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Two-week antibiotic courses have been considered standard care for most patients with bacteremia who do not have sepsis or an untreated primary source (e.g. endocarditis). No good evidence ever supported the practice, which was supported mainly by retrospective data in patients with sepsis. A new study suggests that treating gram-negative bacteremia for seven days is equally effective as 14 days of treatment, if resolution of sepsis and source control are both present.
Researchers randomized 604 patients with gram negative bacteremia at three hospitals in Israel and Italy to receive 7 or 14 days of antibiotics, selected by the treating physicians. They could be enrolled only if sepsis had resolved and source control was achieved. Primary outcome was a composite of all-cause mortality, clinical failure and readmission or extended hospital stay greater than 14 days. The design was non-inferiority.
Most patients had E. coli, Klebsiella or other Enterobacteriacae bacteremia, usually from a urinary source; 90% of the infections were hospital-acquired. There were relatively few Pseudomonas or Acinetobacter infections. Patients were 71 years old on average.
Roughly equal rates of the composite outcome were seen in the 7-day group (46%) and the 14-day group (50%).
There were no differences seen in emergence of resistant bacteria. Patients in the 7-day group received about half the total days of antibiotics.
Prolonged antibiotic courses have sometimes been advocated to prevent the emergence of resistance from an inadequately treated infection. This logic is flawed, as antibiotic resistance rarely emerges at the site of infection. Prolonged courses of antibiotics mainly serve to increase selective pressure for resistance to emerge among colonizing organisms elsewhere in the body.
It's important to note that source control was believed to be achieved in all enrolled patients. If source control cannot be achieved (e.g., an abscess, or an infected heart valve or indwelling catheter that cannot safely be removed), prolonged antibiotic courses are often advisable.
The lead author said in a press release: “This could lead to a change in accepted management algorithms and shortened antibiotic therapy ... [although] we did not show that in our trial, it may lead to reduced cost, resistance development and adverse events.”
Source: Yahav D, et al. Abstract O1120. European Congress of Clinical Microbiology and Infectious Diseases (Madrid); April 21-24, 2018.