Awanui Labs Auckland has successfully implemented a pre-analytical pathway for UTI diagnostic stewardship through e-order, which requests clinical information for laboratory processing of urine specimens.  The information we have been receiving from clinicians is immensely useful in accurate interpretation of urine microscopy and culture results, and facilitates clinically-relevant reporting. 

As recommended by local and international best practice guidelines, evidence of compatible clinical features is required for microbiological investigation of UTI.

So when should we investigate for asymptomatic bacteriuria (ASB)?

Asymptomatic bacteriuria (ASB) is defined as the presence of one or more species of bacteria in urine culture (at significant colony counts of >10⁸ CFU/L) in the absence of signs or symptoms attributable to UTI, regardless of the presence or absence of pyuria.¹ 

A recent systematic review and meta-analysis revealed that there were only two indications for investigation of ASB, for which there is evidence of benefit¹:

• Pregnant women: screening for ASB recommended early in pregnancy (ideally at 12-16 weeks gestation).  If present, ASB should be treated with the shortest effective course of antimicrobials.  Antimicrobials reduce the risk of pyelonephritis and adverse pregnancy outcomes.  There is insufficient evidence of benefit for repeat screening during the pregnancy.
• Prior to invasive endoscopic urological surgery associated with mucosal trauma (e.g. transurethral resection of the prostate (TURP) or bladder, ureteroscopy, lithotripsy, percutaneous stone surgery).  Targeted short-course antimicrobial therapy (1-2 doses initiated 30-60 mins prior to procedure) is administered to prevent post-operative sepsis.

There is no evidence of benefit of ASB screening and treatment for any other types of surgery.

Should asymptomatic bacteriuria (ASB) be screened for in non-catheterised cognitively-impaired elderly patients?

New onset or worsening confusion is one of the most common reasons for suspecting UTI in the elderly.  There are several studies which have investigated whether ASB is associated with an altered mental state in the elderly.

1. There is no evidence of association between ASB and delirium²

• There was only an association between symptomatic UTI and delirium.  In the studies included, the diagnosis of delirium was made according to DSM/ ICD criteria/ validated rating scales, and a diagnosis of UTI was predicated on the presence of UTI symptoms.   These include localised urinary (dysuria, urgency, increased frequency, new suprapubic/ costovertebral angle/ flank tenderness) or systemic (documented fever, hypothermia, chills, rigors, new hypotension/ tachycardia) signs and symptoms.
• There was insufficient evidence to assign causality or direction of causality (i.e. whether UTI precedes delirium, or the other way round), or whether they simply share common risk factors. 

2. Patients with delirium/ altered mental state without features of sepsis should not be investigated for UTI with urine culture (a positive culture would be representative of ASB)^3-5

• In the absence of clinical features of UTI, any association seen in observational studies between ASB and delirium or non-specific symptoms of altered mental state (confusion, restlessness, agitation) is attributable to host factors, and consistent with high frequency of both conditions in the elderly [i.e. high prevalence of perineal colonisation leading to ASB plus altered mental status due to other age-related factors]. 
• Altered mental status by itself is an inappropriate indication for urine culture, as are changes in urine characteristics (colour, smell).  

3. There is no benefit to treating ASB associated with delirium/ “confusion” and antimicrobial treatment may even be harmful^6-11

• ASB in non-catheterised nursing home residents is generally benign and not associated with serious clinical illness.  Change in mental status is likely to be multifactorial and should not prompt investigation or empiric antimicrobial therapy for UTI. 
• Treatment makes no difference to physical or mental functioning, and a significant proportion will continue to have ASB despite treatment and at 3 months post-treatment.  These patients likely have persistent perineal and distal urethral colonisation leading to persistently positive urine culture results.
• Diagnosis of ASB in nursing home residents is associated with increased antibiotic utilisation which is a mediator of resistant gram negative bacilli isolated from urine.
• Delirious patients treated for ASB are more likely to develop C. difficile-associated disease, and treatment may be associated with worse functional recovery (new/ permanent residence in long term care facility or functional decline).  There is no evidence of survival benefit or faster symptomatic improvement of delirium symptoms with antimicrobial treatment.  

4. PINCHES-ME helps direct referrers to consider other causes of delirium, instead of assuming a positive dipstick is indicative of UTI diagnosis.

• It can be difficult to discern localising signs of UTI in elderly patients with delirium; however, the false positive rate of dipstick/urine cultures in the absence of UTI / sepsis symptoms, may mask the true cause of delirium.  A new delirium ideally needs a proper clinical assessment. 
• PINCHES-ME is a useful mnemonic that directs referrers to consider other causes of delirium as well [P – Pain; I – Infection; N – Nutrition; C – Constipation; H – Hydration/Hypoxia; E – Endocrine/Electrolyte; S – Stroke/Seizure; M – Medication/Toxins; E – Environmental].

In summary, there is no evidence of benefit to the screening and treatment of ASB in non-catheterised, cognitively-impaired elderly patients who have no localised/ systemic features of sepsis; however, there is some evidence of harm.  It is recommended, instead, that these patients are carefully assessed for other causes of confusion or delirium.

References

1.  Nicolle L, Gupta K, Bradley S, et al. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2019;68(10):1611-5.
2. Krinitski D, Kasina R, Kloppel S, et al. Associations of delirium with urinary tract infections and asymptomatic bacteriuria in adults aged 65 and older: A systematic review and meta-analysis. J Am Geriatr Soc. 2021;69(11):3312-23.
3. Mayne S, Bowden A, Sundvall P, et al. The scientific evidence for a potential link between confusion and urinary tract infection in the elderly is still confusing – a systematic literature review. BMC Geriatr. 2019;19(1):32.
4. Sundvall P, Ulleryd P, Gunnarsson R. Urine culture doubtful in determining etiology of diffuse symptoms among elderly individuals: a cross-sectional study of 32 nursing homes. BMC Fam Pract. 2011;12:36.
5. Claeys K, Trautner B, Leekha S, et al. Optimal Urine Culture Diagnostic Stewardship Practice-Results from an Expert Modified-Delphi Procedure. Clin Infect Dis. 2022;75(3):382-9.
6. Das R, Towle V, Van Ness P, et al. Adverse outcomes in nursing home residents with increased episodes of observed bacteriuria. Infect Control Hosp Epidemiol. 2011;32(1):84-6.
7. Dasgupta M, Brymer C, Elsayed S. Treatment of asymptomatic UTI in older delirious medical in-patients: A prospective cohort study. Arch Gerontol Geriatr. 2017;72:127-34.
8. Joo P, Grant L, Ramsay T, et al. Effect of inpatient antibiotic treatment among older adults with delirium found with a positive urinalysis: a health record review. BMC Geriatr. 2022;22(1):916.
9. Potts L, Cross S, MacLennan W, et al. A double-blind comparative study of norfloxacin versus placebo in hospitalised elderly patients with asymptomatic bacteriuria. Arch Gerontol Geriatr. 1996;23(2):153-61.
10. Rotjanapan P, Dosa D, Thomas K. Potentially inappropriate treatment of urinary tract infections in two Rhode Island nursing homes. Arch Intern Med. 2011;171(5):438-43.
11. Dufour A, Shaffer M, D’Agata E, et al. Survival After Suspected Urinary Tract Infection in Individuals with Advanced Dementia. J Am Geriatr Soc. 2015;63(12):2472-7.