Anti-infectives: Antibacterials (PDF)

‫بسم الله الرحمن الرحيم‬ Anti-infectives: Antibacterials Cell Wall Inhibitors 11/12/2024 1  OVERVIEW Cell wall Inhibitors: – β-lactam Cell wall Inhibitors – Non-β-lactam Cell wall Inhibitors β-lactam Cel...

‫بسم الله الرحمن الرحيم‬ Anti-infectives: Antibacterials Cell Wall Inhibitors 11/12/2024 1  OVERVIEW Cell wall Inhibitors: – β-lactam Cell wall Inhibitors – Non-β-lactam Cell wall Inhibitors β-lactam Cell wall Inhibitors: – Peptidoglycan - peptide cross-links – require actively proliferating microorganisms Figure 38.1 – shows the classification of agents affecting cell wall synthesis 11/12/2024 2 11/12/2024 3  PENICILLINS R + 6-aminopenicillanic acid the R side chain affects: – The spectrum, acid stability – cross hypersensitivity – susceptibility to enzymes (β- lactamases) (Figure 38.2) 11/12/2024 4 11/12/2024 5  Mechanism of action 1. Inactivatn of Penicillin-binding proteins (PBPs) : – Penicillins inactivate numerous PBPs – Alterations in PBPs: Resistance – Methicillin-resistant S. aureus (MRSA): arose because of such an alteration 11/12/2024 6  2. Inhibition of transpeptidase: – Penicillins inhibit Last step: (transpeptidation or cross-linkage): Cell lysis (Figure 38.3) 11/12/2024 7  PEP: Phospho Enol 11/12/2024 Pyruvate 8  3. Potentiation of autolysins: – Many bacteria, particularly the gram-positive cocci, produce degradative enzymes (autolysins) that participate in the normal remodeling of the bacterial cell wall. – In the presence of a penicillin, the degradative action of the autolysins proceeds in the absence of cell wall synthesis. – Thus, the antibacterial effect of a penicillin is the result of both: 11/12/2024 inhibition of cell wall synthesis 9  Antibacterial spectrum: – G +ve: have cell walls that are easily traversed by penicillins G -ve: have an outer lipopolysaccharide membrane Classes of penicillins: 1. Natural penicillins: penicillin G and penicillin V Other types of penicillins: Semisynthetic – Penicillin G for: G +ve and G -ve cocci G +ve bacilli, 11/12/2024 10 and spirochetes 11/12/2024 11  – Penicillin G: Remains of choice for gas gangrene (Clostridium perfringens) and syphilis (Treponema pallidum). – Penicillin V: similar penicillin G, but not for bacteremia (poor absorption) 2. Antistaphylococcal penicillins: – Methicillin, nafcillin, oxacillin, and dicloxacillin: are β-lactamase (penicillinase)- 11/12/2024 12 resistant penicillins.  – Restricted for methicillin sensitive S. aureus (MSSA) – No activity against G -ve infections 3. Extended-spectrum penicillins: – Ampicillin and amoxicillin: (aminopenicillins) More effective against G -ve bacilli --------------------------------------------- 11/12/2024 13