Penicillins Overview

Penicillins

• Natural Penicillins are effective against Gram-positive bacteria
• Semisynthetic Penicillins, including Aminopenicillins, have a broader spectrum of activity against Gram-negative bacteria
• Carbenicillin and Ticarcillin are semisynthetic penicillins effective against Pseudomonas
• Resistance to Penicillins:
  • Natural Resistance: Bacteria inherently insensitive to a particular antibiotic
  • Acquired Resistance: Bacteria develop resistance through mutations or acquiring genes for resistance mechanisms, such as beta-lactamases
• Beta-lactamases are bacterial enzymes that destroy the beta-lactam ring of penicillin, making it ineffective
• Clavulanate and Sulbactam are beta-lactamase inhibitors, often combined with penicillins to overcome resistance
• Penicillins are frequently combined with Aminoglycosides, antibiotics that inhibit bacterial protein synthesis

Macrolides

• Macrolides are effective against various bacteria, including Gram-positive, Gram-negative, and intracellular bacteria like Mycoplasma, Chlamydia, and Legionella
• Macrolides are alternatives to penicillin for penicillin-allergic patients

Lincosamides

• Lincosamides, like clindamycin, have a similar activity spectrum to macrolides
• Lincosamides are ineffective against Clostridium difficile infections and can induce pseudomembranous colitis, a severe bowel infection caused by Clostridium difficile

Aminoglycosides

• Aminoglycosides are antibiotics with a large, positively charged structure, preventing oral absorption
• Administered parenterally (intravenously or intramuscularly)
• Common Aminoglycosides:
  • Gentamicin: Available as a pre-filled vial
  • Amikacin: Available as a pre-filled vial
  • Neomycin: Limited oral absorption, used topically for skin infections and orally to suppress intestinal flora before surgery
  • Paromomycin: Previously used for amoebiasis, but newer treatments are preferred
  • Streptomycin: Available as a powder to reconstitute, administered intramuscularly, less common for TB treatment
  • Tobramycin: Available as eye drops for conjunctivitis
• Aminoglycosides:
  • Mechanism of action: Inhibit protein synthesis by binding to the 30S ribosomal subunit
  • Spectrum: Primarily effective against Gram-negative bacteria, including Pseudomonas aeruginosa
• Pseudomonas aeruginosa: A common bacterium causing serious infections, commonly infecting burn patients, those with indwelling devices, and immunocompromised individuals
  • Aminoglycosides are a first-line treatment choice for Pseudomonas aeruginosa infections
• Aminoglycosides:
  • Bactericidal antibiotics inhibiting protein synthesis
  • Effective against Gram-negative bacteria (Enterobacteriaceae, Pseudomonas aeruginosa) and some Gram-positive bacteria (e.g., Staphylococcus aureus)
  • Usually not a sole therapy for Staphylococcus aureus but combined with a cell wall synthesis inhibitor
  • Also active against Mycobacterium tuberculosis
  • Post-antibiotic effect: Activity continues below minimum inhibitory concentration (MIC)
  • Narrow therapeutic index, dose-dependent and time-dependent adverse effects
    • Ototoxic and nephrotoxic: Accumulate in inner ear and kidneys
    • Administering total daily dose once reduces ototoxicity and nephrotoxicity risk
    • Can cause neuromuscular blockade
    • Contraindicated in severe renal impairment; use with dose adjustments in mild to moderate impairment
    • Interactions with other nephrotoxic drugs
    • Poorly absorbed orally, typically given intravenously or intramuscularly
    • Not metabolized, eliminated by kidneys

Quinolones

• Quinolones inhibit bacterial DNA synthesis
• Classified by generation based on spectrum and properties
• First-generation quinolones (nalidixic acid, pipemidic acid) are primarily urinary antiseptics for lower urinary tract infections
• Second, third, and fourth-generation (fluoroquinolones, e.g., ciprofloxacin) have a broader spectrum than first-generation drugs
• Certain quinolones have activity against intracellular bacteria
• Quinolones are second-line treatment for intracellular bacteria; macrolides are first-line due to lower toxicity
• Norfloxacin (400 mg BID): Used for lower urinary tract infections (cystitis), not systemic/kidney infections
• Ciprofloxacin (500mg or 1000mg BID/QD, IV 200mg in 200ml solution): Second/third-generation, broad-spectrum (Gram-positive and negative)
  • Also active against Streptococcus pyogenes at higher doses
• Moxifloxacin (400mg QD): Fourth generation, excellent activity against Gram-negative & Gram-positive bacteria, anaerobes, and intracellular organisms
• Levofloxacin (500mg or 750mg QD): Third-generation, good activity against anaerobes
• Inhibitors of DNA gyrase with a post-antibiotic effect
• Potential side effects: Diarrhea, nausea, colitis, convulsions, tendonitis, tendon rupture.
• Not for children, especially those with seizure history
• Metabolized in liver, can affect kidneys
• Avoid combining with bacteriostatic antibiotics or divalent cations (calcium, magnesium, iron, aluminum)