Dataset Information

Timing of antibiotic treatment identifies distinct clinical presentations among patients presenting with suspected septic shock.

ABSTRACT:

Objective

Recent clinical guidelines for sepsis management emphasize immediate antibiotic initiation for suspected septic shock. Though hypotension is a high-risk marker of sepsis severity, prior studies have not considered the precise timing of hypotension in relation to antibiotic initiation and how clinical characteristics and outcomes may differ. Our objective was to evaluate antibiotic initiation in relation to hypotension to characterize differences in sepsis presentation and outcomes in patients with suspected septic shock.

Methods

Adults presenting to the emergency department (ED) June 2012-December 2018 diagnosed with sepsis (Sepsis-III electronic health record [EHR] criteria) and hypotension (non-resolving for ≥30 min, systolic blood pressure <90 mmHg) within 24 h. We categorized patients who received antibiotics before hypotension ("early"), 0-60 min after ("immediate"), and >60 min after ("late") treatment.

Results

Among 2219 patients, 55% received early treatment, 13% immediate, and 32% late. The late subgroup often presented to the ED with hypotension (median 0 min) but received antibiotics a median of 191 min post-ED presentation. Clinical characteristics notable for this subgroup included higher prevalence of heart failure and liver disease (p < 0.05) and later onset of systemic inflammatory response syndrome (SIRS) criteria compared to early/immediate treatment subgroups (median 87 vs. 35 vs. 20 min, p < 0.0001). After adjustment, there was no difference in clinical outcomes among treatment subgroups.

Conclusions

There was significant heterogeneity in presentation and timing of antibiotic initiation for suspected septic shock. Patients with later treatment commonly had hypotension on presentation, had more hypotension-associated comorbidities, and developed overt markers of infection (eg, SIRS) later. While these factors likely contribute to delays in clinician recognition of suspected septic shock, it may not impact sepsis outcomes.

SUBMITTER: Prasad PA

PROVIDER: S-EPMC11002635 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Timing of antibiotic treatment identifies distinct clinical presentations among patients presenting with suspected septic shock.

Prasad Priya A PA Esmaili Armond M AM Oreper Sandra S Beagle Alexander J AJ Hubbard Colin C Raffel Katie E KE Abe-Jones Yumiko Y Fang Margaret C MC Liu Kathleen D KD Matthay Michael A MA Kangelaris Kirsten N KN

Journal of the American College of Emergency Physicians open 20240409 2

<h4>Objective</h4>Recent clinical guidelines for sepsis management emphasize immediate antibiotic initiation for suspected septic shock. Though hypotension is a high-risk marker of sepsis severity, prior studies have not considered the precise timing of hypotension in relation to antibiotic initiation and how clinical characteristics and outcomes may differ. Our objective was to evaluate antibiotic initiation in relation to hypotension to characterize differences in sepsis presentation and outco ...[more]

PMID: 38596320

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Project description:BackgroundSepsis is a highly heterogeneous syndrome, that has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies. The goal of this study was to elucidate pathophysiological pathways and identify pediatric septic shock subclasses based on whole blood RNA expression profiles.MethodsThe subjects were critically ill children with cardiopulmonary failure who were a part of a prospective randomized insulin titration trial to treat hyperglycemia. Genome-wide expression profiling was conducted using RNA-sequencing from whole blood samples obtained from 46 children with septic shock and 52 mechanically ventilated noninfected controls without shock. Patients with septic shock were allocated to subclasses based on hierarchical clustering of gene expression profiles, and we then compared clinical characteristics, plasma inflammatory markers, cell compositions using GEDIT, and immune repertoires using Imrep between the two subclasses.ResultsPatients with septic shock depicted alterations in innate and adaptive immune pathways. Among patients with septic shock, we identified two subtypes based on gene expression patterns. Compared with Subclass 2, Subclass 1 was characterized by upregulation of innate immunity pathways and downregulation of adaptive immunity pathways. Subclass 1 had significantly worse clinical outcomes despite the two classes having similar illness severity on initial clinical presentation. Subclass 1 had elevated levels of plasma inflammatory cytokines and endothelial injury biomarkers and demonstrated decreased percentages of CD4 T cells and B cells, and less diverse T-Cell receptor repertoires.ConclusionsTwo subclasses of pediatric septic shock patients were discovered through genome-wide expression profiling based on whole blood RNA sequencing with major biological and clinical differences.Trial registrationThis is a secondary analysis of data generated as part of the observational CAF PINT ancillary of the HALF PINT study (NCT01565941). Registered 29 March 2012.

