Modified Reporting of Positive Urine Cultures Collected From Long Term Care, a Randomized Controlled Trial
Phase: NA
Conditions: Urinary Tract Infections, Asymptomatic Bacteriuria
Sponsor: Memorial University of Newfoundland

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Modified Reporting of Positive Urine Cultures Collected from Long Term Care, a Randomized 
Controlled Trial Protocol  
Peter Daley, Janice Fitzgerald, Brendan Barrett 
 
Administrative Information 
Protocol Version: 1.0 May 2018 
Registration: www.clinicaltrials.gov identifier pending 
Funding: none 
Roles and responsibilities: 
Protocol: Peter Daley, Associate Professor, Memorial University 
Sponsor: Memorial University of Newfoundland, St. John’s, NL, Canada 
Role of sponsor in design, collection, management, analysis, interpretation, writing, decision to 
publish: none 
Principal Investigator: Peter Daley 
Co-Investigators: Janice Fitzgerald, Brendan Barrett 
Introduction  
 
Background and rationale  
Asymptomatic bacteriuria (ASB) is a condition in which bacteria from the bowel are 
detected in significant numbers by culture in a specimen of collected urine, but the patient does 
not have genitourinary symptoms or signs.(1)  In contrast, urinary tract infection (UTI) is the 
presence of bacteria in urine specimens with defined symptoms or signs.(2, 3) Catheter-
associated urinary tract infection (CA-UTI) is defined as presence of bacteria in urine specimens 
with defined symptoms or signs in the presence of an indwelling urinary catheter, and catheter-
associated asymptomatic bacteriuria (CA-ASB) is defined as presence of bacteria in urine 

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specimens without defined symptoms or signs in the presence of an indwelling urinary 
catheter.(2)  
The use of inappropriate antibiotic treatment for ASB is a systemic antibiotic stewardship 
problem, causing harm due to antibiotic adverse effects, selection of bacteria toward drug 
resistance, and wasted cost.(4)  
UTI’s are among the commonest indications for antimicrobial therapy.  Prevalence of 
ASB varies from 1-5% among healthy premenopausal women, to 25-50% among women in long 
term care, to 100% among patients with chronic indwelling catheters.(5)  Treatment of ASB with 
antimicrobial therapy does not reduce incidence of symptomatic UTI, complications or death, 
and is associated with adverse events.(6) Among women with ASB randomized to treatment, 
resistance to antibiotics among isolated bacteria increased.(7) Even among pregnant women, the 
treatment of ASB may not provide significant benefit.(8, 9) Various interventions have been 
proposed to reduce antibiotic treatment for ASB.  Physicians have difficulty avoiding treatment 
of ASB when presented with positive culture results.   
Recognizing the inappropriate treatment of ASB to be a problem in acute care, a novel 
intervention was defined, in which identification and susceptibility results for positive urine 
culture results were not made available to physicians, unless the physician called the 
microbiology laboratory.(10) This “modified reporting” was associated with a reduction in the 
rate of antibiotic treatment of AB from 48% to 12% (number needed to report for benefit = 3) 
among non-catheterized inpatients, using historical controls.   
 
A randomized, unblinded controlled trial was performed in acute care in St. John’s, 
among patients without indwelling catheters, using the same intervention.(11) Results of positive 
urine cultures from 110 consecutive inpatients at two urban hospitals were randomised to 

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standard report or modified report.  Specimens randomized to the modified report were reported 
as follows: “This POSITIVE urine culture may represent asymptomatic bacteriuria or urinary 
tract infection. If urinary tract infection is suspected clinically, please call the microbiology 
laboratory for identification and susceptibility results.” 
Exclusion criteria were age less than 18 years, pregnancy, presence of an indwelling 
urinary catheter, samples from patients already on antibiotics, neutropenia, or admission to an 
Intensive Care Unit.  Patients were followed for seven days, and physician treatment decisions 
were observed.  76/110 (69%) of positive urine cultures represented ASB.  The proportion of 
appropriate treatment (UTI treated plus ASB not treated) was higher in the modified arm than in 
the standard arm (44/55 (80.0%) vs 29/55 (52.7%), absolute difference=-27.3%, RR=0.42, 
p=0.002, Number needed to report for benefit=3.7).  
There were two bacteremias in the modified report group, and one bacteremia in the 
standard report group, none of which were considered related to the intervention. There were two 
deaths in the modified report group, and one death in the standard report group, none of which 
were considered related to the intervention.  Based on this trial, the intervention was considered 
safe over 7 days of followup, and effective to reduce inappropriate treatment, but further study 
would be required among populations excluded from the trial.      
 
