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What is the mechanism of action of penicillin?
What is the mechanism of action of penicillin?
Penicillin inhibits the transpeptidation reaction in the bacterial cell wall, which weakens the wall, increases its permeability and results in the bacterial cell bursting.
What is the other name for the beta-lactam ring ?
What is the other name for the beta-lactam ring ?
Thiazolidine Ring
Which of the following are the penicillin sources?
Which of the following are the penicillin sources?
What is the function of betalactamases inhibitors in treating bacterial infections?
What is the function of betalactamases inhibitors in treating bacterial infections?
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Which of the following are classified as penicillinase-resistant penicillin?
Which of the following are classified as penicillinase-resistant penicillin?
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Penicillin G is effective against Gram-negative infections.
Penicillin G is effective against Gram-negative infections.
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Which drug can be considered as the drug of choice when treating meningococcal meningitis?
Which drug can be considered as the drug of choice when treating meningococcal meningitis?
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Mention the two examples of Carboxypenicillins.
Mention the two examples of Carboxypenicillins.
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Which drug is most effective in treating infections caused by methicillin-resistant Staphylococcus aureus (MRSA)?
Which drug is most effective in treating infections caused by methicillin-resistant Staphylococcus aureus (MRSA)?
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What is the primary advantage of using amoxicillin over ampicillin?
What is the primary advantage of using amoxicillin over ampicillin?
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Choose the correct examples of the fourth-generation cephalosporins.
Choose the correct examples of the fourth-generation cephalosporins.
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What are the uses of cephalosporins?
What are the uses of cephalosporins?
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Which of the following antibiotic is most effective to treat penicillin allergic patients?
Which of the following antibiotic is most effective to treat penicillin allergic patients?
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Carbapenems have a broader spectrum of activity than other betalactams.
Carbapenems have a broader spectrum of activity than other betalactams.
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Why is Clavulanic acid combined with Amoxicillin ?
Why is Clavulanic acid combined with Amoxicillin ?
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Which of the following statements are true for the combination of penicillin and aminoglycosides?
Which of the following statements are true for the combination of penicillin and aminoglycosides?
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Study Notes
Antimicrobial Agent 2: Beta-lactam antibiotics
- Beta-lactam antibiotics contain a beta-lactam ring.
- Penicillins, Cephalosporins, Carbapenems, and Monobactams are examples of beta-lactam antibiotics.
- The beta-lactam ring in an antibiotic is hydrolysed by the enzyme beta-lactamase, leading to inactivation of the antibiotic.
- Betalactamases/penicillinase are produced by some bacteria resistant to beta-lactam antibiotics.
- 6-aminopenicillanic acid is the active nucleus of penicillin.
- Opening of the beta-lactam ring by beta-lactamase inactivates penicillin.
- Penicillin is a bactericidal antibiotic.
- Penicillin sources include Penicillium notatum & P. chrysogenum.
Specific Learning Outcomes
- Students should be able to describe the mechanism of action, therapeutic uses, adverse effects, and limitations of crystalline penicillin (penicillin G).
- Students should be able to list long-acting penicillins, their duration of action, and uses.
- Students should be able to list and describe different groups of semisynthetic penicillins, advantages over penicillin G, and uses.
- Students should be able to list and describe the role of beta-lactamases inhibitors in the treatment of bacterial infections.
- Students should be able to list different generations of cephalosporins with examples, mechanisms of action, uses, and adverse effects.
Classification of Antimicrobial Agents
- Penicillins (Penicillin G, Amoxicillin)
- Cephalosporins (Cephalexin, Cefotaxime)
- Macrolides (Erythromycin, Azithromycin)
- Aminoglycosides (Streptomycin, Gentamicin)
- Tetracyclines (Doxycycline, Minocycline)
- Fluoroquinolones (Ciprofloxacin, Ofloxacin)
- Others (Sulphonamides, Trimethoprim, Rifampicin, Metronidazole)
Beta-lactam Antibiotics
- Penicillins contain a beta-lactam ring.
- Cephalosporins
- Carbapenems
- Monobactams
Penicillin - Mechanism of Action
- Peptidoglycan component of the bacterial cell wall provides rigid mechanical stability to the cell wall.
- Transpeptidation is the last step in the synthesis of peptidoglycans, where peptide bridges cross-link polymer chains, making the cell wall rigid and the bacterium viable.
- All beta-lactam antibiotics inhibit the transpeptidation reaction in the bacterial cell wall.
- This weakens the cell wall, increases its permeability, and results in the bursting of the bacterium.
- All beta-lactams are bactericidal and act only on multiplying bacteria.
Penicillin G - Spectrum of activity
- Gram-positive & Gram-negative cocci
- Gram-positive bacilli
- Anaerobes
- Spirochaetes
Penicillin G - Limitations
- Acid sensitivity - cannot be given orally. Needs to be given parenterally (IM or IV injection).
- Penicillinase susceptibility - Infections by penicillinase-producing bacteria cannot be treated.
- Narrow spectrum - Not effective against G-ve infections.
- Short duration of action - Repeated administration is necessary.
Penicillin G - Method to Overcome Limitations
- Repository penicillins (long-acting penicillins) - Procaine penicillin (24 h), Benzathine penicillin (2-3 wk).
