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Prospective cohort studies and randomised controlled trials (RCTs) have shown a lack of benefit in treating ASB in non-pregnant populations in terms of morbidity,9 10 mortality,10 18 or quality of life.19 RCTs consistently show that antimicrobial treatment in a patient without clear signs or symptoms of a UTI does not improve the risk of progression to a symptomatic UTI or sepsis.7 10 11 Recurrence rates of ASB are high, and sustained sterilisation of the urine is seldom achieved, as shown in cohort studies and randomised trials.8 9 10 In people with delirium who have no systemic symptoms of sepsis or localising urinary signs or symptoms, antibiotic therapy for ASB does not appear to lead to improved resolution of mental status.20 21 22 23 Two recent North American cohort studies of people with delirium and ASB admitted to hospital found that the functional outcome of those who received antibiotics was not statistically different by day 7 based on the brief confusion assessment method, nor up to two months in terms of risk of death, need for ongoing institutional care, or functional status based the Older Americans Resources and Services questionnaire.20 21

the functional outcome of those who received antibiotics was not statistically different by day 7 based on the brief confusion assessment method, nor up to two months in terms of risk of death, need for ongoing institutional care, or functional status based the Older Americans Resources and Services questionnaire.20 21 Adverse reactions to antibiotics are common, and range from minor rashes and oral or vaginal candidiasis to more severe complications such as severe allergy, acute kidney injury, or drug-drug interactions.9 10 24 One particular complication of antibiotics is infection with Clostridiodes difficile, which can be a life threatening complication in residents of long term care. A retrospective cohort study of residents in two US care homes found that those who received antibiotics for ASB had a 8.5 times higher risk of developing C difficile infection.25 At the facility level, a population based study in Canada found that differences in rates of C difficile infection were explained by the variability in rate of institutional urine culture ordering.26 These data reaffirm that unnecessary urine cultures are the primary drivers of unnecessary antibiotic use and their associated adverse outcomes. Another example is the selection of increasingly antibiotic resistant urinary organisms, which results in fewer therapeutic options, and often with intravenous administration or increased risk of toxicity.10 27

y urine cultures are the primary drivers of unnecessary antibiotic use and their associated adverse outcomes. Another example is the selection of increasingly antibiotic resistant urinary organisms, which results in fewer therapeutic options, and often with intravenous administration or increased risk of toxicity.10 27 An under-appreciated aspect of ASB is that these bacteria that are not causing local infection are part of the normal urinary microbiome that is protective against ascending infection.27 28 Thus, antibiotics aimed at erring on the side of caution to prevent or avoid missing a UTI may do the exact opposite, by increasing UTI risk. An RCT of younger women with a known history of recurrent cystitis in Italy found up to threefold increased risk of symptomatic UTI among those systematically screened and treated for ASB compared with those treated based on symptoms.27 Antibiotics beget more antibiotics, and some patients will enter a cycle of recurrent episodes of ASB, UTI, or both, leading to additional antibiotic related harms. A final harm of treatment of ASB is the premature closure bias that may occur in concluding the presence of UTI, without searching for the true cause of the non-urinary condition or change in a resident’s clinical status.23 29

Requesting urine cultures in the absence of minimum symptoms of UTI leads to detection of ASB, prompting unnecessary antibiotic treatment.8 9 16 Large retrospective and prospective cohort studies conducted in long term care homes across several countries show that only a small fraction of urine specimens collected in long term care meet minimum symptom criteria for culturing, and that up to 80% of residents with ASB had unnecessary urine testing.15 16 17 The urine dipstick, which is known for its sensitivity in ruling out presence of UTI in younger populations and foregoing a urine culture, may contribute to over diagnosis of UTI in older patients.30 Unlike in younger populations, where pyuria is generally absent when non-infected, the prevalence of pyuria among long term care residents is nearly universal, and these positive dipsticks trigger urine cultures and occasionally empiric antibiotics in the absence of localising symptoms of UTI.31

