UTI: More than you ever wanted to know

For this month’s Emergency Medicine Cases, Anton kindly asked me to act as a guest expert on the topic of urinary tract infections. The episode, which I think is fantastic, can be found here. In preparing for the episode, I ended up reading a lot, learning a lot, and taking relatively extensive notes. Although it doesn’t fit with the usual content of First10EM, I decided to share my notes, as I think some people might find them interesting, and they also provide links to all the literature we mention in the podcast.

Basics

Uncomplicated UTI: Healthy, non-pregnant females with normal urinary tracts. (However, I will note that Dr. Andrew Morris, the ID specialist on the EM Cases episode, doesn’t think this distinction is helpful clinically.) Some sources consider all other UTIs complicated. (Lane 2011) However, other experts are more lax in their definitions. Specifically, well controlled diabetes without urological complications can be considered uncomplicated. (IDSA guidelines Gupta 2011)

Differentiation between upper and lower tract infections is clinical. (Lane 2011)

Risk factors for uncomplicated UTI (Lane 2011)

  • Prior episodes of cystitis
  • Recent sexual activity (odds of a UTI increase by a factor of 60 during the initial 48 hours after sexual intercourse)
  • Use of spermicidal agents during intercourse.

Bacteria

  • E coli is the most common – 75-90%
  • Staph saprophyticus 5-10%, mainly in younger women
  • Klebsiella
  • Proteus
  • Enterococci

In complicated UTIs, there is a higher prevalence of vancomycin-resistant enterococcus (VRE), pseudomonas, and ESBL producing E.Coli, although E.Coli still remains the most likely culprit. (Norris 2008)

Prevention

Increased water intake, direction of wiping, cranberry juice, and voiding post intercourse have not been supported by evidence. (Norris 2008)

Diagnosis

From an evidence based medicine standpoint, the literature on diagnosis of UTI is very difficult to interpret. Because, what is the definition of a UTI? It’s not consistent across studies. There is no clear gold standard. It is often defined based on a culture, although a positive culture has many different definitions as well. Unfortunately, we know that people, especially children and the elderly, can have positive urine cultures without having UTIs. UTIs also occur without a positive culture. So culture both over and under calls UTI and can’t be used as a true gold standard. Similarly, the clinical signs and symptoms of UTI overlap with multiple other conditions, so a clinical diagnosis is difficult. Finally, you can’t use resolution with treatment as a diagnosis because UTIs are often self resolving as are other diagnoses on the differential.

The bottom line is that trying to stay strictly evidence based here is difficult. That matters when trying to interpret likelihood ratios, but it probably matters less clinically, as I will discuss in the summary.

History and Physical

Self diagnosis is pretty accurate. If a woman has had a previous UTI and now has similar symptoms, that has a positive LR of 4.0 and is about 90% accurate for UTI. (Lane 2011; Bent 2002) A women telling you that she has a UTI is just as accurate as a positive dipstick (both with positive likelihood ratios of 4). (Aubin 2007) It’s not clear if these two pieces of information are additive, but there is reason to think they wouldn’t be: women without typical symptoms such as dysuria are likely the same group of women who present without pyuria.

No single sign or symptoms is diagnostic of UTI. (Aubin 2007)

The most important piece of diagnostic information in young healthy females is the presence or absence of vaginal symptoms. With just dysuria and frequency, the chance of a UTI is about 50%. However, if you add the absence of symptoms suggesting vaginitis or cervicitis (vaginal irritation, bleeding, and discharge) the likelihood increases to over 90%. (Lane 2011) The combination of dysuria, frequency AND no vaginal discharge or irritation has a positive likelihood ratio of 24.6! (Bent 2002) That being said, the presence of vaginal symptoms does not rule out UTI, as a positive culture is reported in up to 30% of women with vaginitis symptoms. (Lane 2011)

Of course, we all know to ask about fever, nausea, vomiting, and back pain when considering pyelonephritis. However, we sometimes get confused when the patient has bilateral back pain. Up to 25% of patients have bilateral pyelonephritis, so their pain will not be unilateral. (Lane 2011)

Some sources claim that up to 33% of pyelonephritis will present without fever in the elderly. (Norris 2008) This may be a reason for more aggressive treatment of UTI symptoms in the elderly. On the other hand, it might just be the result of a faulty gold standard for pyelonephritis.

In terms of physical exam, it is generally recommended to perform a digital rectal exam in all men with symptoms of cystitis, to assess for prostatitis. (Norris 2008) However, it is not clear to me how accurate this physical exam maneuver is. Another suggestion I have heard is to just empirically treat all men with cystitis as if they have prostatitis.