We propose to repeat the trial using an identical design and intervention, but including 
only urine collected from long term care facilities (LTCF).  The control arm is standard of care.  
We hypothesize that the modified reporting intervention will also reduce treatment of ASB in the 
LTCF population, without causing harm.        
Objectives 

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Research Question: Among patients with positive urine cultures collected from LTCF 
reported by Health Sciences microbiology laboratory, would restricted reporting, as compared to 
standard reporting, lead to a reduction in the rate of inappropriate antibiotic therapy without an 
increase in bacteremia or death over 30 days? 
Trial design 
Randomized controlled trial, 2 parallel groups with equal allocation, superiority analysis. 
Methods: Participants, interventions, and outcomes 
The proposed study is a randomized trial of two methods of laboratory reporting in which 
physicians are the main research participants.  At the time of positive urine culture results, the 
specimen will be randomized in the laboratory using computer generated random numbers 
placed into serially numbered sealed, opaque envelopes, into two equal groups.  One group will 
receive modified reporting, and the other group will receive standard reporting of bacterial 
identification and susceptibility.  Physicians receiving modified reports will have the option to 
calling the laboratory to receive complete results, or not.  Complete results will be released by 
laboratory information system to physicians who call to request them. Physicians will be 
informed about the study prior to initiation, and debriefed about the study after the results have 
been collected. 
The primary efficacy outcome is proportion of appropriate antibiotic therapy prescribed 
by physicians, based on published diagnostic criteria for ASB and UTI among catheterized 
patients.  Appropriate therapy is defined as any treatment for UTI, or no treatment for ASB.  
Inappropriate therapy is defined as no treatment for UTI, or treatment for ASB.  The primary 
safety outcome is rate of bacteremia and death.  The study investigators will determine the 

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diagnosis based on a chart assessment to determine if the patient has UTI, CA-UTI, ASB or CA-
ASB.   
The definition of UTI in LTCF will be based on 2017 Canadian LTCF surveillance 
guidelines.(12)  For residents without an indwelling catheter, criteria 1 and 2 must be present 
with no other identified source of infection, OR criteria 2 and 3. 
1. At least 1 of the following sign or symptom subcriteria: 
a. Acute pain, swelling, or tenderness of the testes, epididymis, or prostate in males 
b. Fever or leukocytosis and at least 1 of the following localizing urinary tract subcriteria: 
i. Acute dysuria 
ii. Acute costovertebral angle pain or tenderness 
iii. Suprapubic pain 
iv. Gross hematuria 
v. New or marked increase in incontinence 
vi. New or marked increase in urgency 
vii. New or marked increase in frequency 
c. In the absence of fever or leukocytosis, then 2 or more of the following localizing 
urinary tract subcriteria: 
i. Acute dysuria 
ii. Suprapubic pain 
iii. Gross hematuria 
iv. New or marked increase in incontinence 
v. New or marked increase in urgency 
vi. New or marked increase in frequency 

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2. ≥ 108cfu/L of no more than 2 species of microorganisms from a midstream urine OR ≥ 105 
cfu/L of any number of organisms in a specimen collected by in-and-out catheter 
3. A blood culture isolate is the same as the organism isolated from the urine and there is no 
alternate site of infection 
For residents with an indwelling catheter (urine is collected from a single catheter urine 
specimen or a midstream voided urine specimen from a resident whose catheter has been 
removed within the previous 48 hours), criteria 1 and 2 must be present with no other identified 
source of infection, OR criteria 2 and 3. 
1. At least 1 of the following sign or symptom subcriteria: 
a. Fever, rigors, or new-onset hypotension, with no alternate site of infection 
b. Either acute change in mental status or acute functional decline, with no alternate 
diagnosis and leukocytosis 
c. New-onset suprapubic pain or costovertebral angle pain or tenderness 
d. Purulent discharge from around the catheter 
e. Acute pain, swelling, or tenderness of the testes, epididymis, or prostate in males 
2. Urinary catheter specimen culture with ≥ 108 cfu/L of any organism(s)  
3. A blood culture isolate is the same species as the organism isolated from the urine, with the 
same resistance pattern, and there is no alternate site of infection 
Study setting  
Specimens will be collected from patients admitted to one (or more?) LTCF in St. John’s, 
Newfoundland, Canada.  The metropolitan area of St. John’s has a population of 219,000 people 
(2017).  Pleasantview Towers (430 beds) provides long term residential accommodation for frail 

