This document discusses beta-lactam antibiotics, including penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors. It describes their mechanism of action as inhibiting bacterial cell wall synthesis. Penicillins were the first antibiotics developed from Penicillium fungi. Cephalosporins are derived from fungi and inhibit bacterial cell wall synthesis like penicillins. Beta-lactamase inhibitors prevent bacterial resistance by inhibiting beta-lactamase enzymes from breaking down the beta-lactam antibiotic ring structure.

1. BETA-LACTAM ANTIBIOTICS
SOS IN PHARMACEUTICAL SCIENCE
JIWAJI UNIVERSITY, GWALIOR (M.P)
Submitted to Submitted by
Dr Manoj Sharma Yogesh Yadav
ASSOCIATE Professor M .Pharmacy (Pharmacology)
(Pharmacology ) 2nd Sem

2. Content
• Introduction
• Beta lactams
• Mechanism of action
1) Penicillin
2) Beta – lactamase inhibitors
3) Cephalosporins
4) Monobactams
5)Carbapenems

3. Introduction:
• An antibiotic is an agent that either kills or inhibits the growth of a microorganism. They may either kill or inhibit the growth of bacteria.
• The first antibiotic was penicillin.
• CLASSIFICATION:
1.CELL WALL SYNTHESIS INHIBITORS
Beta lactams
No lactams
2. PROTEIN SYNTHESIS INHIBITORS
30S inhibitors
50S inhibitors
3. NUCLEIC ACID SYNTHESIS INHIBITORS
DNA topoisomerase inhibitors
Folic acid synthesis inhibitors
4. NITROIMIDAZOLES
5. CLOTRIMOXAZOLE

4. Beta lactams
 Contain a beta-lactam ring in their chemical structure. These drugs are active against many gram-positive, gram-negative and
anaerobic organisms.
 A beta-lactam (β-lactam) ring is a four-membered lactam. A lactam is a cyclic amide, and beta-lactams are named so because the
nitrogen atom is attached to the β-carbon atom relative to the carbonyl.
 Classification:
1. PENICILLINS :
Penicillin G, Penicillin V, Amoxicillin, Azlocillin, Carbenicillin
2. CEPHALOSPORINS:
Cefazolin, Cephalexin , Cefuroxime, Cefixime, Cefpirome
3. CARBAPENAMS:
Imipenem + Cilastatin, Ertapenem, Meropenem
4. MONOBACTAMS:
Aztreonam
5. BETA LACTAMASE INHIBITORS:
Clavulanic Acid, Sulbactam, Tazobactam

5. • MECHANISM OF ACTION
 Beta-lactam antibiotics produce bactericidal effect by inhibiting cell wall synthesis in susceptible
bacteria. Bacterial cell wall is composed of peptidoglycan, which has glycan chain cross-linked by
peptide chain.
 The glycan chain is composed of alternating amino sugars, NAM (N-acetylmuramic acid) and NAG
(N-acetylglucosamine).
 Peptidoglycan is a vital constituent of the bacterial cell wall that provides mechanical stability to it.
 The targets for the actions of beta-lactam antibiotics are known as penicillin-binding proteins
(PBPs).
 The beta-lactam antibiotics inhibit the last step in peptidoglycan synthesis by inhibit the terminal
transpeptidation process by which peptidoglycan forms.
 This binding induces loss of viability and lysis within the bacterial cell.

6.  Penicillin
• These antibiotics have a nucleus of 6-aminopenicillanic acid (lactam plus thiazolidine) ring
with various ringside chains .
• Penicillin was the first antibiotic developed and used clinically. It was discovered
accidentally by Alexander Fleming. The source of penicillin is the high-yielding Penicillium
chrysogenum.
• CLASSIFICATION:
1. Natural penicillin: Penicillin G, Penicillin V
2. Aminopenicillin: Ampicillin, Amoxicillin
3. Penicillinase resistant penicillin: Oxacillin, Dicloxacillin
4. Extend spectrum penicillin: Carbenicillin, Piperacillin, Mezlocillin, Ticarcillin.

