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Moreland RB, Brubaker L, Tinawi L, Wolfe AJ. Rapid and accurate testing for urinary tract infection: new clothes for the emperor. Clin Microbiol Rev 2025; 38:e0012924. [PMID: 39641639 PMCID: PMC11905368 DOI: 10.1128/cmr.00129-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2024] Open
Abstract
SUMMARYUrinary tract infection (UTI) is among the most common infections in clinical practice. In some cases, if left untreated, it can lead to pyelonephritis and urosepsis. In other cases, UTI resolves without treatment. Clinical diagnosis is typically based on patient symptoms and/or urinalysis, including urine dipsticks. The standard urine culture method is sometimes employed to identify the suspected urinary pathogen (uropathogen) and/or guide antimicrobial choice, but results are rarely available before 24 h. The standard urine culture method also misses fastidious, anaerobic, and slow-growing uropathogens and rarely reports polymicrobial infections. The unexplained combination of negative urine cultures with persistent urinary tract symptoms is distressing to both patients and clinicians. Given the broad appreciation of the advantages provided by rapid testing (e.g., for COVID-19 or influenza A), a rapid, accurate diagnostic test is needed to deliver timely treatment to patients seeking care for UTI that optimizes antibiotic stewardship. Herein, we discuss progress being made toward an accessible, timely (i.e., within hours), accurate assay with results that are clinically useful for the treating clinician within the timeframe of the infection (i.e., the growth rate of the pathogen(s)). New and emerging uropathogens often overlooked by current diagnostic techniques are also reviewed.
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Affiliation(s)
- Robert B. Moreland
- Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, USA
| | - Linda Brubaker
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Diego, La Jolla, California, USA
| | - Lana Tinawi
- Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, USA
| | - Alan J. Wolfe
- Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, USA
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2
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Imlay H, Thorpe A, Vaughn VM. When antimicrobial stewardship begins with microbiological test requests: the case of asymptomatic bacteriuria. Curr Opin Infect Dis 2024; 37:565-572. [PMID: 39105674 DOI: 10.1097/qco.0000000000001057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/07/2024]
Abstract
PURPOSE OF REVIEW We aim to review the rationale, methods, and experiences with diagnostic stewardship targeted at urinary tract infection (UTI) and related urinary syndromes. RECENT FINDINGS In the last 18 months, several articles have demonstrated the impact of diagnostic stewardship interventions at limiting inappropriate diagnosis of UTIs or inappropriate antibiotic-prescribing, targeting the urinary tract. Antimicrobial stewardship programs may create and implement interventions at the point of urine test ordering, urine test resulting, or at the point of prescribing antibiotics after results have returned. Specific design and implementation of stewardship interventions depends on context. To maximize their impact, interventions should be accompanied by education and garner buy-in from providers. SUMMARY Diagnostic stewardship can decrease unnecessary antibiotics and inappropriate diagnosis of UTI with multifaceted interventions most likely to be effective. Remaining questions include how to reduce ASB treatment in new populations, such as those with immune compromise, and persistent unknowns regarding UTI diagnosis and diagnostics.
