AHRQ Safety Program for Improving Antibiotic Use

Slide Title and Commentary Slide Number and SlideAsymptomatic Bacteriuria and Urinary Tract InfectionsAcute Care

SAY:

Welcome to the webinar titled, “Asymptomatic Bacteriuria and Urinary Tract Infections”.

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Presenter—Pranita Tamma

SAY:

My name is Pranita Tamma. I am a pediatric infectious diseases physician at Johns Hopkins and I direct the Pediatric Antimicrobial Stewardship Program.

On the screen is contact information for the project. If you have any questions or need to reach me after this webinar, please use this information.

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Asymptomatic Bacteriuria and Urinary Tract Infections

Acute Care

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Objectives:

SAY:

By the end of this webinar you will be able to:• Distinguish between asymptomatic bacteriuria

(ASB) and urinary tract infection (UTI)• Recognize that, based on data, the treatment of

ASB is not beneficial in most patients• Discuss management of asymptomatic

candiduria• Develop empiric treatment recommendations

for UTIs that are institution specific and minimize adverse events

• Discuss opportunities for de-escalation of antibiotic therapy for UTIs

• Discuss reasonable durations of antibiotic therapy for UTIs

• Discuss stewardship approaches to improve management of ASB and UTI

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Asymptomatic Bacteriuria and Pyuria

SAY:

When considering ASB in the context of the four moments of AS, management of ASB largely falls under just the first moment: does my patient have an infection that requires antibiotics? By definition, ASB is not an infection. In the rare cases where treatment is recommended—pregnant women and patients about to undergo a urological procedure involving the mucosa—the prescription of antibiotic should be considered prophylaxis against subsequent infection, rather than treatment of infection.

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Asymptomatic Bacteriuria

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ASB is defined as the isolation of significant colony counts of bacteria in the urine from a person without symptoms of a urinary tract infection.

Common symptoms of cystitis are dysuria, frequency, urgency and suprapubic pain.

Common symptoms of pyelonephritis are fever and flank pain.

Common symptoms of catheter-associated UTI are fever and suprapubic tenderness, although many patients in the hospital have a catheter and fever and most do not have a CAUTI. In addition, a severe CAUTI can lead to pyelonephritis and patients will then have symptoms of pyelonephritis.

Note that mental status changes alone in the absence of other evidence of UTI do not indicate a UTI. Foul smelling or cloudy urine do not indicate a UTI.

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Asymptomatic Bacteriuria:

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ASB is common.

This table shows the prevalence of ASB in certain populations. ASB increases with age, particularly in women with almost half of women older than 90 having ASB in some studies. It is also common in nursing home residents and people with diabetes or on hemodialysis. Many of these patients have impairing urinary voiding. The vast majority of persons with indwelling urinary catheters will grow bacteria in urine cultures because of colonization of biofilm on the catheter.

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Asymptomatic Pyuria:

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Pyuria is common in patients with asymptomatic bacteriuria. The table shows the prevalence of pyuria in patient populations with ASB. The presence of pyuria is not enough to diagnose a UTI and is not an indication for antibiotic therapy. If you do have a patient with pyuria, you should consider whether the patient might have a sexually transmitted infection or interstitial nephritis.

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Treatment of ASB is not Beneficial

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Randomized controlled trials have been performed in many populations to assess whether there is any benefit to treating ASB. Treatment did not decrease the risk of subsequent UTI in healthy women, diabetic women, patients with long term indwelling urinary catheters, older women in the community, elderly nursing home residents, or renal transplant patients. Treatment did not prevent subsequent joint infection in patients undergoing orthopedic surgery.

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Treatment of ASB May Cause Harm

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Treatment of ASB is associated with adverse events related to antibiotics and development of resistant organisms causing future UTI. In addition, a recent study suggested that in healthy women treatment of ASB increased the risk of a subsequent symptomatic UTI.

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Mental Status Changes, ASB, and UTI

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Bacteriuria and delirium are both common in older people; thus, it can be difficult to understand the causal relationship between these two conditions. While a UTI diagnosed based on traditional symptoms that we discussed earlier may also be associated with delirium, there is no evidence that delirium, falls, or confusion are symptoms of a UTI in the absence of development of urinary symptoms. In a study in which 72 elderly residents without traditional UTI symptoms with and without bacteriuria were evaluated, no differences in insomnia, malaise, fatigue, or anorexia was noted between the two groups. This suggests that asymptomatic bacteriuria is not associated with delirium.

It is important to remember that if a patient has symptoms suggestive of systemic infection, antibiotics need to be considered whether or not there is localization to the urinary tract.

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When is Screening/Treating For ASB Indicated?

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Guidelines recommend screening for and treating ASB in two specific situations—

Pregnant women in early pregnancy and individuals about to undergo a urologic procedure in which mucosal bleeding is expected.

