2025/01/17 by Cody A. Cunningham, Dan Ilges · 1 voice
Immunology and Microbiology · Medicine · #Antibiotic Use and Resistance #Antibiotics Pharmacokinetics and Efficacy #Nosocomial Infections in ICU
paper · doi:10.1093/cid/ciaf022
openalex publication_date 2025/01/17 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/16
To the Editor—We applaud Kam et al for their important work in this issue of Clinical Infectious Diseases suggesting improved outcomes in patients with suspected sepsis who underwent appropriate de-escalation from anti-pseudomonal and anti-methicillin-resistant Staphylococcus aureus (MRSA) agents when resistant pathogens were not identified. The authors propose several biologically plausible mechanisms by which de-escalation may improve patient outcomes including reduced antibiotic toxicities, less alteration to the gut microbiome, and fewer new antibiotic-resistant infections. However, there exists significant diversity in terms of spectrum of activity within pseudomonal and MRSA sparing agents that may impact patient outcomes. Recently, authors have used spectrum scores as a means to quantify antibiotic activity and define de-escalation [1]. One such example is the antibiotic spectrum index (ASI), which assigns each antibiotic a score ranging from 1 (oxacillin) to 13 (tigecycline), with broader coverage being assigned a higher score [2]. When multiple agents are used on the same day, the scores are added together. Identifying de-escalation practices using a reduction in ASI has been evaluated in patients with nosocomial pneumonia [3]. De-escalation to a lower spectrum score was recently shown to reduce gram-negative resistance development in patients treated for sepsis or septic shock [4]. The present study included patients on a variety of anti-pseudomonal β-lactams, such as piperacillin-tazobactam (ASI of 8), cefepime (ASI of 6), and meropenem (ASI of 10) with vancomycin (ASI of 5) for MRSA coverage. The composite ASI of piperacillin-tazobactam, cefepime, and meropenem in combination with vancomycin is 13, 11, and 15, respectively. The authors report that the most common antimicrobials in patients who underwent de-escalation included ceftriaxone (ASI of 5), cefazolin (ASI of 3), doxycycline (ASI of 5), metronidazole (ASI of 2), and levofloxacin (ASI of 9). Using this measure, patients classified by Kam et al as undergoing de-escalation were transitioned to antimicrobials with a reduced spectrum index (ASI 12.89 ± 1.63 vs 4.22 ± 2.4 [mean ± SD]). However, it is not clear from the text if these agents were used alone or in combination, which would significantly impact the total spectrum of coverage. The work also highlights the wide range of antibiotic spectrums within the subset of patients who underwent de-escalation in this study. It is possible that the improved patient outcomes (less acute kidney injury, intensive care unit admission, or hospital mortality) depend on the degree to which antimicrobial spectrum is narrowed (beyond discontinuing pseudomonas and MRSA coverage) or cumulative antimicrobial (spectrum) exposure—effects that would go undetected in the current analysis. The work by Kam et al, using a large database encompassing 124 577 patients across 236 US hospitals, represents major step in understanding how antimicrobial stewardship can benefit patients with suspected sepsis. Future studies of similar size and scope that apply spectrum scores to de-escalation practices could provide further granularity on the impact, or lack thereof, on the magnitude of de-escalation on patient outcomes.