In a recent publication in Clinical Infectious Diseases, researchers conducted a retrospective cohort study utilizing a novel cumulative spectrum score to ascertain if beta-lactam (BL) antibiotic de-escalation (ADE) is associated with a decreased incidence of new gram-negative resistance in hospitalized patients with sepsis.

The authors wrote, “To our knowledge, this is the first and largest population-based retrospective study confirming that the practice of BL de-escalation is associated with a reduction in the development of new gram-negative pathogen resistance in a population of hospitalized patients with a discharge diagnosis of sepsis.”

For this study, which was conducted between December 1, 2010, and December 31, 2017, patients with sepsis were enrolled who were treated with at least 3 consecutive days of BL antibiotics—the first 2 days of which were with a broad-spectrum BL agent defined as a spectrum score (SS) of ≥7.

The researchers then grouped patients into three classes: 1) de-escalation of beta-lactam spectrum score (BLSS), 2) no change in BLSS, or 3) escalation of BLSS.

The primary outcome was the isolation of a new drug-resistant, gram-negative bacteria from a clinical culture within 60 days of cohort entry. The researchers also performed Fine-Gray proportional hazards regression modeling while accounting for in-hospital death as a competing risk.

The results revealed that 644 of 7,742 patients developed new gram-negative resistance, with the average time to resistance documented as 23.7 days, generating an incidence rate of 1.85 (95% CI: 1.71-2.00) per 1,000 patient days.

Additionally, the lowest incidence rate was observed in the de-escalated group: 1.42 (95% CI, 1.16-1.68) per 1,000 patient days. The researchers also discovered that statistically significant decreases in the development of new gram-negative resistance were associated with BL de-escalation compared with no change (hazard ratio, 0.59; 95% CI, 0.48-0.73).

Based on their findings, the authors concluded that ADE was linked with a diminished risk of new gram-negative resistance among patients who were hospitalized with sepsis compared with no change in the BL spectrum.

The authors wrote, “Clinicians should be vigilant in their efforts to de-escalate broad-spectrum BL therapy and limit exposure to the shortest effective duration to curb resistance emergence. Future studies are needed to confirm these findings and to rigorously evaluate ADE in other patient populations, including organ transplant and other types of immunosuppressed patients.”

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