Asymptomatic bacteriuria in early pregnancy confers a 20-30 fold increase risk for development of pyelonephritis during the pregnancy compared to women without bacteriuria. It is also associated with pre-term labor and low birth weight. The optimal duration has not been yet determined, although guidelines suggest 3-7 days. No recommendations can be made for or against routine screening of culture negative women in the later phase of pregnancy.

ASB has been associated with urosepsis with the same organism in patients undergoing urologic procedures involving mucosal bleeding. Of note, this does not include placement or removal of a urinary catheter.

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Can I Follow the Same Rules for Candiduria?

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10% of urine cultures in hospitalized patients grow Candida. Asymptomatic candiduria also does not require therapy. During a multicenter placebo controlled trial of fluconazole in patients with candiduriai, half of the patients with indwelling catheters that were required to be removed had persistent candiduria after removal. The study showed that fluconazole eradicated candiduria in 2/3 of patients. However, 1/3 of patients cleared the candiuria without therapy, and 2/3 of patients in both groups had recurrence of candiuria two weeks after fluconazole was stopped.

No patient developed pyelonephritis or candidemia in either group.

Thus, treatment of asymptomatic or mildly symptomatic candida in urine cultures appears to have no clinical benefit.

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Urinary Tract Infections

SAY:

In this discussion of asymptomatic bacteriuria, we’ve discussed the critical distinction between ASB, which is not an infection as it is not associated with signs and symptoms of infection, and urinary tract infections, which are associated with signs and symptoms that are different based on the location of the infection in the urinary tract. Common symptoms of cystitis are dysuria, frequency, urgency and suprapubic pain. Common symptoms of pyelonephritis are fever and flank pain. Common symptoms of catheter-associated UTI are fever and suprapubic tenderness, or these plus flank pain if the infection has ascended to involve the kidneys.

The rest of this presentation will focus on moments 2, 3, and 4.

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Moment 2: Urinalysis and Cultures

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In contrast to diagnosing uncomplicated cystitis in women in the community, the diagnostic work up for hospitalized patients suspected to have UTI should include a urinalysis and urine culture.

Remember, urine cultures should be sent when a patient has signs and symptoms of UTI, so the following situations are not indications for sending a urine culture: foul-smelling or cloudy urine, routinely on admission or pre-op, routinely before or after a catheter change, as part of a fever work up if there are no signs or symptoms localizing to the urinary tract, or as a test of cure for UTI.

It is important to optimize the collection of urine cultures to optimize their clinical utility. They should be collected using the clean catch approach or straight catheterization if clean catch is not possible. Standard guidance should be followed in patients with urinary catheters, and urinary catheters should optimally be changed before cultures are sent in patients with chronic indwelling catheters.

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Moment 2: Urinalysis and Cultures

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Let’s think about how to interpret your appropriately ordered and collected urine tests. The number of WBC that is considered abnormal in reports is based on the machine that is reporting the results and may vary from site to site because of this. However, a general cutoff for a positive UA is greater than 10 WBC per high power field or hpf. Thus, in a patient with fewer WBC than 10 per hpf, there is minimal or no inflammation, making the diagnosis of UTI unlikely.

Leukocyte esterase is also often reported and indicates the presence of WBCs. If the WBC is low, leukocyte esterase can still be detected even though it may not be clinically significant. Nitrites indicate the presence of bacteria in the urine—this result should not be used alone to determine whether there is a UTI.

By current definitions, a positive urine culture is considered to be growth of ≥ 10,000 CFU/mL of a urinary pathogen. Lower cutoffs may be considered if the patient had received antibiotic before the culture was sent, if there is strong clinical suspicion of UTI, or if the culture is from a supra-pubic catheter. However, keep in mind that some laboratories do not have the capability to detect <10,000 CF/mL.

Most patients with UTI do not need blood cultures, although it is reasonable to obtain them in patients with pyelonephritis admitted to the hospital or if urosepsis is suspected.

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Uncomplicated Cystitis

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Uncomplicated cystitis is cystitis in a woman in the absence of urinary tract abnormalities. Oral therapy is preferred for empiric therapy, and you should avoid giving IV therapy just because the patient is in the hospital.

Fluoroquinolones are not considered first line therapy for uncomplicated cystitis because of both increasing E. coli resistance and their side effects that include tendinitis and C. difficile infection. They can also cause changes in mental status in older persons.

First line treatment recommendations include nitrofurantoin, ideally in a twice daily formulation, and trimethoprim/sulfamethoxazole, often referred to as trim/sulfaor TMP/SMX. It is important to know local resistance patterns for both of these agents before using them given increasing resistance particularly with TMP/SMX.