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Affiliation(s)
- Hannah Imlay
- Division of Infectious Diseases, Department of Internal Medicine, University of Utah
- Veteran's Affairs Salt Lake City Healthcare System
| | - Alistair Thorpe
- Department of Population Health Sciences, Spencer Fox Eccles School of Medicine at University of Utah
| | - Valerie M Vaughn
- Department of Population Health Sciences, Spencer Fox Eccles School of Medicine at University of Utah
- Division of General Internal Medicine, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA
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Bradford LM, Yao L, Anastasiadis C, Cooper AL, Blais B, Deckert A, Reid-Smith R, Lau C, Diarra MS, Carrillo C, Wong A. Limit of detection of Salmonella ser. Enteritidis using culture-based versus culture-independent diagnostic approaches. Microbiol Spectr 2024; 12:e0102724. [PMID: 39495170 PMCID: PMC11619426 DOI: 10.1128/spectrum.01027-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 08/28/2024] [Indexed: 11/05/2024] Open
Abstract
To prevent the spread of foodborne illnesses, the presence of pathogens in the food chain is monitored by government agencies and food producers. The culture-based methods currently employed are sensitive but time- and labor-intensive, leading to increasing interest in exploring culture-independent diagnostic tests (CIDTs) for pathogen detection. However, few studies quantify the relative sensitivity and reliability of these CIDTs compared to current approaches. To address this issue, we conducted a comparison of the limit of detection (LOD50) for Salmonella between a culture-based method and three CIDTs: qPCR (targeting invA and stn), metabarcode (16S) sequencing, and shotgun metagenomic sequencing. Samples of chicken feed and chicken caecal contents were spiked with S. serovar Enteritidis and subjected to culture- and DNA-based detection methods. To explore the impact of non-selective enrichment on LOD50, all samples underwent both immediate DNA extraction and overnight enrichment prior to gDNA extraction. In addition to this spike-in experiment, feed and caecal samples acquired from the field were tested with culturing, qPCR, and metabarcoding. In general, LOD50 was comparable between qPCR and shotgun sequencing methods. Overnight microbiological enrichment resulted in an improvement in LOD50 with up to a three-log decrease. However, Salmonella reads were detected in some unspiked feed samples, suggesting false-positive detection of Salmonella. In addition, the LOD50 in feeds was three logs lower than in caecal contents, underscoring the impact of background microbiota on Salmonella detection using all methods. IMPORTANCE The appeal of culture-independent diagnostic tests (CIDTs) is increased speed with lowered cost, as well as the potential to detect multiple pathogen species in a single analysis and to monitor other areas of concern such as antimicrobial resistance genes or virulence factors. This study provides quantitative data on the sensitivity of CIDTs relative to current approaches, which is essential for determining the feasibility of implementing these methods in pathogen surveillance programs.
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Affiliation(s)
- L. M. Bradford
- Department of Biology, Carleton University, Ottawa, Ontario, Canada
| | - L. Yao
- Research and Development, Ottawa Laboratory (Carling), Canadian Food Inspection Agency, Ottawa, Ontario, Canada
| | - C. Anastasiadis
- Research and Development, Ottawa Laboratory (Carling), Canadian Food Inspection Agency, Ottawa, Ontario, Canada
| | - A. L. Cooper
- Research and Development, Ottawa Laboratory (Carling), Canadian Food Inspection Agency, Ottawa, Ontario, Canada
| | - B. Blais
- Research and Development, Ottawa Laboratory (Carling), Canadian Food Inspection Agency, Ottawa, Ontario, Canada
| | - A. Deckert
- Centre for Foodborne Environmental and Zoonotic Diseases, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - R. Reid-Smith
- Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - C. Lau
- Research and Development, Ottawa Laboratory (Carling), Canadian Food Inspection Agency, Ottawa, Ontario, Canada
| | - M. S. Diarra
- Guelph Research and Development Centre, Agriculture and Agri-Food Canada, Guelph, Ontario, Canada
| | - C. Carrillo
- Research and Development, Ottawa Laboratory (Carling), Canadian Food Inspection Agency, Ottawa, Ontario, Canada
| | - A. Wong
- Department of Biology, Carleton University, Ottawa, Ontario, Canada
- Institute for Advancing Health Through Agriculture, Texas A&M University, Fort Worth, Texas, USA
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Haley E, Luke N. From Awareness to Action: Pioneering Solutions for Women's UTI Challenges in the Era of Precision Medicine. Int J Womens Health 2024; 16:1595-1605. [PMID: 39359902 PMCID: PMC11446210 DOI: 10.2147/ijwh.s477476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 09/19/2024] [Indexed: 10/04/2024] Open
Abstract
This article aims to bring clinicians' awareness to the widespread impact of urinary tract infection (UTI) on the lives of women and to the advances that offer hope for future improvements in the diagnosis and management of UTI. Thanks to physiological, anatomical, and lifestyle factor differences, women face heightened vulnerability to UTIs compared to men. In fact, women are four times more likely than men to develop a UTI and around half of these women encounter UTI recurrence, which is a significant source of both physical and psychosocial burdens. Despite the current shortcomings in diagnosis and management, emerging diagnostic technologies promise to identify UTIs more accurately and rapidly, offering women hope for a revolution in UTI management. Meanwhile, clinicians have the opportunity to reduce the psychosocial burden by recognizing the value of patients' lived experiences and ensuring their care plan is in alignment with their patients' goals and expectations for medical care.
