S. Maitra, A. Som, S. Bhattacharjee

To identify sensitivity, specificity and predictive accuracy of quick sequential organ failure assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria to predict in-hospital mortality in hospitalized patients with suspected infection.

José Moreira, Ariane Paixão, Juliana Oliveira, Waldir Jaló, Ofélio Manuel, Rafaela Rodrigues, Alexandra Oliveira, Leonardo Tinoco, João Lima, Beatriz Grinsztejn, Valdiléa G. Veloso, André M. Japiassú, Cristiane C. Lamas

To compare the discriminatory capacity of the quick Sequential Organ Failure Assessment (qSOFA) versus the Systemic Inflammatory Response Syndrome (SIRS) score for predicting 30-day mortality and intensive care unit (ICU) admission in patients with suspicion of infection at an HIV reference center.

Rudd KE, Seymour CW, Aluisio AR, et al.

This pooled cohort analysis assesses the association of quick Sequential (Sepsis-Related Organ Failure Assessment (qSOFA) score with excess hospital death among patients with suspected infection in low- to middle-income countries and compares the mortality association using qSOFA vs systemic inflammatory response syndrome (SIRS) criteria.

Abstract Background Community acquired bloodstream infection (CABSI) in low- and middle income countries is associated with a high mortality. This study describes the clinical manifestations, laboratory findings and correlation of SOFA and qSOFA with mortality in patients with CABSI in northern Vietnam. Methods This was a retrospective study of 393 patients with at least one positive blood culture with not more than one bacterium taken within 48 h of hospitalisation. Clinical characteristic and laboratory results from the first 24 h in hospital were collected. SOFA and qSOFA scores were calculated and their validity in this setting was evaluated. Results Among 393 patients with bacterial CABSI, approximately 80% (307/393) of patients had dysfunction of one or more organ on admission to the study hospital with the most common being that of coagulation (57.1% or 226/393). SOFA performed well in prediction of mortality in those patients initially admitted to the critical care unit (AUC 0.858, 95%CI 0.793–0.922) but poor in those admitted to medical wards (AUC 0.667, 95%CI 0.577–0.758). In contrast qSOFA had poor predictive validity in both settings (AUC 0.692, 95%CI 0.605–0.780 and AUC 0.527, 95%CI 0.424–0.630, respectively). The overall case fatality rate was 28%. HIV infection (HR = 3.145, p = 0.001), neutropenia (HR = 2.442, p = 0.002), SOFA score 1-point increment (HR = 1.19, p 

Viriya Hantrakun, Ranjani Somayaji, Prapit Teparrukkul, Chaiyaporn Boonsri, Kristina Rudd, Nicholas P. J. Day, T. Eoin West, Direk Limmathurotsakul

by Viriya Hantrakun, Ranjani Somayaji, Prapit Teparrukkul, Chaiyaporn Boonsri, Kristina Rudd, Nicholas P. J. Day, T. Eoin West, Direk Limmathurotsakul Infection and sepsis are leading causes of death worldwide but the epidemiology and outcomes are not well understood in resource-limited settings. We conducted a four-year prospective observational study from March 2013 to February 2017 to examine the clinical epidemiology and outcomes of adults admitted with community-acquired infection in a resource-limited tertiary-care hospital in Ubon Ratchathani province, Northeast Thailand. Hospitalized patients with infection and accompanying systemic manifestations of infection within 24 hours of admission were enrolled. Subjects were classified as having sepsis if they had a modified sequential organ failure assessment (SOFA) score ≥2 at enrollment. This study was registered with ClinicalTrials.gov, number NCT02217592. A total of 4,989 patients were analyzed. Of the cohort, 2,659 (53%) were male and the median age was 57 years (range 18–101). Of these, 1,173 (24%) patients presented primarily to the study hospital, 3,524 (71%) were transferred from 25 district hospitals or 8 smaller hospitals in the province, and 292 (6%) were transferred from one of 30 hospitals in other provinces. Three thousand seven hundred and sixteen (74%) patients were classified as having sepsis. Patients with sepsis had an older age distribution and a greater prevalence of comorbidities compared to patients without sepsis. Twenty eight-day mortality was 21% (765/3,716) in sepsis and 4% (54/1,273) in non-sepsis patients (p

Abstract Purpose This retrospective cohort study derived a “quick” version of the Pitt bacteremia score (qPitt) using binary variables in patients with Gram-negative bloodstream infections (BSI). The qPitt discrimination was then compared to quick sepsis-related organ failure assessment (qSOFA) and systemic inflammatory response syndrome (SIRS). Methods Hospitalized adults with Gram-negative BSI at Palmetto Health hospitals in Columbia, SC, USA from 2010 to 2013 were identified. Multivariate Cox proportional hazards regression was used to determine variables associated with 14-day mortality. Results Among 832 patients with Gram-negative BSI, median age was 65 years and 449 (54%) were women. After adjustments for age and Charleston comorbidity score, all five components of qPitt were independently associated with mortality: temperature 

Abstract Purposes Streptococcus pneumoniae is a leading pathogen of severe community, hospital or nursing facility infections. We sought to describe characteristics of invasive pneumococcal infection (IPI) and pneumonia (due to the high mortality of intensive care-associated pneumonia) and to report outcomes according to various types of comorbidity. Methods Multicenter observational cohort study on the prospective Outcomerea database, including adult patients, with a hospital stay 

Cressman A, MacFadden D, Verma A, et al.