Visual clarity or cloudy urine cannot be used to rule out or rule in the diagnosis, although the specificity isn’t too bad compared to everything else we use: The sensitivity, specificity, and positive and negative predictive values were 13.3%, 96.5%, 40.0%, and 86.3%, respectively. (Schulz 2016)

null

Other symptoms to consider

New or increased incontinence in older women.

Delerium, malaise, sepsis: these are difficult, because UTI can probably cause these, but the more common mistake is to blame the delirium on a UTI, when in fact there is something else going on.

Differential diagnosis

Lower tract symptoms (Norris 2008)

  • Vaginitis – bacterial, trichomoniasis, candidiasis
  • Cervicitis/urethritis – gonorrhea and chlamydia
  • Nephrolithiasis

Upper tract symptoms (fever, chills, nausea, vomiting, flank pain) (Norris 2008; Aubin 2009)

  • Appendicitis
  • Diverticulitis
  • Cholecystitis
  • Pancreatitis
  • Perforated viscus
  • Prostatitis
  • Pelvic inflammatory disease
  • Tubo-ovarian abscess
  • Ovarian/ testicular torsion
  • Ectopic pregnancy
  • Nephrolithiasis
  • Lower lobe pneumonia
  • Pulmonary embolism

Testing

The most important and most often overlooked point about testing in UTI is that in most cases testing is not required. There is reasonable evidence from the primary care world that telephone consultation for diagnosis and treatment of simple UTI is safe and effective. (Aubin 2009) Of course, we always need to be careful of spectrum bias when considering primary care literature in the ED. Our patients might be sicker, but most of the patients I see for simple UTI aren’t in the ED because they are too sick to go their family doctor. They are in the ED simply because they couldn’t get a timely appointment with their family doctor. So I think this primary care approach applies to many of the patients we see as well, but like always, you have to use your judgement.

Although midstream clean catch urine samples are considered the gold standard, there are multiple studies that indicate no difference between the midstream clean catch sample and routine collection without cleaning at any time during voiding. (Lifshitz 2000; Leisure 1993; Immergut 1981)

If you are going to test, test promptly. Urine specimens allowed to sit for longer than 2 hours are markedly unreliable because of alkalinization, destruction of cells, and multiplication of bacteria. (Rabinovitch 2001)

Urine dipstick

As compared to history and physical alone, it’s not clear that urine dipstick can mathematically improve diagnosis. The problem is lack of specificity if you are only looking for one item to be positive, and lack of sensitivity if you are looking for both leucocyte esterase and nitrites to be positive.

There are a range of numbers available. Looking a leucocyte esterase alone, a 3+ reading is reported to have a sensitivity of 80.4% and a specificity 82.8%. (Middelkoop 2016) Norris reports the specificity at 54%. (Norris 2008) Nitrites alone are reported as having a sensitivity between 32 and 81% and a specificity between 83 and 94%. (Middelkoop 2016; Norris 2008)

Combining the two so that either leukocyte esterase or nitrite being positive is considered a positive test results in a sensitivity between 75 and 94% and a specificity of 82%. (Norris 2008; Lane 2011) Requiring both leukocyte esterase and nitrite to be positive results in a 50% sensitivity but a close to 100% specificity.

Just a quick glance at this numbers tells us that no combination is great. If we rely on both nitrite and leukocyte esterase being positive, we overtreat 47% of the time and undertreat 13%. (Norris 2008) Negative nitrite and negative leukocyte esterase has a negative predictive value of 88%. (Schulz 2016) In other words, if those criteria are used, we will miss 12% of UTIs.

A quick note about nitrites: they are not produced by S saprophyticus, Pseudomonas, or enterococci. (Lane 2011) Even if we developed a better test – super sensitive nitrites – the nitrite test cannot possibly get to 100% sensitivity, because not all bacteria produce them. They are really a test for E coli, which is the most common cause of UTI, but you will miss infections caused by any of the other species. (Norris 2008)

False negative nitrites: (Norris 2008)

  • Inadequate dietary nitrates can reduce substrates.
  • Vitamin C can prevent the proper chemical reaction to cause dipstick positivity.
  • An old dipstick exposed to air may not properly undergo color change.
  • Unusually high urine urobilinogen or low urine pH (!6.0)
  • Urinary frequency may not allow enough time for conversion from nitrate to nitrite.

The bottom line here is that the urine dipstick has extremely limited value in the diagnosis of UTI. The biggest mistake is taking the urine dip at face value. The problem is the lack of specificity. Many other conditions, often more serious than UTI, can cause pyuria. You can’t just blame pyuria on UTI without a thorough examination. You need to make a clinical diagnosis, and ensure you have excluded other causes of pelvic inflammation like appendicitis, diverticulitis and PID.

