Diagnostic Evidence Co-operative Oxford NIHR Diagnostic Evidence Cooperative Oxford www.oxford.dec.nihr.ac.uk Clinical Question: In diagnosing patients with suspected urinary tract infections, what is the accuracy and utility of point-of- care tests compared to the current standard of urine microscopy, culture and antibiotic sensitivity analysis? Background, Current Practice and Advantages over Existing Technology: Background Urinary tract infections (UTIs) are among the most common types of infections, with an estimated 92 million people affected worldwide in 2013. 1 The global burden of this disease is rising, with 16.1% increase in age- standardised incidence between 1990 and 2013 and 58,000 years lost to disability (YLD) in 2003 alone. 1 UTIs are also a significant cause of mortality especially among the elderly population with 4835 deaths in England and Wales reported in 2012. 2 UTI symptoms accounted for 1-3% of all primary care consultations 3 and it was the main indication for 13.7% of community antibiotic prescriptions. 4 The 1994/5 cost estimates of treating UTIs in the National Health Service were £124 million. 5 Two decades on, it can only be assumed that with the rising prevalence of UTIs combined with the emergence of antibiotic-resistant organisms, the health and economic burden of the disease is likely to have increased. UTIs are broadly defined as infection of the urethra, bladder, ureters or kidneys by non-commensal micro- organisms, most commonly Escherichia coli, Staphylococcus saprophyticus and Enterococcus faecalis. 6 Other causative uropathogens include Enterobacteriaceae sp. (Proteus mirabilis and Klebsiella sp.), group B streptococci, Pseudomonas aeruginosa, and Citrobacter sp. They frequently arise from peri-urethral contamination by uropathogens found in faecal flora which then ascend into the bladder via the urethra. 7 Further migration of uropathogens from the bladder via the ureters into the kidneys results in pyelonephritis. UTIs are categorised as either uncomplicated or complicated. Uncomplicated UTIs can be further sub- classified into cystitis (lower urinary tract) and pyelonephritis (upper urinary tract). Patients with cystitis typically present with dysuria, frequency, urgency, haematuria and/or suprapubic pain; pyelonephritis classically manifests with flank pain, costovertebral angle tenderness, fever, nausea and vomiting in addition Point-of-care testing for urinary tract infections Horizon Scan Report 0045 June 2016
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Chromogenic agar plate with 6 segments - 5 evaluating anti-biotic sensitivities and 1 con-trol segment
Midstream urine sample ; (NS)
1
24 hours ✓
Incubator Semi-quantification of bacte-rial growth, evaluation of the species present, and assess-ment of sensitivity to the antibiotics in each of the plate segments
Store at 2-8 °C.
Culture and susceptibility testing
✓ ✗
Uricult Trio Orion Diagnostics / Finland
Plastic slide with CLED/MacConkey + E.coli agar medium
Randomly voided, mid-stream, clean-catch and catheterized samples ; (NS)1
16-24 hours when incubat-ed at 36.8°C or 1-3 days at room temper-ature
✓ Incubator Semi-quantification of bacte-
rial growth, evaluation of the species present
Room temp (15-25°C)
Culture ✓ ✓
DipStreak (Chro-mostreak)
Novamed / Israel Plastic paddle with two oppos-ing agar media (UriSelect3 chromogenic agar and Mac-Conkey), housed in a closed transparent plastic tube
Midstream urine sample ; (NS)1
18-24 hours ✓ Incubator Semi-quantification of bacte-
rial growth, evaluation of the species present
Store at 2-8 °C.
Culture ✓ ✓
DiaSlide Novamed / Israel Hinged plastic case containing two opposing agar media (CLED/MacConkey or UriSelect3 chromogenic agar and MacConkey)
Midstream urine sample ; (NS)1
24 hours ✓ Incubator Semi-quantification of bacte-
rial growth Room temp (15-25°C)
Culture ? ✓
onSite Trek Diagnostics System / USA
Hinged plastic case containing two opposing agar media (MacConkey agar + one of TSA/Columbia CNA/CLED agar
Midstream urine sample ; (NS)1
Not specified ✓ Incubator Semi-quantification of bacte-
rial growth, evaluation of the species present
2-25°C Culture ? ✗
ENZYMATIC ASSAY
UriScreen Savyon Diagnos-tics Ltd / Israel
Enzymatic (catalase) test Midstream urine sample ; (1.5-2mL)
2 minutes ✓ No Detects bacteriuria / pyuria Room
temp (10-28°C)
Assay ✓ ✓
All of the used tests should be disposed in an infectious laboratory bin. (NS)1 = volume not specified
TABLE 2. ACCURACY OF POINT-OF-CARE UTI CULTURE-BASED DEVICES AND ENZYMATIC ASSAYS Product Manufac-
turer / Location
Number of sam-ples tested ; Test population
Threshold for significant growth
Accuracy Sensitivity (%)(95% CI)
Specificity (%)(95% CI)
PPV (%)(95% CI)
NPV (%)(95% CI)
Ref
CULTURE-BASED DEVICES
FLEXICULT ™
Statens Serum Institut Diagnostica / Denmark
N=200 124 (outpatient set-ting) 76 (secondary care setting)
≥105 CFU/ml — 87.0% (67.9-95.5)
83.2% (74.7-89.2)
54.1% (38.4-69.0)
96.6% (90.4-98.8)
23
Uricult Trio Orion Diag-nostics / Finland
198 (paediatric pa-tients aged 0-7)
≥104 CFU/ml — 68% 82% 81% 71% 26
434 (primary health care setting)
≥103 CFU/ml for primary uropathogens (E.coli, S. saprophyticus) ; ≥104 CFU/ml for secondary uropathogens ; ≥105 CFU/ml for doubtful uropathogens
88% 88% 90% 92% 85% 27
DipStreak (Chromostreak)
Novamed / Israel
N=1070 (251 hospitalized patients and 819 outpatients)
>105 CFU/ml (single organism + mixed cul-ture)
98% 95.7% 99.2% 98.5% 97.7% 28
DiaSlide Novamed / Israel
473 (prescreened hospital urine specimens using UriScreen)
≥104 CFU/ml — 98.3% 97.5% 98.3% 97.5% 29
ENZYMATIC ASSAY
UriScreen ® Savyon Diagnostics Ltd / Israel
378 women (pre-natal screening for bacteriuria)
≥104 CFU/ml — 70% (±13.5%)
45% (±5.5%)
14% (±5%)
92% (±4%)
30
313 (pregnant women)
>105 CFU/ml — 100% 81% (±4.5%)
30% (±10%)
100% 31
150 (catheterised urine samples from pregnant women)
>105 CFU/ml (single organism culture)
— 60.7% (±
18.1%)*
89.3% (±5.6%)*
56.6% 90.8% 32
108 cultures from 57 patients with indwelling cathe-ter
≥103 CFU/ml — 88.5% 42.6% 66.7% 74.1% 33
200 catheterised urine specimens from children
≥ 5x104 CFU/ml 81% 65.2% 85.7% 57.7% 89.2% 34
121 paediatric patients in emer-gency depart-ment)
105 CFU/mL for clean catch or urine bag spec-imens; 103 CFU/mL for bladder catheterization specimens; 102 CFU/mL for urine collected by suprapubic aspiration.
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Abbreviations:
CFU/ml: Colony-Forming Units per millilitre
IDSA: Infectious Diseases Society of America
MRSA: Methicillin-resistant Staphylococcus aureus
NHS: The National Health Service
NICE: The National Institute for Health and Care Excellence