What is it about?

Enterococcus faecalis is a common gut bacterium that can enter the bloodstream and cause serious infections, especially in older and hospitalized patients. Doctors often combine two antibiotics (for example ampicillin plus ceftriaxone or gentamicin), a strategy proven for heart valve infection (endocarditis), but it is unclear whether this helps when the heart is not involved. Using data collected prospectively in 24 hospitals in several countries, we applied a 'target trial emulation' - a statistical method that mimics a randomized trial with real-world data. We studied 373 adults with E. faecalis bloodstream infection and a negative echocardiogram. Treatment failure at 90 days (death, relapse or later endocarditis) occurred in 28% of patients on a single antibiotic and 36% of those on combination therapy, with no advantage for the combination.

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Why is it important?

Combination therapy means more drugs, more side effects, more cost and more pressure for antibiotic resistance. Our results suggest that, when endocarditis has been excluded, a single well-chosen antibiotic such as ampicillin may be enough. If confirmed in randomized trials, this would allow safe simplification of treatment in line with antimicrobial stewardship principles.

Perspectives

This study is a great example of what international collaboration within the ESCMID Study Group for Bloodstream Infections, Endocarditis and Sepsis can achieve. 'More antibiotics' is not always 'better medicine'. I am glad that our unit in Trieste contributed patients to an analysis that may help simplify the treatment of a very common infection.

Professor Stefano Di Bella
Universita degli Studi di Trieste

Read the Original

This page is a summary of: Monotherapy vs. combination therapy for Enterococcus faecalis bacteraemia: a target trial emulation, Clinical Microbiology and Infection, June 2026, Elsevier,
DOI: 10.1016/j.cmi.2026.03.018.
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