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Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients.

ABSTRACT: OBJECTIVES:To determine if time to initial antimicrobial is associated with progression of severe sepsis to septic shock. DESIGN:Retrospective cohort. SETTING:Six hundred fifty-six bed urban academic medical center. PATIENTS:Emergency department patients greater than or equal to 18 years old with severe sepsis and/or septic shock and antimicrobial administration within 24 hours. Patients with shock on presentation were excluded. INTERVENTIONS:Not available. MEASUREMENTS AND MAIN RESULTS:We identified 3,929 severe sepsis patients, with overall mortality 12.8%. Nine hundred eighty-four patients (25.0%) progressed to septic shock. The median time to antimicrobial was 3.77 hours (interquartile range = 1.96-6.42) in those who progressed versus 2.76 hours (interquartile range = 1.60-4.82) in those who did not (p < 0.001). Multivariate logistic regression demonstrated that male sex (odds ratio = 1.18; 95% CI, 1.01-1.36), Charlson Comorbidity Index (odds ratio = 1.18; 95% CI, 1.11-1.27), number of infections (odds ratio = 1.05; 95% CI, 1.02-1.08), and time to first antimicrobial (odds ratio = 1.08; 95% CI, 1.06-1.10) were associated with progression. Each hour until initial antimicrobial administration was associated with a 8.0% increase in progression to septic shock. Additionally, time to broad-spectrum antimicrobial was associated with progression (odds ratio = 1.06; 95% CI, 1.05-1.08). Time to initial antimicrobial was also associated with in-hospital mortality (odds ratio = 1.05; 95% CI, 1.03-1.07). CONCLUSIONS:This study emphasizes the importance of early, broad-spectrum antimicrobial administration in severe sepsis patients admitted through the emergency department, as longer time to initial antimicrobial administration is associated with increased progression of severe sepsis to septic shock and increased mortality.

SUBMITTER: Whiles BB

PROVIDER: S-EPMC5374449 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients.

Whiles Bristol B BB Deis Amanda S AS Simpson Steven Q SQ

Critical care medicine 20170401 4

<h4>Objectives</h4>To determine if time to initial antimicrobial is associated with progression of severe sepsis to septic shock.<h4>Design</h4>Retrospective cohort.<h4>Setting</h4>Six hundred fifty-six bed urban academic medical center.<h4>Patients</h4>Emergency department patients greater than or equal to 18 years old with severe sepsis and/or septic shock and antimicrobial administration within 24 hours. Patients with shock on presentation were excluded.<h4>Interventions</h4>Not available.<h4 ...[more]

PMID: 28169944

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Project description:BackgroundThere is ample literature available on the association between both time to antibiotics and appropriateness of antibiotics and clinical outcomes from sepsis. In fact, the current state of debate surrounds the balance to be struck between prompt empirical therapy and care in the choice of appropriate antibiotics (both in terms of the susceptibility of infecting organism and minimizing resistance arising from use of broad-spectrum agents). The objective of this study is to determine sepsis bundle compliance and the appropriateness of antimicrobial therapy in patients with severe sepsis and septic shock and its impact on outcomes.MaterialThis study was conducted in the ICU of a tertiary care, private hospital in São Paulo, Brazil. A retrospective cohort study was conducted from July 2005 to December 2012 in patients with severe sepsis and septic shock.ResultsA total of 1,279 patients were identified with severe sepsis and septic shock, of which 358 (32.1%) had bloodstream infection (BSI). The inpatient mortality rate was 29%. In evaluation of the sepsis bundle, over time there was a progressive increase in serum arterial lactate collection, obtaining blood cultures prior to antibiotic administration, administration of broad-spectrum antibiotics within 1 hour, and administration of appropriate antimicrobials, with statistically significant differences in the later years of the study. We also observed a significant decrease in mortality. In patients with bloodstream infection, after adjustment for other covariates the administration of appropriate antimicrobial therapy was associated with a decrease in mortality in patients with severe sepsis and septic shock (p = 0.023).ConclusionsThe administration of appropriate antimicrobial therapy was independently associated with a decline in mortality in patients with severe sepsis and septic shock due to bloodstream infection. As protocol adherence increased over time, the crude mortality rate decreased, which reinforces the need to implement institutional guidelines and monitor appropriate antimicrobial therapy compliance.

