Reducing Antimicrobial Overuse Through Targeted Therapy for Patients With Community-Acquired Pneumonia

Not Applicable

Recruiting

• Conditions: Community-Acquired Pneumonia; Antimicrobial Stewardship; Point-of-Care Testing

• 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, 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.

Study Timeline

• Study First Submitted: 2022-10-03
• Study First Submitted QC: 2022-10-03
• Study First Posted: 2022-10-06
• Study Start: 2022-11-01
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-27
• Last Update Posted: 2025-07-02
• Primary Completion: 2026-01-31
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12500

Inclusion Criteria

Not provided

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

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
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
detection of RSV (yes/no)	up to 48 hours	Proportion of patients who test positive for RSV
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
14-day mortality	up to 14 days	proportion of patients who die by 14 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
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)
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
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).
treatment with anti-viral medications	up to 48 hours	treatment with anti-viral medications (oseltamivir, zanamivir, peramivir, baloxavir, ribavirin, remdesivir, nirmatrelvir, COVID-19 medications)
30-day mortality	up to 30 days	proportion of patients who die by 30 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
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
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
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)
Procalcitonin test (PCT) values	up to 48 hours	Procalcitonin test (PCT) values. Proportion of patients with low vs high PCT values

Trial Locations

Locations (12)

Indian River Hospital; 🇺🇸 Vero Beach, Florida, United States

Weston Hospital/Cleveland Clinic Florida; 🇺🇸 Weston, Florida, United States

Akron General Hospital; 🇺🇸 Akron, Ohio, United States

Avon Hospital; 🇺🇸 Avon, Ohio, United States

Lutheran Hospital; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Main Campus; 🇺🇸 Cleveland, Ohio, United States

Euclid Hospital; 🇺🇸 Euclid, Ohio, United States

Fairview Hospital; 🇺🇸 Fairview Park, Ohio, United States

Marymount Hospital; 🇺🇸 Garfield Heights, Ohio, United States

Hillcrest Hospital; 🇺🇸 Mayfield Heights, Ohio, United States

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