Cell Wall Inhibitors - BS (Surgical Technology) PDF

Cell wall inhibitors FROM BS (SURGICAL TECHNOLOGY) Group members  Sidra ishaq  Seeman shafqat  Nimra Riaz Cell wall Inhibitors  Some antimicrobial drugs selectively interfere with synthesis of the bacterial cell wall—a structure that mammalian cells do not possess. ...

Cell wall inhibitors FROM BS (SURGICAL TECHNOLOGY) Group members  Sidra ishaq  Seeman shafqat  Nimra Riaz Cell wall Inhibitors  Some antimicrobial drugs selectively interfere with synthesis of the bacterial cell wall—a structure that mammalian cells do not possess.  The cell wall is composed of a polymer called peptidoglycan that consists of glycan units joined to each other by peptide cross-links  The most important members of this group of drugs are the β-lactam antibiotics (named after the β-lactam ring that is essential to their activity), vancomycin, and daptomycin. Penicillins  The penicillins are among the most widely effective and the least toxic drugs known, but increased resistance has limited their use.  Members of this family differ from one another in the R substituent attached to the 4 member β-lactamas ring.  The nature of this side chain affects the antimicrobial spectrum, stability to stomach acid, crosshypersensitivity, and susceptibility to bacterial degradative enzymes (β-lactamases). Mechanism Of Action  Penicillins work by:  1. Stopping bacteria from building strong cell walls.  2. Weakening the cell wall, making it prone to bursting.  3. Allowing the bacterial cell to break open and die.This process is effective against:- Bacteria with weak cell walls- Rapidly growing bacteria.  However, penicillins are NOT effective against.  Mycobacteria (like TB)  Protozoa  Fungi  Viruses B. Antibacterial spectrum  The ability of penicillins to kill bacteria depends on their ability to  :1. Cross the bacterial cell wall  2. Reach the Penicillin-Binding Proteins (PBPs) in the periplasmic s Pace. Factors Affecting SusceptibilityThe susceptibility of PBPs to penicillins depends on: 1.Size of the antibiotic 2. Charge of the antibiotic 3. Hydrophobicity (water-repelling nature)of the antibiotic. Gram-Positive vs. Gram-Negative Bacteria 1. Gram-Positive Bacteria: Easily susceptible to penicillins due to easily traversed cell walls 2. Gram-Negative Bacteria: Less susceptible due to an outer lipopolysaccharide membrane. However, some gram-negative bacteria have porins (water-filled channels) that allow penicillins to enter. Natural penicillins Natural penicillins (penicillin G and penicillin V) are obtained from fermentations of the fungus Penicillium chrysogenum. Semisynthetic penicillins, such as amoxicillin and ampicillin (also known as aminopenicillins), are created by chemically attaching different R groups to the 6- aminopenicillanic acid nucleus. Antistaphylococcal penicillins: Methicillin [meth-i-SILL-in], nafcillin [naf-SILL-in], oxacillin [ox-a-SILL-in], and dicloxacillin [dye-klox-a-SILL-in] are β-lactamase (penicillinase)-resistant penicillins.  Their use is restricted to the treatment of infections caused by penicillinase- producing staphylococci, including methicillinsensitive Staphylococcus aureus (MSSA).  [Note: Because of its toxicity (interstitial nephritis), methicillin is not used clinically in the United States except in laboratory tests to identify resistant strains of S. aureus. MRSA is currently a source of serious community and nosocomial (hospital- acquired) infections and is resistant to most commercially available β-lactam antibiotics.]  The penicillinase-resistant penicillins have minimal to no activity against gram- negative infections. Extended-Spectrum Penicillins-  Ampicillin and Amoxicillin: Effective against gram-negative bacteria and have a similar spectrum to penicillin G.- Uses: - Treat gram-positive bacillus Listeria monocytogenes and susceptible enterococcal species. - Respiratory infections. - Prophylactic use in dentistry to prevent bacterial endocarditis. Antipseudomonal penicillins: Piperacillin and Ticarcillin: Effective against Pseudomonas aeruginosa and other gram-negative bacilli. Key Features: Parenteral formulations only. - Piperacillin is the most potent. - Not effective against Klebsiella due to its penicillinase.- Extended Spectrum: o Formulating with clavulanic acid or tazobactam extends the antimicrobial spectrum to include penicillinase-producing organisms, such as: - o Enterobacteriaceae o Bacteroides specie β-lactamase  What is β-lactamase?  β-Lactamase is an enzyme that breaks down the β-lactam ring of certain antibiotics, making them ineffective.  How does β-lactamase work?  β-Lactamase hydrolyzes the β-lactam ring, resulting in the loss of bactericidal activity. Types of β-lactamase: 1. Constitutive: Produced by the bacterial chromosome 2. Acquired: Obtained through plasmid transfer. Decreased permeability to the drug  2. : Decreased penetration of the antibiotic through the outer cell membrane of the bacteria prevents the drug from reaching the target PBPs.  The presence of an efflux pump can also reduce the amount of intracellular drug (for example, Klebsiella pneumoniae).  3. Altered PBPs: Modified PBPs have a lower affinity for β-lactam antibiotics, requiring clinically unattainable concentrations of the drug to effect inhibition of bacterial growth.  