AbstractBackgroundPhysicians face competing demands of maximizing pathogen coverage, while minimizing unnecessary use of broad-spectrum antibiotics when managing sepsis. We sought to identify physicians’ perceived likelihood of coverage achieved by their usual empiric antibiotic regimen, along with minimum thresholds of coverage they would be willing to accept when managing these patients.MethodsWe conducted a scenario-based survey of internal medicine physicians from across Canada using a 2 x 2 factorial design, varied by infection source (undifferentiated vs. genitourinary) and severity (mild vs. severe) denoted by the Quick Sepsis Related Organ Failure Assessment (qSOFA) score. For each scenario, participants selected their preferred empiric antibiotic regimen, estimated the likelihood of coverage achieved by that regimen and considered their minimum threshold of coverage.ResultsWe had 238 respondents including 87 (36.6%) residents and 151 attending physicians (63.4%). The perceived likelihood of antibiotic coverage and minimum thresholds of coverage for each scenario were: 1) severe undifferentiated 90% [interquartile range (IQR) 89.5–95.0] and 90% [IQR 80–95], 2) mild undifferentiated 89% [IQR 80–95] and 80% [IQR 70–89.5], 3) severe GU 91% [IQR 87.3–95.0] and 90% [IQR 80.0–90.0], and 4) mild GU 90% [IQR 81.8–91.3%] and 80% [IQR 71.8–90]. Illness severity and infectious diseases specialty predicted higher thresholds of coverage whereas less clinical experience and lower self-reported prescribing intensity predicted lower thresholds of coverage.ConclusionPathogen coverage of 80% and 90% are physician-acceptable thresholds for managing patients with mild and severe sepsis from bacterial infections. These data may inform clinical guidelines and decision-support tools to improve empiric antibiotic prescribing.

Freire, M. P., Pierrotti, L. C., Zerati, A. E., Benites, L., Motta-Leal Filho, J. M. d., Ibrahim, K. Y., Araujo, P. H., Abdala, E.

Objectives: The management of long-term central venous catheters (LTCVCs) infections by multi-drug resistant (MDR) bacteria in cancer patient is a challenger. The objectives of this study were to analyse outcomes in cancer patients with LTCVC-associated infection, identify risks for unfavourable outcomes and determine the impact of MDR bacteria and antibiotic lock therapy (ALT) in managing such infections.Methods: We evaluated all LTCVC-associated infections treated between January 2009 and December 2016. Infections were reported in accordance with international guidelines for catheter-related infections. The outcome measures were 30-day-mortality, and treatment failure. We analysed risk factors by Cox forward-stepwise regression.Results: We identified 296 LTCVC-associated infections, 212 (71.6%) were classified as bloodstream infections (BSIs). The most common agent was Staphylococcus aureus.46 (21.7%) infections were due to multi-drug resistant (MDR) Gram-negative.ALT was used in 62 (29.2%) patients, with a 75.9% success rate. Risk factors identified for failure of the initial treatment were having a high Sequential Organ Failure Assessment (SOFA) score at diagnosis of infection and being in palliative care; introduction of ALT at the start of treatment was identified as a protective factor. Risk factors identified for 30-day-mortality after LTCVC-associated infection were a high SOFA score at diagnosis, infection with MDR bacteria, and palliative care; introduction of ALT at the start of treatment, haematological malignancies, and adherence to an institutional protocol for the management of LTCVC-associated infection were identified as protective factors.Conclusions: Despite the high incidence of infection with MDR bacteria, ALT improves the outcome of LTCVC-associated infection in cancer patients.…

Zhenjun Yu, Ni Zhou, Ali Li, Jie Chen, Huazhong Chen, Zebao He, Fei Yan, Haihong Zhao, Jiansheng Zhu

Shields, R. K., Nguyen, M. H., Chen, L., Press, E. G., Kreiswirth, B. N., Clancy, C. J.