Project description:The role of recombinant activated protein C (aPC) during sepsis is still controversial. It showed anti-inflammatory effect and improved the microvascular perfusion in experimental models of septic shock. The present study was aimed at testing the hypothesis that recombinant aPC therapy improves the microcirculation during severe sepsis.Prospective observational study on patients admitted in a 12-beds intensive care unit of a university hospital from July 2010 to December 2011, with severe sepsis and at least two sepsis-induced organ failures occurring within 48 hours from the onset of sepsis, who received an infusion of aPC (24 mcg/kg/h for 96 hours) (aPC group). Patients with contraindications to aPC administration were also monitored (no-aPC group).At baseline (before starting aPC infusion, T0), after 24 hours (T1a), 48 hours (T1b), 72 hours (T1c) and 6 hours after the end of aPC infusion (T2), general clinical and hemodynamic parameters were collected and the sublingual microcirculation was evaluated with sidestream dark-field imaging. Total vessel density (TVD), perfused vessel density (PVD), De Backer score, microvascular flow index (MFIs), the proportion of perfused vessels (PPV) and the flow heterogeneity index (HI) were calculated for small vessels. The perfused boundary region (PBR) was measured as an index of glycocalyx damage. Variables were compared between time points and groups using non parametric or parametric statistical tests, as appropriate.In the 13 aPC patients mean arterial pressure (MAP), base excess, lactate, PaO2/FiO2 and the Sequential Organ Failure Assessment (SOFA) score significantly improved over time, while CI and ITBVI did not change. MFIs, TVD, PVD, PPV significantly increased over time and the HI decreased (p?<?0.05 in all cases), while the PBR did not change. No-aPC patients (n?=?9) did not show any change in the microcirculation over time. A positive correlation was found between MFIs and MAP. TVD, PVD and De Backer score negatively correlated with norepinephrine dose, and the SOFA score negatively correlated with MFIs, TVD and PVD.aPC significantly improves the microcirculation in patients with severe sepsis/septic shock.NCT01806428.

Project description:Background: Patients with cancer are at high risk for severe sepsis and septic shock (SS/SSh), and a delay in receiving effective antibiotics is strongly associated with mortality. Delays are due to logistics of clinic flow and drug delivery. In an era of increasing antimicrobial resistance, combination therapy may be superior to monotherapy for patients with SS/SSh. Patients and Methods: At the Seattle Cancer Care Alliance, we implemented the Sepsis STAT Pack (SSP) program to simplify timely and effective provision of empiric antibiotics and other resuscitative care to outpatients with cancer with suspected SS/SSh before hospitalization. Over a 49-month period from January 1, 2008, through January 31, 2012, a total of 162 outpatients with cancer received the intervention. A retrospective cohort study was conducted to determine outcomes, including mortality and adverse events associated with the use of a novel care bundle designed for compatibility of broad-spectrum antibiotics and other supportive care administered concurrently via rapid infusion at fixed doses. Results: Of 162 sequential patients with cancer and suspected SS/SSh who received the SSP, 71 (44%) were diagnosed with SS/SSh. Median age was 53 years and 65% were men; 141 (87%) had hematologic malignancies, 77 (48%) were transplant recipients, and 80 (49%) were neutropenic. Median time to completion of antibiotics was 111 minutes (interquartile range, 60-178 minutes). A total of 71 patients (44%) had bacteremia and 17% of 93 isolates were multidrug-resistant. Possibly related nephrotoxicity occurred in 7 patients, and 30-day mortality occured in 6 of 160 patients (4%), including 3 of 71 (4%) with SS/SSh. Risk of developing SSh or death within 30 days increased 18% (95% CI, 4%-34%) for each hour delay to completion of antibiotics (P=.01). Conclusions: Rapidly administered combination antibiotics and supportive care delivered emergently to ambulatory patients with cancer with suspected SS/SSh was well-tolerated and associated with excellent short-term survival.

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Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients.

Publications

Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients.

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