Tasty Morsels of Critical Care 024 | The aminoglycosides

1 Feb

Welcome back to the tasty morsels of critical care podcast. A meandering monologue through critical care exam preparation.

The aminoglycosides see themselves as a bit special. Not content with producing deafness and killing kidneys they’ve also demanded awkward dosing schedules, a need for regular levels and even their own section on most drug kardexes that I’ve seen. They are the divas of the antibiotic world.

That being said they’re a real work horse in the ICU and it’s hard to say you’ve done due diligence on a septic crashing patient without the ubiquitous “shot of gent” that has wormed its way into the medical nomenclature.

In the ED and ICU the only aminoglycosides in town are gentamicin and its lesser used but much respected, big brother, amikacin.

In terms of mechanism, these drugs work by inhibiting bacterial protein synthesis by binding to the 30S sub-unit of the ribosome. The preceding is one of those statements that sounds somewhat impressive when delivered in a viva but is quickly followed by a blank look of panic if anyone asks a follow up question. 

These drugs are a good example of concentration dependant killing. In brief, this means that we need a nice high peak concentration of the drug, well above the MIC of the bug in question. This is in distinction to the beta-lactams which are classed as time dependant killing, where the time above the MIC is more correlated with efficacy.

Aminoglycosides also come with an excellent post antibiotic effect where growth of the bug is inhibited even when the levels of the drug are below the MIC. The idea seems to be that the aminoglycosides bind irreversibly to ribosomes so even when you can’t measure any aminoglycoside in the blood it’s still working away in stopping microbial growth.

Their most common use in critical care is as an adjunctive antibiotic for aerobic gram negative bacilli. Perhaps the commonest context will be in the context of septic shock with the belly as public enemy number 1. The other common use is in sepsis of urinary origin, (the dreaded urosepsis, as opposed to that pesky south east asian sepsis… H/T Mike Park…) where the aminoglycosides come in particularly handy as they are excreted unchanged by the kidneys so that concentrations within the urinary tract can be incredibly high.

They are usually used in combination with other antibiotics but interestingly gentamicin remains first line therapy for plague which is worth keeping in mind when the inevitable apocalypse comes and the following societal collapse and return to the middle ages.

The aminoglycosides penetrate poorly in the acidic environments of the the bronchial secretions and the lung and are thought to be poorly effective here. They also have poor penetration to the CSF and biliary tree.

I’ve never been entirely clear when to reach for amikacin over its much more commonly used brethren gentamicin. This is of course the reason we have timely and excellent input from our micro and ID colleagues but what I’ve gleaned suggests that amikacin has a role particularly in those patients carrying the alphabet soup labels of ESBL, KPC etc…

Our main concern with these drugs is their toxicity, namely to the kidneys and ears. With regards to the kidneys the ubiquitous presence of the green machine (CRRT) has allowed us to prioritise killing bugs before preserving renal function. I know we’d like to have both but given that we can replace the kidneys then we tend to sacrifice them on the alter of microbial killing.  As a result we have a somewhat laissez faire attitude to nephrotoxicity which is probably not the best.

The ototoxicty is somewhat more opaque to us in the ICU as patients are rarely well enough to express their vestibular or cochlear disturbance to us and this is something much more likely to be picked up on the ward following the ICU stay.

Our best tool to avoid these toxicities is careful dosing, regular levels and stopping them whenever we have identified the right bug and the right antibiotics for them. Thankfully aminoglycosides are one of the few drugs that you will be asked to review every day and hopefully stop.

Finally there is the rarely reported phenomenon of neuromuscular block following aminoglycoside administration. However its rarity outside those with myasthenia gravis makes it gentamicin unlikely to be a serious competitor in the roc v sux debate.

References

Deranged Physiology – The post antibiotic effect

UpToDate has a lovely summary article on the aminoglycosides which forms the bulk reference for this podcast

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