Project description:BackgroundSepsis is a highly heterogeneous syndrome, which has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies. The goal of this study was to elucidate pathophysiological pathways and identify pediatric septic shock subclasses based on whole blood RNA expression profiles.MethodsThe subjects were critically ill children with cardiopulmonary failure who were a part of a prospective randomized insulin titration trial to treat hyperglycemia. Genome-wide expression profiling was conducted using RNA sequencing from whole blood samples obtained from 46 children with septic shock and 52 mechanically ventilated noninfected controls without shock. Patients with septic shock were allocated to subclasses based on hierarchical clustering of gene expression profiles, and we then compared clinical characteristics, plasma inflammatory markers, cell compositions using GEDIT, and immune repertoires using Imrep between the two subclasses.ResultsPatients with septic shock depicted alterations in innate and adaptive immune pathways. Among patients with septic shock, we identified two subtypes based on gene expression patterns. Compared with Subclass 2, Subclass 1 was characterized by upregulation of innate immunity pathways and downregulation of adaptive immunity pathways. Subclass 1 had significantly worse clinical outcomes despite the two classes having similar illness severity on initial clinical presentation. Subclass 1 had elevated levels of plasma inflammatory cytokines and endothelial injury biomarkers and demonstrated decreased percentages of CD4 T cells and B cells and less diverse T cell receptor repertoires.ConclusionsTwo subclasses of pediatric septic shock patients were discovered through genome-wide expression profiling based on whole blood RNA sequencing with major biological and clinical differences. Trial Registration This is a secondary analysis of data generated as part of the observational CAF-PINT ancillary of the HALF-PINT study (NCT01565941). Registered March 29, 2012.

Project description:BackgroundIn randomised controlled trials, procalcitonin (PCT)-guided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in intensive care unit (ICU) patients. However, concern was raised on low protocol adherence and high rates of overruling, and thus the value of PCT-guided treatment in real clinical life outside study conditions remains unclear. In this study, adherence to a PCT protocol to guide antibiotic treatment in patients with severe sepsis and septic shock was analysed.MethodsFrom 2012 to 2014, surgical ICU patients with severe sepsis or septic shock were retrospectively screened for PCT measurement series appropriate to make treatment decisions on antibiotic therapy. We compared (1) patients with appropriate PCT measurement series to patients without appropriate series; (2) patients who reached the antibiotic stopping advice threshold (PCT < 0.5 ng/mL and/or decrease to 10% of peak level) to patients who did not reach a stopping advice threshold; and (3) patients who were treated adherently to the PCT protocol to non-adherently treated patients. The groups were compared in terms of antibiotic treatment duration, PCT kinetics, and other clinical outcomes.ResultsOf 81 patients with severe sepsis or septic shock, 14 were excluded due to treatment restriction or short course in the ICU. The final analysis was performed on 67 patients. Forty-two patients (62.7%) had appropriate PCT measurement series. In patients with appropriate PCT series, median initial PCT (p = 0.001) and peak PCT levels (p < 0.001) were significantly higher compared to those with non-appropriate series. In 26 patients with appropriate series, PCT levels reached an antibiotic stopping advice. In 8 of 26 patients with stopping advice, antibiotics were discontinued adherently to the PCT protocol (30.8%). Patients with adherently discontinued antibiotics had a shorter antibiotic treatment (7d [IQR 6-9] vs. 12d [IQR 9-16]; p = 0.002). No differences were seen in terms of other clinical outcomes.ConclusionIn patients with severe sepsis and septic shock, procalcitonin testing was irregular and adherence to a local PCT protocol was low in real clinical life. However, adherently treated patients had a shorter duration of antibiotic treatment without negative clinical outcomes. Procalcitonin peak values and kinetics had a clear impact on the regularity of PCT testing.

