Target Trial Emulation of Empiric Antibiotics on Clinical Outcomes in Moderately Immunocompromised Patients Hospitalized with Pneumonia

Abstract

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 treatment impacts mortality and other clinical outcomes in moderately immunocompromised patients without risk factors for multidrug-resistant organisms 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 multidrug-resistant organisms at 69 hospitals in the Michigan Hospital Medicine Safety ConsortiumThis study compared the receipt of empiric broad-spectrum antibiotics 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 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 broad-spectrum antibiotics. MRSA and resistant gram-negative bacteria were rare (94/2706, 3.5%). After adjustment, empiric broad-spectrum antibiotic treatment was not associated with mortality, but was associated with readmission (adjusted hazard ratio [aHR], 1.32 [1.05-1.66]), transfer to ICU (aHR, 2.65 [1.32-5.30]) and longer hospitalization (adjusted rate ratio [aRR], 1.14 [1.10-1.19]).

Conclusions: Immunocompromised patients hospitalized with pneumonia often receive empiric broad-spectrum antibiotics despite low rates of multidrug-resistant organisms. Empiric broad-spectrum antibiotic use was not associated with mortality, but was associated with harm, including 30-day readmission, transfer to ICU and longer duration of hospitalization.

Keywords: Immunocompromised patients; antimicrobial stewardship; community-acquired pneumonia; empiric antibiotics.