Antimicrobial Stewardship, Community-Acquired Pneumonia, Point-of-Care Testing
Conditions
Brief summary
The purpose of this study is to reduce the exposure of broad-spectrum antimicrobials by optimizing the rapid detection of CAP pathogens and improving rates of de-escalation following negative cultures. To accomplish this, we will perform a 3-year, pragmatic, multicenter 2 X 2 factorial cluster randomized controlled trial with four arms: a) rapid diagnostic testing b) pharmacist-led de-escalation c) rapid diagnostic testing + pharmacist-led de-escalation and d) usual care
Detailed description
Community-acquired pneumonia (CAP) is a leading cause of hospitalization and inpatient antimicrobial use in the United States. However, diagnostic uncertainty at the time of initial treatment and following negative cultures is associated with prolonged exposure to broad-spectrum antimicrobials. We propose a large multicenter cluster randomized controlled trial to test two approaches to reducing the use of broad-spectrum antibiotics in adult patients with CAP a) routine use of rapid diagnostic testing at the time of admission and b) pharmacist -led de-escalation after 48 hours for clinically stable patients with negative cultures. When a patient is admitted with a diagnosis of pneumonia, it will trigger the admission order set and if the physician is in a hospital randomized to the rapid diagnostic testing arm, a CDSS-based alert will be generated in real time, and the form will append orders for viral, UAT and procalcitonin testing. For physicians at a hospital randomized to the control condition, ordering will proceed as usual (standard-of-care). A second CDSS algorithm will identify study patients who have negative culture results (blood and/or sputum) for greater than 48 hours and generate a list for the antimicrobial stewardship pharmacist, who will be a member of the study team. The alerts will be audited by the clinical pharmacist daily on weekdays at a centralized location. In clinically stable patients from hospitals randomized to the de-escalation arm, the pharmacist will communicate their recommendations for de-escalation to the clinical providers via a phone call, Epic chat, or page. The primary outcome will be the duration of exposure to broad-spectrum antimicrobial therapy defined by the number of days of antibiotic therapy from initiation to discontinuation. Secondary outcomes will include detection of influenza/RSV, de-escalation and re-escalation to broad-spectrum antibiotics after de-escalation, total antibiotic duration, in-hospital mortality, ICU transfer after admission, healthcare-associated CDI and acute kidney injury after 48 hours.
Interventions
DIAGNOSTIC_TESTRapid Diagnostic Testing
Eligible patients in hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT and procalcitonin testing. A CDSS-based alert will be generated in real time. If the patient is not being admitted to the intensive care unit, the form will append orders for viral pathogen, UAT and procalcitonin testing.
OTHERPharmacist-led de-escalation
A CDSS algorithm will identify CAP patients who meet study criteria and have negative culture results for greater than 48 hours and generate a list for the antimicrobial stewardship pharmacist, who will be a member of the study team. The alerts will be audited by the pharmacist daily at a centralized location. The pharmacist will attempt to determine whether each patient is clinically stable. The validated measures of clinical stability in patients with CAP are a) resolved vital sign abnormalities (temperature, heart rate, oxygen saturation, blood pressure and respiratory rate) b) normal mental status and c) ability to eat. If the patient appears stable, the pharmacist will communicate their recommendations for de-escalation to the clinical providers via a phone call or page. The de-escalation recommendations made by the pharmacist will be based on a protocol developed by the research team.