7. • Pharmacokinetic
• Penicillin V is preferable for oral administration, given 30 min before the meal or 2 hours after.
• Penicillin G Most of the orally administered penicillin G is destroyed by gastric acid (acid labile); hence
penicillin G is usually given by i.v. route. It can also be administered by i.m. route but is painful. Penicillin G
is widely distributed in body tissues, but poorly crosses the BBB; although during meningitis, adequate
amount reaches the CSF. Penicillin G is rapidly excreted in urine mainly by active tubular secretion.
• Penicillinase-resistant penicillin's (oxacillin, cloxacillin, and dicloxacillin) are available in oral and parenteral
preparations.
• Aminopenicillins: Ampicillin and amoxicillin are available in both oral and parenteral preparations, though
amoxicillin is preferred orally. Ampicillin active against bacteria's which are sensitive to penicillin G.

8. • Indications :
• Natural penicillin's [penicillin G (IV), penicillin V (PO)] are used to treat selected gram-positive and gram-
negative infections.
• Penicillin susceptible Streptococcus pneumonia and meningitis
• Streptococcal pharyngitis, Endocarditis
• Skin and soft tissue infections
• Neisseria meningitides infections, Syphilis
• Beta-lactamase-resistant Agents: These agents [oxacillin (IV), nafcillin (IV), dicloxacillin (PO)] are active
against gram-positive organisms. Despite the occurrence of widespread resistance among staphylococci,
they remain antibiotics of choice in managing methicillin-susceptible staphylococci , Sensitive strains of
Staphylococcus aureus and S. epidermidis infections (abscesses, cellulitis, pneumonia, etc.)
• Skin and soft tissue infections (MSSA)
• Serious infections due to MSSA

9. .
• Aminopenicillins: These antibiotics have activity against gram-positive and gram-negative bacteria (e.g.,
many Enterobacteriaceae) anaerobic organisms. They are commonly used together with beta-lactamase
inhibitors.
• Upper respiratory tract infections (sinusitis, pharyngitis, otitis media)
• Enterococcus faecalis infections,
• Amoxicillin is the most active agent against both penicillin-sensitive and penicillin- resistant Streptococcus
pneumoniae. Ampicillin is highly effective against Listeria infections,
• Upper respiratory tract infections (sinusitis, otitis media)
• Intra-abdominal infections
• Extend spectrum penicillin's
• Piperacillin (ureidopenicillin) has activity against aminopenicillin-resistant gram-negative bacilli
(Pseudomonas aeruginosa). They are commonly combined with beta-lactamase inhibitors.
• Carbenicillin widely used in Infections caused by Pseudomonas aeruginosa and Proteus spp.

10. • Mechanism of bacterial resistance to penicillin's
• Bacteria develop resistance
(i) by producing þ-lactamases, which destroy the b-lactam ring, e.g. S.aureus, E. coli,
gonococci, H. influenzae, etc.
(ii) due to altered PBPs, which have less affinity for þ-lactams, e.g. S. pneumoniae
(iii) due to decreased ability of the drug to penetrate to its site of action
MOA: They inhibit the penicillinase bacteria which break the b-lactam ring .

11. • Adverse Drug Reactions
• They may cause hypersensitivity reactions, such as skin rashes,urticaria, fever, dermatitis, bronchospasm,
angioedema, joint pain, serum sickness or anaphylactic reaction
• Pain and sterile abscess at the site of i.m. injection. Prolonged use of i.v. penicillin G may cause
thrombophlebitis.
• Diarrhea after administer Ampicillin.
• Precautions:
• Before giving penicillin, history of previous administration and allergic manifestations, if any, must be noted.
• In patients with history of asthma, allergic rhinitis, hay fever, etc. there is an increased risk of penicillin allergy;
hence it should be avoided in such cases.
• Inj. adrenaline and hydrocortisone should be kept ready before injecting penicillin to treat the anaphylactic
reaction.
• Penicillin's are contraindicated in patients with previous anaphylactic reactions or serious skin reactions.

