A machine learning approach using endpoint adjudication committee labels for the identification of sepsis predictors at the emergency department

Accurate sepsis diagnosis is paramount for treatment decisions, especially at the emergency department (ED). To improve diagnosis, clinical decision support (CDS) tools are being developed with machine learning (ML) algorithms, using a wide range of variable groups. ML models can find patterns in Electronic Health Record (EHR) data that are unseen by the human eye. A prerequisite for a good model is the use of high-quality labels. Sepsis gold-standard labels are hard to define due to a lack of reliable diagnostic tools for sepsis at the ED. Therefore, standard clinical tools, such as clinical prediction scores (e.g. modified early warning score and quick sequential organ failure assessment), and claims-based methods (e.g. ICD-10) are used to generate suboptimal labels. As a consequence, models trained with these “silver” labels result in ill-trained models. In this study, we trained ML models for sepsis diagnosis at the ED with labels of 375 ED visits assigned by an endpoint adjudication committee (EAC) that consisted of 18 independent experts. Our objective was to evaluate which routinely measured variables show diagnostic value for sepsis. We performed univariate testing and trained multiple ML models with 95 routinely measured variables of three variable groups; demographic and vital, laboratory and advanced haematological variables. Apart from known diagnostic variables, we identified added diagnostic value for less conventional variables such as eosinophil count and platelet distribution width. In this explorative study, we show that the use of an EAC together with ML can identify new targets for future sepsis diagnosis research

Time for first antibiotic dose is not predictive for the early clinical failure of moderate–severe community-acquired pneumonia

The time to first antibiotic dose (TFAD) has been mentioned as an important performance indicator in community-acquired pneumonia (CAP). However, the advice to minimise TFAD to 4 hours (4 h) is only based on database studies. We prospectively studied the effect of minimising the TFAD on the early clinical outcome of moderate–severe CAP. On admission, patients’ medical data and TFAD were recorded. Early clinical failure was expressed as the proportion of patients with clinical instability, admission to the intensive care unit (ICU) or mortality on day three. Of 166 patients included in the study, 27 patients (29.7%) with TFAD <4 h had early clinical failure compared to 23 patients (37.7%) with TFAD >4 h (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.35–1.35). In multivariate analysis, the pneumonia severity index (OR 1.03; 95%CI 1.01–1.04), confusion (OR 2.63; 95%CI 1.14–6.06), Staphylococcus aureus infection (OR 7.26; 95%CI 1.33–39.69) and multilobar pneumonia (OR 2.40; 95%CI 1.11–5.22) but not TFAD were independently associated with early clinical failure. Clinical parameters on admission other than the TFAD predict early clinical outcome in moderate–severe CAP. In contrast to severe CAP necessitating treatment in the ICU directly, in the case of suspected moderate–severe CAP, there is time to establish a reliable diagnosis of CAP before antibiotics are administered. Therefore, the implementation of the TFAD as a performance indicator is not desirable

Prior outpatient antibiotic use as predictor for microbial aetiology of community-acquired pneumonia: hospital-based study

Objective: The causative micro-organism in community-acquired pneumonia (CAP) is often difficult to predict. Different studies have examined chronic morbidity and clinical symptoms as predictors for microbial aetiology of pneumonia. The aim of our study was to assess whether prior outpatient antimicrobial treatment is predictive for determining the microbial aetiology of CAP. Methods: This was a hospital-based prospective observational study including all patients admitted with CAP between 1 October 2004 and 1 August 2006. Microbial investigations included sputum, blood culture, sputum PCR, antigen testing and serology. Exposure to antimicrobial drugs prior to hospital admission was ascertained through community pharmacy dispensing records. Multivariate logistic regression analysis was conducted to assess whether prior outpatient antimicrobial treatment is a predictor of microbial aetiology. Patient demographics, co-morbidities and pneumonia severity were considered to be other potential predictors. Results: Overall, 201 patients were included in the study. The microbial aetiology was determined in 64% of the patients. The five most prevalent pathogens were Streptococcus pneumoniae, Heamophilus influenzae, Legionella spp., Mycoplasma pneumoniae and Influenza virus A+B. Forty-seven of the patients (23%) had received initial antimicrobial treatment as outpatients. Multivariate analyses revealed that initial outpatient beta-lactam treatment was associated with a threefold increased chance of finding atypical pathogens and a threefold decreased probability of pneumococcal infection; the corresponding odds ratios were 3.51 (95% CI 1.25-9.99) and 0.30 (95% CI 0.10-0.90), respectively. Patients who received macrolides prior to hospitalisation had an increased probability of viral pneumonia. Conclusion: Prior outpatient antimicrobial therapy has a predictive value in the diagnostic workup aimed at identifying the causative pathogen and planning corresponding antimicrobial treatment in patients hospitalised for pneumonia

Bacteremic complications of intravascular catheter tip colonization with Gram-negative micro-organisms in patients without preceding bacteremia