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
To accomplish these two aims, we will perform a, pragmatic, multicenter 2 X 2 factorial cluster randomized controlled trial with four arms:
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for patient's records: 1. Men or women greater than or equal to 18 years of age 2. Admitted to a participating (i.e. enrolled and randomized) hospital 3. Admitting diagnosis of pneumonia
Exclusion criteria
1. Admission to intensive care unit within 24 hours of hospital admission 2. Comfort care measures only 3. Cystic fibrosis 4. Discharged from an acute care hospital in the past week 5. Patients not eligible for empiric therapy due to a known pathogen (any positive blood or respiratory cultures in the 72 hours prior to admission)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of days of broad-spectrum antibiotic therapy | first 21 days of admission | duration of exposure to broad-spectrum antimicrobial therapy defined by the number of days of antibiotic therapy in the first 21 days of admission as per National Healthcare Safety Network (NHSN) guidelines |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| treatment with antiviral medications | within 21 days | treatment with antiviral medications (oseltamivir, zanamivir, peramivir, baloxavir, ribavirin, remdesivir, nirmatrelvir, COVID-19 medications) |
| S. pneumoniae urinary antigen test (UAT) performed | up to 48 hours | Proportion of patients in whom UAT is performed |
| positive pneumococcal UAT | up to 48 hours | Proportion of patients with positive pneumococcal UAT |
| de-escalation by 72 hours from admission (yes/no) | within 72 hours from admission. | Proportion of patients whose broad spectrum antimicrobials (imipenem, meropenem, piperacillin-tazobactam, aztreonam, cefepime, ceftazidime, tobramycin, ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, cefiderocol, ceftaroline, tigecycline, eravacycline, amikacin, linezolid or vancomycin) are de-escalated |
| re-escalation to broad-spectrum antibiotics after de-escalation (yes/no) | by 21 days from admission | Proportion of patients whose antibiotics were de-escalated and that were subsequently re-escalated to broad-spectrum antibiotics (imipenem, meropenem, piperacillin-tazobactam, aztreonam, cefepime, ceftazidime, tobramycin, ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, cefiderocol, ceftaroline, tigecycline, eravacycline, amikacin, linezolid or vancomycin). |
| total duration of any antibacterial antibiotic | up to 21 days | Total duration of any antibacterial antibiotic treatment up to 21 days, including re-initiation of antibiotics |
| 14-day mortality | up to 14 days | proportion of patients who die by 14 days |
| 30-day mortality | up to 30 days | proportion of patients who die by 30 days |
| ICU transfer after admission (> 24 hours after admission) | up to 21 days | proportion of patients transferred to the ICU \>24 hours after admission up to 21 days |
| healthcare-associated C.difficile Infection (CDI) (yes/no) | after 72 hours of admission until discharge | CDI after 72 hours of admission. Proportion of patients with CDI after 72 hours of admission (healthcare-associated CDI) until discharge |
| acute kidney injury after 48 hours (yes/no) after 48 hours | up to 21 days | Proportion of patients with AKI after 48 hours of admission, up to 21 days |
| total inpatient cost (from hospital's cost accounting system) | from admission to discharge or 21 days, whichever comes first | total inpatient cost (from hospital's cost accounting system) - from admission to discharge or 21 days, whichever comes first |
| hospital length-of-stay (days, hours) | days from the time of admission to the time of discharge | length of stay will be calculated in days from the time of admission to the time of discharge |
| empyema (yes/no) | from 48 hours to 21 days | empyema (pus in the pleural space) |
| 30-day readmission (yes/no) | up to 30 days after discharge | 30-day hospital readmission |
| Infection with a resistant organism in the future (yes/no) | up to 6 months after discharge | up to 6 months after discharge. Resistance to CAP therapy will be defined as resistance to either a respiratory quinolone or to both a beta-lactam/3rd generation cephalosporin and a macrolide. Multi-drug resistance will be defined as any CAP bacterial isolate that tests either intermediate (I) or resistant (R) to at least one agent in three or more antimicrobial classes |
| Procalcitonin test (PCT) performed | up to 48 hours | Procalcitonin test (PCT) performed. Proportion of patients in whom PCT testing is performed |
| Procalcitonin test (PCT) values | up to 48 hours | Procalcitonin test (PCT) values. Proportion of patients with low vs high PCT values |
| detection of viruses/atypical bacteria in the respiratory panel (yes/no) | up to 48 hours | Proportion of patients who test positive for each of the viruses/atypical bacteria in the respiratory panel |
| viral testing ordered (yes/no) | Up to 48 hours | Proportion of patients in whom viral testing was ordered. We will look at each virus individually as well as all viruses together (i.e. any viral testing) |
| detection of influenza virus (yes/no) | Up to 48 hours | Proportion of patients who test positive for influenza |
| treatment with anti-viral medications | up to 48 hours | treatment with anti-viral medications (oseltamivir, zanamivir, peramivir, baloxavir, ribavirin, remdesivir, nirmatrelvir, COVID-19 medications) |
| detection of RSV (yes/no) | up to 48 hours | Proportion of patients who test positive for RSV |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichael Rothberg, M.D.
The Cleveland Clinic
Outcome results
None listed