Penicillin G-Indication/uses (Prophylactic & Therapeutic)
Penicillin - Indications/Uses
- Pneumococcal meningitis - IV penicillin G in high doses.
- Meningococcal meningitis-Penicillin G is the drug of choice (DOC).
- Pneumococcal pneumonia
- Syphilis - highly effective
- Anaerobic infections
- Streptococcal pharyngitis
- Diphtheria - eliminate carrier state
Semisynthetic Penicillins
- 6-aminopenicillanic acid can be isolated by separating the side chain by enzyme amidase.
- Adding various side chains to the amino group of 6-aminopenicillanic acid produces various semisynthetic penicillins.
- Penicillin V
- Methicillin, Cloxacillin, Dicloxacillin,
Semisynthetic Penicillin (Advantages over Penicillin G)
- Acid-resistant penicillin - effective orally.
- Penicillinase-resistant penicillins - active against beta-lactamase bacteria. Examples: Staphylococci
Semisynthetic Penicillins (Broad Spectrum, Extended Spectrum/Antipseudomonal)
ADME Properties of Penicillins
- Acid-resistant penicillins (Penicillin V, amoxicillin, cloxacillin, dicloxacillin) are absorbed orally.
- Penicillins are well distributed in inflamed tissues.
- Penicillin is mostly excreted by the kidneys in active form (filtration 10%, secretion 90%).
- Probenecid inhibits secretion and maintains high plasma concentration.
Half-Life of Penicillins & Resistance
Adverse effects of Penicillin
- Remarkably low toxicity (0.7%–1.0% patients).
- Hypersensitivity reactions
- Amoxicillin causes skin rash
- Penicillin G injection - Anaphylactic shock, Superinfections (e.g., Fungi – Candida, psudomembranous enterocolitis).
- Diarrhoea (common with ampicillin, less with amoxicillin)
Penicillinase-Resistant Penicillins
- Resistant to hydrolysis by staphylococcal penicillinase. Examples: oxacillin, cloxacillin, dicloxacillin.
- Route: oral and parenteral
- Methicillin Resistant Staphylococcus Aureus (MRSA) are resistant to penicillinase resistant penicillins and also to cephalosporins.
- Infections: bone and joint infections (Staphylococcal), staphylococcal meningitis
Extended Spectrum Penicillins (Aminopenicillins)
- Active against Gram+ve and some Gram−ve organisms
- Combine with penicillinase inhibitors to extend spectrum to penicillinase-producing organisms (H. influenzae, E. coli, Klebsiella, Proteus).
- Ampicillin & Amoxicillin (oral).
- Amoxicillin absorbed almost completely, fewer side effects and longer duration of action. Ampicillin given more frequently due to incomplete absorption.
Extended Spectrum Penicillins (Aminopenicillins)- Uses
Extended Spectrum Penicillins (Antipseudomonal)
- Carboxypenicillins: Carbenicillin, carbenicillin indanyl (oral), Azlocillin.
- Ureido-penicillins: Ticarcillin, Piperacillin.
- Active against Gram+ve, Gram−ve, including pseudomonas.
- Extend activity against penicillinase-producing organisms.
- Piperacillin broadest activity.
- Infections: Intraabdominal, skin & soft tissue, nosocomial pneumonia, UTI, etc.
Beta-lactamase Inhibitors
- Suicide Inhibitors that combine with beta-lactamases and form inhibitory products.
- No antibacterial activity of their own.
- Synergistic combination with beta-lactam antibiotics to protect against inactivation and to extend the antibacterial spectrum.
- Examples: clavulanic acid, sulbactam, tazobactam
Penicillin with Aminoglycosides
- Penicillin interferes with cell wall synthesis/integrity.
- Aminoglycosides interrupt bacterial protein synthesis by influencing ribosomes.
- Aminoglycosides need energy-dependent process for entry into cells, rate limiting process.
- Cell wall damage created by penicillin allows greater penetration of aminoglycosides into bacteria.
Cephalosporins
- Beta-lactam antibiotics that inhibit cell wall synthesis.
- Effective against both G+ve and G−ve bacteria.
- More resistant to beta-lactamase action than penicillins.
- Four generations available.
- 1st to 4th generations more effective against Gram-negative than Gram-positive bacteria.
- More resistant to beta-lactamases
- Cross BBB more easily - suitable for treating meningitis
Cephalosporins - Pharmacokinetics & ADR
- Primarily administered IV or IM, some oral formulations also available.
- Good distribution throughout body fluids, including CSF.
- Safe during pregnancy.
- ADR: Hypersensitivity reactions (especially in those with penicillin allergy), Disulfiram-like effects (with alcohol), bleeding due to platelet dysfunction.
Cephalosporins - Uses
Monobactams
- Active against Gram-negative bacteria.
- Treat patients allergic to penicillin.
- Nosocomial infections (pneumonia, UTI, meningitis).
- No activity against Gram-positive bacteria or anaerobes.
- Route: parenteral
- Occasional skin rashes, elevated serum aminotransferases
Carbapenems
- Broader spectrum of activity than other beta-lactams.
- Imipenem with cilastatin (inhibits degradation by renal enzymes).
- Crosses the blood-brain barrier.
- Broadest spectrum, including anaerobes.
- Routes: IV
- Uses: UTI, Lower respiratory infections, meningitis, skin soft tissue, bone and joint infections.
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