Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections-Article Summary

Summary Author: Allison Horvath

Brief Summary:

Bloodstream infections are a major occurrence seen in the healthcare system, with more than 600,000 cases and 90,000 deaths per year just in North America. They remain within the top 10 causes of death, despite the availability of treatment with antibiotics for many of them. Among the modifiable variables that could impact these outcomes, duration of treatment stands out as one that has not yet been well-studied. Too short a treatment course raises concern for relapse of infection and selective resistance, while excessive duration causes higher risk for adverse events such as C. difficile infection and antimicrobial resistance, which is a growing problem. The current standard of care for bloodstream infections is a 14-day course of antibiotics, but is this too long?

Study Design:

In the BALANCE (Bacteremia Antibiotic Length Actually Needed for Clinical EIectiveness) trial, patients who presented with a positive blood culture were recruited from 74 hospitals across 7 countries. 3,608 patients from both hospital wards and ICUs underwent randomization, equally distributing demographics into two experimental groups where they either received a 7-day (n = 1,814) or 14-day (n = 1,794) course of antibiotics. All 3,608 patients underwent intention-to-treat analyses to assess the primary and secondary outcomes below. The specific antibiotic and delivery method were left to clinician discretion based on the patient presentation. Exclusion criteria were S. aureus bacteremia, severe immunosuppression, cultures suspicious for contaminants, & indications for prolonged antimicrobial treatment.

What did they find?

Primary outcome = death from any cause at 90 days after diagnosis of infection

With death occurring in 14.5% of patients in the 7-day antibiotic course group and 16.1% of patients in the 14-day antibiotic course group, a 95.7% confidence interval showed non-inferiority of the shorter treatment duration.

These findings were consistent across secondary clinical outcomes, including death in the hospital, death in the ICU among the patients enrolled in the ICU or admitted to the ICU after the diagnosis of a bloodstream infection, relapse of bacteremia with the same organism that had caused the original infection, allergy to the antibiotic and adverse events, C. difficile infection in the hospital, etc.

Limitations:

• Placebos were not offered in this study due to the variability of antibiotics given, so patients were aware of their treatment condition.

• Confidence intervals for secondary measures were broad, as they were not widely observed in both groups.

• Non-adherence resulted in treatment variability. Intention for 7-day course had a 23.9% non-adherence rate with a median of an 8-day treatment. Intention for 14-day course had a 16.5% non-adherence rate with a median of 14-day treatment.

Conclusion:

This was the largest study to date to compare a 7-day versus 14-day course of antibiotics for bloodstream bacterial infection that included ICU patients. Although there was non-adherence in both groups, the clinician driven intention-to-treat analysis showed that the 7-day antibiotic course was non-inferior to the 14-day strategy. A shorter standard of care antibiotic course could have long term implications for savings in drug acquisition and the prevention of antibiotic resistance. Additionally, shortening hospital stays would save patients money and free up hospital beds.

Main Takeaway

When comparing mortality rates within 3 months of diagnosis of infection in hospitalized patients with bacteremia, there is preliminary evidence that antibiotic treatment for 7 days is non-inferior to treatment for 14 days.

Reference:

Daneman N, Rishu A, Pinto R, Rogers B, et al. Antibiotic treatment for 7 versus 14 days in patients with bloodstream infections. N Engl J Med. 2024 Nov 20; 392: 1065-1078. doi: 10.1056/NEJMoa2404991.