Antibacterial Drug Adverse Reaction, Urologic Diseases
Conditions
Keywords
anti-bacterial
Brief summary
Antimicrobial resistance is one of today''s most urgent public health problems. An important strategy to slow the spread of antimicrobial resistance is the promotion of judicious antimicrobial use. There are many opportunities to reduce unnecessary antimicrobial-prescribing, including in patients undergoing surgical procedures. The following study will specifically study opportunities to improve antimicrobial use in patients undergoing common urologic procedures at hospitals in the Veterans Health Administration (VHA). Guidelines recommend giving antibiotics for no more than 24-hours after most urologic procedures, but the investigators have shown that the unnecessary use of post-procedural antimicrobials is common in this setting. In a national cohort of nearly 30,000 VHA patients, excessive post-procedural antimicrobials were prescribed after 37.2% of urologic procedures for a median duration of 3.0 excess days. In this study, the investigators will evaluate whether giving regular feedback to providers at 3 VHA hospitals can reduce unnecessary antimicrobial use after urologic procedures.
Detailed description
Trial design: The investigators propose a before/after quasi-experimental design, which will be analyzed with an interrupted time-series analysis. Participants: There will be 3 intervention VHA hospitals. To be eligible, a VHA hospital must perform the following 3 urologic procedures: transurethral resection of the prostate (TURP), transurethral resection of a bladder tumor (TUBRT), and ureteroscopy (URS). Interventions: The study team will conduct an audit-and-feedback intervention focused on the unnecessary use of prolonged antimicrobial therapy after common urologic procedures. The audit-and-feedback intervention will target the urology providers at the 3 intervention sites. Outcomes: The primary outcome for this study will be the frequency of excessive post-procedural antimicrobial-prescribing in the 3 urologic procedures of interest. Secondary outcomes include several safety outcomes, such as late antimicrobial prescriptions, return visits, mortality, C. difficile testing and C. difficile infection. For each site, the pretest period will be the 2-years prior to the intervention. The intervention itself will last 1-year. Selection of sites: Intervention sites will be randomly selected from the top quartile of all sites, as ranked on the frequency of excessive post-procedural antimicrobial-prescribing. If sites refuse to participate, additional sites will be invited until 3 sites agree to be enrolled. Statistical methods: At the conclusion of the pilot trial, a quasi-experimental interrupted time-series (ITS) analysis will be performed to assess the change in monthly antimicrobial use for the 3 intervention sites combined. The time frame for this ITS analysis will be the two-years prior to the pilot trial's initiation through the trial's 1-year intervention period for a total of 36 months.
Interventions
BEHAVIORALAudit-and-feedback
We will provide feedback both at baseline and at regular intervals to the 3 intervention sites. At first, we will schedule one-on-one conference calls with urology providers and the antimicrobial stewardship team at each of the 3 intervention sites. These conference calls will include a review of guidelines, a review of the facility's data on excessive post-procedural antimicrobial use for urologic patients, and an anonymous comparison to all other VHA sites. Next, we will prospectively monitor excessive post-procedural antimicrobial use at all 3 sites and the entire VHA for 1 year. Data on hospital-level excessive post-procedural antimicrobial use specific to urologic patients (primary outcome) will be sent electronically to urology providers and the antimicrobial stewardship team at the intervention site every other month via electronic mail.
Sponsors
Merck Sharp & Dohme LLC
Iowa City Veterans Affairs Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
The behavioral intervention will be delivered at 3 intervention hospitals.
