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Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts.

ABSTRACT: BACKGROUND:Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. METHODS:A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). RESULTS:Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age >?50?years (OR 2.57, 95% CI 1.03-6.41, p?=?0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p?=?0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p?=?0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p?=?0.02). CONCLUSIONS:Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms.

SUBMITTER: Bassetti M

PROVIDER: S-EPMC7099832 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts.

Bassetti Matteo M Bassetti Matteo M Vena Antonio A Meroi Marco M Cardozo Celia C Cuervo Guillermo G Giacobbe Daniele Roberto DR Salavert Miguel M Merino Paloma P Gioia Francesca F Fernández-Ruiz Mario M López-Cortés Luis Eduardo LE Almirante Benito B Escolà-Vergé Laura L Montejo Miguel M Aguilar-Guisado Manuela M Puerta-Alcalde Pedro P Tasias Mariona M Ruiz-Gaitán Alba A González Fernando F Puig-Asensio Mireia M Marco Francesc F Pemán Javier J Fortún Jesus J Aguado Jose Maria JM Soriano Alejandro A Carratalá Jordi J Garcia-Vidal Carolina C Valerio Maricela M Sartor Assunta A Bouza Emilio E Muñoz Patricia P

Critical care (London, England) 20200326 1

<h4>Background</h4>Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia.<h4>Methods</h4>A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes oc ...[more]

PMID: 32216822

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Project description:PurposeAdrecizumab, a non-neutralizing antibody of adrenomedullin (ADM) was recently investigated regarding its potential to restore endothelial barrier function in septic shock patients with high plasma ADM levels. Circulating dipeptidyl peptidase 3 (cDPP3), a protease involved in the degradation of several cardiovascular mediators, represents another biological pathway strongly associated with outcome in septic shock, although unrelated to ADM. Therefore, the prognosis of patients with elevated cDPP3 may not be influenced by Adrecizumab. Also, time until initiation of treatment may influence efficacy.ObjectiveTo evaluate effects of cDPP3-based enrichment on treatment efficacy of Adrecizumab.Materials and methodsPost-hoc analysis of AdrenOSS-2, a phase-II, double-blind, randomized, placebo-controlled biomarker-guided trial of Adrecizumab.ResultsCompared to the total study cohort [HR for 28-day mortality of 0.84 (95% CI 0.53;1.31), p = 0.439], therapeutic benefit of Adrecizumab tended to be more pronounced in the subgroup of 249 patients with low cDPP3 (<50 ng/mL); [HR of 0.61 (95% CI 0.34;1.08), p = 0.085]. Median duration to study drug infusion was 8.5 h. In the subgroup of 129 patients with cDPP3 <50 ng/mL and an early start of treatment (<8.5 h after septic shock diagnosis) HR for 28-day mortality vs. placebo was 0.49 (95% CI 0.21-1.18), p = 0.105. In multivariate interaction analyses corrected for baseline disease severity, both cDPP3, as well as the cDPP3 * treatment interaction term were associated with a reduced HR for 28-day mortality in the Adrecizumab treated group; p = 0.015 for cDPP3 in univariate analysis, p = 0.025 for the interaction term between cDPP3 and treatment group. In contrast, treatment timing was not significantly associated with 28-day mortality in multivariate interaction analyses.DiscussionIn septic shock patients with high ADM levels, a further post-hoc enrichment strategy based on cDPP3 may indicate (with all the caveats to be considered for post-hoc subgroup analyses) that therapeutic efficacy is most pronounced in patients with lower cDPP3 levels.

Project description:PurposeThe EUPHRATES trial examined the impact of polymyxin B hemoperfusion (PMX) on mortality in patients with septic shock and endotoxemia, defined as EAA ≥ 0.60. No difference was found in 28-day all-cause mortality. However, the trial showed that in some patients with septic shock the burden of endotoxin activity was extreme (EAA ≥ 0.9). In a post hoc analysis, we evaluated the impact of PMX use in patients with septic shock and endotoxin activity measured between 0.6-0.89.MethodsPost-hoc analysis of the EUPHRATES trial for the 194 patients with EAA ≥ 0.6-0.89 who completed two treatments (PMX or sham). The primary end point was mortality at 28 days adjusted for APACHE II score and baseline mean arterial pressure (MAP). Additional end points included changes in MAP, cumulative vasopressor index (CVI), median EAA reduction, ventilator-free days (VFD), dialysis-free days (DFD) and hospital length of stay. Subpopulations analyzed were site and type of infection and those with norepinephrine dose > 0.1 mcg/kg/min at baseline.ResultsAt 28 days, 23 patients of 88 (26.1%) in the PMX group died versus 39 of 106 (36.8%) in the sham group [risk difference 10.7%, OR 0.52, 95% CI (0.27, 0.99), P = 0.047]. When unadjusted for baseline variables, P = 0.11. The 28-day survival time in the PMX group was longer than for the sham group [HR 0.56 (95% CI 0.33, 0.95) P = 0.03]. PMX treatment compared with sham showed greater change in MAP [median (IQR) 8 mmHg (- 0.5, 19.5) vs. 4 mmHg (- 4.0, 11) P = 0.04] and VFD [median (IQR) 20 days (0.5, 23.5) vs. 6 days (0, 20), P = 0.004]. There were no significant differences in other end points. There was a significant difference in mortality in PMX-treated patients with no bacterial growth on culture [PMX, 6/30 (20%) vs. sham, 13/31 (41.9%), P = 0.005]. The median EAA change in the population was - 12.9% (range: increase 49.2%-reduction 86.3%). The mortality in the above median EAA change group was PMX: 6/38 (15.7%) vs. sham 15/49 (30.6%), P = 0.08.ConclusionsThese hypothesis-generating results, based on an exploratory post hoc analysis of the EUPHRATES trial, suggest measurable responses in patients with septic shock and an EAA ≥ 0.6 to 0.89 on changes in mean arterial pressure, ventilator-free days and mortality.Trial registrationClinicaltrials.gov Identifier: NCT01046669. Funding Spectral Medical Incorporated.

