Reducing Antimicrobial Overuse Through Targeted Therapy for Patients With Community-Acquired Pneumonia
- Conditions
- Community-Acquired PneumoniaAntimicrobial StewardshipPoint-of-Care Testing
- Interventions
- Diagnostic Test: Rapid Diagnostic TestingOther: Pharmacist-led de-escalation
- Registration Number
- NCT05568654
- Lead Sponsor
- The Cleveland Clinic
- 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 and UAT 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 12500
Not provided
- Admission to intensive care unit within 24 hours of hospital admission
- Comfort care measures only
- Cystic fibrosis
- Discharged from an acute care hospital in the past week
- Patients not eligible for empiric therapy due to a known pathogen (any positive blood or respiratory cultures in the 72 hours prior to admission)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Rapid diagnostic testing (RDT) Rapid Diagnostic Testing Rapid diagnostic testing: Eligible patients at hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT testing. If the patient is not being admitted to the ICU, and the patient has an admitting diagnosis of pneumonia, the form will append orders for viral testing and UAT testing to providers in hospitals randomized to receive it. Rapid diagnostic testing (RDT) and Pharmacist-led de-escalation Pharmacist-led de-escalation Rapid diagnostic testing: Eligible patients at hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT testing. If the patient is not being admitted to the ICU, and the patient has an admitting diagnosis of pneumonia, the form will append orders for viral testing and UAT testing to providers in hospitals randomized to receive it. Pharmacist-led de-escalation: Another CDSS algorithm will identify CAP patients who meet study criteria and have negative culture results for \>48-hours and generate a list for the clinical pharmacist, who will be a member of the study team. The alerts will be audited by the pharmacist daily on weekdays at a centralized location. The pharmacist will attempt to determine whether each patient is clinically stable. If the patient appears stable, the pharmacist will communicate their recommendations for de-escalation to the clinical providers via a phone call or page. Pharmacist-led de-escalation Pharmacist-led de-escalation Pharmacist-led de-escalation: Another CDSS algorithm will identify CAP patients who meet study criteria and have negative culture results for \> 48 hours and generate a list for the clinical pharmacist, who will be a member of the study team. The alerts will be audited by the pharmacist daily on weekdays 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 b) normal mental status 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. Rapid diagnostic testing (RDT) and Pharmacist-led de-escalation Rapid Diagnostic Testing Rapid diagnostic testing: Eligible patients at hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT testing. If the patient is not being admitted to the ICU, and the patient has an admitting diagnosis of pneumonia, the form will append orders for viral testing and UAT testing to providers in hospitals randomized to receive it. Pharmacist-led de-escalation: Another CDSS algorithm will identify CAP patients who meet study criteria and have negative culture results for \>48-hours and generate a list for the clinical pharmacist, who will be a member of the study team. The alerts will be audited by the pharmacist daily on weekdays at a centralized location. The pharmacist will attempt to determine whether each patient is clinically stable. If the patient appears stable, the pharmacist will communicate their recommendations for de-escalation to the clinical providers via a phone call or page.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method detection of influenza virus (yes/no) Up to 48 hours Proportion of patients who test positive for influenza
positive pneumococcal UAT up to 48 hours Proportion of patients with positive pneumococcal UAT
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 RSV (yes/no) up to 48 hours Proportion of patients who test positive for RSV
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 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
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
14-day mortality up to 14 days proportion of patients who die by 14 days
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
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
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
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
empyema (yes/no) from 48 hours to 21 days empyema (pus in the pleural space)
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
30-day readmission (yes/no) up to 30 days after discharge 30-day hospital readmission
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
Trial Locations
- Locations (12)
Weston Hospital/Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Indian River Hospital
🇺🇸Vero Beach, Florida, United States
Akron General Hospital
🇺🇸Akron, Ohio, United States
Avon Hospital
🇺🇸Avon, Ohio, United States
Lutheran Hospital
🇺🇸Cleveland, Ohio, United States
Fairview Hospital
🇺🇸Fairview Park, Ohio, United States
Cleveland Clinic Main Campus
🇺🇸Cleveland, Ohio, United States
Euclid Hospital
🇺🇸Euclid, Ohio, United States
Marymount Hospital
🇺🇸Garfield Heights, Ohio, United States
Hillcrest Hospital
🇺🇸Mayfield Heights, Ohio, United States
South Pointe Hospital
🇺🇸Warrensville Heights, Ohio, United States
Medina Hospital
🇺🇸Medina, Ohio, United States