Pharmacology

Pharmacology

Core47: Considerations for antibiotic choice - comorbidities

抗菌薬選択の考慮事項：併存疾患

🩺 High-yield / 要点：Comorbid liver/kidney disease changes antibiotic PK. Liver disease affects metabolism, protein binding, Vd, first-pass, while kidney disease mainly causes accumulation unless dose-adjusted.

Liver disease / 肝障害

  • Chronic liver disease increases infection risk due to impaired immunity, e.g. reduced neutrophil function.
  • Altered hepatic function can change antibiotic effects via:
    • Reduced CYP activity → reduced metabolism.
    • Reduced hepatic blood flow → higher bioavailability/serum levels.
    • Ascites → increased Vd and half-life.
    • Hypoalbuminemia → reduced protein binding, increased free drug, altered Vd/clearance.
    • Portosystemic shunts → reduced first-pass metabolism.

Antibiotic effect changes in liver disease / 肝疾患での抗菌薬効果変化

  • Hypoalbuminemia can reduce effect of highly albumin-bound antibiotics:
    • Ceftriaxone
    • Ertapenem
    • Teicoplanin
  • Higher Vd can reduce effect of concentration-dependent antibiotics, e.g. aminoglycosides.
  • Higher CL due to hypoalbuminemia can reduce effect of time-dependent antibiotics, e.g. β-lactams.

Antibiotics to avoid in liver disease / 肝疾患で避ける薬

  • Antibiotics mainly metabolized by liver:
    • Macrolides
    • Chloramphenicol
    • Clindamycin
  • Hepatotoxic antibiotics:
    • Especially antimycobacterial therapy.

Kidney disease / 腎障害

  • Impaired renal elimination can cause accumulation and toxicity.
  • Dose adjustment is important for:
    • Glycopeptides
    • Aminoglycosides
    • Clarithromycin
    • Antifolates
    • Most β-lactams
    • Fluoroquinolones

Dose adjustment / 用量調整

Method Meaning
Dosing method Reduce each unit dose; keep same interval
Interval method Keep same unit dose; prolong dosing interval

Safer choices in kidney damage / 腎障害で比較的使いやすい薬

  • Usually no dosage adjustment needed / preferred:
    • Clindamycin
    • Azithromycin
    • Doxycycline
    • Tigecycline
    • Metronidazole
    • Ceftriaxone
    • Moxifloxacin
    • Chloramphenicol
    • Linezolid

Remember / 覚え方

  • Liver disease = metabolism + albumin + ascites
  • Kidney disease = accumulation risk
  • Aminoglycosides/glycopeptides often need renal adjustment