TI in older patients.30 Unlike in younger populations, where pyuria is generally absent when non-infected, the prevalence of pyuria among long term care residents is nearly universal, and these positive dipsticks trigger urine cultures and occasionally empiric antibiotics in the absence of localising symptoms of UTI.31 Residents in long term care homes may have cognitive impairment, which can limit available history, and may present atypically with infection. Staff may fear missing a UTI, or even believe that upfront treatment of ASB can prevent a UTI in the future, despite evidence suggesting the contrary.32 A urine culture may be perceived to be a more objective assessment that provides a possible diagnostic explanation for non-urinary complaints. Therefore, the clinical presentations used to evoke the presence of UTI are excessively broad; common presentations such as falls, poor oral intake, lethargy, and delirium frequently trigger a urine dipstick or culture as a means of excluding a UTI, even in the absence of clear localising urinary symptoms—with positive results used to support that diagnosis.15 16 17 23 30 Urine cultures may also be integrated into existing order sets and routine panels, which drives overuse and detection of ASB.33 A recent US survey presented a case of ASB to 551 primary care physicians, and found that more than 70% would prescribe antibiotics.34 Ninety per cent of those who opted to treat believed the patient had a UTI, even though they lacked any of the cardinal symptoms.

ne panels, which drives overuse and detection of ASB.33 A recent US survey presented a case of ASB to 551 primary care physicians, and found that more than 70% would prescribe antibiotics.34 Ninety per cent of those who opted to treat believed the patient had a UTI, even though they lacked any of the cardinal symptoms. Family members and care givers may specifically request urine testing when a care home resident’s condition is altered. Prior experiences of both prescribers and care givers can generate causal inferences based on prior episodes where urine cultures were positive, and these can become particularly challenging to dissociate if improvement in the person’s condition coincided with receipt of antibiotics previously.32

In recognising the problem of antibiotic overuse in people in long term care facilities, balanced against the risk of poor outcomes from sepsis in this frail population, minimum criteria for antibiotic initiation have been proposed by international infectious disease experts as a safe threshold for people in long term care (box 1).35 These criteria were validated in a cluster randomised trial in Canada, where they were used for ordering of urine culture and interpreting positive results, resulting in a 25% reduction in antibiotic use without any significant difference in risk of hospital admission or mortality.36 This approach has been endorsed by the Society of Healthcare Epidemiology of America and Choosing Wisely Canada, and Public Health England has a similar approach.35 37 38 39 Urine cultures ordered below this threshold are considered inappropriate because they are unlikely to help identify a person with a UTI and lead only to unnecessary antibiotic exposure. Public Health England also recommends against use of urine dipsticks for anyone over 65 or with an indwelling urinary catheter.39 Acute dysuria or Fever (>37.9°C or 1.5°C increase above baseline temperature) AND at least one of the following: new or worsening urgency, frequency, suprapubic pain, gross haematuria, costovertebral angle tenderness, or urinary incontinence Presence of at least one of the following: fever (>37.9°C or 1.5°C increase above baseline temperature) without alternative cause, new costovertebral tenderness, rigors, or new onset of delirium

Fever (>37.9°C or 1.5°C increase above baseline temperature) AND at least one of the following: new or worsening urgency, frequency, suprapubic pain, gross haematuria, costovertebral angle tenderness, or urinary incontinence Presence of at least one of the following: fever (>37.9°C or 1.5°C increase above baseline temperature) without alternative cause, new costovertebral tenderness, rigors, or new onset of delirium Box 2 describes how to incorporate this definition of UTI in the clinical assessment of a long term care resident with a change in clinical status. For example, a resident without a catheter who has new onset delirium but no other signs of sepsis or localising urinary symptoms should not generate a urine culture but instead prompt assessment for other causes.37 38 39 Such non-specific changes should also mean closer monitoring and reassessment for development of any additional signs and symptoms, and if minimum criteria are met, a urine culture submitted at that time. The need for empiric therapy pending a urine culture should be determined based on clinical suspicion and acuity of illness. Any empiric therapy should be reassessed based on clinical response, and results from culture and susceptibility testing. Do not order urine culture and do not initiate antibiotics aimed at urinary tract infection Assess for alternative explanations such as volume depletion, constipation, skin breakdown, medication side effects, and other sources of infection such as respiratory or skin and soft tissue

