin
Extended Spectrum
Penicillins
Amino Penicillin
Amipicillin
Bacampicillin
Amoxicillin
Carboxy Peniclllln
Carbenicillin
Ticarcillin
Ureido Penlcllllns
Piperacillin
Mezlocillin

6. ACID-RESISTANT
ALTERNATIVE TO PENICILLIN-G
Phenoxymethyl penicillin (Penicillin V)
It differs from PnG only in that it is acid stable.
Oral absorption is better; peak blood
level is reached in I hour and plasma t½ is 30-60
min.
The antibacterial spectrum of penicillin V is
identical to PnG, but it is about l/5 as active
against Neisseria, other gram negative bacteria

7. It cannot be depended upon for
more serious infections and is occasionally used
for streptococcal pharyngitis, sinuitis, otitis
media, prophylaxis of rheumatic fever (when
an oral drug has to be selected), less serious
pneumococcal infections and trench mouth.

8. PENICILLINASE-RESISTANT
PENICILLINS
These congeners have side chains that protect
the B-lactam ring from attack by staphylococcal
penicillinase.
However, this also partially protects
the bacteria from the B lactam ring:
Non-penicillinase producing organisms are less
sensitive to these drugs than to PnG.

9. Their only indication
is infections caused by penicillinase producing
Staphylococci.
Which are not methicillin resistant as well.
Utility of these penicillins has markedly
declined, because methicillin resistant Staph.
aureus'(MRSA) have become universally
prevalent.

10. EXTENDED SPECTRUM PENICILLINS
These semisynthetic penicillins are in addition
active against a variety of gram-negative
bacilli because of improved ability to penetrate
through their celI membrane.
However, they are susceptible to several B-
lactamases.

11. 1. Amino penicillins
This group includes ampicillin, its prodrug
bacampicill in, and amoxicillin.
Ampicillin
lt is active against all organisms sensitive to PnG.
In addition, non-B-lactamase producing strains
of many gram- negative
bacilli, e.g. H. influenzae, E. coli, Proteus,
Salmonella, Shigella and Helicobacter pylori
are inhibited.

12. However, due to widespread use, many of these
have developed resistance; usefulness of this
antibiotic has decreased considerably.
Ampicillin is more active than PnG for
Strep. viridans, enterococci and Listeria;
Equally active for
pneumococci, gonococci and meningococci,
But penicillin- resistant strains are
resistant to ampicillin as well.

13. Pharmacokinetics
Ampicillin is not degraded by gastric acid;
oral absorption is incomplete but adequate.
Food interferes with absorption.
It is partly excreted in bile and reabsorbed-enterohepatic
enterohepatic
circulation occurs.
However, primary channel of excretion is kidney, but tubular
tubular secretion is slower than for PnG;

14. Uses
1.Respiratory Tract
Infection
2.Urinary Tract Infection
3.Meningitis
4.Gonorrhea
5.Typhoid
6.Dysentry
7.Cholecystitis
8.Subacture Bacterial
Endocarditis
9.H.Pyroli

15. Adverse effects
Diarrhea is frequent after oral administration.
Ampicillin is incompletely
absorbed- the unabsorbed drug irritates the lower
intestines as well as causes marked alteration
of bacterial flora.
It produces a high incidence (up to 10%)
of rashes, especially in patients with AIDS,
TB virus infections or lymphatic leukaemia.

16. Concurrent administration of allopurinol also
increases the incidence of rashes.
Patients with a history of immediate type
of hypersensitivity to PnG should not be given
ampicillin as well.

17. Interactions
Hydrocortisone inactivates ampicillin
if mixed in the i.v. solution.
By inhibiting colonic flora, it may interfere
with de-conjugation and enterohepatic cycling
of oral contraceptives resulting in failure of
oral contraception.
Probenecid retards renal excretion of ampicillin.

18. Amoxicillin
It is a close congener of ampicillin
similar to it in all respects except:
• Oral absorption is better; food does not
interfere with absorption;
higher and more sustained blood levels are
produced.
Amoxicillin given 3 times a day is equivalent
to ampicillin given 4 times a day.
• Incidence of diarrhea is lower.

