Aminoglycosides and Glycopeptides
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Direct answer
Aminoglycosides and glycopeptides are bactericidal antibiotics whose main dangers are nephrotoxicity and ototoxicity. Aminoglycosides such as gentamicin and amikacin bind the 30S ribosomal subunit, while vancomycin and teicoplanin block peptidoglycan assembly and are reserved for resistant Gram-positive infection such as MRSA. Both groups need level monitoring, because drug accumulation in renal impairment is the usual cause of harm.
What you must remember
- Aminoglycoside toxicity: Nephrotoxicity is usually reversible and proximal tubular, while ototoxicity is largely irreversible; streptomycin and gentamicin favour vestibular damage, and amikacin favours cochlear damage.
- Neuromuscular blockade: Aminoglycosides can cause respiratory paralysis, with risk rising alongside neuromuscular blockers, hypermagnesaemia or hypocalcaemia, and calcium salts are used for reversal.
- Level monitoring: Peak levels track efficacy and troughs track toxicity, so troughs are kept low and intervals lengthened in renal impairment.
- Red man syndrome: An infusion-rate-dependent histamine release with flushing and pruritus after vancomycin, not a true allergy; slowing the infusion and antihistamine pretreatment manage it.
- Vancomycin toxicity: Nephrotoxicity and ototoxicity, with higher risk alongside other nephrotoxic drugs, and area-under-curve guided dosing is preferred where available.
- Teicoplanin: Less prone to infusion reactions and can be given intramuscularly after a loading dose.
A worked pathway: rising creatinine on gentamicin
Consider a 62-year-old in septic shock from a urinary source, started on gentamicin. On day three the creatinine rises above baseline and urine output falls. The team checks the trough level, which is higher than intended, and reviews other nephrotoxins such as furosemide and vancomycin. They lengthen the dosing interval, avoid further nephrotoxins and switch to a non-nephrotoxic agent where possible, since an isolate that responds to a beta-lactam does not need an aminoglycoside. Hearing, tinnitus and balance are documented, because ototoxicity can go unnoticed until it is established. Daily creatinine and urine output tracking continues until recovery, and the team remembers that aminoglycoside kidney injury is often non-oliguric and may lag behind the true fall in filtration. Once the infection settles, the team stops the aminoglycoside as soon as possible, documents the cumulative exposure and arranges audiometry if hearing symptoms appeared during treatment. A sentence in the discharge letter about renal function and hearing protects the patient if the next admission involves another nephrotoxic drug.
Where the exam tries to catch you
Examiners exploit confusion between the two classes. Vancomycin is nephrotoxic, but its ototoxicity is far less prominent than an aminoglycoside's, and its infusion reaction is red man syndrome rather than anaphylaxis, so flushing and hypotension during a rapid infusion is not an allergy question. Another classic trap concerns spectrum: aminoglycosides are ineffective against anaerobes because uptake depends on oxygen-dependent transport, and their activity falls in acidic conditions such as an abscess. Vancomycin does not act on Gram-negative bacilli because the outer membrane blocks its entry. Aminoglycosides are also synergistic with beta-lactams in enterococcal endocarditis, a favourite viva question.
Frequently asked questions
Why are aminoglycosides ineffective against anaerobic infections?
Aminoglycosides need an oxygen-dependent transport step to enter bacterial cells, so obligate anaerobes are not killed. Their activity is also reduced in acidic conditions such as abscesses, which is why they are poor choices for anaerobic infection despite good Gram-negative coverage.
What is red man syndrome and how is it managed?
Red man syndrome is a histamine-mediated infusion reaction to vancomycin, causing flushing of the face, neck and upper trunk, pruritus and sometimes hypotension. It is managed by slowing the infusion, and antihistamines can be given before later doses, with the drug usually continued.
Which level should be checked to prevent gentamicin toxicity?
The trough level is checked to prevent toxicity, because high troughs indicate drug accumulation that damages the kidney and inner ear. Peak levels confirm adequate exposure for efficacy, and the target trough is set by local protocol or pharmacokinetic dosing.
Why is vancomycin used for MRSA but not for Gram-negative bacilli?
Vancomycin is a large glycopeptide that cannot cross the outer membrane of Gram-negative bacilli, so it cannot reach the peptidoglycan precursors in those organisms. It is therefore reserved for resistant Gram-positive infections such as MRSA, where its action on the cell wall is effective.