Stepdown Tx for Uncomplicated Gram-Negative BSI: Beta-Lactam vs. Fluoroquinolone

The researchers compared the effectiveness of oral beta-lactams to fluoroquinolones in the treatment of Enterobacteriaceae bloodstream infections (EBSI) in adult patients.

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SAN DIEGO—For uncomplicated Gram-negative bloodstream infections, oral beta-lactam therapy may be an appropriate stepdown option, with fewer side effects, compared to fluoroquinolones. Findings from this study were presented at IDWeek 2017.

“Stepdown from intravenous (IV) to oral antibiotics is a common practice that effectively reduces healthcare costs, even for severe infections,” said lead author Nicholas Mercuro, PharmD, from Maine Medical Center, Portland, ME. While fluoroquinolones may be considered an optimal choice for stepdown therapy, they have been associated with significant adverse effects.

For this retrospective study, Dr. Mercuro and his team compared the effectiveness of oral beta-lactams to fluoroquinolones in the treatment of Enterobacteriaceae bloodstream infections (EBSI) in adult patients (≥18yrs old) who were started on IV antibiotics and then subsequently switched to oral therapy. Patients with complicated infection, ESBL-producing isolates, concomitant infections, and those discharged to hospice were excluded from the study. 

The primary efficacy outcome was non-inferior clinical success (assessed up to 30 days following completion of oral stepdown therapy) with secondary outcomes that included microbiological success, 30-day readmission, and adverse effects. In addition, subgroup analysis included comparisons of early (≤3 days IV) and late stepdown (>3 days IV) and short (≤10 days total) and extended treatment duration (>10 days total). “Logistic regression was performed to identify predictors of clinical success,” the authors added.

The researchers found that stepdown therapy with oral beta-lactam (n=84) was non-inferior to oral fluoroquinolone (n=140) (86.9% vs. 87.1%, odds ratio [OR] 1.24; 0.57–2.71). With regards to secondary outcomes, microbiologic success (94.0% vs. 97.9%, OR 0.35; 0.08–1.49) and 30-day readmission (14.3% vs. 14.3%, OR 0.94; 0.44–2.02) were found to be similar between the two antibiotic classes; patients were also more likely to tolerate beta-lactam treatment vs. fluoroquinolones (90.5% vs. 79.3%, OR 2.16; 1.05–4.56).

Subgroup analysis showed comparable clinical success between patients who had early or late stepdown (86.7% vs 87.5%, P=0.86) and in those who had short or extended treatment duration (88.2% vs. 86.7%, P= 0.76); uncontrolled diabetes and urinary abnormalities were found to be negative predictors of clinical success.

Based on the study results, the authors concluded that oral beta-lactams may be a non-inferior stepdown option for uncomplicated Gram-negative bloodstream infections. “The retrospective nature and inability to review events and admissions outside of our EMR were limitations and prospective studies are warranted.”

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Mercuro, N; Stogsdill, P; Wungwattana, M. Comparative Efficacy of Oral Fluoroquinolones and Beta-lactams as Stepdown Therapy for Enterobacteriaceae Bloodstream Infection. Poster presented at IDWeek; October 4–8, 2017; San Diego, CA.