Early de-escalation from intravenous to oral antibiotics may be appropriate for uncomplicated gram-negative bacteremia

1. In this cohort study, patients with uncomplicated gram-negative bacteremia who were switched from intravenous (IV) to oral antibiotics demonstrated similar 90-day all-cause mortality to those receiving prolonged IV antibiotic treatment. 

2. Patients in the early switch arm were no more likely to experience infection recurrence or complications related to antibiotic use at 30 and 90 day follow-up. 

Evidence Rating Level: 2 (Good)        

Study Rundown: Gram-negative bacteremia poses a significant health concern, and clinicians are tasked with assigning the proper antibiotic treatment and duration for these patients. However, antibiotic stewardship and the rising rates of resistance to antibiotics. One such example is the rise of extended spectrum beta-lactamase (ESBL) infections in the hospital setting. The effectiveness of an early switch from IV to oral antibiotics in treating such infections is a topic of interest to researchers. The current study sought to analyze data from a large cohort of patients to assess whether an early switch from IV to oral antibiotics was effective and would lead to changes in 90-day all-cause mortality. The study used the target trial emulation framework to analyze outcomes in over 900 patients with uncomplicated gram-negative bacteremia from four Dutch inpatient centers. Overall, Patients who were switched early from IV to oral antibiotics showed comparable recovery outcomes to those who continued with prolonged IV antibiotic therapy. Early transition to oral antibiotics did not lead to an increase in infection recurrence or other complications, suggesting comparable efficacy of IV-to-oral treatment to IV-only antibiotic treatment. While more research is required to determine this efficacy in other more complicated and diverse clinical presentations of bacteremia, this provides a potentially promising alternative to prolonged exposure to IV antibiotics.

Click to read the study in JAMA Network Open

Relevant Reading: Intravenous-only or Intravenous Transitioned to Oral Antimicrobials for Enterobacteriaceae-Associated Bacteremic Urinary Tract Infection

In-Depth [retrospective cohort]: Recent medical research has begun addressing concerns surrounding antibiotic stewardship and methods by which to balance proper treatment with an increasing risk for antibiotic resistance. A key area of this endeavor is the ability to transition from IV to oral antibiotics in treating infections. The current study sought to address this concern in the context of gram-negative bacteremia, which presents fairly commonly and has serious potential impacts on patient morbidity and mortality. This multicentre observational cohort study made use of a target trial emulation framework for patients diagnosed with uncomplicated gram-negative bacteremia. These patients were found to have positive blood cultures and initially received IV antibiotics (within 24 hours of presentation). A total of 914 patients with gram-negative bacteremia diagnosed on blood cultures (512 [56.0%] male; median age 74.5 years) were included, and 433 of them were transitioned to early oral antibiotic treatment, whereas the remaining patients (n = 481; 52.6%) continued to receive IV antibiotics for the duration of treatment (of at least 5 days from initial blood culture). The exclusion of complicated cases helped isolate the effects of the antibiotic switch. Ninety-day all-cause mortality was measured as the primary outcome.  A total of 99 patients died within the follow-up period, with a somewhat smaller proportion of deaths belonging to the early switch to oral antibiotics group (30 individuals, or 6.9%) compared to the IV antibiotic only group (69 individuals, or 14.3%). Per-protocol analyses determined that patients in the early switch group were more likely to adhere to treatment (89.4% versus 74.8%), and that ninety-day all-cause mortality risk was 9.6% and 9.7% for each group, respectively, with a -0.1% risk difference (95% CI, -3.4% to 3.1%). Thus, patients switched early to oral antibiotics demonstrated similar recovery rates to those who continued on IV therapy for the entirety of treatment. Moreover, the early switch did not lead to increased rates of complications, recurrence of infection, or increased 30- or 90-day mortality.  These results suggest that for uncomplicated gram-negative bacteremia, early transition to oral antibiotics could serve as an effective and safe practice. However, the study also acknowledges certain limitations, including its limit of scope to uncomplicated cases of gram-negative bacteremia. Another limitation is a lack of control for patient characteristics impacting the duration of IV antibiotic treatment; these regimens were observed to be longer in individuals with more severe progression, higher burden of comorbidity, and who were older. Overall, the study provides compelling evidence for the efficacy and safety of early transition to oral antibiotics in treating uncomplicated gram-negative bacteremia, which has the potential to reduce hospital stays, lower healthcare costs, and minimize the risk of hospital-acquired infections. Further research is required to expand on current findings to other bacteremic presentations. 

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