Beta-lactam de-escalation may be an important tool in AMR prevention
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Key takeaways:
- De-escalation of beta-lactam antibiotics was associated with a decreased risk of new resistance among patients with sepsis.
- Limiting exposure to the shortest effective duration could curb resistance.
De-escalation of beta-lactam antibiotics was associated with a decreased risk of new resistance development compared with no change in beta-lactam antibiotic use, researchers found.
“[This study was done] to determine if there is an association between beta-lactam de-escalation and the prevention of new gram-negative pathogen resistance,” Scott T. Micek, PharmD, professor of pharmacy practice in the St. Louis College of Pharmacy at the University of Health Sciences and Pharmacy in St. Louis, told Healio.
Micek and colleagues explained in the paper that antibiotic de-escalation has been recommended for nearly a quarter century.
The idea is to attempt to balance the need for early administration of broad-spectrum antibiotics intended to increase the probability of an appropriate empiric regimen while also having a plan to reduce the risk of subsequent antibiotic resistance by narrowing the spectrum of antibiotics and/or discontinuing antibiotics as soon as possible.
“In accordance with clinical practice guideline recommendations, clinicians routinely implement the practice of antibiotic de-escalation[ however, the reward of reduced antibiotic resistance downstream is supported by limited evidence,” the researchers wrote.
Micek and colleagues conducted a retrospective cohort study using a novel, cumulative spectrum score to evaluate exposure to beta-lactams based on the risk of isolation of gram-negative pathogens with new resistance phenotypes in hospitalized patients.
Patients with sepsis were enrolled if they had been treated with at least 3 consecutive days of beta-lactam antibiotics — the first 2 days of which were with a broad-spectrum beta-lactam agent defined as a spectrum score of 7 or higher.
According to the study, patients were then grouped into three categories: de-escalation of beta-lactam spectrum score, no change in beta-lactam spectrum score or escalation of beta-lactam spectrum score. The primary outcome of the study was the isolation of a new drug-resistant gram-negative bacteria from a clinical culture within 60 days of cohort entry.
In total, 644 of 7,742 patients developed new gram-negative resistance. The study demonstrated that the average time to resistance development was 23.7 days, with an incidence rate of 1.85 (95% CI, 1.71-2) per 1,000 patient-days.
The lowest incidence rate was observed in the de-escalated group — 1.42 (95% CI, 1.16-1.68) per 1,000 patient-days — followed by the escalation group (1.8; 95% CI, 1.46-2.15) and the no-change group (2.03; 95% CI, 1.84-2.22).
The researchers also found that statistically significant reductions in the development of new gram-negative resistance were associated with beta-lactam de-escalation compared with no change (HR = 0.59; 95% CI, 0.48-0.73).
“Clinicians should be vigilant in their efforts to de-escalate broad-spectrum beta-lactam therapy and limit exposure to the shortest effective duration to curb resistance emergence,” the authors concluded.
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