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* A practicing urologist at an intervention site, OR * A member of the antimicrobial stewardship team at an intervention site
Exclusion criteria
None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Cases Who Received Excessive Post-procedural Antimicrobials | Within 1 day of the urologic procedure | Excessive post-procedural antimicrobial use is defined as a prescription for a antimicrobial agent on post-procedural day one. For this specific outcome measure, the numerator will be the number of patients who received an excessive post-procedural antimicrobial, and the denominator will be all patients at the site who underwent a qualifying urologic procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Cases Who Received a Late Antimicrobial Prescription | Within 30-days of the urologic procedure | Late antimicrobial prescription is defined as the prescription of a designated antimicrobial that does not qualify as a post-procedural antimicrobial (see above) by any provider within 7-30 days of the date of the patient's urologic procedure. For this specific outcome measure, the numerator will be the number of patients who received a late antimicrobial, and the denominator will be all patients at the site who underwent a qualifying urologic procedure. |
| Percentage of Cases Who Were Re-admitted to the Hospital or Presented to an Emergency Department or an Urgent Care Clinic | Within 30-days of the urologic procedure | Return visits: sought urgent/emergent healthcare for any indication within 30 days of the patient's index urologic procedure. For this specific outcome measure, the numerator will be the number of patients who had a return visit for any reason within 30-days of the urologic procedure, and the denominator will be all patients at the site who underwent a qualifying urologic procedure. |
| Excessive Post-procedural Antimicrobial Duration (Mean) | Within 30-days of the urologic procedure | Excessive post-procedural antimicrobial duration is defined as the duration of continuous excessive post-procedural antimicrobial use, as quantified as days of therapy per National Healthcare Safety Network methodology. This outcome will be calculated for each patient who underwent a qualifying procedure and received a post-procedural antimicrobial (primary outcome). |
| Percentage of Cases Who Underwent Clostridioides Difficile Testing | Within 30-days of the urologic procedure | Clostridioides difficile testing is defined as any laboratory test ordered for C. difficile within 30-days of the patient's urologic procedure. For this specific outcome measure, the numerator will be the number of patients who underwent C. difficile testing within 30-days of the procedure, and the denominator will be all patients at the site who underwent a qualifying urologic procedure. |
| Percentage of Cases Who Acquired Clostridioides Difficile Infection | Within 30-days of the urologic procedure | Clostridioides difficile infection (CDI) is defined as a positive laboratory test for C.difficile within 30-days of the patient's urologic procedure. For this specific outcome measure, the numerator will be the number of patients who had a positive test for C. difficile within 30-days of the procedure, and the denominator will be all patients at the site who underwent a qualifying urologic procedure. |
| Percentage of Cases Who Died (Mortality) | Within 30-days of the urologic procedure | Mortality: all-cause death within 30-days of the patient's index urologic procedure. For this specific outcome measure, the numerator will be the number of patients who died for any reason within 30-days of the urologic procedure, and the denominator will be all patients at the site who underwent a qualifying urologic procedure. |
Countries
United States
Participant flow
Pre-assignment details
All patients who underwent a qualifying urologic procedure during 8/1/2022-7/31/2023 at a participating site were included in the intervention phase. These procedures were ureteroscopy (URS), transurethral resection of the prostate (TURP), and transurethral resection of a bladder tumor (TURBT). Outcomes in these enrolled patients were compared to outcomes in patients who underwent these qualifying procedures during a baseline period (n=1272); the baseline period spanned from 7/1/2020-6/30/2022.