Urine Microscopy

Although using laboratory microscopy improves the numbers a little, the conclusions are still the same. Using more than 3 WBCs per HPF and more than 5 RBCs per HPF as cutoffs, the overtreatment rate is 44% and undertreatment rate is 11%. (Norris 2008)

If you are using microscopy, the best accuracy is seen if there are fewer than 5 epithelial cells per HPF. (Schulz 2016) You can see false positives (elevated WBCs at 6-10/HPF) with oliguria and dehydration. (Schulz 2016)

Urine Gram stain

When comparing the gram stain to the ultimate culture, you get:

  • Sensitivity: 96.2% (Norris 2008)
  • Specificity: 93.0% (Norris 2008)

Out of all the tests, this one actually looks the best, but in most institutions gram stains aren’t easy to get. Also, the reported sensitivity and specificity are only for a positive culture (which is not the same thing as a UTI) and don’t account for asymptomatic bacteriuria and culture negative UTIs.

Cultures

Contrary to my experience in practice, there is general consensus that urine cultures are not required in uncomplicated UTIs. (Lane 2011; Norris 2008; BC Guidelines 2009; National Institute for Health and Care Excellence 2015)

I’ll emphasize that:

Clearly, not every patient needs a urine culture in the workup of UTI. In young women with uncomplicated cystitis, it is not generally indicated to perform a urine culture.” (Norris 2008)

In uncomplicated community-acquired UTI, culture is rarely required when antibiotics are being prescribed.” (BC Guidelines 2009)

Urine cultures have never been shown to help clinically important outcomes. However, there is an argument that they might decrease the need for follow up visits (a somewhat questionable benefit) if we can find the resistant strains and change the antibiotics over the phone. It’s not clear this works. Johnson (2011) performed a retrospective study looking at 779 females diagnosed with cystitis at a family medicine clinic. The follow-up rate was 8.7% with culture and and 8.4% without (not statistically significant, adjusted OR 1.11, 95% CI 0.65-1.90). On the other hand, McNulty (2006) performed a prospective cohort of 497 women with uncomplicated UTI and calculated a number needed to test of 23 to prevent one follow up consultation. The cost of 23 cultures to prevent one office visit probably outweighs the benefit. I think this all indicates that cultures should not be routinely performed in uncomplicated cystitis.

So when might a culture be helpful? NICE recommends culture if the UTI is not responding to initial antibiotics treatment. (National Institute for Health and Care Excellence 2015) The culture also has a role in complicated UTIs, recurrent UTIs, and pyelonephritis (Lane 2011; Norris 2008) but it still probably isn’t needed in all cases. The IDSA recommends a C+S in pyelonephritis, but not simple cystitis. (IDSA guidelines Gupta 2011)

Note: Some labs will only do a culture is the dipstick is positive. However, some patients, such as neutropenic patients, might not develop white cells in their urine. If you have a complicated patient who you think needs a culture despite a negative urine, it might be a good idea to speak to the lab, depending on your system. (Schulz 2016)

There is not a clear definition of a positive culture.

  • The traditional definition is 10^5 colony forming units per mL of a urinary pathogen
  • However, it has been shown that many women with UTI symptoms have only 100, or 10^2 CFUs per mL (Lane 2011)
  • If there is more than one type of bacteria present, you should probably use the higher cut-off
  • Suprapubic aspirates can be considered positive if there is any degree of bacteriuria

A urine culture is just not a good enough test. Even in a perfect, catheter sample, there will always be about a 5% false positive rate because of asymptomatic bacteriuria. The false negative rate is even worse – maybe 25% of UTIs will have a negative culture. (Middelkoop 2016)

Diagnosis in the chronically catheterized patient

Laboratory tests are particularly useless in chronically catheterized patients. 98% chronically catheterized patients have bacteriuria at all times. (Schulz 2016) There is no relationship between the level of pyuria and infection in people with indwelling catheters (the presence of the catheter invariably induces pyuria without the presence of infection). (National Institute for Health and Care Excellence 2015) Therefore, NICE recommends “healthcare professionals do not use dipstick testing to diagnose urinary tract infections in adults with urinary catheters. (NICE 2015) Therefore, these patients should be treated on the basis of symptoms, not urine dip or culture findings alone. (Schulz 2016) (This is actually no different than non-catheterized patients.)

Imaging

In general, imaging is unnecessary in the diagnosis of urinary tract infection, whether upper, lower, complicated or uncomplicated. Patients with signs or symptoms of renal colic need imaging to rule out an infected stone. Likewise, any patient with signs of shock from a presumed urinary sources need emergent imaging to rule out an infected kidney stone. Pyelonephritis with no response within 48-72 hours needs imaging to rule out perinephric abscess. Otherwise, the role of imaging in urinary tract infection is limited to the workup of alternative diagnoses, if relevant based on the history and physical.