For patients unable to take these agents, oral cephalosporins can also be used. Fosfomycin is also studied for uncomplicated cystitis, but is expensive. When making empiric treatment decisions, remember to look at prior urine culture information as previous susceptibility patterns may help guide antibiotic choice.

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Uncomplicated Cystitis

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The de-escalation and IV to PO conversion components of Moment 3 in management of uncomplicated cystitis are hopefully uncommon as most patients will be treated with relatively narrow spectrum oral agents.

However, it is important to re-examine the diagnosis of cystitis daily and if an alternative diagnosis is found, stop antibiotics.

Moment 4, optimal duration, should also be straightforward for uncomplicated cystitis. The table shows both first line agents (in bold) and second line agents and the recommended durations of therapy based on clinical trials of these agents. Note that most of the cephalosporins were studies for 5 day courses except cefpodoxime (3 days) and cephalexin (7 days).

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UTI in Men

SAY:

UTIs in men traditionally are considered complicated because they are usually associated with obstructive pathology such as renal stones, strictures, or enlarged prostate. In the absence of these risk factors, UTI is a rare diagnosis in men, and you should critically evaluate this diagnosis, particularly if it is being driven by a positive urine culture and non-specific symptoms.

Other causes of urinary symptoms in men to consider include prostatitis, epididymitis, and sexually transmitted infections.

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Pyelonephritis

SAY:

The next few slides primarily refer to uncomplicated pyelonephritis in women. As previously noted, men with UTI often have additional contributing pathology that should be assessed for and may require longer durations of antibiotic therapy.

Empiric therapy for uncomplicated pyelonephritis in women has become more challenging because of emerging E. coli resistance.

Fluoroquinolones or trim/sulfa are preferred given excellent penetration into kidney. In addition, they can be given orally given excellent bioavailability. However, you must consider local E. coli resistance data as these agents cannot be recommended for empiric therapy if resistance is seen in a large proportion of isolates—some have proposed a cut off of greater than 20% of isolates.

Options when this is the case include third generation cephalosporins such as ceftriaxone. For patients with severe PCN allergy, aztreonam or gentamicin can be used.

In a patient with a history of colonization or infection with an ESBL-producing organism, ertapenem can be considered.

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Pyelonephritis

SAY:

For Moment 3 of pyelonephritis management, if the isolated organism is susceptible to fluoroquinolones or trim/sulfa, continuation of or conversion to these agents is reasonable. If neither can be used because of resistance, then consider converting to an oral cephalosporin once the patient has improved.

Duration of therapy depends on the agent used. In women, seven days of a fluoroquinolone has been shown to be equivalent to longer courses (5 days has been shown to be effective for levofloxacin).

Most patients can also receive 7 days of trim/sulfa, although a 10 day course could be considered in patient who was slow to respond. There is less clinical data with oral cephalosporins in treatment of pyelonephritis, but if you must use them because of resistance, a longer course of 10-14 days should be considered based on clinical response and duration of preceding IV therapy (longer IV therapy likely allows for a shorter PO course).

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Catheter-Associated UTI Slide 21

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SAY:

For patients with catheter-associated UTI, or CAUTI, you can take the same general approach when interpreting urine results as with non-CAUTI with a few caveats.

First, for patients with chronic catheters, the catheter should be removed before urine cultures are obtained. If this is not done, results are likely to show polymicrobial growth because of colonizing bacteria in the biofilm around the catheter. Thus, determining the causative organisms will be potentially challenging.

Second, patients with catheters often have pyuria in the absence of CA-UTI because of local inflammation of the bladder from the catheter.

Third, a positive urine culture is considered ≥ 1000 CFU/mL of a urinary pathogen.

All patients with CAUTI should have their catheters removed whenever possible. Empiric therapy for CAUTI depends on how ill the patient appears and where you think the infection is—bladder vs. upper tract.

A patient that is not ill, has no evidence of upper tract disease and has resumption of normal urine flow after the catheter is removed may do fine with just removal of the catheter. If antibiotics are given, narrower spectrum agents that do not have pseudomonas activity could be considered for lower-tract infection. Most would recommend an agent with pseudomonas activity for an ill patient or one in whom pyelonephritis is suspected.

Catheter-Associated UTI Slide 22

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SAY:

If the isolated organism is susceptible to fluoroquinolones or trim/sulfa, continuation of or conversion to these agents is reasonable. If neither can be used because of resistance, then consider converting to an oral cephalosporin once the patient has improved.

Duration of therapy depends on the clinical scenario. If the catheter is removed in a female patient, ≤ 65 years, and no upper tract disease is present, 3 days of therapy has been shown to be effective.

For other patients, if there is prompt resolution of symptoms, the catheter is removed and there is no residual obstruction of urine flow, 7 days of therapy will likely suffice. If there is delayed response or persistent obstruction, a 10-14 day course may be required.

