A Systematic Review of the Effect of Delayed Appropriate Antibiotic Treatment on the Outcomes of Patients With Severe Bacterial Infections

Abstract

BACKGROUND: Patients with severe bacterial infections often experience delay in receiving appropriate treatment. Consolidated evidence of the impact of delayed appropriate treatment is needed to guide treatment and improve outcomes. RESEARCH QUESTION: What is the impact of delayed appropriate antibacterial therapy on clinical outcomes in patients with severe bacterial infections? STUDY DESIGN AND METHODS: Literature searches of MEDLINE and Embase, conducted on July 24, 2018, identified studies published after 2007 reporting the impact of delayed appropriate therapy on clinical outcomes for hospitalized adult patients with bacterial infections. Where appropriate, results were pooled and analyzed with delayed therapy modeled three ways: delay vs no delay in receiving appropriate therapy; duration of delay; and inappropriate vs appropriate initial therapy. This article reports meta-analyses on the effect of delay and duration of delay. RESULTS: The eligibility criteria were met by 145 studies, of which 37 contributed data to analyses of effect of delay. Mortality was significantly lower in patients receiving appropriate therapy without delay compared with those experiencing delay (OR, 0.57; 95% CI, 0.45-0.72). Mortality was also lower in the no-delay group compared with the delay group in subgroups of studies reporting mortality at 20 to 30 days, during ICU stay, or in patients with bacteremia (OR, 0.57 [95% CI, 0.43-0.76]; OR, 0.47 [95% CI, 0.27-0.80]; and OR, 0.54 [95% CI, 0.40-0.75], respectively). No difference was found in time to appropriate therapy between those who died and those who survived (P ¼ .09), but heterogeneity between studies was high. INTERPRETATION: Avoiding delayed appropriate therapy is essential to reduce mortality in patients with severe bacterial infections.

Best diagnostic accuracy of sepsis combining SIRS criteria or qSOFA score with Procalcitonin and Mid-Regional pro-Adrenomedullin outside ICU

“…To reduce antimicrobial resistance, however, would be desirable to administer an appropriate antimicrobial treatment basing on the results of microbiological specimen even if these latter yield positive results just in less than 50% of cases 9 , 10 . Two recent systematic review and meta-analysis highlighted as an earlier than delayed antimicrobial treatment administration seemed not to reduce mortality in patients with septic shock, despite the effect of other specific treatment were not considered within the analysis 30 , 31 . These contrasting results is responsible for the lack of standardized treatment strategies.…”

Key Challenges in Providing Effective Antibiotic Therapy for Critically Ill Patients with Bacterial Sepsis and Septic Shock

“…Mortality rates are ~ 20% for sepsis and may exceed 40% for patients with septic shock 2,3 . Early administration of effective antibiotic therapy substantially improves the probability of survival, as demonstrated in multiple studies and meta‐analyses 4–7 . Initiation of effective antimicrobial administration within the first hour of documented hypotension was found to be associated with increased survival in septic shock, whereas each hour of delay decreased survival 4 .…”

“…2,3 Early administration of effective antibiotic therapy substantially improves the probability of survival, as demonstrated in multiple studies and meta-analyses. [4][5][6][7] Initiation of effective antimicrobial administration within the first hour of documented hypotension was found to be associated with increased survival in septic shock, whereas each hour of delay decreased survival. 4 Similarly, the median time to administration of antibiotics was 1 hour in patients with sepsis and septic shock, and a longer time was associated with higher risk-adjusted in-hospital mortality.…”

Narrow-Spectrum Antibacterial Agents—Benefits and Challenges

“…While several clinical syndromes are caused by individual bacterial species, the majority can be caused by multiple species, and indeed in some cases can be polymicrobial, with the added challenge of distinguishing pathogen from colonizer. Rapid initiation of appropriate treatment correlates with reduced mortality and improved clinical outcomes, a trend most notable with bloodstream infections and sepsis [ 19 , 20 , 21 , 22 ]. This becomes especially important when considering narrow-spectrum agents, as there is a need for rapid identification of the infecting pathogen, along with the susceptibility profile, to ensure the administration of an appropriate agent in a timely fashion.…”