Pharmacology II - Cell Wall Inhibitors III PDF

CELL WALL INHIBITORS III Dr. Sheryar Afzal College of veterinary Medicine King Faisal University  2 Glycopeptide antibiotics Vancomycin (Clinical use) Against gram-positive microbes, including MRSA and methici...

CELL WALL INHIBITORS III Dr. Sheryar Afzal College of veterinary Medicine King Faisal University  2 Glycopeptide antibiotics Vancomycin (Clinical use) Against gram-positive microbes, including MRSA and methicillin-resistant Staphylococcus epidermidis (MRSE), as well as enterococcal infections. First-line treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by MRSA. Treatpseudomembranous colitis caused by Clostridium difficile in cases of relapse or infection is unresponsive to metronidazole.  9 Glycopeptide antibiotics Vancomycin (Clinical use) Vancomycin in combination with gentamicin is an alternative regimen for treatment of enterococcal endocarditis in a patient with serious penicillin allergy. Vancomycin in combination with cefotaxime, ceftriaxone, or rifampin for the treatment of meningitis caused by a highly penicillin-resistant strain of pneumococcus. Restricting the use of vancomycin to the treatment of serious infections caused by β- lactam resistant, gram-positive microorganisms or gram-positive infections in patients who have a serious allergy to the β- lactams (To reduce the increase in vancomycin-resistant bacteria (for example, Enterococcus faecium and Enterococcus faecalis).  8 Glycopeptide antibiotics stops polymerization of NAM/NAG-subunits to form long chains (binding of vancomycin to the D-Ala-D-Ala). Vancomycin (Resistance) plasmid-mediated changes in drug’s permeability or decreased binding to target molecules (Alanine).  11 Glycopeptide antibiotics Vancomycin (Adverse reaction) Ototoxicity and nephrotoxicity are uncommon. However, administration with another ototoxic or nephrotoxic drug, such as an aminoglycoside, increases the risk of these toxicities. Pain, thrombophlebitis (inflammation of the wall of a vein with associated thrombosis) and "Red man" or "red neck" syndrome (hypersensitivity, caused by release of histamine). These can be prevented by prolonging the infusion period to 1–2 hours.  Polymycin Polypeptide [Polymyxin B and colistin (polymyxin E)] Bind to phospholipids on the bacterial cell membrane of gram-negative bacteria. Polymyxin B Disrupts cell membrane integrity, leading to leakage of cellular components. concentration-dependent bactericidal agents with activity against most clinically important gram-negative bacteria, including P. aeruginosa, E. coli, K. pneumoniae, Colistin Acinetobacter species, and Enterobacter species. Nephrotoxicity and neurotoxicity (for example, slurred speech, muscle weakness)  22 Fosfomycin A bactericidal. It blocks cell wall synthesis by inhibiting the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase, which catalyzes the first step in peptidoglycan synthesis. Treat urinary tract infections caused by E. coli or E. faecalis (maintains high concentrations in the urine over several days (one-time dose). Unlikely to have cross reactivity due to unique structure. Diarrhoea, vaginitis, nausea, and headache.  21 Daptomycin Mechanism of action Bind to the cell membrane via calcium-dependent insertion of its lipid tail. This results in depolarization of the cell membrane (Leakage of ions) leading to inhibition of protein, DNA, and RNA synthesis, which results in bacterial cell death.  Bacitrac 23 in Bacitracin inhibits bacterial cell wall synthesis. against gram-positive microorganisms. no cross-resistance with other antimicrobial drugs Interferes with the dephosphorylation of C55- Highly nephrotoxic when isoprenyl pyrophosphate administered systemically It is only used topically for the suppression of mixed bacterial flora in surface lesions of the skin, in wounds, or on mucous membranes  20 Lipopeptide Daptomycin Bactericidal, concentration-dependent cyclic lipopeptide. An alternative to other agents, such as linezolid and quinupristin/dalfopristin, for treating infections caused by resistant gram-positive organisms, including MRSA and vancomycin- resistant enterococci (VRE). Treat complicated skin and skin structure infections and bacteremia caused by S. aureus, including those with right-sided infective endocarditis. Unique adverse effect: Myalgias, rhabdomyolysis  Cycloserin 24 e It is water soluble but unstable at acid pH. It is restricted for multiple drug- resistant and extensively drug- resistant strains of Mycobacterium tuberculosis after first-line treatment is failed. The drug is widely distributed in tissues and mainly excreted unchanged in urine. CNS toxicity (headaches, Disrupt D-alanine tremors, acute psychosis, and incorporation into the convulsions). bacterial cell wall  27 H A N  O U ;) K