Participants by arm
| Arm | Count |
|---|---|
| Intervention We will select 3 intervention sites that were above the median in their frequency of excessive post-procedural antimicrobial use after the 3 urologic procedures of interest, based on data from the 24-month baseline period. We will provide feedback both at baseline and at regular intervals to the 3 intervention sites. At first, we will schedule one-on-one conference calls with urology providers and the antimicrobial stewardship team at each of the 3 intervention sites. These conference calls will include a review of guidelines, a review of the facility's data on excessive post-procedural antimicrobial use for urologic patients, and an anonymous comparison to all other VHA sites. Next, we will prospectively monitor excessive post-procedural antimicrobial use at all 3 sites and the entire VHA for 1 year. Data on hospital-level excessive post-procedural antimicrobial use specific to urologic patients (primary outcome) will be sent electronically to urology providers and the antimicrobial stewardship team at the intervention site every other month via electronic mail. These data will include an anonymous comparison to all other VHA hospitals. | 525 |
| Baseline Patients in the baseline group underwent one of the qualifying procedures at the 3 intervention sites during a period of time (7/1/2020-6/30/2022) before the intervention was implemented. | 1,272 |
| Total | 1,797 |
Baseline characteristics
| Characteristic | Baseline | Total | Intervention |
|---|---|---|---|
| Age, Continuous | 71.6 Years STANDARD_DEVIATION 10 | 71.7 Years STANDARD_DEVIATION 10.2 | 71.9 Years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 55 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1175 Participants | 1630 Participants | 455 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 61 Participants | 112 Participants | 51 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 7 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 155 Participants | 252 Participants | 97 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 82 Participants | 126 Participants | 44 Participants |
| Race (NIH/OMB) White | 1026 Participants | 1404 Participants | 378 Participants |
| Sex: Female, Male Female | 44 Participants | 59 Participants | 15 Participants |
| Sex: Female, Male Male | 1228 Participants | 1738 Participants | 510 Participants |
| Transurethral resection of a bladder tumor | 731 Participants | 1013 Participants | 282 Participants |
| Transurethral resection of prostate | 260 Participants | 390 Participants | 130 Participants |
| Ureteroscopy | 281 Participants | 394 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 525 | 4 / 1,272 |
| other Total, other adverse events | 0 / 525 | 0 / 1,272 |
| serious Total, serious adverse events | 113 / 525 | 186 / 1,272 |
Outcome results
Primary
Percentage of Cases Who Received Excessive Post-procedural Antimicrobials
Excessive post-procedural antimicrobial use is defined as a prescription for a antimicrobial agent on post-procedural day one. For this specific outcome measure, the numerator will be the number of patients who received an excessive post-procedural antimicrobial, and the denominator will be all patients at the site who underwent a qualifying urologic procedure.
Time frame: Within 1 day of the urologic procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Percentage of Cases Who Received Excessive Post-procedural Antimicrobials | 216 Participants |
| Baseline Period | Percentage of Cases Who Received Excessive Post-procedural Antimicrobials | 644 Participants |
Comparison: To model the primary outcome for site 3, we used a logistic regression model and a set of three explanatory variables: time, a binary indicator for an observation occurring within the intervention phase, and an interaction term between these two main effects (time and intervention).p-value: 0.00495% CI: [0.016, 0.445]Regression, Logistic
Comparison: To model the primary outcome for site 1, we used a logistic regression model and a set of three explanatory variables: time, a binary indicator for an observation occurring within the intervention phase, and an interaction term between these two main effects (time and intervention).p-value: 0.25995% CI: [0.71, 3.585]Regression, Logistic
Comparison: To model the primary outcome for site 2, we used a logistic regression model and a set of three explanatory variables: time, a binary indicator for an observation occurring within the intervention phase, and an interaction term between these two main effects (time and intervention).p-value: 0.73895% CI: [0.135, 4.147]Regression, Logistic
Secondary
Excessive Post-procedural Antimicrobial Duration (Mean)
Excessive post-procedural antimicrobial duration is defined as the duration of continuous excessive post-procedural antimicrobial use, as quantified as days of therapy per National Healthcare Safety Network methodology. This outcome will be calculated for each patient who underwent a qualifying procedure and received a post-procedural antimicrobial (primary outcome).
Time frame: Within 30-days of the urologic procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Excessive Post-procedural Antimicrobial Duration (Mean) | 4.1 Days of antimicrobial therapy | Standard Deviation 6.4 |
| Baseline Period | Excessive Post-procedural Antimicrobial Duration (Mean) | 5.3 Days of antimicrobial therapy | Standard Deviation 6.4 |
Comparison: The median duration of post-procedural antimicrobial prescriptions at site 3 were compared using the Wilcoxon rank-sum test.p-value: 0.001Wilcoxon (Mann-Whitney)
Comparison: The median duration of post-procedural antimicrobial prescriptions at site 1 were compared using the Wilcoxon rank-sum test.Type of statistical testp-value: 0.013Wilcoxon (Mann-Whitney)
Comparison: The median duration of post-procedural antimicrobial prescriptions at site 2 were compared using the Wilcoxon rank-sum test.p-value: 0.14Wilcoxon (Mann-Whitney)
Secondary
Percentage of Cases Who Acquired Clostridioides Difficile Infection
Clostridioides difficile infection (CDI) is defined as a positive laboratory test for C.difficile within 30-days of the patient's urologic procedure. For this specific outcome measure, the numerator will be the number of patients who had a positive test for C. difficile within 30-days of the procedure, and the denominator will be all patients at the site who underwent a qualifying urologic procedure.
