Diagnosis and treatment of urinary tract infections

Expert opinions from Dr Ewan Chirnside
The diagnosis and treatment of urinary tract infections (UTIs) is currently a balance between starting empirical treatment immediately or waiting a minimum of 48|hours to begin treatment based on the results of pathogen identification and antibiotic susceptibility testing, which provides better antibiotic stewardship but prolongs patient suffering. As part of this issue’s focus on Urine Analysis, Dr Ewan Chirnside (Director of Research Collaborations and co-founder of ODx Innovations, Inverness, UK) shares his knowledge of UTI diagnostics.

What are urinary tract infections and why is the diagnosis and treatment of them so important?

Urinary tract infections (UTIs) result from the presence and multiplication of microorganisms in one or more structures of the urinary tract with associated tissue invasion.
Uncomplicated UTI is one of the most common problems for young women and accounts for considerable mortality and healthcare costs. It can occur in otherwise healthy individuals with no underlying lesions of the urinary tract or systemic diseases predisposing the host to bacterial infection.
Complicated UTI occurs in patients in whom there may be residual inflammatory changes which interfere with drainage of urine in part of the tract which encourages prolonged colonization. Accurate diagnosis and treatment are fundamental because of rising antimicrobial resistance and the increasing risk of hospitalization in patients if effective treatment is not provided immediately.

How are UTIs usually diagnosed and treated?

In many countries UTIs are diagnosed empirically by a healthcare professional based on clinical signs alone and, without any analytical testing to support the initial diagnosis, the patient will be prescribed a course of antibiotics.
Alternatively, when a patient presents with the common symptoms of a lower UTI they will generally provide a midstream urine (MSU) or clean-catch urine sample for dipstick testing. If the dipstick test is positive for leucocyte esterase, and the patient history suggestive of a UTI, the healthcare practitioner has a choice to make; do they empirically prescribe an antibiotic that may fight the infection? Or do they submit a urine sample for laboratory investigation, await that result and then prescribe an appropriate antibiotic? Delaying antibiotic prescription for three days to perform laboratory tests allows positive confirmation that the patient has an active infection and ensures that the antibiotic they prescribe will be effective.
The gold standard laboratory investigation of urine samples from suspected UTI is firstly quantitative culture to isolate the pathogen causing the infection [1], followed by further testing on the isolated pathogen(s) to confirm its identity (ID) and antibiotic susceptibility profile. The most common organism implicated in UTI is E. coli and bacterial counts of >105|CFU/mL are indicative of an infection. Isolation of the pathogen causing the UTI takes 24|hours in the laboratory, and antibiotic susceptibility testing (AST) a further 16–24|hours to provide an antibiotic susceptibility profile. Therefore, there is a significant delay between a urine sample being provided by a patient, to a laboratory result being available to confirm infection and antibiotic prescription.
These outlined timings don’t take into consideration transport to laboratories, delays caused during busy times and any delay in contacting the patient to prescribe the correct antibiotics.
Waiting the 2–3|days for a result can have a variety of effects on the individual patient – people often suffer in silence as they experience painful urination, burning, pressure, urgency and frequency while they wait for the most effective treatment to be identified. Healthcare practitioners can overcome this by providing an empiric prescription on day one and hope that it is effective in treating the infection. However, approximately 40% of empiric antibiotic prescriptions for suspected UTIs are incorrect because either (i) the patient does not have a UTI or (ii) the pathogen causing the UTI is resistant to the first-line antibiotic prescribed. In addition, owing to the growing problem of antibiotic resistance physicians are being encouraged to follow better antibiotic stewardship, limiting the use of broad spectrum, non-targeted antibiotics.

In order to provide better treatment of UTIs, we need to know more about the causative pathogen – what it is and its antibiotic susceptibility profile. How is this typically achieved?

The phenotypic identification of pathogens and AST are mainstays of the clinical microbiology laboratory. Phenotypic pathogen ID typically takes 24|hours with another 12–24|hours or more for AST. These delays in test results can lead to sub-optimal disease management pathways, hospitalization, increased cost and patient mortality. The current microbiology tests can only be carried out at level 3 and level 4 laboratory facilities and there are no suitable comparable tests available that can provide rapid, accurate patient results in point-of-care (POC) settings.
For complicated UTI where ID will allow for improved clinical care, these longer and more thorough laboratory tests are necessary and provide significant benefit. However, for the majority of uncomplicated cases confirming infection and identifying an antibiotic that will inhibit growth of the organism are sufficient to treat the patient and improve antibiotic stewardship.

