BROAD-SPECTRUM antibiotics may worsen outcomes in immunocompromised patients with pneumonia, according to new data from a multi-center target trial emulation. The study analyzed clinical outcomes among moderately immunocompromised adults hospitalized with community-acquired pneumonia (CAP) and found that broad-spectrum empiric antibiotics were associated with increased harm, including higher ICU transfer rates, longer hospital stays, and greater risk of 30-day readmission, despite no mortality benefit.
Researchers conducted a target trial emulation across 69 hospitals participating in the Michigan Hospital Medicine Safety Consortium. The cohort included 2,706 patients with moderate immunocompromise due to conditions such as asplenia, solid organ malignancies under chemotherapy, or long-term immunosuppressive therapy, all of whom lacked risk factors for multidrug-resistant organisms. On hospital day one or two, 59% (n=1,596) received empiric broad-spectrum antibiotics, while others received agents targeting typical respiratory pathogens.
The primary outcome was mortality, while secondary endpoints included ICU transfer, hospital length of stay, 30-day readmission, emergency department visits, Clostridioides difficile infection, and antibiotic-related adverse events. Notably, only 3.5% of patients had infections with resistant gram-negative organisms or MRSA, suggesting that overuse of broad-spectrum antibiotics may not be clinically justified in this population.
Adjusted analyses revealed no mortality difference between groups. However, broad-spectrum antibiotic use was significantly associated with higher 30-day readmission (adjusted hazard ratio [aHR], 1.32), ICU transfer (aHR, 2.65), and prolonged hospitalization (adjusted rate ratio [aRR], 1.14). These findings underscore the potential harms of unnecessary broad-spectrum therapy in moderately immunocompromised patients and support more tailored antibiotic stewardship strategies.
This study challenges the routine use of broad-spectrum antibiotics in immunocompromised patients with CAP and no known risk for multidrug resistance. As antibiotic resistance and stewardship efforts gain urgency, careful consideration of empiric therapy may reduce harm and improve hospital resource utilization.
Reference:
Saravolatz L et al. Target Trial Emulation of Empiric Antibiotics on Clinical Outcomes in Moderately Immunocompromised Patients Hospitalized with Pneumonia. Clin Infect Dis. 2025:ciaf344.