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elderly with high care needs.  One centralized microbiology laboratory performs all testing for 
the city.  
Inclusion and exclusion criteria for participants 
Consecutive positive urine cultures collected from patients admitted to LTCF will be 
included.  All methods of urine collection will be included (midstream, in-and-out 
catheterization, indwelling catheter). Exclusion criteria will be urine cultures not collected from 
LTCF patients, pregnancy, antibiotic treatment at the time of collection, and patients known to 
have blood neutrophils <1.0 within 7 days.   
Interventions  
The modified report states “This POSITIVE urine culture may represent asymptomatic 
bacteriuria or urinary tract infection.  If urinary tract infection is suspected clinically, please call 
the microbiology laboratory at 777-6936 between 0900 to 2300, or the microbiology technologist 
on-call at 570-9133 at night, for identification and susceptibility results.”  The standard report 
provides bacterial count, bacterial identification and bacterial susceptibility results. 
The report is provided to the physician approximately 24 hours after receipt of the 
specimen, when cultures have been examined after overnight incubation.  The intervention is a 
single report, so it is not possible to discontinue the intervention, or change allocation during the 
trial.  There will no other influence on concomitant care or treatment.        
Outcomes 
Primary efficacy outcome:  
Proportion of appropriate antibiotic therapy prescribed by physicians.  Appropriateness is 
determined by investigators based on chart review, based on diagnosis of UTI or ASB.  
Appropriateness is determined within two days from positive urine culture.     

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Secondary efficacy outcomes:  
Proportion of calls from physicians requesting complete report 
Primary safety outcomes:  
Mortality rate over thirty days from positive urine culture.   
Bacteremia rate over thirty days from positive urine culture.   
Adverse event rate over seven days from positive urine culture.  
Participant timeline  
 
STUDY PERIOD 
 
Enrolment 
Allocation 
Post-allocation 
TIMEPOINT 
Day -1 
Day 0 
Day 2 
Day 7 
Day 30 
ENROLMENT: 
Urine 
specimen 
received at 
microbiology 
laboratory 
Urine 
culture 
result 
reported to 
physician 
Physician 
treatment 
decision 
made 
Safety 
assessment 
Safety 
assessment 
Eligibility screen 
X 
 
 
 
 
Allocation 
 
X 
 
 
 
INTERVENTIONS: 
 
 
 
 
 
Reporting 
 
X 
 
 
 
 ASSESSMENTS: 
 
 
 
 
 
Appropriateness  
 
 
X 
 
 
 
Adverse Events 
 
 
X 
X 
X 
Bacteremia 
 
 
X 
X 
X 
Mortality 
 
 
X 
X 
X 
 
Sample size  

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In the previous trial of the same intervention, modified reporting increased the 
appropriateness of treatment from 29/55 (52.7%) to 44/55 (80.0%) (p=0.002), for an absolute 
difference of +23%.(11)  Accepting a risk of type 1 error of five percent, and a risk of type 2 
error of twenty percent, the study will require 2N=90 patients.  To account for missing data, 
recruitment will be increased to 100 patients.   
The microbiology laboratory receives 130 urine specimens per day, with 30 percent 
reported as significant growth (40 specimens per day).   Ten percent are submitted from LTCF (4 
positive specimens per day).  In the previous trial, approximately 40% of eligible specimens 
were excluded based on exclusion criteria.  Recruitment of 100 specimens will require 
approximately 40-60 days.   
The statistical test to be used is a comparison of proportions between two groups (T test, 
two-sided analysis).  Because true diagnosis may be biased by lack of access to clinical 
information, an intention to treat analysis including all patients randomized will be performed.  
Recruitment 
Every urine specimen received for culture during the study period will be assessed for 
inclusion.   
Allocation: 
 
 
Sequence generation 
Randomization sequence will be generated without blocking or stratification (Research 
Randomizer 4.0)(13).  
Allocation concealment 
Reporting assignments will be placed into serially numbered, sealed, opaque envelopes.  
Implementation 

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Allocation sequence will be generated by investigators.  Investigators will enroll 
specimens and assign specimens to reporting interventions.   
 