12.  Beta-lactamase inhibitors
• Beta lactamase is an enzyme produced by many gram positive and gram negative bacteria's
which inactivates beta lactam antibiotics by opening the beta lactam ring.
• They are : Clavulanic acid,
Sulbactam
Tazobactam
• MOA: It competitively and irreversibly inhibits Beta-lactamases. After binding to the
enzyme, clavulanic acid itself gets inactivated; hence it is called a ‘suicide’ inhibitor.
• It is a progressive inhibitor i.e. inhibition increases by increase time.
• ADR : Skin rashes, vaginitis
Hepatic injury

13. • Drug combination and uses
Clavulanic acid + Amoxicillin : Oral, i.m., i.v.
Treat Skin, respiratory and urinary tract infections caused by b-lactamase-producing strains of S.
aureus, E. coli ,H. influenzae and gonococci.
Sulbactam + Ampicillin: i.m., i.v., oral
Intra-abdominal and pelvic infections (mixed aerobic and anaerobic infections) due to b-lactamase
producing strains of S. aureus, gram negative aerobes and anaerobes.
Tazobactam +piperacillin (Tazobac) : i.v.
Severe infections caused by þ-lactamase-producing strains of gram-negative bacilli.
Clavulanic acid +ticarcillin (Timentin): i.m., i.v.
Mixed nosocomial infections due to aerobic gram-negative bacilli, S. aureus and Bacteroides spp.

14.  CEPHALOSPORINS
• Cephalosporins are beta-lactam antimicrobials used to manage a wide range of infections
from gram-positive and gram-negative bacteria.
• The first cephalosporins were obtained from a fungus, Cephalosporium acremonium.
• Like penicillin's, the cephalosporins also inhibit the synthesis of bacterial cell wall and
produce bactericidal effect.
• CLASSIFICATION
• 1st generation: cefazolin, cephalin, cephradine, cefadroxil, cephalexin.
• 2nd generation: cefaclor, cefuroxime., cefotetan, and cefoxitin
• 3rd generation: cefixime, ceftazidime, cefdinir, ceftriaxone, cefpodoxime
• 4th generation: cefepime, cefpirome

15. • Pharmacokinetics
• Cephalosporins are administered either orally or parenterally.
• These drugs are excreted mainly unchanged through kidney either by glomerular
filtration or by tubular secretion.
• Some cephalosporins are metabolized in the body before their excretion.
• Cefotaxime is deacetylated in the body before its excretion.
• Cefoperazone is mainly excreted through bile.
• Like penicillin's, the active tubular secretion of cephalosporins is blocked by probenecid,
resulting in higher blood levels and longer duration of action.

16. • Indications :
• First-generation cephalosporins have active coverage against most gram-positive cocci such
as staphylococci spp. and streptococci spp. while having minimal coverage against gram-negative
bacteria Proteus mirabilis, E. coli, and Klebsiella pneumoniae.
• Additionally, clinicians can use them for bone, respiratory tract, genitourinary tract, biliary tract,
bloodstream infection, otitis media, and surgical prophylaxis. In fact, cefazolin is the cephalosporin
of choice for surgical prophylaxis.
• Cefuroxime has increase coverage against H. influenza. Indications for cefuroxime also include
Lyme disease in pregnant women and children. The cephamycin subgroup has increased coverage
against Bacteroides species.
• Third-generation can penetrate the blood-brain barrier and cover bacteria in the cerebral spinal fluid,
especially ceftriaxone and cefotaxime. Ceftazidime, very importantly,
has Pseudomonas aeruginosa coverage.
• Cefepime is a broad-spectrum antimicrobial that can penetrate the cerebral spinal fluid. cefepime
can cover Streptococcus pneumoniae and methicillin-sensitive Staphylococcus aureus (MSSA).
cefepime can provide coverage against beta-lactamase-producing gram-negative bacilli.

17. • Adverse Drug Reactions.
1. Hypersensitivity: The most common adverse effects are allergic reactions. They are skin rashes,
urticaria and rarely anaphylaxis. Cross-reactivity to penicillin is seen in few patients.
2. Gastrointestinal disturbances—mainly diarrhoea, vomiting and anorexia can also occur.
3. Pain at the site of i.m. injection mainly with cephalothin. Intravenous cephalosporins can cause
thrombophlebitis.
4. Nephrotoxicity may occur. Co-administration of cephalothin and gentamicin increases the
nephrotoxicity.
5. Intolerance to alcohol (a disulfiram-like reaction) has been reported with cefotetan and cefoperazone.
6. Severe bleeding can occur either due to hypoprothrombinemia (which responds to vitamin K
therapy) or thrombocytopenia or platelet dysfunction.

