Genesis of Antibiotic Resistance (AR) LVIII: Discordant Antibiotic Stewardship contort Early Goal Directed Fluid Resuscitation therapy (EGDT) with higher incidence of Mortality in severe Sepsis: A global melee
Authors: Rueda Alejandra , Trejo Natalia , Miramontes Mariana , Montejano Claudia , Mercado Deisy , Chavarria Mayra , Kannan Subburaj 
Published: April 2020

A retrospective analysis of EGDT trials from 2000 to 2018 registered in national clinical trials is presented here: (PRISM‐U) Study group attributed that the sepsis cohort with Mycobacterium tuberculosis (MTB) bacteremia for higher rate of in‐hospital mortality. FEAST (ISRCTN69856593) trial observed that fluid resuscitation in children with sepsis significantly increased mortality (48‐hour) possibly due to impaired perfusion. SSSP trail (NCT01449916) showed that though hypoxemic respiratory failure as contributing factor for mortality in addition to tissue hypoperfusion as inclusion criteria of patients with hypovolemia but excluding the patients with severe respiratory distress when ventilator support is not readily available could have potentially improved the survival rate. ARISE (NCT00975793) presented their report on the effectiveness of EGDT compare to that of usual sepsis care had similar (~18%) mortality rate concluding that EGDT did not reduce all‐cause mortality at 90 days.
PRISM (NCT02030158) reported that, EGDT miss the mark to relieve mortality rate compare to that of usual care cohort. ProCESS (NCT00510835) reported that among 1341 patients, of whom 439 were randomly assigned to protocol‐based EGDT, 446 to protocol‐based standard therapy, and 456 to usual care in which protocol‐based resuscitation of patients in whom septic shock was diagnosed in the ER did not improve outcomes. ProMISe (ISRCTN36307479) concluded that septic shock cohort identified early and treated with intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol showed that no difference in mortality rate by 90 days. The IMPreSS study group found that compliance with “all of the evidence‐based bundle metrics” had a 40 % reduction in the odds of dying in hospital with the 3‐h bundle and 36 % for the 6‐h bundle.
ProCESS Investigators (NCT00793442,
NCT00510835
) showed that increase in leucocyte rolling and adhering to dysfunctional endothelial surface in the cohort of septic shock compare to that of control, attributed to an increase in endothelial permeability‐hemostasis as cause for mortality. SSSP‐2 (NCT01663701) reported that cohort with sepsis and hypotension, most of whom were positive for HIV, in a resource‐limited setting, a protocol for early resuscitation with administration of intravenous fluids and vasopressors increased in‐hospital mortality compared with usual care. MOSAICS Study Group attributed the high mortality rate in severe sepsis treatment for the variation in adhering to the “all of the evidence‐based bundle metrics” for sepsis treatment. GENESIS project comparing 6‐hour resuscitation bundle (RB) for severe sepsis cohort showed decreased mortality rate compare to that of no RB bundle. Taken together it is suggested that lack coherent antibiotic stewardship practices across the globe warrant immediate review during EGDT and implementation of such guidelines would likely improve the survival rate in both low and high resource setting.

Support or Funding Information

Supported by the professional development funds by SWTJC to Subburaj Kannan