I frequently say on rounds, “Giving a dose of amikacin is both a treatment and a diagnostic test for gram negative infection”

People just nod sagely & we move on

But am I right?

Time for a WHO, WHAT, WHERE, WHEN, WHY #tweetorial 🧵

#FiveW /1
WHEN should we use amikacin?

Well, it’s probably the best empirical choice for treatment of suspected gram -ve infections as it has wide activity across Enterobacteriaceae (e coli, klebs etc), pseuds & mycobacteria, and interestingly many staphs & TB /2
WHERE in the cell does amikacin work?

Well the answer is “kind of everywhere”

Downstream effects at the membrane allow more amikacin in to the cell do its primary work

A lot of the uptake steps are electron transport dependent hence why it doesn’t work against anaerobes /3
WHAT is its primary bactericidal effect?

Inhibition of protein synthesis at the ribosome

Amikacin alters conformation of the 16S A-site➡️mistranslation through misreading of codons ➡️erroneous polypeptides that subsequently cause cell membrane damage (see pic) /4
Ok so that’s how it works

WHY do aminoglycosides have a nephrotoxic rep?

Historically 10-25% of courses saw nephrotoxicity

The move to single daily dosing & understanding that over 2 doses are rarely needed if dosing is right, seems to have lessened that number

Phew
/5
WHO is at risk of nephrotoxicity?

Some of these associations strike me as a bit like old thinking (contrast/NSAIDs) but some are VERY real (pregnancy) /6
Ok that's it. I'll try and post more #FiveW #tweetorial content. They're not meant to be exhaustive

Final amikacin tips: if two doses haven't done the trick, think again, and if you're treating neutropenic sepsis and you haven't grown any gram -ves by 48h, stop the drug

/7

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More from @toates_19

27 Feb
"Long lie & a bit of an AKI"

This is a common medical presentation, usually meaning "I'm worried this pt has rhabdomyolysis"

What is rhabdo anyway & how do I know my pt has it?

Lets do a WHO, WHAT, WHERE, WHEN, WHY #tweetorial

#FiveW 🧵 /1
WHAT is rhabdo?

It’s predominantly a clinical entity where damaged skeletal muscle leaks intracellular contents into the blood

Obvs the one we know & measure is CK but myoglobin is a key player in kidney injury & aldolase, LDH & iron are all important /2
WHERE does CK come from?

Muscle right? Direct or indirect (due to ATP depletion) damage ⬆️ free ionized Ca causing mitochondrial dysfunction & cell death

CK, an 82kDa enzyme found in cytosol & mitochondria of hi energy tissues therefore enters the plasma w/ other moleclues /3 Image
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