Box 2 describes how to incorporate this definition of UTI in the clinical assessment of a long term care resident with a change in clinical status. For example, a resident without a catheter who has new onset delirium but no other signs of sepsis or localising urinary symptoms should not generate a urine culture but instead prompt assessment for other causes.37 38 39 Such non-specific changes should also mean closer monitoring and reassessment for development of any additional signs and symptoms, and if minimum criteria are met, a urine culture submitted at that time. The need for empiric therapy pending a urine culture should be determined based on clinical suspicion and acuity of illness. Any empiric therapy should be reassessed based on clinical response, and results from culture and susceptibility testing. Do not order urine culture and do not initiate antibiotics aimed at urinary tract infection Assess for alternative explanations such as volume depletion, constipation, skin breakdown, medication side effects, and other sources of infection such as respiratory or skin and soft tissue Do not order a urine culture but do order other targeted investigations as needed, and consider the need for encouraging increased fluid intake, monitoring, and early re-assessment for development of additional signs or symptoms Assess resident for causes of change in status and in absence of clear alternative explanation (eg, medication change leading to delirium, other focus of infection) Urine culture indicated in presence of minimum criteria for UTI without a clear alternative explanation

Do not order a urine culture but do order other targeted investigations as needed, and consider the need for encouraging increased fluid intake, monitoring, and early re-assessment for development of additional signs or symptoms Assess resident for causes of change in status and in absence of clear alternative explanation (eg, medication change leading to delirium, other focus of infection) Urine culture indicated in presence of minimum criteria for UTI without a clear alternative explanation Consider the need for empiric therapy based on clinical suspicion and resident status, with plan to reassess based on urine culture results

Acute dysuria or Fever (>37.9°C or 1.5°C increase above baseline temperature) AND at least one of the following: new or worsening urgency, frequency, suprapubic pain, gross haematuria, costovertebral angle tenderness, or urinary incontinence

Assess for alternative explanations such as volume depletion, constipation, skin breakdown, medication side effects, and other sources of infection such as respiratory or skin and soft tissue Do not order a urine culture but do order other targeted investigations as needed, and consider the need for encouraging increased fluid intake, monitoring, and early re-assessment for development of additional signs or symptoms

Assess resident for causes of change in status and in absence of clear alternative explanation (eg, medication change leading to delirium, other focus of infection) Urine culture indicated in presence of minimum criteria for UTI without a clear alternative explanation Consider the need for empiric therapy based on clinical suspicion and resident status, with plan to reassess based on urine culture results

Discuss the prevalence and protective role of ASB with prescribers and other members of the care team, including nursing staff, personal care givers, and family members.40 Box 3 provides examples of communication strategies for promoting judicious ordering of urine cultures. I am concerned about the change in clinical status that has occurred and want to assess possible causes What specific symptoms have been voiced and what have you noticed? Discuss findings Based on my assessment, there is no evidence of bladder infection and antibiotics would cause unnecessary harm If we collect a urine culture in this situation, we may identify only protective bacteria and not indicate presence of infection. Implement a safety net plan We should encourage oral intake and I have requested more frequent monitoring over the next 24 hours Should there be any new or worsening symptoms, a fresh assessment should be performed Pamphlets and posters can be used to target prescribers and nursing staff to reduce urine culture ordering, as well as face-to-face synchronous sessions, webinars, workshops, one-to-one coaching, identified facility team leaders, prompts and best practice advisories, and a centralised support website.40 41 Education should focus on dispelling and recalibrating the perceived benefits of treating urine culture results for preventing infection against the harms of UTI over-diagnosis and antibiotic overuse.

