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Alkaline Urine = Nitrofurantoin Resistance?

February 14, 2022

Written by Clay Smith

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When urine pH is ≥8, culprit bacteria are more often caused by Proteeae group bacteria, which are associated with resistance to nitrofurantoin.

Why does this matter?
Nothing says Valentine’s Day like a UTI. Nitrofurantoin is a first-line drug for uncomplicated cystitis, but the Proteeae group bacteria (Proteus spp., Morganella morganii, and Providencia spp.) are more often resistant to nitrofurantoin. These bacteria are urease producing, meaning they often make the urine pH alkaline. Could alkaline urine pH offer us an early clue that nitrofurantoin might not be the best choice for empiric treatment?

This is so basic…
This was a retrospective study of a health system that looked at 13,456 urine cultures that grew a single bacteria over an almost 4 year period. As expected, Proteeae bacteria were associated with a more alkaline urine pH. The higher the pH, the greater the association with nitrofurantoin resistance. For a urine pH 5-7, 80% of cultures were sensitive to nitrofurantoin, whereas just 54.6% were sensitive if the urine pH was >9. The authors thought a reasonable cut point to use an alternate drug, such as cefazolin or TMP/SMX, was at a urine pH ≥8. Of note, this is far from perfect. Other bacteria, like Klebsiella spp and S. aureus also produce urease. And many other factors alter urine pH, such as diet, BMI, time of day, etc. However, there was an association with higher urine pH and nitrofurantoin resistance. Here is the money shot.

From cited article

Alkaline Urine in the Emergency Department Predicts Nitrofurantoin Resistance. J Emerg Med. 2022 Jan 6:S0736-4679(21)00763-0. doi: 10.1016/j.jemermed.2021.10.022. Epub ahead of print.

What are your thoughts?