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Affiliation(s)
- Emery Haley
- Department of Clinical Research, Pathnostics, Irvine, CA, USA
| | - Natalie Luke
- Department of Clinical Research, Pathnostics, Irvine, CA, USA
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Hertz MA, Skjøt-Arkil H, Heltborg A, Lorentzen MH, Cartuliares MB, Rosenvinge FS, Nielsen SL, Mogensen CB, Johansen IS. Clinical characteristics, factors associated with urinary tract infection and outcome in acutely admitted patients with infection; an exploratory cross-sectional cohort study. Heliyon 2024; 10:e32815. [PMID: 38984294 PMCID: PMC11231541 DOI: 10.1016/j.heliyon.2024.e32815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 06/08/2024] [Accepted: 06/10/2024] [Indexed: 07/11/2024] Open
Abstract
Background Urinary tract infections (UTIs) remain a leading infectious disease cause of admission to the emergency department (ED) and antibiotic prescription. Heterogeneity of disease presentation challenges early diagnostics, leading to improper antibiotic prescription and delayed diagnosis. Prior studies have relied on positive urine cultures for diagnosis, but its performance suffers from false positives and false negatives. This study aimed to identify factors associated with UTIs and describe patient characteristics and outcomes while not using positive urine culture as an obligatory part of diagnosis. Methods Adult patients admitted to the ED suspected of infection were prospectively included in an exploratory cross-sectional cohort study. An expert panel retrospectively determined the final diagnosis. Factors associated with a UTI were identified using univariate and multivariate logistic regression analysis, outcomes were evaluated with adjusted Cox regression analysis, and length of stay was compared with a zero-inflated negative binomial logistic regression model. Results Of 966 patients who were enrolled, 200 were diagnosed with a UTI by the expert panel. We found a significant association between a UTI diagnosis and the typical UTI symptoms: dysuria (OR 7.8), change of urine appearance (OR 3.9), suprapubic or flank pain (OR 3.7), and increased urinary frequency (OR 3.2). Urinary dipstick analysis for white blood cells (WBCs) (OR 6.0-24.0), nitrite (OR 4.7), and blood (OR 3.6-12.0) was also significantly associated. Subgroup analysis of urinary dipstick analysis of men and women still showed significance in both groups. No significant difference in outcome or length of stay was found. Conclusion Typical UTI symptoms are associated with a UTI diagnosis, which underlines the importance of exploring a patient's medical history. Urinary dipstick analysis for WBC, nitrite, and blood is also strongly associated and should be considered when evaluating patients admitted to the ED with suspicion of infection.