Project description:IntroductionDespite recent advances in the management of septic shock, mortality remains unacceptably high. Earlier initiation of key therapies including appropriate antimicrobials and fluid resuscitation appears to reduce the mortality in this condition. This study examined whether early initiation of vasopressor therapy is associated with improved survival in fluid therapy-refractory septic shock.MethodsUtilizing a well-established database, relevant information including duration of time to vasopressor administration following the initial documentation of recurrent/persistent hypotension associated with septic shock was assessed in 8,670 adult patients from 28 ICUs in Canada, the United States of America, and Saudi Arabia. The primary endpoint was survival to hospital discharge. Secondary endpoints were length of ICU and hospital stay as well as duration of ventilator support and vasopressor dependence. Analysis involved multivariate linear and logistic regression analysis.ResultsIn total, 8,640 patients met the definition of septic shock with time of vasopressor/inotropic initiation documented. Of these, 6,514 were suitable for analysis. The overall unadjusted hospital mortality rate was 53%. Independent mortality correlates included liver failure (odds ratio (OR) 3.46, 95% confidence interval (CI), 2.67 to 4.48), metastatic cancer (OR 1.63, CI, 1.32 to 2.01), AIDS (OR 1.91, CI, 1.29 to 2.49), hematologic malignancy (OR 1.88, CI, 1.46 to 2.41), neutropenia (OR 1.78, CI, 1.27 to 2.49) and chronic hypertension (OR 0.62 CI, 0.52 to 0.73). Delay of initiation of appropriate antimicrobial therapy (OR 1.07/hr, CI, 1.06 to 1.08), age (OR 1.03/yr, CI, 1.02 to 1.03), and Acute Physiology and Chronic Health Evaluation (APACHE) II Score (OR 1.11/point, CI, 1.10 to 1.12) were also found to be significant independent correlates of mortality. After adjustment, only a weak correlation between vasopressor delay and hospital mortality was found (adjusted OR 1.02/hr, 95% CI 1.01 to 1.03, P <0.001). This weak effect was entirely driven by the group of patients with the longest delays (>14.1 hours). There was no significant relationship of vasopressor initiation delay to duration of vasopressor therapy (P?=?0.313) and only a trend to longer duration of ventilator support (P?=?0.055) among survivors.ConclusionMarked delays in initiation of vasopressor/inotropic therapy are associated with a small increase in mortality risk in patients with septic shock.

Project description:ObjectivesTo assess trends in timing of mortality among patients with septic shock.DesignRetrospective cohort study.SettingAgency for Healthcare Research and Quality's Healthcare Cost and Utilization Project's National Inpatient Sample, 1994-2014.PatientsHospitalized adults (≥ 18 yr) with International Classification of Diseases, 9th Edition, Clinical Modification codes consistent with septic shock; secondary analysis: adults with International Classification of Diseases, 9th Edition, Clinical Modification codes consistent with acute respiratory failure receiving invasive mechanical ventilation and patients with both septic shock and acute respiratory failure receiving invasive mechanical ventilation.InterventionsNone.Measurements and main resultsFrom 1994 to 2014, 48-hour mortality rates decreased among patients with septic shock (21.2% to 10.8%) and septic shock with acute respiratory failure receiving invasive mechanical ventilation (19.1% to 13.4%) but increased among patients with acute respiratory failure receiving invasive mechanical ventilation (7.9% to 9.8%; p value for all trends, < 0.001). Three-to-14-day mortality decreased among patients with septic shock (22.1% to 15.5%), septic shock with acute respiratory failure receiving invasive mechanical ventilation (28.7% to 22.4%) and acute respiratory failure receiving invasive mechanical ventilation (16.8% to 15.0%; p value for all trends, < 0.001). Mortality after 14 days decreased among all groups (septic shock: 12.6% to 6.7%; septic shock with acute respiratory failure receiving invasive mechanical ventilation: 20.3% to 11.3%; and acute respiratory failure receiving invasive mechanical ventilation: 12.7% to 5.8%; p value for all trends, < 0.001). Cox proportional hazard ratio for declining risk in mortality per year (adjusted for patient and hospital characteristics) was 0.96 (95% CI, 0.96-0.96) for septic shock, 0.97 (0.97-0.97) for acute respiratory failure receiving invasive mechanical ventilation and septic shock, and 0.99 (0.99-0.99) for acute respiratory failure receiving invasive mechanical ventilation.ConclusionsSeptic shock 48-hour, 3-14-day and greater than 14-day mortality declined markedly over two decades; in contrast, patients with acute respiratory failure only experienced marked decreases in greater than 14-day in-hospital mortality rates.

Dataset Information

Timing of antibiotic treatment identifies distinct clinical presentations among patients presenting with suspected septic shock.

Objective

Methods

Results

Conclusions

Publications

Timing of antibiotic treatment identifies distinct clinical presentations among patients presenting with suspected septic shock.

Similar Datasets

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