7 days antibiotics as good as 14 days course in gram negative bacteremia: JAMA

CRP guided 7 days antibiotic treatment as good as 14 days treatment in uncomplicated gram-negative bacteremia, finds a JAMA study.

Gram-negative bacteremia is a common infection that results in substantial antibiotic use.It is well known that antibiotic overuse leads to antibiotic resistance.

Researchers conducted a study to ascertain whether antibiotic treatment with C-reactive protein (CRP)–guided duration or fixed 7-day duration, compared with fixed 14-day duration was noninferior in patients with uncomplicated gram-negative bacteremia.They compared the clinical effectiveness of C-reactive protein (CRP)–guided, 7-day, and 14-day antibiotic durations 30, 60, and 90 days after treatment initiation.

The researchers conducted a multicenter, noninferiority, point-of-care randomized clinical trial including adults hospitalized with gram-negative bacteremia conducted in 3 Swiss tertiary care hospitals between April 2017 and May 2019, with follow-up until August 2019.The randomized clinical trial included 504 adults with uncomplicated gram-negative bacteremia.

The patients and physicians were blinded between randomization and antibiotic discontinuation. Adults (aged ≥18 years) were eligible for randomization on day 5 (±1 d) of microbiologically efficacious therapy for fermenting, gram-negative bacteria in blood culture(s) if they were afebrile for 24 hours without evidence for complicated infection (eg, abscess) or severe immunosuppression.

A 30-day clinical failure occurred in 2.4% of patients assigned to receive CRP-guided antibiotic treatment duration, 6.6% assigned to 7-day treatment, and 5.5% assigned to 14-day treatment. The differences between CRP-guided treatment and 7-day treatment compared with 14-day treatment met the noninferiority criterion of 10%, but adherence to the CRP strategy or planned follow-up did not occur in 23% of patients.

The primary outcome was the clinical failure rate at day 30, defined as the presence of at least 1 of the following, with a non-inferiority margin of 10%: recurrent bacteremia, local suppurative complication, distant complication (growth of the same organism causing the initial bacteremia), restarting gram-negative–directed antibiotic therapy due to clinical worsening suspected to be due to the initial organism, or death due to any cause. Secondary outcomes included the clinical failure rate on day 90 of follow-up.

The researchers found that CRP-guided treatment and 7-day treatment were noninferior to 14-day treatment in patients with uncomplicated gram-negative bacteremia, but interpretation is limited by the large noninferiority margin compared with the low observed event rate and lower adherence in the CRP-guided group.

The researchers concluded that among adults with uncomplicated gram-negative bacteremia, 30-day rates of clinical failure for CRP-guided antibiotic treatment duration and fixed 7-day treatment were noninferior to fixed 14-day treatment. However, interpretation is limited by the large noninferiority margin compared with the low observed event rate, as well as low adherence and wide range of treatment durations in the CRP-guided group.

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JAMA. 2020;323(21):2160-2169.