Early Switch to Oral Antibiotics Safe in Uncomplicated, Gram-Negative Bacteremia?

Risk of all-cause mortality was similar in patients with uncomplicated gram-negative bacteremia who switched early to oral antibiotics from IV antibiotics, according to retrospective, cohort study.

Of patients who transitioned early to oral antibiotics, 6.9% died within a 3-month follow-up, compared with 14.3% of patients who received prolonged IV antibiotic treatment, Sandra Tingsgard, MD, from Copenhagen University Hospital–Amager and Hvidovre in Denmark, and colleagues, reported in JAMA Network Open.

Risk of 90-day all-cause mortality was similar in both the intention-to-treat population (risk ratio [RR] 0.78, 95% CI 0.60-1.10) and the per-protocol analysis (RR 0.99, 95% CI 0.70-1.40).

“Overall, we found comparable rates of 90-day all-cause mortality between clinically stable individuals transitioning early to oral antibiotics compared with individuals receiving prolonged IV antibiotic treatment,” the authors commented.

In the intention-to-treat population (n=914), the risk of 90-day all-cause mortality was 9.1% for those switching early to oral antibiotics and 11.7% for patients receiving prolonged IV antibiotics, with a risk difference of -2.5% (95% CI -5.7% to 0.7%). In the per-protocol analysis (n=747), the 90-day risk of all-cause mortality was 9.6% in the early-switch group and 9.7% in the prolonged IV antibiotic group, with a risk difference of -0.1% (95% CI -3.4% to 3.1%).

Tingsgard and colleagues used a unique hypothetical trial framework that emulated the phase III INVEST trial study protocol to analyze observational data collected at four hospitals in Denmark from January 2018 to January 2022. Trial target emulation analyses mimic randomized clinical trials (RCTs), but use observational data and can therefore be conducted in a more timely and cost-effective manner, the authors explained.

In an accompanying editorial, David Paterson MBBS, PhD, from the National University of Singapore, and Helmi bin Sulaiman, MBBS, from the University of Malaya in Kuala Lumpur, Malaysia, commented that the results of the study were consistent with recently published findings of the SOAB randomized clinical trial. The SOAB trial showed an early oral switch after 3 to 5 days of initial IV antimicrobial therapy is noninferior to continuing IV therapy in clinically stable patients with Enterobacterales bacteremia.

“Can clinicians bypass the need for RCTs and simply base their decision-making on observational data?” they asked, when rigorous observational studies reach the same conclusions as RCTs. “Confounding may still occur, leading to erroneous conclusions,” they posited. “We favor data from RCTs when it comes to making evidence-based prescribing decisions,” Paterson and bin Sulaiman concluded.

The retrospective cohort study looked at data from patients who had positive blood cultures for gram-negative bacteria, were clinically stable within 4 days of an initial culture, and who had received initial IV antibiotic treatment within 24 hours of blood culture. The trial excluded data from patients who were immunosuppressed, had an established uncontrolled focus of infection, entered hospice care shortly after diagnosis with bacteremia, or had multiple bacteria isolated from blood cultures.

Among enrolled patients, 47.4% had an early switch to oral antibiotics from initial IV antibiotic treatment and 52.6% continued IV treatment for a minimum of 5 days after initial blood culture. Approximately 63% of patients in the early-switch group received oral beta-lactams and about 17% received oral ciprofloxacin. No patients in the early-switch group were restarted on IV antibiotics.

Individuals who switched to early oral antibiotics were younger (median age 73) and had fewer comorbidities, with a median Charlson Comorbidity Index (CCI) of 4. Those who remained on IV treatment had a median age of 76 and median CCI of 5. Those in the early-switch group were also more likely to have community-acquired bacteremia, with the urinary tract being the most common source of infection. Patients in this group also had lower median plasma C-reactive protein levels at initial culture (11 vs 14 mg/dL).

The authors noted that the study relied on electronic health records for patient information and it was not possible to consider all variables that may have led to decisions to switch patients to oral antibiotics. Also, the findings of the study are not applicable to patients with severe or complicated gram-negative bacteremia, they pointed out.

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