أسئلة الخامسة ميكرو دمياط (قبل التعديل)

Antimicrobial Definitions

• Antimicrobials: Naturally occurring or synthetically derived compounds that inhibit or destroy bacteria.
• Ideal Antibiotic: Shows selective toxicity, does not develop bacterial resistance, is non-allergenic, water-soluble, and stable with good tissue distribution.
• Bactericidal: Kill bacteria; examples include aminoglycosides, beta-lactams, vancomycin, quinolones, rifampin, and metronidazole.
• Bacteriostatic: Inhibit bacterial growth; examples include chloramphenicol, clindamycin, erythromycin, sulfonamides, trimethoprim, and tetracyclines.
• Antifungal: Targets fungi.
• Antiviral: Targets viruses.
• Antiprotozoal: Targets protozoa.
• Antihelminth: Targets parasitic worms.

Mechanisms of Action of Antibiotics

• Cell Wall Synthesis Inhibitors: Prevent the synthesis of peptidoglycans needed for the bacterial cell wall.
  • Penicillins: Interfere with the synthesis of bacterial cell walls.
    • Natural penicillins are effective against gram-positive cocci except Staphylococcus aureus.
    • Penicillinase-resistant penicillins are effective against Staphylococci aureus.
    • Extended-spectrum penicillins work against many gram-negative bacteria.
  • Cephalosporins: Broad-spectrum antibiotics that work similarly to penicillins.
  • Glycopeptides (Vancomycin): Important in treating methicillin-resistant Staphylococcus aureus (MRSA).
  • Monobactam (Aztreonam): Specifically works on Pseudomonas aeruginosa.
  • Carbapenems (Imipenem): Powerful drugs that are generally effective against gram-negative organisms, including Pseudomonas.

Inhibitors of Protein Synthesis

• 30S Inhibitors: Bind to the bacterial 30S ribosomal subunit, disrupting protein synthesis.
  • Examples: Aminoglycosides (gentamicin, amikacin), Tetracyclines (oxytetracycline).
• 50S Inhibitors: Bind to the 50S ribosomal subunit, also disrupting protein synthesis.
  • Examples: Macrolides (erythromycin), Chloramphenicol, Streptogramins (retapamulin).

Alteration of Cell Membrane Function

• Polymyxins: Topical antibiotics that disrupt the bacterial membrane.
• Daptomycin: Active against gram-positive bacteria, including MRSA and VRSA.

Inhibitors of Nucleic Acid Synthesis

• Co-trimoxazole: Treatment for urinary tract infections (UTIs). Combines sulphamethoxazole and trimethoprim.
• Quinolones (Ciprofloxacin, Levofloxacin): Inhibit DNA gyrase.
• Rifampicin: Inhibits RNA polymerase, inhibiting mRNA synthesis, and is used to treat tuberculosis.

Antimicrobial Combinations (Synergistic/Antagonistic)

• Additive Effects: Results in a sum of individual antimicrobial effects.
• Synergistic Effects: A combination of antimicrobials that produce a result better than that of the individual acting alone.
• Antagonistic Effects: A combination of antimicrobials that produce a result worse than that of the individual effect alone

Probiotics

• Live, nonpathogenic bacteria and/or yeasts used to treat or prevent diseases.
• Mechanisms: Exclude pathogens by colonizing the mucosa, enhance immune response, reduce inflammation, and treat antibiotic-associated diarrhea. Examples of probiotic foods: Yogurt, tempeh, sourdough, kimchi, kombucha, and sauerkraut.

Bacterial Resistance to Antibiotics & Failure of Treatment

• Misuse of Antibiotics Leading to emergence of multidrug-resistant bacteria including the following: MRSA, VRSA, and Pan-resistant Gram-negative bacteria.
• Causes for failure: Choice of antibiotic, inadequate dosage, or duration of treatment, route of antibiotic administration, or using antagonistic antibiotic combination.
• Bacterial resistance mechanisms: Reduction in intracellular antibiotic accumulation (decreasing permeability) or active efflux (efflux pumps) of the antibiotic. Enzymatic inactivation (inactivating enzymes) of antibiotics or alteration or inactivation of the target receptors of the antibiotic.
• Failure of antibiotic treatment can result from viral or mixed bacterial infection, inappropriate antibiotic choice, inadequate dosage, or treatment duration, incorrect administration route, or antagonistic antibiotic combinations.
• Misuse of antibiotics leads to the development of resistant strains, including multidrug-resistant (MDR) bacteria, which can cause life-threatening infections.

Clinical Case and Questions (Page 8)

• Clinical Case: A 45-year old female presenting with fever, burning urination, frequency, and dysuria; microbiological tests revealed gram-negative bacilli, Nitrofurantoin was prescribed.
• Inhibitors of protein synthesis: Tetracyclines, Aminoglycosides, Macrolides, Chloramphenicol
• Mechanisms of Antibiotic Resistance:
• Decreased permeability of the cell wall to the antibiotic.
• Active efflux pumps remove the antibiotic from the bacterial cell.
• Enzymatic inactivation of the antibiotic (e.g., inactivation of penicillins by β-lactamases).
• Modification of the bacterial target site (e.g., alteration of the ribosome preventing antibiotic binding).