Ceftazidime-avibactam was used to treat 77 patients with carbapenem-resistant Enterobacteriaceae (CRE) infections at our center. Thirty- and 90-day survival rates were 81% and 69%, respectively; rates were higher than predicted by SAPS II and SOFA scores at the onset of infection. Clinical success was achieved in 55% of patients, but varied by site of infection. Success rates were lowest for pneumonia (36%) and higher for bacteremia (75%) and urinary tract infections (88%). By multivariate analysis, pneumonia (P=0.045) and receipt of renal replacement therapy (RRT; P=0.046) were associated with clinical failure. Microbiologic failures occurred in 32% of patients, and occurred more commonly among patients infected with KPC-3-producing than KPC-2-producing CRE (P=0.002). Pneumonia was an independent predictor of microbiologic failures (P=0.007). Ceftazidime-avibactam resistance emerged in 10% of patients, including 14% infected with Klebsiella pneumoniae and 32% with microbiologic failures. RRT was an independent predictor for the development of resistance (P=0.009). Resistance was identified exclusively among K. pneumoniae harboring variant KPC-3 enzymes. Upon phylogenetic analysis of whole genome sequences, resistant isolates from 87.5% (7/8) of patients clustered within a previously defined sequence type (ST)258, clade II sub-lineage; resistant isolates from one patient clustered independently from other ST258, clade II isolates. In conclusion, our report offers new insights into the utility and limitations of ceftazidime-avibactam across CRE infection types. Immediate priorities are to identify ceftazidime-avibactam dosing and therapeutic regimens that improve upon the poor outcomes among patients with pneumonia, and in those receiving RRT.…

Shahin Gaini, Mette Marie Relster, Court Pedersen, Isik Somuncu Johansen

Abstract Purpose Endogenous fungal endophthalmitis (EFE) is a severe consequence of candidemia. The prevalence of, and risk factors for, EFE is not well studied. Methods We retrospectively collected cases of patients with candidemia who had undergone ophthalmological examination between April 2011 and March 2016 in five regional hospitals. We conducted bivariate and multivariate analyses using patients’ age, gender, causative Candida species, diabetes status, corticosteroid use, cancer status, neutropenia, intensive care unit admission, presence of central venous catheter (CVC), presence of shock, prior antibiotic use, 30-day mortality, and highest Sequential Organ Failure Assessment (SOFA) score. Data on sustained positive blood culture, β-d glucan, CVC removal, empirical antifungal drug used, and time to appropriate antifungal therapy were also collected if available. Results Of 174 patients with candidemia, 35 (20.1%) were diagnosed with EFE, including 31 (17.8%) with chorioretinitis and 4 (2.3%) with vitritis. Bivariate analysis (EFE group vs. non-EFE group) found that Candida albicans candidemia (77.1 vs. 34.5%, P 

Adhikari NJ, Rubenfeld GD.

In the past 2 years, sepsis has received considerable attention from the global community. In 2017, the World Health Assembly passed a resolution urging all 194 UN Member States to implement actions to reduce the burden of sepsis, and for the World Health Organization to report on the public health implications of sepsis and its global consequences. It has become clear that early resuscitation targeted to hemodynamic goals is more expensive and no more effective than routine care in high-income countries. In Zambia, a protocolized resuscitation strategy actually increased mortality. These data and other studies continue to suggest that some evidence on sepsis therapy does not generalize on a global scale.

Christian Brun-Buisson

Meta-analyses of accuracy of the qSOFA to predict hospital mortality of patients with suspected infection show suboptimal performance of this abridged score. However, a score composed of only 3 clinical variables, such as the qSOFA or CRB can hardly be very accurate, but can serve as a warning integrated into clinical decision making, to help triaging patients in the ED. qSOFA does not help identifying infection. More complete, generic severity scores are nevertheless of major interest for stratification or analyses of epidemiolgical studies and clinical trials in septic patients.

Abstract Background In the new Sepsis-3 definition, sepsis is defined as “life-threatening organ dysfunction due to a dysregulated host response to infection.” We tested the predictive validity of the systematic inflammatory response syndrome (SIRS) criteria in patients in the Sepsis-3 cohort. Methods Among 1243 electronic health records from 1 January to 31 December 2015 at Sichuan University West China Hospital, we identified patients with sepsis and septic shock according to the Sepsis-3 definition and divided them into 2 subsets: SIRS-positive and SIRS-negative. We compared their characteristics and outcomes as well as the predictive validity of the SIRS criteria for in-hospital mortality. Results Of the 1243 patients, 631 were enrolled. Among these, 538 (85.3%) patients had SIRS-positive sepsis or septic shock, 168 (31.2%) of whom died, and 93 (14.7%) had SIRS-negative sepsis or septic shock, 20 (21.5%) of whom died (p = 0.06). Over a 1-year period, these groups had similar characteristics and changes in mortality. Among patients of the Sepsis-3 cohort admitted to the intensive care unit, the predictive validity for in-hospital mortality was lower for the SIRS criteria (area under the receiver operating characteristic curve [AUROC], 0.53; 95% confidence interval [95% CI], 0.49–0.57) than for the sequential (sepsis-related) organ failure assessment (SOFA) criteria (AUROC, 0.70; 95% CI, 0.66–0.74; p ≤ 0.01 for both). The SIRS score had poor predictive validity for the risk of in-hospital mortality. Conclusions In this cohort study of the new Sepsis-3 definition, we found that the SIRS criteria are weaker than the SOFA criteria with respect to their predictive efficacy for in-hospital death.…