Time frame: Within 30-days of the urologic procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Percentage of Cases Who Acquired Clostridioides Difficile Infection | 0 Participants |
| Baseline Period | Percentage of Cases Who Acquired Clostridioides Difficile Infection | 0 Participants |
Secondary
Percentage of Cases Who Died (Mortality)
Mortality: all-cause death within 30-days of the patient's index urologic procedure. For this specific outcome measure, the numerator will be the number of patients who died for any reason within 30-days of the urologic procedure, and the denominator will be all patients at the site who underwent a qualifying urologic procedure.
Time frame: Within 30-days of the urologic procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Percentage of Cases Who Died (Mortality) | 4 Participants |
| Baseline Period | Percentage of Cases Who Died (Mortality) | 4 Participants |
Secondary
Percentage of Cases Who Received a Late Antimicrobial Prescription
Late antimicrobial prescription is defined as the prescription of a designated antimicrobial that does not qualify as a post-procedural antimicrobial (see above) by any provider within 7-30 days of the date of the patient's urologic procedure. For this specific outcome measure, the numerator will be the number of patients who received a late antimicrobial, and the denominator will be all patients at the site who underwent a qualifying urologic procedure.
Time frame: Within 30-days of the urologic procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Percentage of Cases Who Received a Late Antimicrobial Prescription | 83 Participants |
| Baseline Period | Percentage of Cases Who Received a Late Antimicrobial Prescription | 169 Participants |
Comparison: To model this secondary outcome, we used a logistic regression model and a set of four explanatory variables: time, a binary indicator for an observation occurring within the intervention phase, an interaction term between these two main effects (time and intervention), and a binary indicator for the primary outcome. This last variable was included to assess the risk of these secondary outcomes in patients who were not exposed to post-procedural antimicrobials compared to those who were exposed.p-value: 0.0495% CI: [0.58, 0.99]Regression, Logistic
Secondary
Percentage of Cases Who Underwent Clostridioides Difficile Testing
Clostridioides difficile testing is defined as any laboratory test ordered for C. difficile within 30-days of the patient's urologic procedure. For this specific outcome measure, the numerator will be the number of patients who underwent C. difficile testing within 30-days of the procedure, and the denominator will be all patients at the site who underwent a qualifying urologic procedure.
Time frame: Within 30-days of the urologic procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Percentage of Cases Who Underwent Clostridioides Difficile Testing | 1 Participants |
| Baseline Period | Percentage of Cases Who Underwent Clostridioides Difficile Testing | 6 Participants |
Secondary
Percentage of Cases Who Were Re-admitted to the Hospital or Presented to an Emergency Department or an Urgent Care Clinic
Return visits: sought urgent/emergent healthcare for any indication within 30 days of the patient's index urologic procedure. For this specific outcome measure, the numerator will be the number of patients who had a return visit for any reason within 30-days of the urologic procedure, and the denominator will be all patients at the site who underwent a qualifying urologic procedure.
Time frame: Within 30-days of the urologic procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Percentage of Cases Who Were Re-admitted to the Hospital or Presented to an Emergency Department or an Urgent Care Clinic | 113 Participants |
| Baseline Period | Percentage of Cases Who Were Re-admitted to the Hospital or Presented to an Emergency Department or an Urgent Care Clinic | 186 Participants |
Comparison: To model this secondary outcome across all sites, we used a logistic regression model and a set of four explanatory variables: time, a binary indicator for an observation occurring within the intervention phase, an interaction term between these two main effects (time and intervention), and a binary indicator for the primary outcome.p-value: <0.0195% CI: [0.53, 0.87]Regression, Logistic