19. • It is less active against Shigella and H. infiuenzae.
• It is more active against relatively penicillin
resistant
Strep. pneumoniae.
Many physicians now prefer amoxicillin over
ampicillin for bronchitis , urinary infections,
SABE and gonorrhoea.
It is a component of
most triple drug H. pylori eradication regimens

20. 2. Carboxypenicillins
Carbenicillin
The special feature of this penicillin congener
is its activity against Pseudomonas aeruginorn and
indole positive Proteus which are not inhibited by
PnG
or amino penicillins.
It is less active against Salmonella, E. coli and
Enterobacrer, while Klebslella and gram-positive cocci
are unaffected by it.

21. Carbenicillin is not penicillinase-resistant.
It is inactive orally and is excreted rapidly in urine
(t½ I hr).
It is used as sodium salt in a dose of 1-2 g i.m.
or 1-5 g i.v. every 4-6 hours.
At the higher doses, enough Na may be
administered to cause fluid retention and CHF
in patients with borderline renal or cardiac function.
High doses have also caused bleeding by interfering

22. Ticarcillin
It is the second carboxypenicill in,
similar in properties to carbenicillin, but is
more active and produces fewer adverse effects.
Its combination with clavulanic acid
extends efficacy to cover B-lactamase producing
strains.
For the treatment of serious Pseudomonas
infections it is often used a long with gentamicin.

23. Ureidopenicillins
Piperacillin
This antipseudomonal penicillin
is about 8 times more active than carbenicillin.
In addition, it has good activity against
Klebsiella, many Enterobacteriaceae and
some Bacteroides.

24. Piperacillin is frequently employed for treating serious gram-
gram-negative infections in
neutropenic/immunocompromised
or burn patients.
Elimination t½ is I hr. It is combined with tazobactam to

25. BETA-LACTAMASE INHIBITORS
B-lactamases are a family of enzymes produced by
many gram-positive and gram-negative bacteria
that inactivate B-lactam antibiotics by opening
the B-lactam ring.
Different B-lactamases differ
in their substrate affinities.
Three inhibitors of this enzyme clavulanic acid,
sulbactam and tazobactam are available for clinical
in combination with specific penicillins

26. Clavulanic acid
Obtained from Streptomyces clavuligerus,
it has a B-lactam ring but no/weak antibacterial
activity of its own.
It inhibits a wide variety of B lactamases produced
by both gram-positive and gram-negative bacteria.
Clavulanic acid is a ' progressive' inhibitor,
because binding with B-lactamase is reversible
initially, but becomes covalent later- inhibition
increases with time.

27. Called a 'suicide' inhibitor,
it gets inactivated after binding to the enzyme.
Clavulanate permeates the outer layers of the cell
wall of gram-negative bacteria and inhibits
the periplasmically located B-lactamase.
Pharmacokinetics
Clavulanic acid has rapid oral absorption and a
bioavailability of 60%.
It can also be injected. The elimination t½ o f 1 hr
and
tissue distribution matches amoxicillin,

28. However, clavulanate is eliminated mainly by
glomerular filtration
Moreover, it is largely hydrolysed and decarboxylated
before excretion.
Uses : Addition of clavulanic acid re-establishes
the activity of amoxicillin against B-lactamase
producing resistant Staph. aureus (but not
MRSA that have altered PBPs), H. inf/uenzae,
N. gonorrhoeae, E. coli, Proteus, Klebsiella,
Salmonella and Shigella.

29. Though Bact. fragilis
and Branhamella catarrhalis are not responsive
to amoxicillin alone, they are inhibited by the
combination.
Coamoxiclav is indicated for empirical therapy of:
• Skin and soft tissue infections, intra-abdominal
and gynaecological sepsis, urinary, biliary
and respiratory tract infections: especially
for hospital acquired infections.
•

30. Adverse effects are the same as for amoxicillin
alone; but g. i. tolerance is poorer- especially
in children.
Other adverse effects are
stomatitis/vaginitis and rashes.
Some cases of
hepatic injury have been reported with the
combination.

31. O