Seven-day antibiotic course as effective as 14-day for gram-negative bacteraemia
Patients hospitalized with gram-negative bacteraemia have similar outcomes regardless of whether they receive a 7-day or 14-day course of antibiotic therapy, according to a study presented at ECCMID 2018.
“In patients hospitalized with gram-negative bacteraemia and sepsis resolution before day seven, a course of 7 antibiotic days was not inferior to 14 days, reduced antibiotic days, and resulted in a more rapid return to baseline activity,” said Dr Dafna Yahav from Tel Aviv University, Tel Aviv, Israel, who presented the findings.
“This could lead to a change in accepted management algorithms and shortened antibiotic therapy,” she said, also pointing out the potential reduction in cost, adverse events, and development of antimicrobial resistance.
Researchers of this multicentre (three hospitals in Israel and Italy), open-label, non-inferiority trial randomized 604 hospitalized patients to receive either 7 days (n=306, mean age 71 years, 51.0 percent female) or 14 days (n=298, mean age 71 years, 54.7 percent female) of antibiotic therapy for the treatment of community- or hospital-acquired gram-negative bacteraemia. The causative organism in 90 percent of the cases was Enterobacteriaceae and the majority of cases were urinary tract infections (UTIs; 68 percent). Patients with an uncontrolled source of infection and those with ongoing sepsis were excluded.
At 90 days, 46.1 percent of patients who were treated for 7 days experienced the composite of all-cause death, clinical failure (relapse of bacteraemia, new local suppurative complications, or distant complications), readmission to hospital, or extended hospitalization (>14 days) compared with 50.0 percent of patients who were treated for 14 days (absolute risk difference [ARD], -3.9 percent, 95 percent confidence interval [CI], -11.9 to 4.0 percent). [ECCMID 2018, abstract 01120]
The results were consistent in the per-protocol analysis which comprised the 556 patients who received antibiotics for the full treatment period ± 2 days (n=280 and 276 in the 7-day and 14-day groups, respectively; 46.1 percent vs 49.6 percent, ARD, -3.5 percent, 95 percent CI, -11.9 to 4.7 percent).
Between randomization and the 90-day mark, patients in the 7-day group had significantly fewer antibiotic exposure days compared with those in the 14-day group (median, 5 vs 12 days; p<0.001), as well as a shorter time to return to baseline activity (median, 2 vs 3 weeks; p=0.001).
The mortality rate at 90 days was comparable between patients in the 7-day and 14-day treatment groups (11.8 percent vs 10.7 percent, ARD, 1.0, 95 percent CI, -4.0 to 6.1).
According to Yahav, there is limited data available to guide the appropriate duration of antibiotic therapy, with few patients included in randomized controlled trials and retrospective studies producing inconclusive data.
While the shorter treatment course did not appear to be associated with any disadvantages, Yahav highlighted that the results of this study may not be applicable to all patients with gram-negative bacteraemia, given the majority of patients in this study had UTIs and Enterobacteriaceae-related infections.
“It is safe to stop antibiotics after 7 days … for gram-negative bacteraemia patients [who are] haemodynamically stable, non-neutropenic at day 7, and with no uncontrolled source [of infection],” she said.