Asymptomatic bacteriuria

Asymptomatic bacteriuria is very common. It should not be treated. (National Institute for Health and Care Excellence 2015) Although we generally talk about asymptomatic bacteriuria in the elderly and in children, it is even present in 1-8% of healthy young women. (Norris 2008)

null
From Nicolle 2005

Pyuria is NOT an indication for treatment of asymptomatic bacteriuria. (IDSA guidelines Nicolle 2005) There have been a number of trials and although women with asymptomatic bacteriuria are more likely to go on to have symptomatic UTIs than those without (there are some problems with gold standard in those trials), asymptomatic bacteriuria is not associated with long-term adverse outcomes, such as hypertension, chronic kidney disease, genitourinary cancer, or decreased duration of survival. Furthermore, treatment with antibiotics does not decrease the rate of symptomatic UTI in placebo controlled trials. (IDSA guidelines Nicolle 2005)

The only groups that we should be treating are:

  • Pregnant patients (leads to premature labour, hypertension, and low birth weight) (Norris 2008; Nicolle 2005)
    • RCTs show decreased pyelonephritis and probably decreased low birth weight and preterm delivery with treatment (IDSA guidelines Nicolle 2005)
  • Prior to any urologic procedure in the OR (Lane 2011) or that will produce bleeding (Nicolle 2005)
  • Recommended treatment: nitrofurantoin 100mg po bid for 3 days or cephalexin 500mg po QID

Treatment

Cranberry juice

Despite their popularity, cranberry products do not prevent UTIs. (Cayley 2013) The same is probably true of cranberry products for treatment of UTIs, but the most recent Cochrane review found no quality studies to answer the question. (Jepson 2010)

Antibiotics

No treatment

When discussing antibiotic treatment of cystitis, it is important to keep in mind that the majority of these infections are self resolving. There is a paper in the BMJ in 2015 that compared ibuprofen to antibiotics (fosfomycin) in women with proven UTI. Although the antibiotic group did a little better, 70% of the women in the ibuprofen group was completely symptom free at 3 days. (Gagyor 2015) Christiaens (2002) compared nitrofurantoin against placebo and the clinical cure rate was 88% versus 55%. So more than half of UTIs were cured (early) with placebo. (Christiaens 2002)

So although I think we should definitely be treating women with UTIs, this tells us a lot about our management. Cultures mostly can’t help because 55-70% clear even without antibiotics. And we don’t have to get to fancy with our antibiotic choice, because again, even if we guess wrong, most women will be cured at 3 days.

The IDSA tells us we need to be careful about the harms of our treatment because, for uncomplicated cystitis, there is minimal risk of progression to tissue invasion or sepsis and clinical cure can be achieved in a large number of women with placebo or with antibiotics without in vitro activity against the uropathogen. (IDSA guidelines Gupta 2011) This “spontaneous resolution may attenuate differences in clinical outcomes when a drug with 80% efficacy is compared with one with 95% efficacy.” (IDSA guidelines Gupta 2011) These limited benefits of antibiotics have to be balanced against the harms.

Finally, we have to remember the inaccuracy of our tests when prescribing antibiotics. Are we really treating a UTI? The CDC has reported that 40% of all antibiotics prescribed for presumed UTI could have been avoided. (Schulz 2016)

Antibiogram

The best choice of antibiotics will almost always be based on your local antibiogram. That being said, you have to remember that antibiograms are biased. They are heavily focused on inpatient infections, so they may misrepresent the degree of resistance in the community. (Many women with simple cystitis never have a culture done, nor should they, but that means that simple infections aren’t represented in the data.) They also frequently don’t assess outpatient medications, like fosfomycin, so we are left in the dark. (Lane 2011) Finally, I think it’s important to remember the difference between test tube antibiotic resistance and clinical resistance. Well more than half the time that I call people who have infections that are supposedly resistant to the antibiotics that have been prescribed, they are already better by the time the culture is back. There is no need to start a new antibiotic in those patients, assuming there are no complicating factors, like pregnancy.

