Aminoglycosides — Gentamicin, Tobramycin, Amikacin & the Three Toxicities

Also known as Aminoglycoside · Gentamicin · Tobramycin · Amikacin · Once-daily dosing · Extended-interval dosing · Concentration-dependent killing · Post-antibiotic effect · Hartford nomogram · Ototoxicity · Neuromuscular blockade

The aminoglycosides (gentamicin, tobramycin, amikacin) are bactericidal inhibitors of the 30S ribosomal subunit — concentration-dependent killers with a post-antibiotic sub-MIC effect and adaptive resistance, which justify extended-interval once-daily dosing targeting a Cmax/MIC of 8-10. They retain activity against multidrug-resistant Gram-negatives including Pseudomonas and Acinetobacter and are used empirically in severe sepsis while awaiting susceptibilities. Dosing: gentamicin 7 mg/kg once daily by the Hartford nomogram (single-level, creatinine-clearance-banded intervals), amikacin 15 mg/kg once daily. The defining toxicities: nephrotoxicity (proximal tubule, megalin-dependent uptake), ototoxicity (cochlear and vestibular, often irreversible), and neuromuscular blockade that worsens myasthenia.

high24 referencesUpdated 20 Aug 202624 min readSource-verified · Oct 2026

Checked against its sources on 5 Oct 2026

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8 MCQs

The one-paragraph exam answer

The aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin) are bactericidal inhibitors of the 30S ribosomal subunit — they are actively transported into the bacterial cell and derange protein synthesis there.^[14] They are concentration-dependent killers whose post-antibiotic sub-MIC effect and adaptive resistance make extended-interval once-daily dosing the pharmacodynamically optimal scheme, targeting a Cmax/MIC ratio of 8–10 with an AUC of about 100 mg·h/L per 24 hours.^[13] They retain good activity against MDR Gram-negatives including Pseudomonas aeruginosa and Acinetobacter spp.^[13] Dosing: gentamicin/tobramycin 7 mg/kg once daily set by the Hartford nomogram (single serum level, CrCl-banded q24/36/48 h intervals)^[1] and amikacin 15 mg/kg once daily.^[15] The defining constraint is toxicity: nephrotoxicity (proximal-tubular, delayed)^[14]^[1] and ototoxicity (streptomycin/gentamicin primarily vestibulotoxic; amikacin/neomycin primarily cochleotoxic; damage often permanent),^[12] plus neuromuscular blockade that worsens myasthenia gravis.^[18]

Meet the patient

A 64-year-old man rolls into the unit in septic shock from a urinary source — noradrenaline 0.3 mcg/kg/min, lactate 4.2 mmol/L, urine output trickling at 0.4 mL/kg/h, creatinine climbing. The empirical sepsis bundle adds once-daily gentamicin 7 mg/kg to his piperacillin-tazobactam, and the registrar asks the question that frames this whole topic: "how do I get the kill without the three toxicities?"^[1]

The answer is the entire design of aminoglycoside dosing. Push the peak high enough to kill (Cmax/MIC 8–10)^[13] and let the drug wash out completely between doses — adaptive resistance is minimised when the drug clears before the next dose.^[13] And stop as soon as cultures allow: in the Hartford program the median course was just 3 days.^[1] Hold that tension — efficacy versus nephro- and oto-toxicity — and every section below slots into place.^[14]

References24Show

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