18. • Contraindications
• One of the contraindications of cephalosporin is if patients are allergic to them or those that have had
an anaphylactic reaction to penicillin or other beta-lactams antimicrobials.
• Ceftriaxone is contraindicated in hyperbilirubinemia neonates because of reports that ceftriaxone
displaces bilirubin from albumin, increasing the free bilirubin concentrations and increases the risk
of jaundice in neonates
• Ceftriaxone reacts to a calcium-containing solution, and it can precipitate in the lungs and kidneys of
infants less than 28 days old, which could be life-threatening. Therefore, ceftriaxone is also
contraindicated in infants less than 28 days old if they are expected to receive any calcium-
containing products.

19.  Monobactams
• Monobactams are a subgroup of beta-lactam antibiotics, wherein the beta-lactam ring is alone and
not fused to another ring (other beta-lactams have at least two rings).
• Monobactams work only against aerobic gram-negative bacteria (Neisseria, Pseudomonas).
• Monobactams work by inhibiting the peptidoglycan synthesis process (a process essential to
maintain bacterial cell wall integrity); as a result, the bacteria lose the ability to resist and burst,
leading to cell death.
• Monobactam antibiotics are administered intravenously or intramuscularly.
• Drug used: Aztreonam

20. • Uses
• Monobactams are used to treat the following:
• Pyelonephritis (severe kidney infection)
• Uncomplicated cystitis (inflammation of the urinary bladder)
• Urinary tract infection
• Lower respiratory tract infection
• Septicemia (serious bloodstream infection)
• Skin infections (postoperative wounds, ulcers, and burns)
• Peritonitis (inflammation of the membrane that lines the inner abdominal wall)
• Endometritis (inflammation of the lining of the uterus)
• As an inhalational antibiotic in children with cystic fibrosis (a condition that produces abnormally thick mucus leading to
blockage of bronchi in the lungs)

21. • Adverse drug Reactions
• Common side effects include:
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain, Skin rash
• Abnormal taste in the mouth
• Other rare side effects include:
• Phlebitis (inflammation of a vein)
• Tightness in chest/throat
• Fever
• Confusion
• Tinnitus (ringing sound in one or both the ears)

22.  CARBAPENEM
• Carbapenems are a class of very effective antibiotic agents most commonly used for the treatment
of severe bacterial infections. This class of antibiotics is usually reserved for known or
suspected multidrug-resistant (MDR) bacterial infections.
• Carbapenems include
• Doripenem
• Ertapenem
• Imipenem
• Meropenem
• Many multidrug-resistant hospital-acquired bacteria are sensitive only to carbapenems.

23. • Indications
• Carbapenems are parenteral bactericidal beta-lactam antibiotics that have an extremely broad spectrum. They are active against
• Haemophilus influenzae
• Anaerobes
• Most Enterobacteriaceae (including those that produce AmpC beta-lactamase and extended-spectrum beta-lactamase [ESBL],
although Proteus mirabilis tends to have a higher imipenem minimum inhibitory concentrations.
• Methicillin-sensitive staphylococci and streptococci, including Streptococcus pneumoniae (except possibly strains with reduced
penicillin sensitivity)
• Most Enterococcus faecalis and many Pseudomonas aeruginosa strains, including those resistant to broad-spectrum penicillin's
and cephalosporins, are susceptible to imipenem, meropenem, and doripenem but are resistant to ertapenem.
• However, meropenem and doripenem are less active against E. faecalis than imipenem. Carbapenems are active synergistically
with aminoglycosides against P. aeruginosa. However, E. faecium, Stenotrophomonas melophilia, and methicillin-resistant
staphylococci are resistant.

24. • Imipenem
Imipenem is rapid hydrolysed by the enzyme dehydropeptidase-1 located at brush border of renal tubule in kidney.
Thus Cilastatin is given with imipenem which is an inhibitor of that enzyme Cilastatin, a dehydropeptidase
inhibitor, increases the concentration of imipenem in urine. Hence, it is combined with imipenem.
 IMIPENEM + CILASTATIN (0.5gm I.V. 6hr ) (4g/day)
• Imipenem–Cilastatin combination increases the antibacterial efficacy and is used in mixed bacterial infections, such as
urinary, respiratory, intra-abdominal, gynecologic, skin, soft tissue, bone and joint infections. It may exhibit cross-
reactivity with penicillin's and cephalosporins.
• Nausea, vomiting and skin rashes are the common side effects and, rarely, seizures have also been reported.

25. THANKYOU
.