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Affiliation(s)
- Mathias Amdi Hertz
- Department of Infectious Diseases, Odense University Hospital, University of Southern Denmark, Denmark
- Research Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark, Denmark
| | - Helene Skjøt-Arkil
- Department of Regional Health Research-Odense, University of Southern Denmark, Denmark
- Emergency Department-Aabenraa, University Hospital of Southern Denmark, Denmark
| | - Anne Heltborg
- Department of Regional Health Research-Odense, University of Southern Denmark, Denmark
- Emergency Department-Aabenraa, University Hospital of Southern Denmark, Denmark
| | - Morten Hjarnø Lorentzen
- Department of Regional Health Research-Odense, University of Southern Denmark, Denmark
- Emergency Department-Aabenraa, University Hospital of Southern Denmark, Denmark
| | - Mariana Bichuette Cartuliares
- Department of Regional Health Research-Odense, University of Southern Denmark, Denmark
- Emergency Department-Aabenraa, University Hospital of Southern Denmark, Denmark
| | - Flemming S Rosenvinge
- Department of Clinical Microbiology, Odense University Hospital, University of Southern Denmark, Denmark
- Research Unit of Clinical Microbiology, University of Southern Denmark, Denmark
| | - Stig Lønberg Nielsen
- Department of Infectious Diseases, Odense University Hospital, University of Southern Denmark, Denmark
- Research Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark, Denmark
| | - Christian Backer Mogensen
- Department of Regional Health Research-Odense, University of Southern Denmark, Denmark
- Emergency Department-Aabenraa, University Hospital of Southern Denmark, Denmark
| | - Isik Somuncu Johansen
- Department of Infectious Diseases, Odense University Hospital, University of Southern Denmark, Denmark
- Research Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark, Denmark
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Gleicher S, Karram M, Wein AJ, Dmochowski RR. Recurrent and complicated urinary tract infections in women: Utility of advanced testing to enhance care. Neurourol Urodyn 2024; 43:161-166. [PMID: 37822027 DOI: 10.1002/nau.25280] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 08/03/2023] [Accepted: 08/28/2023] [Indexed: 10/13/2023]
Abstract
BACKGROUND The United States currently faces a public health crisis with regarding to antibiotic-resistant bacteria, and new urinary tract infection (UTI) diagnostics are needed. Women with recurrent UTI (rUTI) and complicated UTI (cUTI) are at particular risk given their complexity and the paucity of adequate testing modalities. The standard urine culture (SUC) is the cornerstone for diagnosis, but it has many shortcomings. These pitfalls lead to dissatisfaction and frustration among women afflicted with rUTI and cUTI, as well as overuse of antibiotics. One innovation is PCR UTI testing, which has been shown to outperform SUC among symptomatic women. AIMS This article discusses UTI PCR testing, as well as a possible role in clinical practice. MATERIALS AND METHODS Published literature was reviewed and summarized. RESULTS Management of rUTI and cUTI is complex, and providers should have all diagnostics available to facilitate providing optimal care. Urine PCR testing faces reimbursement issues despite fulfilling clinical indication parameters as described by insurance companies. DISCUSSION The role of UTI PCR testing remains unclear. Reimbursement issues have led to underuse and limited real-world outcomes reinforcing benefit. CONCLUSION This study proposes an algorithm for PCR testing among women with rUTI and cUTI.
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Affiliation(s)
| | - Mickey Karram
- The Christ Hospital Physicians, Cincinnati, Ohio, USA
| | - Alan J Wein
- University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
| | - Roger R Dmochowski
- Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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Weng X, Liu Y, Hu H, Wang M, Huang X. Changes of microbiota level in urinary tract infections: A meta-analysis. Open Med (Wars) 2023; 18:20230702. [PMID: 37251539 PMCID: PMC10224615 DOI: 10.1515/med-2023-0702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 04/02/2023] [Accepted: 04/04/2023] [Indexed: 05/31/2023] Open
Abstract
No consensus has been reached on the dysbiosis signs of microbiota in patients with urinary tract infections (UTIs). This meta-analysis aimed to verify the relationship between microbiota levels and UTIs. PubMed, Web of Science, and Embase databases were retrieved for related articles published from inception until October 20, 2021. The standardized mean difference (SMD) and its related 95% confidence intervals (CIs) of the microbiota diversity and abundance were pooled under a random-effects model. Twelve studies were included in this meta-analysis. The pooled analysis revealed that the microbiota diversity was lower in patients with UTIs than in healthy individuals (SMD = -0.655, 95% CI = -1.290, -0.021, I 2 = 81.0%, P = 0.043). The abundance of specific bacteria was higher in UTI subjects compared with healthy control individuals (SMD = 0.41, 95% CI = 0.07-0.74, P = 0.017), especially in North America patients with UTIs. Similar results were also found in studies with the total sample size being greater than 30. Importantly, Escherichia coli levels were increased in patients with UTI, whereas Lactobacillus levels decreased. E. coli and Lactobacilli have huge prospects as potential microbiota markers in the treatment of UTIs.