When interpreting your antibiogram, the IDSA generally recommends avoiding antibiotics with more than 20% resistance for empiric treatment of simple cystitis, but the cut-off is 10% for pyelonephritis. (IDSA guidelines Gupta 2011)

If you don’t know your local resistance patterns, there are individual factors you can consider as well. Use of an antibiotic in the last 3-6 months increases your risk of having an infection resistant to that antibiotic. (IDSA guidelines Gupta 2011)

Remember, the lab doesn’t test all antibiotics. You don’t have to follow the sheet in front of you. I’ve seen a number of healthy women with simple UTIs grow ESBL who have been coming into the department for IV meropenem because that it the only antibiotic that was listed as sensitive. But no one tried fosfomycin first, which our lab doesn’t test for, but which Canadian data indicates is more than 90% effective even in the setting ESBL. (Karlowsky 2014)

Empiric ABX Tx

  • Nitrofurantoin 100 mg BID 7 days (IDSA says 5 days) (IDSA guidelines Gupta 2011)
    • Overall cure rate about 90%
    • Bacteriostatic and requires the 7 day course
  • Trimethoprim sulfamethoxazole 1 DS tab BI for 3 days
    • 95% effective
  • Trimethoprim alone (100mg BID for 3 days) is preferred in some countries (IDSA guidelines Gupta 2011)
  • Fosfomycin 3 grams PO once
    • Equivalent to 7 days of nitrofurantoin and 3 days of TMP-SMX.
    • Also effective against ESBL and VRE

Fluoroquinolones will definitely work, but personally I think they are too valuable for other sick patients to use in this population, so I don’t think they have any role in simple cystitis. In complicated, sick patients, they are a great option, especially for outpatients because of their excellent bioavailability. The IDSA recommends avoids fluoroquinolones because they have more “collateral damage” than other regimens (referring to interfering with normal flora). They should only be used when other agents cannot be. (IDSA guidelines Gupta 2011)

There is some evidence comparing antibiotics against each other in UTI, which form the basis of these recommendations, but we have to be careful about antibiotic studies. In EBM we always ask about external validity. With such a huge variance in antibiotic resistance around the globe, there is good reason to think that results of these studies might be inapplicable at other sites. Knowledge of your own antibiogram probably trumps published studies.

null
From the IDSA guidelines: Gupta 2011

ESBLs

ESBLs, or extended spectrum beta-lactamases, are a growing problem in the management of UTIs. The current approach often sees patients on courses of IV medications like meropenems. For healthy individuals with simple cystitis, there are probably more appropriate options. The most important thing to remember is that your lab does not test for susceptibility to all available antibiotics. The list in front of you does not contain every possible treatment option.

Although local numbers will vary, ESBL producing E. coli are consistently reported to have greater than 90% susceptibility to fosfomycin. (Sultan 2015; Falagas 2010) Nitrofurantoin is also often an option, with greater than 90% susceptibility reported against ESBL E. Coli. (Karlowsky 2014) Amoxicillin-clavulanic acid will also work approximately 60% of the time. (Karlowsky 2014)

We don’t use fosfomycin all that often. As a reminder:

  • Dose: 3 grams PO x1
  • Safe in pregnancy: category B, as good as we get for UTI antibiotics
  • Probably a little more expensive than our usual options (about $50 a dose), but if expense is an issue, the single dose can be given in the ED.

Don’t give an IV dose before discharging

Not only does this not make any sense, there is evidence it is harmful. Haran et al (2014) looked at a prospective cohort of 247 patients, all of whom were being treated with outpatient oral antibiotics. They compared those who received an IV dose in the ED to those who did not. 25.7% of the IV group developed antibiotic associated diarrhea versus 12.3% in the no IV group (a number needed to harm of 7.5). Unnecessary IV antibiotics harm our patients.

Pyelonephritis

Uncomplicated

  • Cipro 500 bid for 7 days
  • Levofloxacin 750 bid for 5 days

2nd line

  • TMP-SMX BID for 14 days
  • Cefpodoxime 400mg BID 10-14 days

Need pseudomonas coverage if septic shock, immunosuppressed, or history of resistant organism. For severe pyelonephritis, ampicillin and gentamicin is generally the recommended regimen.

Most patients with pyelonephritis can be managed as an outpatient. 48 hours is my cutoff for being fever free and clearly better in the patient’s eyes. I ask all patients to follow up at 48 hours, but if they are still febrile and don’t think they have improved at all, I ask them to come back to the ED, because that is probably the right time to get some imaging. At this point, you need imagining to rule out pyonephrosis (septic stone), renal abscess, and emphysematous pyelonephritis.

null
From Norris 2008

Other complicated UTIs

Emphysematous pyelonephritis

  • Necrotizing infection with gas formation in the renal parenchyma
  • Mortality ranging from 20% to 40% even when treated
  • Patients with diabetes represent approximately 95% of reported cases
  • An infected obstructing renal calculus is the major predisposing risk factor
  • Patients are typically very ill appearing, requiring aggressive cardiopulmonary stabilization and early broad-spectrum antibiotic therapy, followed by urologic consultation for either percutaneous drainage or immediate nephrectomy.

Emphysematous cystitis (Ankle 1990)

  • Evidence limited to case reports
  • Middle aged females with diabetes
  • Not systemically Ill
  • The only change is that management is usually IV (although people have been managed with PO, and given the amazing bioavailability of the fluoroquinolones, it’s not clear that IV is needed.)

