Restricted Reporting for Positive Urine Cultures Randomized Controlled Trial
Phase: NA
Conditions: Bacteriuria, Urinary Tract Infection
Sponsor: Memorial University of Newfoundland

 
 
 
 
 
 
 
Restricted Reporting for Positive Urine Cultures Randomized Controlled Trial Protocol 
July 26, 2016 
 
 
 
 
NCT: 02797613 
 
 
 
 

Restricted Reporting for Positive Urine Cultures Randomized Controlled Trial Protocol 
Peter Daley, Carla Penney, Sarah Boyd, Emeka Chinaka 
 
Introduction  
Asymptomatic bacteriuria (AB) 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 urinary-specific 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] The use of 
inappropriate antibiotic treatment for AB is a systemic stewardship problem, causing harm due to 
antibiotic adverse effects, selection of bacteria toward drug resistance, and wasted cost.[4]  
 
Recognizing the inappropriate treatment of AB to be a concern among long term care 
(LTC) residents, Peter Daley, Carla Penney and colleagues performed an observational study in 
St. John’s.[5] 101 consecutive positive urine cultures submitted from six LTC facilities were 
included, and nurses were interviewed regarding reasons for collection, antibiotic treatment 
given, and patient response to treatment after seven days.  In most cases, basic investigations 
such as vital signs and urinalysis were not performed.  The rate of positive cultures was the same 
as the expected AB rate.  Most considered reasons for urine collection did not correlate with 
positive culture.  Physicians did not treat according to culture results, and treatment did not 
correlate with improvement in activities of daily living score.  The conclusion was that urine 
culture may not be a useful investigation in LTC, and that changes were required in the selection 
of patients for testing and antibiotic treatment decisions.   
 
Because urine represents half of all specimens received in Eastern Health microbiology 
laboratories, with 30 percent of specimens requiring bacterial identification and antibiotic 
susceptibility testing, significant cost savings may be realized by improvements in policy, so 
further research is being proposed.      

Literature Review 
UTI’s are among the commonest indications for antimicrobial therapy, among inpatients, 
outpatients and LTC patients.  Prevalence of AB varies from 1-5% among healthy 
premenopausal women, to 25-50% among women in LTC, to 100% among patients with chronic 
indwelling catheters.[6]  Treatment of AB with antimicrobial therapy does not reduce incidence 
of symptomatic UTI, complications or death, and is associated with adverse events.[7] Among 
women with AB randomized to treatment, resistance to antibiotics among isolated bacteria 
increased.[8] Even among pregnant women, the treatment of AB may not provide significant 
benefit.[9, 10] 
Various interventions have been proposed to reduce inappropriate antibiotic treatment for 
AB.  Physicians have difficulty avoiding treatment when presented with positive culture results.  
A cluster randomized trial of an algorithm for diagnosis and treatment of UTI failed to reduce 
urine culture collection rate.[11]  169 residents and staff physicians demonstrated poor 
knowledge of published AB treatment guidelines, suggesting education may be of benefit.[12]  
Prospective audit and feedback to physicians reduced treatment duration, but not treatment 
initiation decisions in one study,[13] and reduced culture orders and treatment during and after 
an intervention period in another study.[14] An educational intervention reduced inappropriate 
treatment during the intervention period.[15] Audit and educational interventions require 
considerable effort and may not lead to sustainable change.       
A novel approach to inappropriate therapy changes the way urine culture results are 
provided to physicians.  In a pilot study, non-catheterized inpatients with positive urine cultures 
were reported by the microbiology laboratory with a general statement suggesting the physician 
call the lab if specific culture information was considered clinically necessary.[16] This provided 

a barrier to access to positive culture results.  In the intervention group (415 specimens, 17.8% 
culture positive, 2% had clinical evidence of UTI), restricted reporting reduced inappropriate 
therapy from 48% to 12%, with no incidence of UTI or sepsis.  Among 37 positive cultures 
reported in the restricted way, only 5 calls were received to the laboratory requesting complete 
culture report.  The study used retrospective and catheterized control groups.  
The use of restricted reporting could provide a cheap and sustainable intervention to 
reduce inappropriate treatment for AB.  Because the study was not randomized, the estimate of 
true effect may be biased.  An ideal design would include randomization of positive cultures 
between restricted and standard reporting.  
Research Objectives 
Research Question: Among inpatients with positive urine cultures 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 UTI or 
pyelonephritis (kidney infection)? 
Primary efficacy outcome: proportion of inappropriate antibiotic therapy prescribed by 
physicians based on published diagnostic criteria for AB and UTI [2, 4, 17] in an intention to 
treat population.  Inappropriate therapy is defined as any treatment for AB, or no treatment for 
UTI, or treatment for UTI to which the isolated bacteria is resistant. 
Primary safety outcome: proportion of untreated UTI and untreated bacteremia. 
Secondary efficacy outcomes: proportion of calls from physicians requesting complete report, 
drug cost savings based on reduction in treatment. 
Methodology 