The crucial issue, therefore, with UTIs is to determine the best antibiotic for the individual patient very quickly – how can this be done?

The World Health Organization [2] has identified that nearpatient testing methods for antimicrobial susceptibility and resistance are inadequate and identified a need for a range of priority diagnostics against antimicrobial resistance for primary and secondary healthcare facilities including a simple, easy-to-use test/platform for AST only.
Additionally, the Longitude Prize (LP) [3] chose the resistance of antibiotics as one of the major problems that need an urgent solution. The challenge set by the LP is to create an affordable, accurate, rapid and easy-to-use diagnostic test for bacterial infections that will allow health professionals to administer the right antibiotics at the right time. Contestants in the LP come from all around the world and are investigating a range of both genotypic and phenotypic methodologies to determine antibiotic susceptibility; the main challenges that need to be addressed are (i) the time to result, (ii) accuracy, and (iii) cost. None of the tests submitted quite meet the criteria yet, and the LP panel has had to extend the competition deadline.

Diagnosis of UTI can be particularly challenging in certain populations, such as asymptomatic bacteriuria, patients with catheters and the elderly. Will the anticipated new technologies help with these diagnoses?

Symptoms in children and the elderly, when present, may be non-specific and difficult to interpret. Confirmation of UTI in children is dependent on the quality of the specimen, which is often difficult to obtain cleanly. UTI incidence increases with age for both sexes and is one of the most common infections associated with this age group. Underlying health issues can make this condition particularly difficult to diagnose and prone to resistant strains.
The new near-patient and POC tests being developed are unlikely to totally replace the need for urine tests in microbiology laboratories. The very young, the elderly and catheterized patients will most-likely still rely on lab-based tests for their correct diagnosis and treatment. However, POC testing has the capacity to substantially reduce demand for laboratory urine testing and to put patients with UTIs on the correct treatment pathways much faster than is possible at the moment. The ability to prescribe the right antibiotic at the right time will aid the fight against increasing antimicrobial resistance and help antibiotic stewardship.

What role is ODx playing in the development of new technologies for this issue and what is its vision for the future diagnosis and treatment of UTIs?

Antibiotic-resistant bacteria are a serious threat to global health. Our current healthcare procedures are too weak to win the war against antibiotic-resistant bacteria and without serious action, simple infections that were easily treated with antibiotics in the past will become lethal. The ODx system offers the potential to revolutionize the turnaround time for the assessment of suspected UTIs, reduce the use of antibiotics and improve patient satisfaction and outcomes through providing faster access to optimal antimicrobial therapy.
ODx are a medical technology company based in Inverness, UK. Our dedicated teams of specialist microbiologists, engineers and laboratory technicians are supported by partners and experts in medical technology and diagnostics from across the world. Working in partnership with The Technology Partnership our proprietary detection technique technology provides rapid antimicrobial susceptibility profile testing at the POC for patients with a suspected UTI.
It’s simple. After a UTI has been clinically diagnosed and antibiotic treatment has been chosen as being appropriate, our technology aims to detect bacterial growth and provide antibiotic sensitivities of the isolated pathogen. The critical choice of what to prescribe is available within minutes, rather than days.
Once released, it is expected that the system will be placed near to patients in doctors’ offices, hospital outpatient clinics and, potentially, pharmacies. This will help assess suspected UTIs at the POC, ensuring the most appropriate antibiotics are identified as quickly as possible. Facilitating the development of personalized treatment plans, the system will help tackle antibiotic resistance by reducing unnecessary prescriptions, while making sure that antibiotic courses have the maximum possible effectiveness for a given patient.
ODx has been recognized for work on antimicrobial resistance with a prestigious Longitude Prize Discovery Award and the coveted Innovative Prize at the Scottish Life Sciences Awards. We are relentlessly focused on transforming the speed at which antibiotic sensitivity tests are performed on patients with UTI. We aim to bring our ground-breaking microbiological technology to patients so that diagnosis and treatment can be delivered at the right time on the day that counts.
The expert
Ewan Chirnside BSc PhD, Director of Research Collaborations
and co-founder
ODx Innovations, Inverness IV2 5NA, UK

For further information contact Lana MacGregor
(lana.macgregor@odxinnovations.com) or
visit ODx Innovations https://odxinnovations.com/