Project description:IntroductionIt is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock.MethodsThis is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP > or = 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles > or = 70 mmHg and mortality or the frequency and occurrence of disease-related events.ResultsThere was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.28-2.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.38-2.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01).ConclusionsMAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. Elevating MAP >70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.

Project description:BackgroundLittle is known about the characteristics and impact of septic shock (SS) on the outcomes of infective endocarditis (IE). We aimed to investigate the characteristics and outcomes of patients with IE presenting with SS and to compare them to those of IE patients with sepsis (Se) and those with neither Se nor SS (no-Se-SS).MethodsThis is a prospective cohort study of 4864 IE patients from 35 Spanish centers (2008 to 2018). Logistic regression analyses were performed to identify risk factors for SS and mortality.ResultsSeptic shock and Se presented in 597 (12.3%) and 559 (11.5%) patients, respectively. Patients with SS were younger and presented significantly higher rates of diabetes, chronic renal and liver disease, transplantation, nosocomial acquisition, Staphylococcus aureus, IE complications, and in-hospital mortality (62.5%, 37.7% for Se and 18.2% for no-Se-SS, P < .001). Staphylococcus aureus (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.34-2.81; P < .001), Gram negative (OR, 2.21; 95% CI, 1.25-3.91; P = .006), nosocomial acquisition (OR, 1.44; 95% CI, 1.07-1.94; P = .015), persistent bacteremia (OR, 1.82; 95% CI, 1.24-2.68; P = .002), acute renal failure (OR, 3.02; 95% CI, 2.28-4.01; P < .001), central nervous system emboli (OR, 1.48; 95% CI, 1.08-2.01; P = .013), and larger vegetation size (OR, 1.01; 95% CI, 1.00-1.02; P. = 020) were associated with a higher risk of developing SS. Charlson score, heart failure, persistent bacteremia, acute renal failure, mechanical ventilation, worsening of liver disease, S aureus, and receiving aminoglycosides within the first 24 hours were associated with higher in-hospital mortality, whereas male sex, native valve IE, and cardiac surgery were associated with lower mortality.ConclusionsSeptic shock is frequent and entails dismal prognosis. Early identification of patients at risk of developing SS and early assessment for cardiac surgery appear as key factors to improve outcomes.

Project description:BackgroundCapillary refill time (CRT) may improve more rapidly than lactate in response to increments in systemic flow. Therefore, it can be assessed more frequently during septic shock (SS) resuscitation. Hyperlactatemia, in contrast, exhibits a slower recovery in SS survivors, probably explained by the delayed resolution of non-hypoperfusion-related sources. Thus, targeting lactate normalization may be associated with impaired outcomes. The ANDROMEDA-SHOCK trial compared CRT- versus lactate-targeted resuscitation in early SS. CRT-targeted resuscitation associated with lower mortality and organ dysfunction; mechanisms were not investigated. CRT was assessed every 30 min and lactate every 2 h during the 8-h intervention period, allowing a first comparison between groups at 2 h (T2). Our primary aim was to determine if SS patients evolving with normal CRT at T2 after randomization (T0) exhibited a higher mortality and organ dysfunction when allocated to the LT arm than when randomized to the CRT arm. Our secondary aim was to determine if those patients with normal CRT at T2 had received more therapeutic interventions when randomized to the LT arm. To address these issues, we performed a post hoc analysis of the ANDROMEDA-SHOCK dataset.ResultsPatients randomized to the lactate arm at T0, evolving with normal CRT at T2 exhibited significantly higher mortality than patients with normal CRT at T2 initially allocated to CRT (40 vs 23%, p = 0.009). These results replicated at T8 and T24. LT arm received significantly more resuscitative interventions (fluid boluses: 1000[500-2000] vs. 500[0-1500], p = 0.004; norepinephrine test in previously hypertensive patients: 43 (35) vs. 19 (19), p = 0.001; and inodilators: 16 (13) vs. 3 (3), p = 0.003). A multivariate logistic regression of patients with normal CRT at T2, including APACHE-II, baseline lactate, cumulative fluids administered since emergency admission, source of infection, and randomization group) confirmed that allocation to LT group was a statistically significant determinant of 28-day mortality (OR 3.3; 95%CI[1.5-7.1]); p = 0.003).ConclusionsSeptic shock patients with normal CRT at baseline received more therapeutic interventions and presented more organ dysfunction when allocated to the lactate group. This could associate with worse outcomes.

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Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts.

Publications

Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts.

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