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 
patient will be randomized by computer generated random number placed into serially numbered 
sealed, opaque envelopes in two equal groups.  One group will receive restricted reporting, with 
a report that 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 other group will 
receive conventional 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 Meditech 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. 
   Inclusion criteria will include consecutive positive urine cultures collected from adults 
in acute care that are greater than or equal to 18 years of age.  Inpatients must be admitted to 
Health Sciences Center or St. Clare’s Mercy hospitals only, in order to facilitate access to 
inpatient records.  Exclusion criteria will include pregnancy, antibiotic treatment at the time of 
collection, collection from an indwelling urinary catheter, patients in the Intensive Care Unit and 
patients with blood neutrophils <1.0 within 7 days, which will help protect immunocompromised 
individuals.  Furthermore, Dr. Peter Daley will review patient charts at 24 and 72 hours and 7 
days after collection to ensure patients experience minimal adverse events. 
After randomization and reporting, a physician investigator will assess inpatients for the 
true diagnosis of AB or UTI.  Health records will be accessed including demographics, treatment 

decisions and outcomes (untreated UTI or pyelonephritis).  Frequency of physician calls 
requesting complete reporting will be recorded. 
The microbiology laboratory at Health Sciences Center receives 130 urine specimens per 
day, with 30 percent reported as significant growth (40 specimens per day).   Twenty-five 
percent are submitted from inpatients.  Method of collection will be determined prior to 
randomization.  Study data collection and analysis will take place at the microbiology laboratory 
only.     
The research hypothesis is that restricted reporting will reduce the rate of inappropriate 
treatment prescribed by physicians.  Among inpatients, the expected rate of inappropriate 
treatment in the control group will be  45 percent, and 15 percent in the intervention group.    
Accepting a risk of type 1 error of five percent, and a risk of type 2 error of twenty percent, the 
study will recruit 84 patients.  In order to account for missing data, recruitment will be increased 
to 100 patients.  This will require approximately ten days of recruitment.  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.  
Physicians must remain unaware of the research project so that their treatment decisions 
are unbiased. However, a general notice will be sent to all physicians regarding the study design, 
and a debrief will be provided in which study results are presented and the option to withdraw 
data will be provided. This will cause physicians to feel less deceived while still not informing 
them of the study and thus will not change their behavior. 

Physicians of discharged inpatients will be contacted at 7 days to assess for adverse 
events.  Because recruitment will be brief, it is unlikely that physicians will have a second patient 
in the study.               
Ethics permission will be sought from the local ethics board.  Consent of patients or 
physicians will not be requested. In compliance with TCPS requirements, participants will 
experience no more than minimal risk.  Dr. Daley who will assess inpatient charts at 24 and 72 
hours and 7 days to surveil adverse events.  If an adverse event occurs, the patient will be 
removed from the study immediately and given standard treatment.  Physician consent will not 
be requested, as awareness of the study would bias treatment decisions.  
The benefit of this study to patients includes a reduction in adverse events caused by 
inappropriate treatment.  The risk to patients includes possible untreated UTI.  The benefit to 
physicians includes education toward appropriate treatment of AB.  The risk to physicians 
includes additional effort to access laboratory results for UTI.   
Data collection will use a paper case report form, and entry into a password protected 
online database.  Analysis will be performed using SPSS 20.0 (IBM).  The only expense of the 
project will be the graduate student to collect the data, perform the analysis and write the 
manuscript.  The manuscript will be published in a peer-reviewed journal and presented at a 
national conference.   
Implications 
The implications of significant results will be powerful.  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.  A demonstration 
that untreated UTI or pyelonephritis is rare may educate physicians and nurses to be more 

selective in urine collection.  This could reduce workload and cost in the microbiology 
laboratory.  The results will generalize to adult inpatients in Canada and around the world.  If the 
results agree with the previous study, evidence may justify restriction of access to urine culture 
based on pretest probability of UTI.                 
 
 

References 
 
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