Pharmacy Practice News - August 2022

Page 10

10 Clinical

Pharmacy Practice News • August 2022

Infectious Disease

Is De-Escalation an Effective Stewardship Strategy? By David Wild

W

hile a number of organizations recommend “spectrum de-escalation” have narrowing the spectrum of antibiotic therapy not convinced her that it is in hospitalized patients in light of laboratory find- necessary to pursue this meaings, some are questioning the primacy of the prac- sure to prevent resistance. tice, including one expert who said there are no For example, a single-center convincing data concerning spectrum de-escalation retrospective study of 7,118 patients with severe sepsis or to judge whether it improves outcomes. “I would question whether it really should be the septic shock showed that each standard of practice based on the available data,” said additional day of treatment Meghan Jeffres, PharmD, an associate professor in the with anti-pseudomonal betaDepartment of Clinical Pharmacy at Skaggs School of lactams increased the chances Pharmacy and Pharmaceutical Sciences, University of of developing new resistance by 4% (Pharmacotherapy 2019;39[3]:261-270), Colorado Anschutz Medical Campus, in Aurora. Transitioning from a broad-spectrum antibiotic and a follow-up analysis of those data found resisto that of a narrower spectrum based on culture tance to these broad-spectrum agents increased results is one form of antibiotic de-escalation, a from around 2% during the first three days to broader term encompassing, for example, discontin- roughly 10% between 10 and 18 days, rising slightly uing redundant or unnecessary antibiotics or switch- more between 19 and 21 days (Infect Control Hosp Epidemiol 2020;41[4]:484-485). ing from IV to oral antibiotics. “While the authors’ theory is that resistance conWhile Dr. Jeffres said she does not dispute that use drives antibiotic resistance, she said the data behind tinues to increase with prolonged duration of these

‘We know that shortening the length of antibiotic administration is arguably the highest-impact measure we can take to prevent antibiotic resistance and improve patient outcomes.’ —Meghan Jeffres, PharmD broad-spectrum agents, I would suggest the same phenomenon would be present if they looked at a different narrower spectrum antibiotic,” Dr. Jeffres asserted. “Why would we assume this relationship to be unique to the antipseudomonal beta-lactams?” Other studies supporting the practice of spectrum de-escalation may not have adequately accounted for possible confounding variables, she said, pointing to findings that show administering antipseudomonal beta-lactams for longer than 48 hours in patients with Enterobacteriaceae bloodstream infections leads to a higher risk for Clostridioides difficile infection (CDI) within 90 days (7% for >48 hours vs. 1.8% for ≤48 hours) (Clin Infect Dis 2019;69[3]:414-420). In this case, Dr. Jeffres said, the risk factors for longer treatment—such as older age, female sex, more comorbidities and bacteremia, and longer lengths of hospital stays prior to bloodstream infections—are some of the same established risk variables for CDI. “Arguably, this study does not support the early discontinuation of antipseudomonal beta-lactams in decreasing CDI risk,” Dr. Jeffres said. Other data are “at best, indifferent to the idea that spectrum de-escalation is important,” she said. For example, a trial of 116 patients with severe sepsis who received empiric treatment and were then randomly assigned to undergo spectrum deescalation or continue with this treatment found that ICU stays were longer among the de-escalation group (median 3.4 days longer), that de-escalation was associated with more days of antibiotic use (14 vs. 10 days) and that the practice was linked with higher rates of superinfections (27% vs. 11%; P=0.03) (Intensive Care Med 2014;40[10]:1399-1408). The authors’ finding that 44% of those who underwent de-escalation and had a superinfection developed resistance to the index pathogen, compared with 67% of those who continued empiric treatment, provides insight into the mechanism behind these results, she said. “It looks like when you de-escalate and expose patients to a second antibiotic, you may raise the risk of developing resistance to additional pathogens,” said Dr. Jeffres, noting the study’s small size and that results need to be validated in larger trials.

Shorten Duration Rather than focusing on spectrum de-escalation efforts, Dr. Jeffres suggested implementing other stewardship interventions, such as shortening the duration of antibiotic exposure. “We know that shortening the length of antibiotic administration is arguably the highest-impact measure we can take to prevent antibiotic resistance and improve patient outcomes,” she said. see STEWARDSHIP, page 12


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