Antimicrobial toxicities

Antimicrobial toxicities

Antimicrobial toxicities

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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.

Aminoglycoside ototoxicity in the cochlea

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.

SJS vs TEN: Skin detachment and mucosal involvement

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.

Practice Questions: Antimicrobial toxicities

Test your understanding with these related questions

You are taking care of a patient with renal failure secondary to anti-fungal therapy. The patient is a 66-year-old male being treated for cryptococcal meningitis. This drug has a variety of known side effects including acute febrile reactions to infusions, anemia, hypokalemia and hypomagnesemia. What is the mechanism of action of this drug?

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Flashcards: Antimicrobial toxicities

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Which chemotherapeutic drugs are associated with nephrotoxicity, ototoxicity, and peripheral neuropathy?_____

TAP TO REVEAL ANSWER

Which chemotherapeutic drugs are associated with nephrotoxicity, ototoxicity, and peripheral neuropathy?_____

Platinum analogs

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