Asymptomatic Bacteriuria & Risk of Urinary Tract Infection in Renal Transplants (ASB)

The goal of this research program is to understand the natural history of asymptomatic bacteriuria in the renal transplant patients, to determine if screening for asymptomatic bacteriuria and identification of key host characteristics and virulence factors present on uropathogenic bacteria identifies a sub-population of patients with asymptomatic bacteriuria that are at risk to develop symptomatic urinary tract infection. Ultimately, the knowledge obtained from this study will prevent inappropriate antibiotic use and may identify whether certain bacterial isolates predispose to renal allograft injury. We will test the hypothesis that (i) asymptomatic bacteriuria is common in the renal allograft recipient and (ii) that symptomatic urinary tract infection and renal allograft dysfunction do not occur unless key host susceptibility factors and uropathogenic bacterial virulence factors are present.

Study Overview

• Status: Unknown
• Conditions: Bacteriuria; Urinary Tract Infections; Transplantation Infection; Asymptomatic Infections
• Intervention / Treatment: Drug: Antibiotic

Detailed Description

Blood samples and urine cultures will be obtained from asymptomatic renal transplant clinic patients. If the urine culture is positive (> or = 105 cfu/ml), we will determine the host and bacterial virulence factors associated with asymptomatic bacteriuria (ASB) and compare these results to transplant patients that develop a symptomatic UTI. The patient's clinical information, laboratory data and the bacterial isolate responsible for the UTI will be collected at the time of their clinic visit and subsequently analyzed.

After the first visit (Day 0 after signing consent) blood and urine will be collected, subjects will be put into either ASB Positive or ASB Negative groups based upon the results of their urine culture. From that point, those who test into the ASB Negative group will have an additional urine culture, either by returning to the clinic or by sending a urine culture mailer kit, and if cultures remain negative, they will be discharged from the study after reviewing medications, adverse events and completing a urinary tract infection risk questionnaire.

For those who test into the ASB Positive group, those subjects will be monitored by the subject returning to the clinic on Day 10-14, at 1 month, 2 month, 3 month and 6 months for blood and urine collection, review of medications and adverse events, and completing a urinary tract infection risk questionnaire. Should the subject have symptoms of a UTI, the subject will be treated with the appropriate antibiotic for which the bacterial isolated from their urine culture is sensitive. Patients will return to the clinic 10-14 days later for a repeat urine culture, complete a urinary tract infection risk questionnaire, and have a repeat urine culture to confirm they are urinary tract infection free. At this point, the subject will be discharged from the study after reviewing medications and adverse events.

It is predicted that 75% of patients will test into the ASB Negative Group and do not require antibiotic therapy. We predict that 25% of patients will test into the ASB Positive Group, but that less than 5% of these patients will ultimately develop a symptomatic UTI and require antibiotic treatment.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Green Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Kidney Transplant Patients

Description

Inclusion Criteria:

• must be 18 years old or older,
• had a kidney transplant,
• be at least 30 days post operation.

Exclusion Criteria:

• Pregnant women, those planning to become pregnant or nursing mothers;
• Renal transplant patients less than 30 days post transplant; Use of an indwelling Foley catheter;
• Patients without a renal transplant;
• Patients having concurrent surgical/wound infection and presumed hematogenous dissemination for the urinary tract.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Positive Group; Positive for ASB	Drug: Antibiotic; Antibiotic (drug) sensitive to most recent culture for these subjects testing ASB positive and also experience Signs and symptoms of a UTI; Other Names: Ampicillin; Trimethoprim sulfamethoxazole (Bactrim); Levofloxacin (Levaquin); SUSCEPTIBILITY; Organism >100,000 col/ml Escherichia coli (presumptive); Susceptibility type MIC (BY VITEK 2); Ampicillin >=32 Resistant; Ampicillin/Sulbactam 16 Intermediate; Cefazolin <=4 Suscep.; Ciprofloxacin <=0.25 Suscep.; Gentamicin <=1 Suscep.; Levofloxacin <=0.12 Suscep.; Nitrofurantoin <=16 Suscep.; Tobramycin <=1 Suscep.; Trimeth-Sulfa >=16/304 Resistant
Negative Group; Negative for ASB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Asymptomatic Bacteriuria and Risk of Developing Symptomatic Urinary Tract Infections or Renal Allograft Injury in Renal Transplant Patients	Determine the prevalence and natural history of asymptomatic bacteriuria (ASB) and the host factors associated with the development of symptomatic UTI in renal allograft recipients. We will enroll renal transplant recipients, perform urine cultures and follow all patients with ASB to determine the prevalence of ASB and the host characteristics associated with ASB and the development of symptomatic UTI.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Host Characteristics of Renal Transplant Patients with Asymptomatic Bacteriuria at Risk to Develop Symptomatic Urinary Tract Infection	We will measure blood and urine immunoglobulin and cytokine levels in patients with ASB and symptomatic UTI to determine if these host's immune parameters predict the outcome of ASB, including the development of symptomatic UTI.	2 years
Determine the characteristics of uropathogenic bacteria that cause acute allograft injury in renal transplant patients.	We will determine the expression of key uropathogenic virulence factors, including P fimbriae, Dr adhesins, and mono-mannose-binding type 1 fimbriae, on E. coli isolated from RTPs with ASB to determine if strains that express such virulence factors are more likely to cause symptomatic UTI and AAI, compared to E. coli that do not express these virulence factors.	2 years

Collaborators and Investigators

• Sponsor: Rice, James C., M.D.
• Collaborators: University of Alabama at Birmingham
• Investigators: Principal Investigator: James C. Rice, MD, Scripps

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Study Completion (Anticipated): May 1, 2013

Study Registration Dates

• First Submitted: May 4, 2011
• First Submitted That Met QC Criteria: May 5, 2011
• First Posted (Estimate): May 9, 2011

Study Record Updates

• Last Update Posted (Estimate): September 1, 2011
• Last Update Submitted That Met QC Criteria: August 31, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Asymptomatic Diseases; Infections; Communicable Diseases; Urinary Tract Infections; Bacteriuria; Asymptomatic Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Cytochrome P-450 CYP1A2 Inhibitors; beta-Lactamase Inhibitors; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Ampicillin; Anti-Bacterial Agents; Gentamicins; Ciprofloxacin; Cefazolin; Levofloxacin; Ofloxacin; Tobramycin; Trimethoprim; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination; Nitrofurantoin; Sulbactam
• Other Study ID Numbers: ASB in Transplants