Target Trial Emulation of Empiric Antibiotics on Clinical Outcomes in Moderately Immunocompromised Patients
Louis Saravolatz1, Tejal N Gandhi1, Valerie M Vaughn2,3,4
1Division of Infectious Diseases, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan, USA.
Background:
Immunocompromised patients are often excluded from pneumonia trials, guidelines, and stewardship interventions. The objective of this study was to evaluate whether empiric broad-spectrum antibiotic (BSA) treatment impacts mortality and other clinical outcomes in moderately immunocompromised patients without risk factors for multidrug-resistant organisms (MDROs) hospitalized with community-acquired pneumonia.
Methods:
This was a target trial emulation including moderately immunocompromised (asplenia, hematologic malignancies, solid organ malignancy receiving chemotherapy, kidney transplant >1 year prior, congenital/acquired immunodeficiency, and receiving immunosuppressive medications) patients with pneumonia without risk factors for MDROs at 69 hospitals in the Michigan Hospital Medicine Safety Consortium. This study compared the receipt of empiric BSAs against antibiotics targeting typical respiratory pathogens on hospital day 1 or 2. The primary outcome was mortality. Secondary outcomes included length of stay, transfer to the intensive care unit (ICU) and 30-day readmission, emergency department visit, Clostridioides difficile infection, and antibiotic-associated adverse events.
Results:
Of 2706 moderately immunocompromised patients with pneumonia, 59% (n = 1596) received empiric BSAs. Methicillin-resistant Staphylococcus aureus and resistant gram-negative bacteria were rare (94/2706 [3.5%]). After adjustment, empiric BSA treatment was not associated with mortality, but was associated with readmission (adjusted hazard ratio [aHR], 1.32 [95% confidence interval {CI], 1.05-1.66]), transfer to ICU (aHR, 2.65 [95% CI, 1.32-5.30]), and longer hospitalization (adjusted rate ratio, 1.14 [95% CI, 1.10-1.19]).
Conclusions:
Immunocompromised patients hospitalized with pneumonia often receive empiric BSAs despite low rates of MDROs. Empiric BSA use was not associated with mortality, but was associated with harm, including 30-day readmission, transfer to ICU, and longer duration of hospitalization.
Insights
Empiric broad-spectrum antibiotics in immunocompromised pneumonia patients did not affect mortality but increased readmissions and ICU transfers. This suggests narrower antibiotic spectrums may be safer for this population.
Area of Science:
- Infectious Diseases
- Clinical Medicine
- Pharmacology
Background:
- Immunocompromised patients are frequently excluded from pneumonia research and treatment guidelines.
- This exclusion limits evidence-based care for community-acquired pneumonia (CAP) in this vulnerable group.
Purpose of the Study:
- To assess the impact of empiric broad-spectrum antibiotics on mortality and clinical outcomes in moderately immunocompromised patients with CAP.
- To evaluate outcomes in patients without risk factors for multidrug-resistant organisms (MDROs).
Main Methods:
- A target trial emulation study was conducted across 69 hospitals.
- Included were moderately immunocompromised patients hospitalized with pneumonia, excluding those with MDRO risk factors.
- Compared were empiric broad-spectrum antibiotics versus targeted antibiotics on hospital day 1 or 2, with mortality as the primary outcome.
Main Results:
- Of 2706 patients, 59% received empiric broad-spectrum antibiotics; MDROs were rare (3.5%).
- Empiric broad-spectrum antibiotic use was not linked to mortality.
- However, it was associated with increased 30-day readmission (aHR 1.32), ICU transfer (aHR 2.65), and longer hospitalization (aRR 1.14).
Conclusions:
- Despite low MDRO rates, immunocompromised pneumonia patients often receive empiric broad-spectrum antibiotics.
- This practice was not associated with reduced mortality but led to adverse outcomes like readmission and longer hospital stays.
More Related Videos
07:46Use of Artificial Sputum Medium to Test Antibiotic Efficacy Against Pseudomonas aeruginosa in Conditions More Relevant to the Cystic Fibrosis Lung
Published on: June 5, 2012
03:22Author Spotlight: Advancing Pathogen Detection and Disease Assessment in Real-Time Using M-ROSE
Published on: March 1, 2024
Related Concept Videos
01:28Antimicrobial Effectiveness
01:30Pneumonia III: Complications and Assessment
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...
01:28Pneumonia IV: Management
Bacterial Pneumonia Treatment
For bacterial pneumonia, antibiotics serve as the cornerstone of therapy. Initial treatment often begins with empirical antibiotics, tailored to the anticipated causative organism and adjusted based on culture results. Key antibiotic choices include:
01:26Pulmonary Tuberculosis IV
Several diagnostic approaches are used to detect TB. The conventional method is the Tuberculin Skin Test (TST), also known as the Mantoux test. However, this method has...
01:11Clinical Trials: Overview