By Stan Deresinski, MD, FIDSA, FACP
Clinical Professor of Medicine, Stanford University
Dr. Deresinski reports no financial relationships relevant to this field of study.
SYNOPSIS: Oral step-down antibiotic therapy (IV to oral conversion) is safe and effective in patients with bloodstream infection due to Enterobacteriaceae.
SOURCE: Tamma PD, Conley AT, Cosgrove SE, et al; Antibacterial Resistance Leadership Group. Association of 30-day mortality with oral step-down vs continued intravenous therapy in patients hospitalized with Enterobacteriaceae bacteremia. JAMA Intern Med 2019; Jan 22. doi: 10.1001/jamainternmed.2018.6226. [Epub ahead of print].
Tamma and colleagues examined the efficacy and safety of oral step-down therapy (IV to oral conversion) in patients with bacteremia due to commonly isolated Enterobacteriaceae in a multicenter retrospective study using propensity analysis. Only 2,161 of 4,967 bacteremic patients met entry criteria, 876 (40.5%) of whom underwent step-down of their therapy. Compared to those who received their entire course of therapy intravenously, the step-down group was less likely to be severely neutropenic or severely ill or to have received combination antibiotic therapy for at least 48 hours. In the step-down group, the urinary tract was more likely to be the source of bacteremia.
To overcome these differences in their analysis, the authors performed propensity analysis with matching yielding 739 in each study arm. The most frequently isolated pathogens, in decreasing order of frequency, were Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Proteus mirabilis, Serratia marcescens, and Citrobacter spp. Approximately two-fifths of infections arose from the urinary tract, one-fifth each from an intra-abdominal source and a venous catheter, one-seventh from the biliary tract, and the remainder from the lungs and skin or skin structure.
The patients in the IV-only group received a median of 14 days of IV therapy, while the step-down cohort received only a median of three days of therapy by that route. In comparisons of the oral step-down and IV groups, there were no significant differences in 30-day mortality (13.1% vs. 13.4%) or recurrent bacteremia (0.8% vs. 0.5%). The duration of hospitalization was two days shorter in the step-down group: five days vs. seven days.
Antibiotics considered to have high oral bioavailability (fluoroquinolones and trimethoprim-sulfamethoxazole) were administered to 83.9% of patients receiving step-down therapy, with the remaining receiving oral beta-lactams, with all considered to have low bioavailability. No significant differences in outcomes were observed in a comparison of the two groups.
The number of patients in this study who received step-down therapy with low bioavailability drugs was small, making the finding that they appeared to do as well as those who received high bioavailability oral antibiotics potentially suspect. However, the authors pointed out that this finding is consistent with the results of other retrospective analyses. This is not terribly surprising, especially in view of a recent randomized trial that found that seven days of IV therapy was noninferior in a randomized trial in patients with Gram-negative bacteremia.1,2
It seems likely to me that the median of five days of IV therapy given to step-down patients by Tamma and colleagues may have been sufficient to cure most cases of bacteremia, and the subsequent oral therapy may have been irrelevant. We have been using step-down commonly as early as day 3 of IV antibiotic therapy to complete a total of seven days of therapy in uncomplicated cases with good initial responses.
- Yahav D, Franceschini E, Koppel F, et al; Bacteremia Duration Study Group. Seven versus fourteen days of antibiotic therapy for uncomplicated Gram-negative bacteremia: A non-inferiority randomized controlled trial. Clin Infect Dis 2018; Dec 11. doi: 10.1093/cid/ciy1054. [Epub ahead of print].
- Deresinski S. Treatment of Gram-negative bacteremia: How long is long enough? Infect Dis Alert 2019;38:49-50.