Although Gram-negative micro-organisms are frequently associated with catheter-related bloodstream infections, the prognostic value and clinical implication of a positive catheter tip culture with Gram-negative micro-organisms without preceding bacteremia remains unclear. We determined the outcomes of patients with intravascular catheters colonized with these micro-organisms, without preceding positive blood cultures, and identified risk factors for the development of subsequent Gram-negative bacteremia. All patients with positive intravascular catheter tip cultures with Gram-negative micro-organisms at the University Medical Center, Utrecht, The Netherlands, between 2005 and 2009, were retrospectively studied. Patients with Gram-negative bacteremia within 48 h before catheter removal were excluded. The main outcome measure was bacteremia with Gram-negative micro-organisms. Other endpoints were length of the hospital stay, in-hospital mortality, secondary complications of Gram-negative bacteremia, and duration of intensive care admission. A total of 280 catheters from 248 patients were colonized with Gram-negative micro-organisms. Sixty-seven cases were excluded because of preceding positive blood cultures, leaving 213 catheter tips from 181 patients for analysis. In 40 (19%) cases, subsequent Gram-negative bacteremia developed. In multivariate analysis, arterial catheters were independently associated with subsequent Gram-negative bacteremia (odds ratio [OR] = 5.00, 95% confidence interval [CI]: 1.20–20.92), as was selective decontamination of the digestive tract (SDD) (OR = 2.47, 95% CI: 1.07–5.69). Gram-negative bacteremia in patients who received SDD was predominantly caused by cefotaxime (part of the SDD)-resistant organisms. Mortality was significantly higher in the group with subsequent Gram-negative bacteremia (35% versus 20%, OR = 2.12, 95% CI: 1.00–4.49). Patients with a catheter tip colonized with Gram-negative micro-organisms had a high chance of subsequent Gram-negative bacteremia from any cause. This may be clinically relevant, as starting antibiotic treatment pre-emptively in high-risk patients with Gram-negative micro-organisms cultured from arterial intravenous catheters may be beneficial

Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP – Results from the German competence network CAPNETZ

<p>Abstract</p> <p>Background</p> <p>Aim of this study was to evaluate the correlation of inflammatory markers procalcitonin (PCT), C-reactive protein (CRP) and leukocyte count (WBC) with microbiological etiology of CAP.</p> <p>Methods</p> <p>We enrolled 1337 patients (62 ± 18 y, 45% f) with proven CAP. Extensive microbiological workup was performed. In all patients PCT, CRP, WBC and CRB-65 score were determined. Patients were classified according to microbial diagnosis and CRB-65 score.</p> <p>Results</p> <p>In patients with typical bacterial CAP, levels of PCT, CRP and WBC were significantly higher compared to CAP of atypical or viral etiology. There were no significant differences in PCT, CRP and WBC in patients with atypical or viral etiology of CAP. In contrast to CRP and WBC, PCT markedly increased with severity of CAP as measured by CRB-65 score (p < 0.0001). In ROC analysis for discrimination of patients with CRB-65 scores > 1, AUC for PCT was 0.69 (95% CI 0.66 to 0.71), which was higher compared to CRP and WBC (p < 0.0001). CRB-65, PCT, CRP and WBC were higher (p < 0.0001) in hospitalised patients in comparison to outpatients.</p> <p>Conclusion</p> <p>PCT, CRP and WBC are highest in typical bacterial etiology in CAP but do not allow individual prediction of etiology. In contrast to CRP and WBC, PCT is useful in severity assessment of CAP.</p

Value of hospital antimicrobial stewardship programs [ASPs]:a systematic review

Abstract Background Hospital antimicrobial stewardship programs (ASPs) aim to promote judicious use of antimicrobials to combat antimicrobial resistance. For ASPs to be developed, adopted, and implemented, an economic value assessment is essential. Few studies demonstrate the cost-effectiveness of ASPs. This systematic review aimed to evaluate the economic and clinical impact of ASPs. Methods An update to the Dik et al. systematic review (2000–2014) was conducted on EMBASE and Medline using PRISMA guidelines. The updated search was limited to primary research studies in English (30 September 2014–31 December 2017) that evaluated patient and/or economic outcomes after implementation of hospital ASPs including length of stay (LOS), antimicrobial use, and total (including operational and implementation) costs. Results One hundred forty-six studies meeting inclusion criteria were included. The majority of these studies were conducted within the last 5 years in North America (49%), Europe (25%), and Asia (14%), with few studies conducted in Africa (3%), South America (3%), and Australia (3%). Most studies were conducted in hospitals with 500–1000 beds and evaluated LOS and change in antibiotic expenditure, the majority of which showed a decrease in LOS (85%) and antibiotic expenditure (92%). The mean cost-savings varied by hospital size and region after implementation of ASPs. Average cost savings in US studies were $732 per patient (range:$2.50 to $2640), with similar trends exhibited in European studies. The key driver of cost savings was from reduction in LOS. Savings were higher among hospitals with comprehensive ASPs which included therapy review and antibiotic restrictions. Conclusions Our data indicates that hospital ASPs have significant value with beneficial clinical and economic impacts. More robust published data is required in terms of implementation, LOS, and overall costs so that decision-makers can make a stronger case for investing in ASPs, considering competing priorities. Such data on ASPs in lower- and middle-income countries is limited and requires urgent attention