Antibiotics for Sepsis—Finding the Equilibrium

Abstract

Sepsis is medicine's last remaining preserve for unrestrained antibiotic prescribing. The Surviving Sepsis Campaign guidelines recommend empirical broadspectrum therapy within one hour of triage for both sepsis and septic shock. 1 This recommendation, and mandates that compel it, encourage clinicians to adopt an approach of "treat first, ask questions later" for patients with any possibility of serious infection. This approach fails to account for the difficulties clinicians face with diagnosing infection, especially when patients initially present to care, and the high rate of overdiagnosis of sepsis, and thus risks promoting excess antibiotic use and causing unintended harm.The recommendation to treat quickly and aggressively may seem sensible because sepsis and septic shock are potentially deadly conditions. Delays in appropriate antimicrobial therapy have been associated with higher mortality rates, and quality improvement initiatives that encouraged earlier prescribing have reported substantial decreases in mortality. Many of the studies supporting these assertions, however, may be biased. Most of these investigations failed to account for VIEWPOINT

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

“…The definition of "timely" in this context represents an area of controversy relating to challenges in the accurate recognition of patients with sepsis and septic shock and the need to consider balancing QI metrics such as unnecessary antimicrobial usage [44,73,74]. One pediatric study [63] indicated a dose-response gradient such that the longer time to antimicrobial therapy, the higher the mortality.…”

Mathematical modeling links benefits of short and long antibiotic treatment to details of infection

“…Because of the variety of bacterial infections humans are exposed to, for many infections the duration of antibiotic treatment has not been tested in randomized clinical trials. Recently, the necessity of a relatively long antibiotic treatment has been questioned [15,16,17], including with the use of mathematical models [18,19] suggesting that longer treatment may in fact result in poorer outcomes, for example, in increased antibiotic resistance. Other studies have shown that longer treatment is needed to guarantee bacterial control [20,21], suggesting that an optimum duration exists and should be adopted when treating bacterial infections.…”

“…An increasing number of clinical studies on bacterial infections are showing that shorter treatment may be as effective as longer treatment, while minimizing adverse effects and resistance risk [22,23,15,17]. Support for shorter durations of therapy than previously administered has been growing for infections such as community-acquired pneumonia, ventilator-associated pneumonia, intraabdominal infections, urinary tract infections, cellulitis, and gram-negative bacteremia [15].…”

Effects of Delayed Antibiotic Therapy on Outcomes in Children with Streptococcus pneumoniae Sepsis

“…The Surviving Sepsis Campaign recommended that antibiotics should be administered within 1 h after the recognition of severe sepsis or septic shock (11,12); however, this recommendation has been challenged recently (15). Efforts to meet the aggressive 1-h goal may lead to the overuse of antibiotics, which may cause unintended harm (13)(14)(15). Moreover, the proper antibiotic administration time is different in different populations (6-10).…”