2. Bacterial Cell Wall Synthesis Inhibitors Flashcards
Classification of bacterial cell wall synthesis inhibitors
Beta lactams:
a. Penicillins
1. Natural penicillins
2. Penicillinase resistant penicillins
3. Aminopenicillins + BL inhibitors
4. Anti pseudomonal pencillins + BL inhibitors
b. Cephalosporins
c. Carbapenems
d. Monobactam
Glycopeptide: Vancomycin
MOA of beta lactams
- Interfere with the synthesis of the bacterial cell wall peptidoglycan
- They act by binding to the active site of the enzyme, transpeptidase, which catalyses the cross-linking of the terminal peptide components of the linear polymer chains
- In actively growing cell → results in weakening of the cell wall structure → build up in intracellular osmotic pressure and lysis of the bacterial cells → bactericidal to actively growing cells
Types of natural penicillins
- Penicillin G
2. Penicillin V
Examples of penicillinase-resistant penicillins
Cloxacillin, Oxacillin, Flucloxacillin
Types of aminopenicillins
- Ampicillin
- Amoxicillin
- Piperacillin
MOA of beta-lactamse inhibitors
- They work primarily by inactivating serine beta-lactamases, which are enzymes that hydrolyse and inactivate the beta-lactam ring
- Strong affinity for beta-lactamases → allow them to either bind and inactivate it thus protecting beta-lactams from being targeted by the beta-lactamases
Types of beta-lactamse combination drugs
- Amoxicillin clavulanic acid
- Ampicillin sulbactam
- Piperacillin tazobactam
Mechanism of resistance to penicillin
- Transpeptidase can be altered → reduced affinity for penicillin
- Production of beta-lacatamase → hydrolysis of beta-lacatam ring
- Decreased ability of the antibiotic to reach the transpeptidase when the bacteria decreases porin production → decrease in intracellular drug conc.
- Presence of efflux pumps
Adverse reactions to penicillins
- Allergy / hypersensitivity
- Steven Johnson syndrome (SJS)
- Toxic Epidermal Necrolysis (TEN) - Clostridium difficile-associated diarrhoea (CDAD) (with ampicillin, co-amoxiclav)
- Neurotoxicity
- Hepatotoxicity (penicillinase-resistant penicillin)
- Anosmia
- High dose penicillins in renal failure → seizures
Examples of 1st Gen Cephalosporins
- Cefazolin
2. Cephalexin
Examples of 2nd Gen Cephalosporins
Cefuroxime
Examples of 3rd Gen Cephalosporins
- Cefotaxime
- Ceftriaxone
- Ceftazidime
Examples of 4th Gen Cephalosporins
Cefepime
Examples of 5th Gen Cephalosporins
- Ceftaroline
2. Ceftobiprole
1st to 4th Gen Cephalosporins lack activity against?
LAME Listeria monocytogenes Atypicals (mycoplasma, chlamydia, legionella spp.) MRSA Enterococcus spp.
Adverse reactions to cephalosporins
- Hypersensitivity - as with penicillin
* patients with a history of anaphylaxis with penicillin should not be given a cephalosporin* - GIT - diarrhoea, CDAD
- Thrombophlebitis
Types of Carbapenems
- Imipenem and Cilastatin
- Meropenem
- Ertapenem
Adverse effects of carbapenems
- GIT-related symptoms (nausea, vomiting, diarrhoea)
- Rashes
- Neurotoxicity at high blood conc.
- Cross-hypersensitivity with penicillin
Example of monobactam
Aztreonam
Example of glycopeptide
Vancomycin
MOA of vancomycin
Binds with high affinity to the D-ala-D-ala terminus of pentapeptide of NAM component of peptidoglycan and interferes with transglycosylation of the cell wall precursor units, hence inhibiting bacterial cell wall synthesis
Adverse effects of vancomycin
- Thrombophlebitis with fever, chills
- “Red-neck” or “Red man syndrome”
- Nephrotoxicity and ototoxicity
- Pregnancy: Cat C (for parental formation), Cat B (for oral capsules)
Vancomycin resistance
- Enterococcal resistance → due to expression of enzymes that modify cell wall precursor by substituting the terminal D-alanine, for D-lactate or D-serine → reducing vancomycin binding affinity
- Emergence of S. aureus that expresses reduced or “intermediate” susceptibility to vancomycin → major concern
