Antimicrobial toxicities

Nephro & Ototoxicity - Kidneys & Ears Under Siege

• Aminoglycosides (e.g., Gentamicin, Amikacin)
  • Nephrotoxicity: Acute Tubular Necrosis (ATN). Usually reversible.
  • Ototoxicity: Auditory (cochlear) & vestibular damage. Often irreversible. Monitor peak/trough levels.
• Vancomycin
  • Nephrotoxicity: ATN, interstitial nephritis. Monitor trough levels (15-20 mg/L for severe infections).
  • Ototoxicity: Rare, but risk ↑ with high doses or renal impairment.
• Amphotericin B
  • Nephrotoxicity: Severe vasoconstriction & direct tubular damage (Distal RTA), leading to ↓K⁺, ↓Mg²⁺.
• Polymyxins (Colistin, Polymyxin B)
  • Nephrotoxicity: Dose-dependent ATN.

⭐ Synergistic Toxicity: Risk of ototoxicity ↑ when aminoglycosides are co-administered with loop diuretics (e.g., furosemide). Nephrotoxicity risk ↑ with concurrent use of vancomycin, amphotericin B, or cyclosporine.

Systemic & Skin Reactions - The Great Rash

• Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN):
  • Severe, blistering mucocutaneous reactions. Common triggers: Sulfa drugs, Allopurinol, Lamotrigine, Penicillins.
  • Defined by % Body Surface Area (BSA) detachment: SJS <10%, SJS/TEN overlap 10-30%, TEN >30%.
  • Positive Nikolsky's sign (skin sloughing with gentle pressure).
• DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms):
  • Features: Fever, rash, facial edema, eosinophilia, atypical lymphocytes, internal organ (liver, kidney) involvement.
  • Common culprits: Allopurinol, anticonvulsants.

⭐ DRESS syndrome has a characteristic long latency period, typically appearing 2-8 weeks after starting the offending drug.

Neuro & MSK Mayhem - Nerves, Bones & Groans

• Aminoglycosides: Ototoxicity (vestibular & cochlear damage), neuromuscular blockade.
• Fluoroquinolones: Tendon rupture (Achilles), cartilage damage. 📌 "FluoroquinoLONES hurt attachments to your BONES."
• Isoniazid (INH): Peripheral neuropathy (give with Vitamin B6/pyridoxine to prevent), seizures.
• Daptomycin: Myopathy, ↑ CPK levels (monitor weekly).
• Linezolid: Peripheral & optic neuropathy, serotonin syndrome.
• Metronidazole: Peripheral neuropathy, disulfiram-like reaction.

⭐ Fluoroquinolones have a black box warning for tendon rupture. The risk is highest in patients over 60, on corticosteroids, or with renal failure.

Heme & Hepatic Hits - Blood, Guts & Gall

• Hematologic Toxicity:

  • Chloramphenicol: Dose-related suppression (reversible); aplastic anemia (irreversible).
  • Sulfonamides (TMP-SMX): Megaloblastic anemia, hemolysis in G6PD deficiency.
  • Linezolid: Thrombocytopenia, pancytopenia with prolonged use.
  • Zidovudine (NRTI): Myelosuppression → macrocytic anemia.

• Hepatotoxicity:

  • Isoniazid (INH): Age-dependent hepatitis. 📌 INH = Injures Neurons & Hepatocytes.
  • Macrolides (Erythromycin): Acute cholestatic hepatitis.
  • Antifungals (-azoles): General hepatotoxicity (monitor LFTs).
  • Valproic Acid: Fatal hepatotoxicity (esp. in children).

⭐ Gray Baby Syndrome: Chloramphenicol toxicity in newborns lacking UDP-glucuronosyltransferase, leading to accumulation, shock, and death.

High‑Yield Points - ⚡ Biggest Takeaways

• Aminoglycosides (Gentamicin, Tobramycin) are notorious for nephrotoxicity and ototoxicity.
• Vancomycin infusion can cause Red Man Syndrome (a histamine-release reaction) and is also nephrotoxic.
• Daptomycin is associated with myopathy; monitor creatine phosphokinase (CPK) levels.
• Linezolid may cause bone marrow suppression (especially thrombocytopenia) and serotonin syndrome.
• Fluoroquinolones carry a risk of tendon rupture and cartilage damage.
• Clindamycin has a strong association with Clostridioides difficile colitis.