Beta-lactam antibiotics include penicillins, cephalosporins, carbapenems, and monobactams. They work by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins. Penicillins are further classified into natural, semisynthetic, and extended spectrum categories. Semisynthetic penicillins like amoxicillin have better oral absorption. Beta-lactamase inhibitors are often combined with antibiotics to prevent bacterial inactivation of the drug. Cephalosporins have a wider spectrum than penicillins and are classified in generations based on their antimicrobial activity. Carbapenems and monobactams also inhibit cell wall synthesis but have even broader
4. CLASSIFICATION OF
ANTIBIOTICS
(Based on structural similarities)
Beta Lactams
Penicillins
Cephalosporins
Monobactams
Carbapenems
Fluoroquinolones
Macrolides
Tetracyclines
Aminoglycosides
5. Antibiotics: Mode of action
Inhibitors of DNA synthesis
Inhibitors of bacterial protein synthesis
Inhibitors of bacterial cell wall synthesis
Interference with metabolism
Impairment of nucleic acids
7. Peptidoglycan layer is composed of alternating units of N-acetyl
glucosamine(NAGA) and N-acetyl muramic acid(NAMA)
NAGA and NAMA are crosslinked by a class of transpeptidases
known as penicillin binding proteins (PBPs)
Interfering with this cross linking disrupts the cell wall synthesis.
POINT TO REMEMBER :
8. Beta Lactam antibiotics
• Contains a beta lactam ring in their molecular structure.
• Nitrogen is attached to the beta carbon relative to the carbonyl ring and
hence the name.
9. Classification of beta lactam antibiotics
Penicillins
Cephalosporins
Carbapenems
Monobactams
B lactamase inhibitors
10. Mechanism of action
The beta lactam antibiotics bind to Penicillin Binding
proteins(PBPs). ( transpeptidase , other enzymes and related
proteins )
PBPs are unable to crosslink peptidoglycan chains.
Bacteria is unable to synthesize a stable cell wall.
Hence, the bacteria is lysed.
11. Penicillins
Sir Alexander Fleming discovered penicillin from penicillium
notatum
Now obtained from Penicillium chrysogenum for therapeutic
use
15. Adverse effects
Hypersensitivity – skin rash, urticaria, pruritus, bronchospasm, fever,
anaphylaxis
hence intradermal skin injection test dose is a must before administration.
Other than the rare event of anaphylaxis penicillins are one of the safest
antibiotics
Local pain at injection site
CNS : confusion,convulsions,coma
Suprainfections
16. ANAPHYLATIC SHOCK TREATMENT
DRUG OF CHOICE : )
dose : 0.2 - 0.5 ml of 1: 1000 solution S.C ( if mild )
50 - 100 ug of 1: 10,000 solution I.V ( if severe )
corticosteroid : hydrocortisone
others : antihistaminic , iv fluids , oxygen therapy , dopamine.
17. Semisynthetic penicillins
1.Acid resistant – Penicillin V
Use : Streptococcal pharyngitis, sinusitis and trench mouth.
2.Penicillinase resistant – cloxacillin, methicillin, oxacillin, nafcillin
Use : Staphylococcal infections ,treatment of human bites .
19. Amoxicillin vs Ampicillin
Amoxicillin is better absorbed orally
Food does not interfere with its absorption
Attains high blood levels after oral administration
Diarrhoea is rare
Longer acting than ampicillin (given thrice daily)
Does not reduce the effectiveness of oral contraceptives.
21. Beta lactamase inhibitors
Beta lactamases are enzymes produced by bacteria which open up
the beta lactam ring and inactivates the beta lactam antibiotics.
Beta lactamase inhibitors bind to and inactivates beta lactamases
thereby preventing destruction of beta lactam antibiotics.
Clavulanic acid
Sulbactam
Tazobactam
24. Classification
First generation - effective against gram positive organisms
Second generation - more active against gram negative
organisms
Third generation - effective against gram negative organisms
and anaerobes
Fourth generation - gram positive and gram negative
organisms
Fifth generation – MRSA and gram negative organisms
25.
26.
27. first and second generation cephalosporins are used as
substitutes to penicillins in those who have mild allergic reaction to
penicillin
NOT IN THOSE WITH SEVERE REACTIONS LIKE
ANAPHYLAXIS/ ANGIOEDEMA .
Used as a first line empirical therapy along with aminoglycosides
in treatment of bacteremia / septicemia.
Cefoxitin , cefotetan ( both 2 nd generation )are used in anaerobic
infections.
28. CEFTRIAXONE : THIRD GENERATION
ITS a third generation cephalosporin
highly resistant to beta lactamases.
good activity against gram positive and negative organisms,
moderate against psuedomonas .
has the longest half life amongst beta lactam antibioitics ( 8 hrs )
enters csf when meninges are inflammed , hence used in treatment
of meningitis .
other uses : complicated UTI ,abdominal sepsis, chancroid
29. FOURTH GENERATION
Similar to third generation but more resistant to beta
lactamases .
active against enterobacteriacea ( gram negative ) and
psuedomonas resistant to group 3
examples cefepime , cefpirome
given parenterally .
32. Carbapenems :
imipenem, meropenem, ertapenem, doripenem, faropenem
Spectrum : gram positive, gram negative and anaerobic
organisms.
Mechanism of action: inhibits bacterial cell wall synthesis
Uses : UTI, respiratory, skin, bone, soft tissue, intra abdominal
and gynecological infections
only FAROPENEM IS ORALLY ACTIVE , hence can be given
orally . rest are given IV parenterally.
33. IMIPENEM
BACTERICIDAL
broad spectrum beta lactam antibiotic
effective against gram positive , enterobacteriacea , psuedomonas
, anaerobes ( like clostridia difficile).
rapidly hydrolysed by enzyme dehydropeptidase in renal tubules.
hence combined with cilastin that reversibly blocks this enzyme
and protects imipenem .
not absorbed from GIT , given parenterally .
34. Monobactam:
aztreonam
Single beta lactam ring
Effective against gram negative organisms but not against gram
positive and anaerobes.
spectrum similar to aminoglycosides,hence used as a reserve drug in
treating gram -ve infections in those whom aminoglycosides are
contraindicated .
MoA : inhibits bacterial cell wall synthesis ( bactericidal )
Given parenterally
Uses : nosocomial pseudomonas infections and other gram negative
infections