UTI was once a simple-to-treat infection which has become more challenging to treat over the last 25 years. (1) Half of the population can expect to get a UTI at least once in their lifetime. This common community- or hospital-acquired infection accounts for considerable morbidity and health-care expenditure with an estimated annual cost of US$3.5 billion in the USA.
The majority of UTIs are caused by Gram-negative pathogens, primarily from the Enterobacteriaceae family including E. coli, Proteus, Klebsiella, and Enterobacter species. Gram positive and fungal organisms also cause UTI in certain populations, such as patients with indwelling catheters, diabetes, or recent antibiotic use. Multidrug-resistant organisms (MDROs) are becoming more common due to antibiotic overuse. MDROs limit empiric treatment options and cause frequent treatment failures. Untreated UTI can lead to kidney, bloodstream infections and sepsis.
Why PCR Testing?
Fast, accurate identification of uropathogens and antimicrobial susceptibility is paramount to effectively treat UTIs. Real-time PCR utilizes highly specific assays for rapid, accurate profiling of polymicrobial infections. The most common uropathogens are identified quickly and accurately. Rapid turn-around time coupled with detection of antibiotic resistance markers supports intelligent prescribing and better antibiotic stewardship.
Urine dipsticks are quick and easy for point-of-care testing, but do not provide a microbiological diagnosis. Urine dipsticks can give false-negative results in the case of non-nitrite-producing pathogens, such as Enterococcus and Staphylococcus spp., making them less sensitive in screening for UTI in the elderly and pregnant patients who have higher rates of gram positive infections.
Urine Culture vs Molecular
Potential UTI urine samples are cultured on agar plates to grow and identify uropathogens. Standard 24 hr urine culture fails to spot a high proportion of uropathogens that may be clinically relevant, especially gram positives and fungal pathogens (12% detection rate of non-E. coli pathogens)(2,6). Expanded Quantitative Urine Culture (EQUC) method identifies more pathogens but takes 48 hours of growth time(6). If a pathogen is isolated and identified with culture, antimicrobial susceptibility testing (AST) takes an additional 1 to 2 days.
Even the most common uropathogen, E. coli may be missed by standard culture. In a recent Belgian study, one quarter of women symptomatic for UTI had a negative urine culture result, and almost all of these symptomatic women (95%) actually had an E. coli infection, as determined by quantitative PCR. In addition, 90% of asymptomatic women were negative for E. coli by qPCR (this matches the 10% asymptomatic bacteruria rate) indicating high specificity of the test.(3)
Real-Time PCR takes less than 8 hours of lab time and identifies antibiotic resistance markers concurrently with the most common gram negative, gram positive, and fungal uropathogens. In comparison to culture, PCR takes a fraction of the time, is more sensitive, and is more likely to identify polymicrobial infections.
Ipsum Diagnostics RESIST-UTI panel targets pathogens and antibiotic resistant (ABR) genes commonly found in UTIs. This includes gram positive and gram negative bacterial pathogens, ABRs and fungal species. Antibiotic resistant genes are tested to rapidly identify resistant organism and make targeted treatment decisions.
3. Heytens, S. et al., Women with symptoms of a urinary tract infection but a negative urine culture: PCR-based quantification of Escherichia coli suggests infection in most cases, Clinical Microbiology and Infection, Volume 23, Issue 9, 647 – 652 https://doi.org/10.1016/j.cmi.2017.04.004
4. Michael L. Wilson, Loretta Gaido, Laboratory Diagnosis of Urinary Tract Infections in Adult Patients, Clinical Infectious Diseases, Volume 38, Issue 8, 15 April 2004, Pages 1150–1158, https://doi.org/10.1086/383029
5. Kalpana Gupta, et al, 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, Volume 52, Issue 5, 1 March 2011, Pages e103–e120, https://doi.org/10.1093/cid/ciq257
6. Price TK, Dune T, Hilt EE, et al. Detecting clinically relevant microorganisms: we can do better. Presented at: ASM Microbe 2017; New Orleans, LA; June 1-5. Session 206-CPHM03. Poster 459.