Episode 80- One-time aminoglycosides for cystitis

Hello and welcome to Episode 80 of ER-Rx- a podcast tailored to your clinical needs. I’m your host, Adis Keric, and in this Pharmacy Consult episode, I’m gonna remind you of a great way to make use of an old drug. For whatever reason, this is something that always makes me weirdly happy. Whether it’s using procainamide for atrial fibrillation (like we talked about in Episode 25) or phenobarbital for alcohol withdrawal (as we discussed in Episodes 71-73), sometimes it’s just cool to go back to OG drugs.

So, picture this scenario- which actually happened to me last week. You’re working in the ER the provider asks you about treatment options for a patient with a pseudomonal cystitis. The patient’s here because they’re failing empiric outpatient Bactrim therapy (go figure) and they have a documented and real fluoroquinolone allergy. You also find out that in the past, someone else tried to treat this pseudomonal UTI with fosfomycin. Now, the patient doesn’t want to be admitted and you’re already boarding 20 patients in the ER- so beds are very hard to come by. What options do we have to get this patient discharged?

We know that the only oral options we have to treat a pseudomonal UTI are fluoroquinolones- which the patient can’t have. You could possibly consider trying fosfomycin again- another pretty old drug- but your lab doesn’t automatically run fosfomycin sensitivities, and I’m not sure you’d want to treat pseudomonas with fosfomycin anyway given its very high failure rates- as the patient can attest to. In this scenario, we can revive a strategy that’s discussed in IDSA guidelines but most people forget about or just gloss over—and that is giving a one-time dose of an aminoglycoside.

Let me remind you of how great these agents are for these types of situations. The aminoglycosides first came out in the 1940s and given their almost exclusive renal elimination and high activity against most uropathogens, they were a heavy favorite for treating UTIs. One of the cleverest ways to use them is by giving a higher, one-time IM or IV dose. Giving a one-time dose means we don’t have to worry about the patient taking, or even picking up their antibiotics, figuring out how long to treat the UTI, or admitting them to the hospital. Pharmacokinetically, aminoglycosides reach concentrations in the urine that are 100 times that of the blood and lead to peak urine concentrations that greatly exceed the peak-to-MIC ratio that’s recommended by the CLSI guidelines for at least 72 hours.

So that’s great and all, but do we have any data that this works? Back in 2019, a group of pharmacists published a systematic review- which I’ll link to in the show notes- that talks about this. They looked at 13 studies that included over 13,000 adult and pediatric patients. Most of the patients received netilmicin, which I don’t think is available in the US, amikacin, or gentamicin, and all doses were given IM- but remember there’s no reason why IV wouldn’t work. Most of the uropathogens were E. coli (72%), Proteus, and Klebsiella, but unfortunately only 2% of the strains were Pseudomonas. They found that the overall cure rate was ~ 95% with an adverse event rate of 0.5%- which mostly included nephrotoxicity.

Back to our case: you and the provider get very excited that you don’t have to admit the patient, and that you get to use an old drug in a fancy, old way. You order 5 mg/kg IV gentamicin, since the patient already had an IV line, the wonderful nurse gives it over 30 minutes- and the patient gets sent home with primary care follow-up. Keep in mind that you could also use 5 mg/kg of tobramycin or even 15 mg/kg of amikacin. Also please get an accurate weight for your patient and use an adjusted body weight instead of an actual body weight for any obese patients weighing > 120% of their ideal body weight.

So, let’s wrap up with the main points. If you have a patient with an uncomplicated cystitis caused by Pseudomonas, or for that matter, any sensitive uropathogen, that is unwilling or unable to take oral antibiotics who also doesn’t want to be admitted for a course of IV antibiotics, consider giving a one-time dose of an aminoglycoside. At the moment this shouldn’t be done in patients who have urosepsis or bacteremia, pyelonephritis, those who have grown an aminoglycoside-resistant organism in the past, or those with severe renal dysfunction. This strategy leads to high cure rates with minimal adverse events mostly including nephrotoxicity- which is almost always reversible and is mainly an issue in very elderly patients or those who have underlying kidney disease.

And remember, this is a great option not only for patients you really don’t think need to be admitted, but also for difficult-to-treat resistant uropathogens as well. This is discussed in the new IDSA guidelines on the treatment of antimicrobial-resistant gram- negative infections, which was published in March of 2022.

As always, thank you so much for your time, and thank you for wanting to learn more about pharmacotherapy. If you have any comments or anything you’d like to add to this episode, please give me a shout out on the @errxpodcast Instagram page, or reach out to me on errxpodcast.com- I’d love to respond to all comments and criticisms.

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