Modified Reporting of Positive Urine Cultures Collected From Indwelling Catheters, a Randomized Controlled Trial
Phase: NA
Conditions: Urinary Tract Infections
Sponsor: Memorial University of Newfoundland

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Modified Reporting of Positive Urine Cultures Collected from Indwelling Catheters Among 
Inpatients, a Randomized Controlled Trial Protocol  
www.clinicaltrials.gov NCT03488355 
Peter Daley, David Garcia, Brendan Barrett 
 
Administrative Information 
Protocol Version: 1.0 April 2018 
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: Brendan Barrett, David Garcia 
Introduction  
 
Background and rationale  
Asymptomatic bacteriuria (ASB) is a condition in which bacteria from the bowel are 
detected in significant numbers by culture of 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 
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 

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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 
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 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 acute care hospitals were randomised to 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 

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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 indwelling catheters.  The control arm is standard of care.  We 
hypothesize that the modified reporting intervention will also demonstrate effectiveness at 
reducing treatment of ASB in this population, without causing harm.        
Objectives 
Research Question: Among inpatients with positive urine cultures collected from 
indwelling catheters reported by Health Sciences microbiology laboratory, would restricted 

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reporting, as compared to standard reporting, lead to a reduction in the rate of inappropriate 
antibiotic therapy without an increase in bacteremia or death? 
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 by computer generated random number 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 identification and susceptibility.  
Physicians will then have the option of calling the laboratory to receive the results or not.  
Complete results will be released by telephone and 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 definition of CA-UTI will be based on the Infectious Diseases Society of America 
guidelines,(2) not the Centers for Disease Control National Health Safety Network surveillance 
definition, which is not designed for clinical care.(12) The definitions to be used in patients with 
indwelling urethral, indwelling suprapubic, or intermittent catheterization are as follows: 
CA-UTI 
1. presence of symptoms or signs compatible with UTI with no other identified 
source of infection AND  
2. ⩾103 colony-forming units (cfu)/mL of ⩾1 bacterial species in a single catheter 
urine specimen or in a midstream voided urine specimen from a patient whose 

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urethral, suprapubic, or condom catheter has been removed within the previous 
48 h 
CA-ASB 
1. presence of ⩾105 cfu/mL of ⩾1 bacterial species in a single catheter urine 
specimen in a patient without symptoms compatible with UTI. 
Signs and symptoms compatible with CA-UTI include new onset or worsening of fever, 
rigors, altered mental status, malaise, or lethargy with no other identified cause; flank pain; 
costovertebral angle tenderness; acute hematuria; pelvic discomfort; and in those whose catheters 
have been removed, dysuria, urgent or frequent urination, or suprapubic pain or tenderness.  In 
patients with spinal cord injury, increased spasticity, autonomic dysreflexia, or sense of unease 
are also compatible with CA-UTI. 
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.  The 
primary safety outcome is rate of bacteremia and death. 
Study setting  
Specimens will be collected from inpatients admitted to one of the two tertiary care 
academic hospitals in St. John’s, Newfoundland, Canada.  Health Sciences Center (346 acute 
care beds) provides medicine, pediatric and surgery inpatient services, critical care, cardiac 
surgery, neurosurgery, plastic surgery, burn unit, obstetrics/gynecology and acute psychiatry.  St. 
Clare’s Mercy Hospital (205 acute care beds) provides medicine and surgical inpatient services, 
critical care, general surgery, vascular surgery, thoracic surgery, otolaryngology, orthopedics, 

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and ambulatory services.  The metropolitan area of St. John’s has a population of 219,000 people 
(2017).  One centralized microbiology laboratory performs all testing for the city.  
Inclusion and exclusion criteria for participants 
Consecutive positive urine cultures collected from indwelling catheters from patients 
greater than or equal to 18 years of age, admitted to acute care will be included.  Inpatients must 
be admitted to Health Sciences Center or St. Clare’s Mercy hospitals only, to facilitate access to 
inpatient records.  Exclusion criteria will include urine cultures not collected from indwelling 
catheters, pregnancy, antibiotic treatment at the time of collection, patients in the Intensive Care 
Unit and patients with blood neutrophils <1.0 within 7 days, which will help protect 
immunocompromised individuals, and admission to a urologist.    
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:  

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Proportion of appropriate antibiotic therapy prescribed by physicians.  Appropriateness is 
determined by investigators based on chart review, based on diagnosis of CA-UTI or CA-ASB.  
Appropriateness is determined within seven days from positive urine culture.     
Secondary efficacy outcomes:  
Proportion of calls from physicians requesting complete report 
Primary safety outcomes:  
Mortality rate over seven days from positive urine culture.   
Bacteremia rate over seven 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 
ENROLMENT: 
Urine specimen 
received at 
microbiology 
laboratory 
Urine culture 
result reported 
to physician 
Physician 
treatment 
decision 
made 
Safety 
assessment 
Eligibility screen 
X 
 
 
 
Allocation 
 
X 
 
 
INTERVENTIONS: 
 
 
 
 
Reporting 
 
X 
 
 
 ASSESSMENTS: 
  
  
 
 
Appropriateness  
 
 
X 
  
  
Adverse Events 
 
 
X  
X 
Bacteremia 
 
 
X 
X  
Mortality 
 
 
X 
 X 

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Sample size  
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).   Twenty-five percent are submitted from 
inpatients (10 specimens per day).  Approximately 33% of inpatient urines are collected from 
catheters, however collection method is not always provided to the laboratory.  This leaves 
approximately three urine specimens per day which may be eligible for inclusion.  In the 
previous trial, approximately 40% of eligible specimens were excluded based on exclusion 
criteria.  Recruitment of 100 specimens will require approximately 60-90 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).  

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Allocation concealment 
Reporting assignments will be placed into serially numbered, sealed, opaque envelopes.  
Implementation 
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.  One investigator will serve as outcome assessor, 
and will be blinded to assignment.  Data analyst will not be blinded to assignment.   
Data collection methods 
After randomization and reporting, a blinded physician investigator will assess inpatients 
for the true diagnosis of CA-ASB or CA-UTI at two days after reporting.  Health records will be 
accessed including demographics, symptoms, treatment decisions and outcomes (treated CA-
ASB, treated CA-UTI, untreated CA-ASB, untreated CA-UTI).   
If patients are discharged from hospital before seven days, primary care physicians will 
be contacted by phone for additional clinical information.  If patients die before seven 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. 

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Data collection form attached.       
Data management 
Data will be entered into the trial dataset by a single investigator.  Data collection will 
use a paper case report form, and entered into a trial database by a single investigator.  Variables 
will be coded appropriately. The dataset will be protected using a 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 will not be performed.  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 significan  
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 and day 7.  Patients with adverse events will 
be provided care in hospital.  
Auditing 

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There will not be auditing of trial conduct during or after the trial.   
Research ethics approval 
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 CA-UTI.  The 
benefit to physicians includes education toward appropriate treatment of CA-ASB.  The risk to 
physicians includes additional effort to access laboratory results for CA-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 

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The trial dataset and protocol will be accessible to the investigators during the trial, and 
made publically available after the analysis is completed.    
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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