Treating UTI in delirium

“Elderly patients with acute mental status changes accompanied by bacteriuria and pyuria, without clinical instability or other signs or symptoms of UTI, can reasonably be observed for resolution of confusion for 24–48 h without antibiotics, while searching for other causes of confusion” (Schulz 2016)

When to treat cultures with indwelling foleys

Sorry, there isn’t a simple answer. You have to make a call clinically. The only clear advice is that you cannot base your decision to treat on either urine microscopy or culture. (National Institute for Health and Care Excellence 2015; Schulz 2016)

Candida UTI

Very common in catheterized patients. There is a very low risk of systemic infection or complication. Don’t treat if not symptomatic unless patients is neutropenic. Treatment involves replacement or removal of the catheter. (Schulz 2016)

Symptom therapy

We don’t have it in Canada, but phenazopyridine is used in many places as a urinary anesthetic. The evidence of its effectiveness is not great, and it does have a few significant problems. It causes hemolysis if you have G6PD and it also causes methemoglobinemia, which I believe is the reason it was removed from the market in Canada.

UTIs in Men

The incidence of UTI in males is is less than 1/30th of the incidence in females. (Brusch 2016) In addition to cystitis, pyelonephritis and urethritis, the male specific diagnoses to consider are prostatitis, epididymitis, and orchitis. Bacterial UTI is rare in men under 50 years old (5/year/10,000 population), so based on statistics alone, you should be much more suspicious of sexually transmitted infections in males with UTI symptoms than you are of bacterial cystitis. (Brusch 2016)

If you do diagnosis bacterial cystitis, treatment options include fluoroquinolone, trimethoprim-sulfamethoxazole (TMP-SMZ), minocycline, or nitrofurantoin, all given for 10-14 days. (Brusch 2016) Guidance by a local antibiogram is still essential.

Unfortunately there is very little evidence, but I know a lot of urologists argue that is a man has a UTI, he has prostatitis and deserves longer treatment with an antimicrobial appropriate for prostatitis. NICE recommends that all men with symptoms of an upper UTI should get referred for urological investigation. (National Institute for Health and Care Excellence 2015)

Prostatitis

Acute and chronic prostatitis may be separate pathophysiologies, as acute rarely results in chronic and chronic is rarely preceded by acute. (Brusch 2016) (This is a just a statement made in this paper. I haven’t seen evidence supporting the claim.)

In general, the only work-up required for prostatitis, whether acute or chronic, is a good history and physical exam, plus a urine culture (plus or minus a second culture after prostatic massage). (Sharp 2010) A 2 step pre and post-massage test is as good as the old classic 4 glass test for diagnosis prostatitis. (Sharp 2010) In questionable cases, a semen culture is more accurate than any of the urine cultures. (Sharp 2010)

The bacteria that cause prostatitis are the same that cause cystitis, plus chlamydia and gonorrhea. (Sharp 2010)

Acute bacterial prostatitis

Acute bacterial prostatitis most often presents as a febrile UTI. (Brede 2011) It can also be associated with malaise, myalgias, and pelvic pain. (Brusch 2016)

Every article I came across said that you should not massage the prostate for fear of inducing bacteremia, but not a single one of those statements had a citation, so I have no idea if this is a real thing or just another medical myth. However, prostate exam, revealing tenderness, swelling, and possible warmth, should be performed. (Brusch 2016) Pain and swelling will be present on prostate exam in more that 90% of cases. (Brede 2011) I distinguish acute prostatitis from cystitis based on fever and tenderness of the prostate.

Because chronic complications and treatment failures are common, urine cultures should be routinely performed. Blood cultures only change management in approximately 1% of patients, so should not be performed routinely, but are reasonable in septic patients. (Brede 2011)

Length of treatment is questionable. 2-4 weeks is commonly suggested, but 6 weeks might be better. (Brede 2011; Sharp 2010) First line is generally a fluoroquinolone, but trimethoprim/sulfamethoxazole is also reasonable. (Brede 2011; Sharp 2010) For sick inpatients, ampicillin and gentamicin is the recommended regimen. (Sharp 2010)

Be careful of prostatitis after prostate biopsy. It occurs about 1-2% of the time, but because of prophylactic antibiotics, the fluoroquinolone resistance might be as high as 88%. (Brede 2011)

null

Chronic bacterial prostatitis

By definition, chronic bacterial prostatitis requires symptoms for at least 3 months. (Brusch 2016) The primary complaint is chronic irritative voiding symptoms, but it can be difficult to distinguish from the more common nonbacterial chronic prostatitis. Patients should not look ill and will not be febrile. (Sharp 2010)

