Recent stewardship efforts have rightly focused on ensuring proper choice and duration of antimicrobial therapy for community-acquired pneumonia, with longer and excessively broad courses associated with potentially negative outcomes. For immunocompromised patients presenting with CAP, there is typically a lower threshold to prescribe broad-spectrum therapy, even in those who may not have a high risk of infection with a multidrug-resistant pathogen. Further clouding the issue is that immunocompromised patients are often excluded from CAP clinical trials.
Researchers affiliated with the Michigan Hospital Medicine Safety Consortium recently published in Clinical Infectious Diseases a study that examined outcomes in moderately immunocompromised patients hospitalized with CAP as to whether broad-spectrum (anti-pseudomonal with or without anti-MRSA) therapy was received in the first two days of admission. Moderate immunocompromise included asplenia, active hematologic malignancy, solid organ malignancy receiving chemotherapy, kidney transplant > 1 year prior, congenital or acquired immunodeficiency and receipt of immunosuppressive medications. Patients who met IDSA guideline criteria for receipt of empiric broad-spectrum therapy for CAP were excluded. Inverse probability treatment weighting was conducted with a sensitivity analysis using nested target trial emulation according to receipt of broad-spectrum therapy on day 1 versus day 2.
Of 2,016 moderately immunocompromised patients with CAP, 59% received broad-spectrum agents. They were different than those receiving standard therapy in several aspects that were balanced with IPTW. Pseudomonas and MRSA were isolated from respiratory samples in 2.1% and 1.1% of patients, respectively, with similar distribution between groups. Mortality was similar among those treated with broad-spectrum versus standard therapy (adjusted hazard ratio, 1.19; 95% confidence interval, 0.85-1.67), but those receiving broad-spectrum therapy were more likely to be readmitted (aHR, 1.32; 95% CI, 1.05-1.66), transferred to the intensive care unit (aHR, 2.65; 95% CI, 1.32-5.30) and have increased length of hospital stay (adjusted rate ratio, 1.14; 95% CI, 1.10-1.19), with sensitivity analysis yielding similar findings.
This study supports the notion that moderately immunocompromised patients do not need empiric broad-spectrum therapy for CAP if they do not meet IDSA guideline criteria. If anything, the combination of an anti-MRSA agent with an antipseudomonal penicillin that these patients typically receive may be an inferior regimen to ceftriaxone and azithromycin because of its lack of atypical coverage. This article will be an important tool for antimicrobial stewards in audit and feedback as well as their overall programmatic approach to CAP.
(Saravolatz et al. Clin Infect Dis. Published online: July 2, 2025.)