This explains MRSA resistance to most commercially available β-lactams D. Pharmacokinetics  1. Administration:  The route of administration of a β-lactam antibiotic is determined by the stability of the drug to gastric acid and by the severity of the infection.  Routes of Administration for Penicillins. o Intravenous (IV) or Intramuscular (IM) only: Piperacillin with tazobactam - Nafcillin o Oxacillin  Oral preparations only:  Penicillin V  Amoxicillin  Dicloxacillin Available in oral, IV, or IM routes:  Others (varies depending on the specific penicillin)  4. Special case:  Amoxicillin with clavulanic acid:  Only available in oral formulation in the United States  Depot forms:  Procaine penicillin G and benzathine penicillin G are administered IM and serve as depot forms.  They are slowly absorbed into the circulation and persist at low levels over a long time period. Absorption of Penicillins1 . Oral Administration: Most penicillins are not fully absorbed  2. Effect on Intestinal Flora: Unabsorbed penicillins reach the intestine, altering the gut flora.  3. Food Impact: Food decreases absorption of penicillinase-resistant penicillins.  4. Reason: Delayed gastric emptying exposes drugs to stomach acid, destroying them.  5. Recommendation: Take penicillinase-resistant penicillins on an empty stomach. Distribution & Metabolism:  :1. Penicillins distribute well throughout the body.  2. Cross the placental barrier, but no teratogenic effects.  3. Limited penetration into:  - Bone  - Cerebrospinal fluid (CSF), unless inflamed  - Prostate  Metabolism:  1. Host metabolism of penicillins is usually insignificant.  2. Some metabolism of penicillin G may occur in patients with impaired renal function  Excretion of Penicillins1 . Primary Excretion Route: 1. Kidneys, through: 2. urine  -secondary excretion route: 1. bile 2. saliva 3. sweat Adverse Reactions to Penicillins  1. Hypersensitivity Reactions:  2. Gastrointestinal 1. - Nausea 2. - Vomiting 3. - Diarrhea  3. Neurological: 1. Rare adverse effects. 2. - Seizures (high doses) 3. - Confusion 4. - Hallucinations Ephalosporins:  β-Lactam Antibiotics Similarities to Penicillins: 1. Structurally related 2. Functionally related 3. Same mode of action (inhibiting cell wall synthesis) 4. Affected by same resistance mechanisms  Key Differences: 1. Produced semi synthetically from 7-aminocephalosporanic acid. More resistant to certain β-lactamases than penicillins. A. Antibacterial spectrum  Cephalosporins are grouped into 5 generations based on:  1. What bacteria they kill  2. How well they resist antibiotic-destroying enzymes  They don't work against:  1. Listeria  3. C. difficile  4. Enterococci Cephalosporin Generations First Generation: Treats MSSA, Proteus, E. coli, and K. pneumoniae. Second Generation: Treats H. influenzae, Enterobacter, and some Neisseria. Weaker against gram-positive organisms. Third Generation: Treats gram-negative bacilli, including meningitis. Examples: ceftriaxone, cefotaxime, and ceftazidime. Fourth Generation: Cefepime treats streptococci, staphylococci, and aerobic gram-negative organisms. Advanced Generation: Ceftaroline treats MRSA, complicated skin infections, and community-acquired pneumonia.  These inhibitors:-  Block beta-lactamase enzymes  Protect antibiotics from breakdown  Extend antibiotic effectiveness against resistant bacteria Vancomycin  1. Type: Glycopeptide antibiotic  2. Mechanism: Inhibits cell wall synthesis in bacteria o 3. Spectrum: Effective against gram-positive bacteria, including: MRSA (methicillin-resistant Staphylococcus aureus) o Enterococci  4. Administration: IV or oral (for C. difficile infections)  5. Resistance: Increasing resistance reported, especially among enterococci Daptomycin  1. Type: Cyclic lipopeptide antibiotic  2. Mechanism: Disrupts cell membrane function in bacteria  3. Spectrum: Effective against gram-positive bacteria, including: - MRSA - Enterococci - Vancomycin-resistant strains  4. Administration: IV only  5. Resistance: Limited resistance reported Telavancin 1. Type: Lipoglycopeptide antibiotic 2. Mechanism: Inhibits cell wall synthesis and disrupts cell membrane function 3. Spectrum: Effective against gram-positive bacteria, including: o Enterococci o Vancomycin-susceptible strains o MRSA 1.. Administration: IV only5. 2. Use: 3. Treats complicated skin and skin structure infections, and hospital- acquired pneumonia Fosfomycin  1. Type: Phosphonic acid antibiotic  2. Mechanism: Inhibits cell wall synthesis o 3. Spectrum: Effective against gram-positive and gram-negative bacteria, including o E. coli o Klebsiella o MRSA o 4. Administration: Oral or IV o 5. Use: Treats urinary tract infections and uncomplicated skin infections polymyxins  1. Type: Polypeptide antibiotics  2. Mechanism: Disrupts cell membrane function  3. Spectrum: Effective against gram-negative bacteria, including: o Pseudomonas aeruginosa o Acinetobacter baumannii o Multidrug-resistant strains  4. Administration: IV, inhalation, or topical  5. Use: Treats serious infections, including pneumonia and sepsis conclusion  Cell wall biosynthesis inhibitors (CBIs) have historically been one of the most effective classes of antibiotics.  They are the most extensively used class of antibiotics and their importance is exemplified by the β-lactams and glycopeptide antibiotics.