Recurrent UTIs in a man? Consider and test for chronic prostatitis. (It is often asymptomatic in between episodes). (Brusch 2016)

First line agents are still fluoroquinolones or trimethoprim/sulfamethoxazole, but second line options include doxycycline and azithromycin. (Sharp 2010)

null

Type 3 prostatitis – chronic pelvic pain syndrome

The symptoms are similar to chronic bacterial prostatitis, but the cultures are negative. (Sharp 2010) The causes aren’t fully known, but include, BPH, cancer, interstitial cystitis, eosinophilic cystitis, and neuropathic pain. (Sharp 2010)

Summary

Because of the issues with the gold standard, trying to stay too evidenced based here can be a disaster. If we are talking healthy, low risk women – forget about the culture. If she tells you she has UTI symptoms, that really all that matters. Ask about sexually transmitted symptoms and vaginal itch or discharge. If those factors are not present, just make the empiric diagnosis of UTI and have a good conversation about follow up.

UTI should be treated based on symptoms. If the symptoms go away, your treatment was successful. If not, that’s the only time to worry about resistance.

UTI is not a diagnosis you need to be 100% sure of. We should be honest with ourselves: when we make the diagnosis, we often think of it as a final diagnosis, but the post test probability of many of the women we see is probably more likely to be 60% or maybe 80%. The antibiotics we use are safe, and the NNT of antibiotics high enough, that we can empirically treat most of these women without any testing. As long as we are not missing a dangerous alternative diagnosis, the benefit-harm ratio will work out in our favour, even if we a wrong about the diagnosis of UTI for some women.

This is similar to what most people do with strep throat (without getting into the weeds of whether we should be treating strep throat at all.) If you have all 5 of the modified Centor criteria for strep throat, most people just go ahead and treat. Actually, most people are treating with less than 5. But what does having 5 centor criteria mean? It means you have a 50% chance of having strep throat. We don’t worry much about that. We should think about most UTIs the same way. They are low risk entities and we just need to be in the ballpark.

Once you have decided to treat, use your antibiogram to guide management, remembering that not all possible antibiotics will be listed. (Remember fosfomycin.) Of the antibiotics with a local susceptibility greater than 80%, choose the option with the fewest side effects and the least likely to cause what the IDSA calls “collateral damage”. You don’t need a culture, but if the patient’s symptoms haven’t resolved in 48 hours they should be reassessed. If UTI is still the most likely diagnosis, in addition to changing the empiric antibiotic, a culture is probably reasonable.

References

Ankel F, Wolfson AB, Stapczynski JS. Emphysematous cystitis: a complication of urinary tract infection occurring predominantly in diabetic women. Annals of emergency medicine. 19(4):404-6. 1990. [pubmed]

Aubin C. Evidence-based emergency medicine/rational clinical examination abstract. Does this woman have an acute uncomplicated urinary tract infection? Annals of emergency medicine. 49(1):106-8. 2007. [pubmed]

BC Guidelines. Guidelines and Protocols Advisory Committee. Macroscopic and Microscopic Urinalysis and the Investigation of Urinary Tract Infections. 2009. www.BCGuidelines.ca

Bent S, Nallamothu BK, Simel DL, Fihn SD, Saint S. Does this woman have an acute uncomplicated urinary tract infection? JAMA. 287(20):2701- 10. 2002. [pubmed]

Brede CM, Shoskes DA. The etiology and management of acute prostatitis. Nat
Rev Urol. 2011 Apr;8(4):207-12. PMID: 21403661

Brusch J. Urinary Tract Infection in Males. Medscape. 2016. [article]

Cayley WE. Are cranberry products effective for the prevention of urinary tract infections? American family physician. 88(11):745-6. 2013. [pubmed]

Christiaens TC, De Meyere M, Verschraegen G, Peersman W, Heytens S, De Maeseneer JM. Randomised controlled trial of nitrofurantoin versus placebo in the treatment of uncomplicated urinary tract infection in adult women. The British journal of general practice. 52(482):729-34. 2002. [pubmed]

Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE. Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum beta-lactamase producing, Enterobacteriaceae infections: a systematic review. The Lancet. Infectious diseases. 10(1):43-50. 2010. [pubmed]

Gágyor I, Bleidorn J, Kochen MM, Schmiemann G, Wegscheider K, Hummers-Pradier E. Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial. BMJ (Clinical research ed.). 351:h6544. 2015. [pubmed]

Gupta K, Hooton TM, Naber KG. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 52(5):e103-20. 2011. [pubmed]

Haran JP, Hayward G, Skinner S, et al. Factors influencing the development of antibiotic associated diarrhea in ED patients discharged home: risk of administering IV antibiotics. Am J Emerg Med. 2014;32:(10)1195-9. PMID:25149599

