Duration of Antibiotic Treatment for Gram-Negative Bacteremia
eClinicalMedicine Journal: The LANCET: Published on December, 2022
Gram-negative bacteremia is common
in both community and health care settings, with a significant increase in
incidence described for some Gram-negative bacteria in recent years.
Prolonged duration of antibiotic
therapy for such common infections may lead to increased resistance emergence;
adverse events and secondary infections, including Clostridioides
difficile infection; prolonged hospital-stay; and excess cost.
Prolonged courses are still
commonly used and current guidelines still recommend the range of 7–14 days.
In addition, it is unclear whether
shorter courses of antibiotics are appropriate for specific sub-groups of
patients, such as those with non-urinary source of bacteremia; intensive care
patients, elderly, and others.
TAKE-HOME MESSAGE
This systematic review and
meta-analysis of three studies involving 1186 patients with gram-negative
bacteremia compared the outcomes of short-duration versus long-duration
antibiotic treatment.
There was no significant difference
in mortality rate, relapse of bacteremia between
patients receiving 7 or 14 days of antibiotics.
Notably, 94% of the patients had
Enterobacterales bacteremia, and all patients were afebrile and hemodynamically
stable for 48 hours before antibiotic discontinuation.
This is the largest comparison of
antibiotic administration duration for gram-negative bacteremia to date, which
finds consistent noninferiority of shorter durations across multiple subgroups,
including urinary versus nonurinary bacteremia source, age above/below 65
years, and immunocompetent versus immunocompromised status, men vs women.
In conclusion, for patients with uncomplicated and controlled Gram-negative bacteremia, 7 days of antibiotic therapy for enterobacterales bacteremia result in similar outcomes as 14 days, in terms of mortality, relapse, complications of infection, resistance emergence, and adverse events.
Shorter courses of antibiotic
therapy may be encouraged in eligible patients and may shorten length of
inpatient stay, decrease antibiotic exposure and reduce costs without impacting
mortality or other adverse outcomes.
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Background: We aim to
compare the effect of short versus long treatment duration in Gram-negative
bacteremia on all-cause mortality in pre-specified sub-groups.
Methods: Individual
participant data meta-analysis of randomized controlled trials (RCTs) comparing
short (≤7) versus longer (>7 days) antibiotic treatment for Gram-negative
bacteremia. Participants were adults (≥18 years), with Gram-negative bacteremia
during hospital stay. We searched PubMed, Cochrane Central Register of
Controlled Trials, and Web of Science to identify trials conducted up to May
2022. Primary outcome was 90-day all-cause mortality. Secondary outcomes were
30-day mortality, relapse of bacteremia, length of hospital stay, readmission,
local or distant infection complications, adverse events, and resistance
emergence.Outcomes were assessed in pre-specified subgroups: women vs men;
non-urinary vs urinary source; presence vs absence of hypotension on initial
presentation; immunocompromised patients versus non-immunocompromised patients,
and age (above/below 65).
Findings: Three RCTs
(1186 patients) were included; 1121 with enterobacterales bacteremia.
No significant difference in mortality was demonstrated between 7- and 14-days
treatment. Relapse; length of hospital stay; readmission; and infection
complications, were without significant difference, and so were adverse events
or resistance emergence.No significant difference in clinical outcomes between
7 and 14 days of antibiotics was demonstrated in the subgroups of gender, age,
hemodynamic status, immune status, and source of infection.
Interpretation: For
patients hemodynamically stable and afebrile at 48 h prior to discontinuation,
seven days of antibiotic therapy for enterobacterales bacteremia
result in similar outcomes as 14 days, in terms of mortality, relapse, length
of hospital stay, complications of infection, resistance emergence, and adverse
events. These results apply for any adult age group, gender, source of
infection, immune status, and hemodynamic status on presentation.
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