Professional Documents
Culture Documents
infections
KumaraswamyKademane@imu.edu.my
Twitter: @kumaraswamy16
Learning objectives
Beta-lactam antibiotics:
Penicillins
Cephalosporins
Carbapenems
Macrolides & Ketolides
Tetracyclines
Others
Beta-lactam antibiotics
Beta-lactams inhibit the cell wall synthesis
Bacterial cell wall
Rigid peptidoglycan layer, maintains cell shape and
integrity
Peptidoglycan (polysaccharide and polypeptide)
Cross linking of polypeptides (transpeptidase/PBP)
gives the rigidity
Penicillins bind to and inhibit PBPs leading to halt in
peptidoglycan formation and cell death
Diagram of MOA of beta-lactams
Classification of Penicillins
Natural penicillin: penicillin G
Acid resistant alternative to PnG:
Phenoxymethyl Penicillin (Penicillin V)
Penicillinase resistant Penicillins: antistaphylococcal
penicillins
Acid labile: Methicillin Recall [MRSA]
Methicillin Resistant
Staphylococcus Aureus
Classification of Penicillins
Natural penicillin: penicillin G
Acid resistant alternative to PnG:
Phenoxymethyl Penicillin (Penicillin V)
Penicillinase resistant Penicillins: antistaphylococcal
penicillins
Acid labile: Methicillin, Nafcillin, Cloxacillin, Dicloxacillin
Acid resistant: Flucloxacillin
Beta-lactamase inhibitors:
Clavulanate, sulbactam, tazobactam
Extended spectrum penicillin
Aminopenicillins: G+ve and G-ve
Ampicillin, Amoxicillin, Bacampicillin
Carboxypenicillins: Pseudomonas, Enterobacter, and Proteus
Carbenicillin, Ticarcillin
Ureidopenicillins: Pseudomonas, lysteria
Piperacillin, Mezlocillin, Azlocillin
Amidino penicillins:
Mecillinam, Pivmecillinam
Clinical uses of penicillin
Pneumococcal pneumonia/meningitis
Pharyngitis/recurrent rheumatic fever
Syphilis (treponema pallidum)
Gas gangrene (Cl. perfringens)
Staphylococcal infections (penicillinase resistant
penicillins)
Clinical uses of penicillin contd..
Cephalothin • Cephalexin
• Cephradine
Cefazolin
• Cefadroxil
Cefaclor
Cefuroxime
Cefuroxime axetil
Cefoxitin (B. Fragilis)
Parenteral agents
Cefepime
cefpirome
Adverse reactions
Hypersensitivity reactions: anaphylaxis, fever, skin
rashes, nephritis, and hemolytic anemia
Ceftriaxone: biliary sludging syndrome & cholelithiasis
Contraindications:
Allergy (~1 to 20% cross-reactivity with penicillin)
Carbapenems
Imipenem
Broad spectrum
Gram +ve, G-ve aerobes, anaerobes
Given by parenteral route
Rapidly hydrolysed by renal dehydropeptidase – I
Cilastatin – reversible inhibitor of enzyme
Uses: severe hospital acquired infections, LRTI
ADRs: propensity to induce seizures at higher doses
Newer agents: Meropenem, Ertapenem
Monobactam: aztreonam
Macrolides
Macrocyclic lactone ring
MOA: Binds to 50s ribosomal
subunit and Inhibits bacterial
protein synthesis
Inhibits translocation of
peptidyl-tRNA
Same binding site as
Chloramphenicol & Clindamycin
MOA of protein synthesis inhibitors
Indications: Azithromycin, clarithromycin
Respiratory tract infections due to Streptococcus
pneumoniae, Haemophilus influenzae, and atypical
pathogens (Mycoplasma, Chlamydia, Legionella)
Acute exacerbations of chronic bronchitis, acute otitis
media, acute streptococcal pharyngitis, and acute
bacterial sinusitis
Chlamydial infections, diphtheria, pertussis,
Helicobacter Pylori infection, erysipelas and cellulitis
of skin
Adverse effects of macrolides
Cholestatic jaundice
GI disturbances: nausea, vomiting, diarrhoea
QT prolongation and vent. Arrhythmia
Enzyme inhibition
Enhance the effect of warfarin, theophylline, digoxin,
CCBs
Tetracyclines
Tetracycline, doxycycline, minocycline, tigecycline
Binds to 30S subunit
and inhibit tRNA
binding to acceptor site
Clinical indications of tetracyclines
Mechanism of Action
Vancomycin inhibit the synthesis of the cell wall in
sensitive bacteria by binding with high affinity to the
D-alanyl-D-alanine terminus of cell wall precursor units.
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Vancomycin indications
HAP
Cefotaxime or ceftazidime, or anti-pseudomonal
penicillin or quinolone