Blinding 
Trial participants (physicians) will not be blinded to the intervention because the 
laboratory report will reveal the intervention.  Investigators will be blinded to assignment.  Data 
analyst will not be blinded to assignment.   
Data collection methods 
After randomization and reporting, a physician investigator will assess inpatients for the 
true diagnosis of UTI or ASB at two days after reporting.  Health records will be accessed 
including demographics, symptoms, treatment decisions and outcomes. 
If patients are discharged from hospital before thirty days, primary care physicians will 
be contacted by phone for additional clinical information.  If patients die before thirty days, 
available data will be analyzed.     
Frequency of physician calls requesting complete reporting will be recorded. 
Urine culture is reported according to laboratory protocol by licenced medical laboratory 
technologists, in categories of significant growth, non-significant growth, and no growth, based 
on quantity of growth and number of bacterial types detected.  Antimicrobial susceptibility is 
reported according to laboratory protocol, including selected first and second-line antibiotics, as 
susceptible, intermediate or resistant.  Drug cost and dosage suggestion are provided. 
Data collection form attached.       
Data management 
Data collection will use a paper case report form, and entered into a trial database by a 
graduate student.  Variables will be coded appropriately. The dataset will be protected using a 

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password and stored on a laptop computer during data entry.  After data entry is completed, data 
integrity will be reviewed by a second investigator, and then the dataset will be locked for 
analysis.    
Statistical methods  
All specimens randomised and reported will be included in the Intention-to-treat (ITT) 
analysis.  Specimens inappropriately included will be excluded from the Per-protocol (PP) 
analysis.  The proportion of appropriate treatment will be compared using two-sided Pearson chi 
squared test (SPSS 23.0, IBM, USA).  Adjusted analysis may be performed if appropriate.  A 
subgroup defined as specimens in which physicians requested complete reporting will be 
analysed for appropriateness, compared to the standard reporting arm.  Missing data will not be 
imputed.  
Data monitoring 
A data monitoring committee will not be used, as a single investigator will assume 
responsibility for data quality.  A single interim analysis at approximately 50% recruitment will 
be performed, and the study stopped if the primary outcome achieves statistical significance. 
Harms 
Serious adverse events will be reported to the ethics committee within 24 hours.  Adverse 
events will be collected by the investigators at day 2, day 7 and day 30.  Patients with adverse 
events will be provided care in hospital.  
Auditing 
There will not be auditing of trial conduct during or after the trial.   
Research ethics approval 

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The protocol will be submitted to the Provincial Health Research Ethics Board.  
Physician consent requirement will be requested to be waived because the intervention poses no 
more than minimal risk to participants.  Patient consent requirement will be requested to be 
waived because physicians were the research subjects.  A letter will be sent to all inpatient 
physicians informing them about the study prior to recruitment, and a debrief meeting, offering 
an opportunity to withdraw physician participation, will be provided.   
The benefit of this study to patients includes a reduction in adverse events caused by 
inappropriate antibiotic treatment.  The risk to patients includes possible untreated UTI.  The 
benefit to physicians includes education toward appropriate treatment of ASB.  The risk to 
physicians includes additional effort to access laboratory results for UTI.   
Protocol amendments 
Protocol amendments will be submitted to the ethics committee and trial registry and 
informed to investigators.   
Consent or assent 
Not applicable. 
 
Confidentiality 
Identification of patients will be required during data collection, but will be removed 
from trial dataset before analysis.  No identifiers will be included in reporting of results.    
Declaration of interests 
The investigators and sponsor hold no financial interests in the trial.   
 
Access to data 
The trial dataset and protocol will be accessible to the investigators during the trial, and 
made publically available after the analysis is completed.    

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Ancillary and post-trial care 
There will be no post-trial care provided.  
 
Dissemination policy 
Investigators will communicate trial results via unrestricted publication.  All investigators 
are eligible for authorship, according to contribution.   
Biological specimens 
There will be no collection, testing or storage of biological specimens for genetic or 
molecular analysis.    
Budget 
           The only expense of the project will be the graduate student to collect the data, perform 
the analysis and write the manuscript.  
Implications 
A reduction in inappropriate antibiotic treatment may reduce complications of treatment 
such as diarrhea due to Clostridium difficile, selection of bacteria towards drug resistance, and 
cost of treatment.  If the intervention is determined to be safe, it may be considered for 
implementation in routine laboratory practice.  The results will generalize to adult inpatients in 
Canada and around the world.  
 
 

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