Iram Yunus, Anum Fasih, Yanzhi Wang

by Iram Yunus, Anum Fasih, Yanzhi Wang Objective The primary objective of this study was to determine the correlation between procalcitonin values and illness severity by evaluating the degree of end organ dysfunction using the Sequential Organ Failure Assessment score, length of stay and the severity of sepsis (sepsis alone vs. septic shock), The hypothesis that procalcitonin values would be higher in sicker patients was formulated before data collection began. Secondary outcomes studied in relation to procalcitonin levels included infection characteristics such as the site of infection, microbial agent and dialysis dependent CKD. Design Unblinded retrospective cohort study. September 2014-December 2016. Setting 364 patients with a diagnosis of sepsis or severe sepsis who were admitted to the general medical ward and ICU at Methodist Medical Center and Proctor Hospital in Peoria, Illinois, USA. Results This study demonstrates the following: Weak positive correlation between procalcitonin and SOFA score. Negligible correlation with length of stay. Higher values in patients who died than in patients who survived to discharge (p = 0.058). Sensitivity and specificity of procalcitonin for septic shock was 63 and 65% respectively. Sites typically infected by gram negative bacteria have higher procalcitonin values than sites infected by gram positive bacteria (p = 0.03). Higher procalcitonin in bacteremia than non-bacteremic infections (p = 0.004). Higher procalcitonin in dialysis-dependent CKD patients (p = 0.020). Conclusions Procalcitonin has a higher specificity for bacterial infections than other acute phase reactants. Although initial procalcitonin value may be helpful in the determination of illness severity, it is not always a reliable prognostic indicator and carries little significance as a standalone value. Procalcitonin values may be influenced by preexisting comorbid conditions such as chronic kidney disease, which are associated with higher procalcitonin values at baseline. Procalcitonin can provide invaluable information when viewed as one piece of a clinical puzzle, and is most powerful when the interpreting physician is aware of how values are influenced by the different clinical scenarios presented in this article.…

Abstract Background The prognostic capability of the quick Sequential Organ Failure Assessment (qSOFA) bedside scoring tool is uncertain in non-ICU patients with sepsis due to bacteremia given the low number of patients previously evaluated. Methods We performed a retrospective cohort study of adult hospitalized patients with Staphylococcus aureus bacteremia (SAB). Medical charts were reviewed to determine qSOFA score, systemic inflammatory response syndrome (SIRS) criteria, and Pitt bacteremia score (PBS) at initial presentation; their predictive values were compared for ICU admission within 48 h, ICU stay duration > 72 h, and 30-day mortality. Results Four hundred twenty-two patients were included; 22% had qSOFA score ≥2. Overall, mean age was 56y and 75% were male. More patients with qSOFA ≥2 had altered mentation (23% vs 5%, p 

Lewis JM, Henrion M, Rylance J.

To the Editor Dr Rudd and colleagues concluded that the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score was superior to the systemic inflammatory response syndrome (SIRS) score and a baseline risk model in predicting in-hospital mortality in low- and middle-income countries (LMICs), an issue that has been debated since its introduction in the Sepsis-3 definitions. We are concerned that the treatment of missing data may have introduced significant bias.

Rudd KE, Seymour CW, Angus DC.

In Reply We agree with Dr Lewis and colleagues that missing data can be an important limitation in clinical research, including our analysis of the predictive validity of the qSOFA score and SIRS criteria. There are 2 issues related to missing data: (1) why missing data are present and (2) the approach to missing data during analysis. First, missing data were present in all 9 cohorts included in the study. Many sites lacked electronic health record systems, had limited medical staff available to collect and record serial vital signs, and were unable to routinely perform laboratory testing for every patient with suspected infection because of limited laboratory and financial resources. Given this reality, the diagnosis of sepsis in LMICs will not always be informed by complete data. Therefore, it is useful for clinicians in low-resource settings to understand the performance of alternative scoring systems in situations in which some variables, though important predictors of clinical outcome, may be missing.

F. Wu, Y. Ye, X. Zhou

We read with interest the meta-analysis by Maitra et al. who found that quick Sequential (sepsis-related) Organ Failure Assessment (qSOFA) seemed to be a poorly sensitive predictive marker for in-hospital mortality in hospitalized patients with suspected infection [1]. Though the review sounds comprehensive and scientific, we have some different views to address.