Core46: Antibiotic selection considerations - infections affecting specific compartments

🧠 High-yield / 要点：Antibiotic choice depends on whether the drug reaches the infected compartment. Penetration depends on tissue factors + drug properties + local environment.

Why compartments matter / なぜ感染部位が重要か

• Most infections are extravascular.
• Treatment requires movement of antibiotic into:
  • Interstitial fluid.
  • Sometimes intracellular fluid.
  • Special compartments such as CSF, prostate, bone, abscess.

Determinants of penetration / 移行性を決める因子

Factor type	Examples
Tissue-related	Perfusion, vascular surface area, tight junctions, capillary pores
Drug-related	Lipid solubility, molecular size, pKa, plasma protein binding
Barrier/transport	BBB, efflux pumps, vitreous barriers
Local environment	pH, oxygen level, bacterial growth rate

Lipid-soluble vs hydrophilic drugs / 脂溶性と親水性

• Lipid-soluble drugs penetrate nonfenestrated capillary beds better:
  • Metronidazole
  • Chloramphenicol
  • Rifampin
• More water-soluble drugs penetrate less well:
  • β-lactams
  • Aminoglycosides
  • Glycopeptides
• Inflammation can partly improve penetration of hydrophilic drugs into restricted tissues.

Efflux and special barriers / 排出ポンプと特殊バリア

• Efflux pumps can reduce antibiotic levels in compartments.
• Examples:
  • Some β-lactams and fluoroquinolones are actively transported out of CSF.
  • β-lactams may be transported out of vitreous humor.

Local activity changes / 局所環境による効果変化

• Even if antibiotic reaches the site, activity may decrease.
• Aminoglycosides:
  • Less active at low pH, e.g. abscesses.
  • Less active in anaerobic environments.
• Abscesses and meningitis may have slower bacterial growth.
  • β-lactams, which act best on dividing bacteria, may be less effective.
• Ion trapping:
  • Weak bases may accumulate in low-pH compartments.
  • Examples: clindamycin and erythromycin in prostatic fluid; azithromycin in lysosomes.

Remember / 覚え方

• Right drug = right pathogen + right compartment
• Lipophilic drugs penetrate barriers better
• Inflammation can improve penetration
• Abscess: low pH/anaerobic/slow growth can reduce antibiotic activity