Stewardship for ASB and UTI

SAY:

Prevention of treatment of ASB and optimal management of UTI can be addressed through stewardship, particularly around urine cultures.

Interventions may include not sending cultures in the absence of symptoms, developing strategies for re-evaluation of a patient when urine cultures return positive but it is not certain how to interpret them, and providing guidance on the approach to treatment of true UTIs.

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Urine Culture Ordering Stewardship Slide 24

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SAY:

Both front-line providers and stewardship teams should consider strategies to reduce ordering urine cultures that are not needed. As we have discussed, front-line providers should not order urine cultures in the absence of signs and symptoms of UTI, including in patients undergoing pre-operative evaluation or patients with urinary catheters.

ASPs can consider several approaches to reduce the sending of urine cultures. It can be helpful to identify prescribers or services that send many urine cultures and then determine why they are being sent. For example if many urine cultures are sent as part of pre-op testing that is not guideline-based, a meeting can be convened with the relevant surgeons to discuss revisiting this approach and determining strategies for dissemination of new recommendations not to send pre-op cultures.

ASPs can also consider working with the clinical lab to set up reflex testing protocols where urine cultures are only performed if certain parameters on the UA are met such as increased WBCs.

Also, ASPs can consider working with IT to develop prompts in the EHR that require documentation of an indication for urine cultures.

Positive Urine Culture Stewardship Slide 25

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SAY:

Both front-line providers and stewardship teams should consider strategies to optimize management of positive urine cultures.

Front-line providers should make a habit of asking patients if they have urinary symptoms before initiating antibiotic therapy for positive urine cultures. They should work with colleagues to improve communication about why a urine culture was sent through documentation in the medical record or during hand-offs.

It may also be useful to determine if a urine culture was sent using a proper collection technique if there is doubt about whether it represents a real infection.

ASPs should ensure that UTI guidelines emphasize non-treatment of ASB. They can consider reviewing all positive urine culture and providing feedback to prescribers in areas that have high rates of ASB. They can also work with the microbiology lab to operationalize approaches that limit reporting results of urine cultures unless they are requested by a treating clinician.

Modifying Urine Culture Reporting Slide 26

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SAY:

This slide describes an interesting approach to prevent unnecessary treatment of positive urine cultures that likely did not represent a true UTI.

In a 16-week quasi-experimental study on medical and surgical wards, urine cultures were processed per usual routine but not automatically reported. Instead providers saw the following statement in the EHR:

“The majority of positive urine cultures from inpatients without an indwelling urinary catheter represent asymptomatic bacteriuria. If you strongly suspect that your patient has developed a urinary tract infection, please call the microbiology laboratory.”

Only 14% of patient’s results led to phone calls to the microbiology laboratory, leading to a 36% reduction in treatment of ASB. In addition, no clinical signs of UTI at 72 hours were seen in non-treated patients.

Only 4 urinary tract infections occurred in non-catheterized patients and in each of these cases, clinicians had empirically started therapy with the presumption that clinically significant symptoms of UTI were present.

Larger studies are needed to confirm safe implementation of this approach.

In this study the ASP monitored all results but that would not be practical if this was routine practice.

This approach, adapted from behavioral economics concepts, advocates the selective use of, “asymmetric paternalism to improve health behaviors.” Asymmetric paternalism is a policy approach that attempts to help individuals achieve their own goals, especially when individuals are prone to decisional biases and errors, without actually limiting choices or freedoms. The most common strategy consists of reframing the description of choices to bias decision making in favor of more beneficial option.

Take Home Messages Slide 27

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SAY:

Here are the take home messages we want you to remember:

Send urine cultures only when you suspect UTI based on clinical symptoms

Asymptomatic bacteriuria is common particularly in older people and should not be treated in the vast majority of patients

Uncomplicated cystitis should be treated with a short course of an oral antibiotic

UTIs in men are rare in the absence of urinary tract pathology

Seven day courses of therapy work for uncomplicated pyelonephritis if you can use a fluoroquinolone or TMP/SMX, but increasing rates of E. coli that are resistant to these agents is of concern in many parts of the US

There are many opportunities for stewardship in improving when urine cultures are sent, non-treatment of ASB, and optimization of UTI therapy

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SAY:

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Questions

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At this point, does anyone have any questions about content we just discussed? You can type in your questions or speak up on the conference line.

Disclaimer

SAY

• The findings and recommendations in this webinar are those of the authors, who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

• Any practice described in this webinar must be applied by health care practitioners in accordance with professional judgment and standards of care in regard to the unique circumstances that may apply in each situation they encounter.

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Next Steps

SAY:

Your next webinar is on Team Approach to Stewardship of Community-Acquired Lower Respiratory Tract Conditions. Contact us at antibioticsafety@norc.org between now and your next call if you have any questions or concerns.

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References Slide 32

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References Slide 35

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