POTD: UTI? How to interpret your UAs and micros.

We diagnose UTIs nearly everyday, but are all of these true UTIs? Below, I will go into a quick review of what makes a UTI positive and various other tidbits. As usual, TL;DR is on the bottom of the post.

First off, patient should be instructed to provide a mid-stream sample, preferably clean-catch, however studies have shown that cleaning does not decrease contamination. 

Once collected, samples should be send immediately or refrigerated within 2 hours. This is to prevent proliferation of bacteria within the container itself. That being said, samples should still be analyzed expeditiously because refrigeration can also alter urinary leukocytes. 

Before you consider ordering any tests at all, consider this - does your patient really need testing?

UTI is a clinical diagnosis! In patients with classic symptoms for UTI (dysuria, urinary frequency, urinary urgency in the absence of symptoms that could suggest cervicitis or vaginitis), a negative dip or UA may actually falsely reassure you due to false negative results. In short, a negative result should not change your management 

Likewise, in a non-pregnant, asymptomatic patient, a false positive may lead to unnecessary treatment (besides, asymptomatic bacturia in a non-pregnant patient should not be treated anyway!!)

Now if you think a patient should be tested...

Nitrites
Nitrites are found in urine as a result of conversion of urinary nitrates to nitrites by gram negative bacteria that have been sitting in the bladder for > 4 hours. Studies have shown that they are highly specific (92-100%), but not very sensitive (19-48%). False negatives occur because nitrites require > 4 hours incubation, are not formed by some bacteria (Enterococcus faecalis) or are formed in small amounts, low urinary pH, or ingestion of foods/drugs that color the urine red. However, false positives can occur due to treatment with pyridium (phenazopyridine) and testing with strips that have been exposed to air. 

Leukocyte Esterase
Leukocyte esterase (if you remember back to your microbiology days) is produced by neutrophils and is associated with pyuria (positive requires > 10 WBC/hpf). Abnormal LE has been found to be highly sensitive (72-97%), butnot very specific (41-86%). To put that in perspective, the PPV is only 43-56%, meaning that of the patients that test positive, on the high end of the spectrum, only 56% of patients will have a culture-confirmed UTI. False positives can occur from contamination, false negatives occur from glycosuria, ketonuria, proteinuria, high urine specific gravity (increases cell lysis), vitamin C, or some oxidizing drugs (e.g. keflex, macrobid, tetracycline, gentamicin).  

What about microscopy?
So we tend to look a lot at the WBC/hpf to aid in our decision making. This is actually the less accurate method for determining pyuria - things like vaginal secretions can affect the leukocyte count. The more accurate method is hemocytometry. However, using what we have available, up to date recommends using a cut off of 8cells/microL, which corresponds to 2-5 cells/hpf. The question is how to use this information knowing that contamination can falsely increase your WBC count.

Some biostats:

  • Bacteria: sensitivity 46-58%, specificity 89-94%

  • > 5 WBC/hpf: sensitivity 90-96%, specificity 47-50%

Looks pretty similar to your stats for nitrites and leuk esterase, right?

There are several situations which can arise: 

  • Bacteria without pyuria: absence of pyuria with a UTI are rare, so this is usually indicative of contamination and a repeat test should be done. However if the patient has symptoms, they may have an entity called "acute urethral syndrome". Likewise, if your sample is from a patient that is chronically catheterized, lack of pyuria is likely due to colonization and not infection. Keep in mind though, patients that are immunosuppressed may not have pyuria due to blunted immune response. 

  • Sterile pyuria: can occur in patients that have already taken antimicrobials (your "partially treated" UTIs), contamination by sterilizing cleaning solution used to clean the urethra, vaginal leukocytes, dehydration, chronic interstitial nephritis, interstitial cystitis, uroepithelial tumors, appendicitis, diverticulitis, or atypical organisms such as ChlamydiaUreaplasma, and TB. 

Take home points:
Don't test all urine! In a young, non-pregnant female with symptoms typical of UTI, go ahead and treat! A negative result may cloud your judgement. In other situations (pregnant female, symptomatic males, the elderly with AMS that may be due to UTI), learn to use your UA and microscopy to aid in your decision making. Figure out what can cause false negatives and false positives. Positive nitrites and positive leuks? Treat! Only have bacteria? Test again! Only have leuks? Look for other causes! In short, only use testing as an adjunct to your clinical decision making. 

TL;DR:

  • Think about who you're testing! Not everyone needs a UA. 

  • Nitrites are highly specific, but not sensitive

  • Leukocyte esterase is highly sensitive, but not specific

  • Absence of pyuria is rare in UTI, so if you see bacteria, but no pyuria, it's likely not a UTI

  • Pyuria can occur in many different conditions, so if you have pyuria without bacteria, think about alternative diagnoses

Sources:
https://www.aafp.org/afp/2005/0315/p1153.html
http://epmonthly.com/article/lowly-urinalysis-avoid-common-pitfalls/
https://www.uptodate.com/contents/sampling-and-evaluation-of-voided-urine-in-the-diagnosis-of-urinary-tract-infection-in-adults
https://www.acepnow.com/article/avoiding-overdiagnosis-overtreatment-urinary-tract-infection-emergency-department/
https://emergencymedicinecases.com/uti-myths-misconceptions/

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