aching, identified facility team leaders, prompts and best practice advisories, and a centralised support website.40 41 Education should focus on dispelling and recalibrating the perceived benefits of treating urine culture results for preventing infection against the harms of UTI over-diagnosis and antibiotic overuse. Family members and care givers are valuable partners in the de-adoption of ordering urine culture in long term care. Communication tools may help emphasise that not ordering cultures for those who do not meet minimum criteria does not mean no care is offered. On the contrary, not settling on a diagnosis of UTI prematurely means that other diagnostic possibilities for non-urinary concerns will be considered and are less likely to be missed. Other important interventions, such as a physical examination, detailed medication review, encouraging oral intake, and increasing monitoring for new signs or symptoms, may all be reasonable and highly accepted interim plans pending reassessment for whether a urine culture is warranted.32

Beyond education and training, system changes are usually needed to support change in practice.33 In settings that utilise order sets, these should be updated to remove all non-evidence based urine testing outside of minimum accepted UTI symptoms. Removing access to urine dipsticks in long term care homes can reduce unnecessary urine cultures.38 39 Decision support systems and requiring the input of clinical indication for each urine culture may have limited impact, possibly because prescribers select UTI for all cases,42 but a US intervention across 11 hospitals and 70 outpatient clinics showed a 20% reduction in urine cultures with this approach.43 Audit and feedback of urine culture ordering or prescriptions of antibiotics commonly used for UTI may also drive reductions and at minimum limit antibiotic duration.44 45 46 Finally, interventions within the laboratory to reject or modify reporting of urinary isolates that are likely to be ASB can markedly improve antibiotic prescribing practices while preserving prescriber autonomy, although these strategies require additional study in long term care settings.47 48 49 50 One example is increasing the threshold for defining significant growth in urine culture based on data suggesting that low colony counts are only rarely associated with infection in older adults admitted to hospital wards.50 Further research in long term care homes is needed before implementing this change more broadly.

ne example is increasing the threshold for defining significant growth in urine culture based on data suggesting that low colony counts are only rarely associated with infection in older adults admitted to hospital wards.50 Further research in long term care homes is needed before implementing this change more broadly. Finally, a key lesson from the cluster randomised trial that implemented minimum criteria for UTI diagnosis is that although educational algorithms alone led to early practice changes, the reduction in urine culture ordering was not sustained.36 The combination of multiple process changes is likely necessary to enable a shift in the established culture of culturing across many long term care homes. Education initiatives to address knowledge gaps in healthcare providers, patients, and family members Clinical decision support, academic detailing, audit, and feedback Removing urine cultures from order sets Making urine dipsticks unavailable Rejection of urine specimens that do not meet clinical indication for urine culture Increase in the threshold of colony forming units for “positive” urine culture reporting Modification of culture reporting to include messaging to the healthcare provider about prevalence of asymptomatic bacteriuria What investigations do you order for a resident in long term care who appears generally unwell or confused? Do they include urine culture? How are urine specimens collected and submitted for culture at your institution? Are they collected by healthcare personnel, prior to an order being written by a physician?

Modification of culture reporting to include messaging to the healthcare provider about prevalence of asymptomatic bacteriuria What investigations do you order for a resident in long term care who appears generally unwell or confused? Do they include urine culture? How are urine specimens collected and submitted for culture at your institution? Are they collected by healthcare personnel, prior to an order being written by a physician? This article was co-authored by Johanna Trimble, a dedicated caregiver of a patient who has experienced adverse drug effects and unnecessary polypharmacy. Johanna is a published advocate for older adults related to medication misuse and drug safety. Her input was particularly valuable in describing the barriers to change, including the caregiver’s perspective.

Rejection of urine specimens that do not meet clinical indication for urine culture Increase in the threshold of colony forming units for “positive” urine culture reporting Modification of culture reporting to include messaging to the healthcare provider about prevalence of asymptomatic bacteriuria