Immergut MA, Gilbert EC, Frensilli FJ, Goble M. The myth of the clean catch urine specimen. Urology. 17(4):339-40. 1981. [pubmed]

Jepson RG, Mihaljevic L, Craig J. Cranberries for treating urinary tract infections. The Cochrane database of systematic reviews. 2010. [article]

Johnson JD, O’Mara HM, Durtschi HF, Kopjar B. Do urine cultures for urinary tract infections decrease follow-up visits? Journal of the American Board of Family Medicine : JABFM. 24(6):647-55. 2011. [pubmed]

Karlowsky JA, Denisuik AJ, Lagacé-Wiens PR. In Vitro activity of fosfomycin against Escherichia coli isolated from patients with urinary tract infections in Canada as part of the CANWARD surveillance study. Antimicrobial agents and chemotherapy. 58(2):1252-6. 2014. [pubmed]

Lane DR, Takhar SS. Diagnosis and management of urinary tract infection and pyelonephritis. Emergency medicine clinics of North America. 29(3):539-52. 2011. [pubmed]

Leisure MK, Dudley SM, Donowitz LG. Does a clean-catch urine sample reduce bacterial contamination? The New England journal of medicine. 328(4):289-90. 1993. [pubmed]

Lifshitz E, Kramer L. Outpatient urine culture: does collection technique matter? Archives of internal medicine. 160(16):2537-40. 2000. [pubmed]

McNulty CA, Richards J, Livermore DM. Clinical relevance of laboratory-reported antibiotic resistance in acute uncomplicated urinary tract infection in primary care. The Journal of antimicrobial chemotherapy. 58(5):1000-8. 2006. [pubmed]

Middelkoop SJ, van Pelt LJ, Kampinga GA, Ter Maaten JC, Stegeman CA. Routine tests and automated urinalysis in patients with suspected urinary tract infection at the ED. The American journal of emergency medicine. 34(8):1528-34. 2016. [pubmed]

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE (NICE), 2015. Urinary tract infections in adults. London: NICE.

Nicolle LE, Bradley S, Colgan R. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 40(5):643-54. 2005. [pubmed]

Norris DL, Young JD. Urinary tract infections: diagnosis and management in the emergency department. Emergency medicine clinics of North America. 26(2):413-30, ix. 2008. [pubmed]

Rabinovitch A: Urinalysis and Collection, Transportation and Preservation of Urine Specimens: Approved Guideline. Wayne, Pa: National Committee for Clinical Laboratory Standards, 2001.

Schulz L, Hoffman RJ, Pothof J, Fox B. Top Ten Myths Regarding the Diagnosis and Treatment of Urinary Tract Infections. The Journal of emergency medicine. 51(1):25-30. 2016. [pubmed]

Sharp VJ, Takacs EB, Powell CR. Prostatitis: diagnosis and treatment. Am Fam Physician. 2010 Aug 15;82(4):397-406. PMID: 20704171

Sultan A, Rizvi M, Khan F, Sami H, Shukla I, Khan HM. Increasing antimicrobial resistance among uropathogens: Is fosfomycin the answer? Urology annals. 7(1):26-30. 2015. [pubmed]

Author: Justin Morgenstern

Community emerg doc, FOAM enthusiast, evidence junkie “One special advantage of the skeptical attitude of mind is that a man is never vexed to find that after all he has been in the wrong.” - William Osler

8 thoughts on “UTI: More than you ever wanted to know”

  1. This was a great effort and an excellent read, thank you for publishing this. It has been so difficult to synthesis all of the information on UTIs

    Thank you

    Like

  2. thanks. I wrote a review paper about 15 years ago on the very same subject and then couldn’t be bothered to publish it. Great to see someone else cover it as I think badly done in ED, and elsewhere. Other point I came across was when local resistance rate reaches > 30% to any particular Ab then you should consider removing from first line choice. Caveats are that periodic laboratory reports usually are derived from a different patient population (ie include inpatients) and your points about the difference between clinical cure rate and resistance rate.

    Like

  3. Great summary article, thank you. Of note, phenazo can be compounded by Pharmacy in Canada. Health Canada Pyridium (phenazopyridine HCl) product monograph (no longer available) states indicated in those 18 and older, “for the symptomatic relief of pain, burning, urgency, frequency, and other discomforts resulting from irritation of the mucosa of the lower urinary tract caused by infection, trauma, surgery, endoscopic procedures, or the passage of sounds or catheters. Phenazopyridine is compatible with antimicrobial therapy and can help relieve pain and discomfort during the interval before an antimicrobial therapy controls the infection. Treatment with phenazopyridine should not exceed 2 days because of potential organ damage.”

    Like

Leave a Comment

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s