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Affiliation(s)
- Xia Weng
- Urology Department, Zhejiang Hospital, Hangzhou310013, Zhejiang Province, China
| | - Yajun Liu
- Neurosurgery Department, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China
| | - Haiping Hu
- Urology Department, Zhejiang Hospital, Hangzhou310013, Zhejiang Province, China
| | - Meichai Wang
- Urology Department, Zhejiang Hospital, Hangzhou310013, Zhejiang Province, China
| | - Xiaoqin Huang
- Orthopedics Department, Zhejiang Hospital, No. 1229, Gudun Road, Hangzhou 310013, Zhejiang Province, China
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Molecular Diagnostic Methods Versus Conventional Urine Culture for Diagnosis and Treatment of Urinary Tract Infection: A Systematic Review and Meta-analysis. EUR UROL SUPPL 2022; 44:113-124. [PMID: 36093322 PMCID: PMC9459428 DOI: 10.1016/j.euros.2022.08.009] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2022] [Indexed: 11/23/2022] Open
Abstract
Context Objective Evidence acquisition Evidence synthesis Conclusions Patient summary
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Applying Diagnostic Stewardship to Proactively Optimize the Management of Urinary Tract Infections. Antibiotics (Basel) 2022; 11:antibiotics11030308. [PMID: 35326771 PMCID: PMC8944608 DOI: 10.3390/antibiotics11030308] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 02/05/2022] [Accepted: 02/17/2022] [Indexed: 02/06/2023] Open
Abstract
A urinary tract infection is amongst the most common bacterial infections in the community and hospital setting and accounts for an estimated 1.6 to 2.14 billion in national healthcare expenditure. Despite its financial impact, the diagnosis is challenging with urine cultures and antibiotics often inappropriately ordered for non-specific symptoms or asymptomatic bacteriuria. In an attempt to limit unnecessary laboratory testing and antibiotic overutilization, several diagnostic stewardship initiatives have been described in the literature. We conducted a systematic review with a focus on the application of molecular and microbiological diagnostics, clinical decision support, and implementation of diagnostic stewardship initiatives for urinary tract infections. The most successful strategies utilized a bundled, multidisciplinary, and multimodal approach involving nursing and physician education and feedback, indication requirements for urine culture orders, reflex urine culture programs, cascade reporting, and urinary antibiograms. Implementation of antibiotic stewardship initiatives across the various phases of laboratory testing (i.e., pre-analytic, analytic, post-analytic) can effectively decrease the rate of inappropriate ordering of urine cultures and antibiotic prescribing in patients with clinically ambiguous symptoms that are unlikely to be a urinary tract infection.
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A New Gold Rush: A Review of Current and Developing Diagnostic Tools for Urinary Tract Infections. Diagnostics (Basel) 2021; 11:diagnostics11030479. [PMID: 33803202 PMCID: PMC7998255 DOI: 10.3390/diagnostics11030479] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/03/2021] [Accepted: 03/05/2021] [Indexed: 11/16/2022] Open
Abstract
Urinary tract infections (UTIs) are one of the most common infections in the United States and consequently are responsible for significant healthcare expenditure. The standard urine culture is the current gold standard for diagnosing urinary tract infections, however there are limitations of the test that directly contribute to increased healthcare costs. As a result, new and innovative techniques have been developed to address the inefficiencies of the current standard-it remains to be seen whether these tests should be performed adjunctly to, or perhaps even replace the urine culture. This review aims to analyze the advantages and disadvantages of the newer and emerging diagnostic techniques such as PCR, expanded quantitative urine culture (EQUC), and next generation sequencing (NGS).
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