Blood Culture Results Before and After Antimicrobial Administration in Patients With Severe Manifestations of Sepsis: A Diagnostic Study.

Background: Administering antimicrobial agents before obtaining blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear how this strategy affects diagnostic sensitivity. Objective: To determine the sensitivity of blood cultures obtained shortly after initiation of antimicrobial therapy in patients with severe manifestations of sepsis. Design: Patient-level, single-group, diagnostic study. (ClinicalTrials.gov: NCT01867905). Setting: 7 emergency departments in North America. Participants: Adults with severe manifestations of sepsis, including systolic blood pressure less than 90 mm Hg or a serum lactate level of 4 mmol/L or more. Intervention: Blood cultures were obtained before and within 120 minutes after initiation of antimicrobial treatment. Measurements: Sensitivity of blood cultures obtained after initiation of antimicrobial therapy. Results: Of 3164 participants screened, 325 were included in the study (mean age, 65.6 years; 62.8% men) and had repeated blood cultures drawn after initiation of antimicrobial therapy (median time, 70 minutes [interquartile range, 50 to 110 minutes]). Preantimicrobial blood cultures were positive for 1 or more microbial pathogens in 102 of 325 (31.4%) patients. Postantimicrobial blood cultures were positive for 1 or more microbial pathogens in 63 of 325 (19.4%) patients. The absolute difference in the proportion of positive blood cultures between pre- and postantimicrobial testing was 12.0% (95% CI, 5.4% to 18.6%; P < 0.001). Sensitivity of postantimicrobial culture was 52.9% (CI, 42.8% to 62.9%). When the results of other microbiological cultures were included, microbial pathogens were found in 69 of 102 (67.6% [CI, 57.7% to 76.6%]) patients. Limitation: Only a proportion of screened patients were recruited. Conclusion: Among patients with severe manifestations of sepsis, initiation of empirical antimicrobial therapy significantly reduces the sensitivity of blood cultures drawn shortly after treatment initiation. Primary Funding Source: Vancouver Coastal Health, St. Paul's Hospital Foundation Emergency Department Support Fund, the Fonds de recherche Santé-Québec, and the Maricopa Medical Foundation.

qSOFA does not predict bacteremia in patients with severe manifestations of sepsis.

BACKGROUND: Bloodstream infections in septic patients may be missed due to preceding antibiotic therapy prior to obtaining blood cultures. We leveraged the FABLED cohort study to determine if the quick Sequential Organ Failure Assessment (qSOFA) score could reliably identify patients at higher risk of bacteremia in patients who may have false negative blood cultures due to previously administered antibiotic therapy. METHODS: We conducted a multi-centre diagnostic study among adult patients with severe manifestations of sepsis. Patients were enrolled in one of seven participating centres between November 2013 and September 2018. All patients from the FABLED cohort had two sets of blood cultures drawn prior to the administration of antimicrobial therapy, as well as additional blood cultures within 4 hours of treatment initiation. Participants were categorized according to qSOFA score, with a score ≥2 being considered positive. RESULTS: Among 325 patients with severe manifestations of sepsis, a positive qSOFA score (defined as a score ≥2) on admission was 58% sensitive (95% CI 48% to 67%) and 41% specific (95% CI 34% to 48%) for predicting bacteremia. Among patients with negative post-antimicrobial blood cultures, a positive qSOFA score was 57% sensitive (95% CI 42% to 70%) and 42% specific (95% CI 35% to 49%) to detect patients who were originally bacteremic prior to the initiation of therapy. CONCLUSIONS: Our results suggest that the qSOFA score cannot be used to identify patients at risk for occult bacteremia due to the administration of antibiotics pre-blood culture.

HISTORIQUE: Les infections sanguines peuvent rester non diagnostiquées chez les patients septiques avant l'obtention des cultures sanguines, en raison d'une antibiothérapie antérieure. Les chercheurs ont puisé dans l'étude de cohorte FABLED pour déterminer si le score rapide de l'évaluation séquentielle d'insuffisance des organes (Sequential Organ Failure Assessment, qSOFA) pourrait dépister les patients à plus haut risque de bactériémie avec fiabilité, malgré la possibilité de cultures sanguines faussement négatives en raison d'une antibiothérapie antérieure. MÉTHODOLOGIE: Les chercheurs ont réalisé une étude diagnostique multicentrique chez des patients adultes ayant de graves manifestations de sepsis. Les patients ont été inscrits dans l'un des sept centres participants entre novembre 2013 et septembre 2018. Tous les patients de l'étude de cohorte FABLED avaient subi deux séries de cultures sanguines avant de recevoir une thérapie antimicrobienne, de même qu'une autre série de cultures sanguines dans les quatre heures suivant le début du traitement. Les participants ont été classés en fonction de leur score de qSOFA, un score d'au moins 2 étant considéré comme positif. RÉSULTATS: Chez les 325 patients ayant de graves manifestations de sepsis, un score de qSOFA positif (défini comme un score d'au moins 2) à l'admission était sensible à 58 % (IC à 95 %, 48 % à 67 %) et spécifique à 41 % (IC à 95 %, 34 % à 48 %) pour prédire la bactériémie. Chez les patients dont les cultures sanguines étaient négatives après la prise d'antimicrobiens, un score de qSOFA positif était sensible à 57 % (IC à 95 %, 42 % à 70 %) et spécifique à 42 % (IC à 95 %, 35 % à 49 %) pour dépister les patients atteints d'une bactériémie avant le début du traitement. CONCLUSIONS: Selon les résultats, le score de qSOFA ne peut pas être utilisé pour dépister les patients à risque de bactériémie occulte à cause de l'administration d'antibiotiques avant la culture sanguine.

Review article: comprehensive analysis of cirrhotic cardiomyopathy.

BACKGROUND: Patients with cirrhosis are at risk of developing cirrhotic cardiomyopathy. This syndrome is unique to cirrhosis and is generally defined as subnormal cardiac function in the absence of prior heart disease. There is no systematic or comprehensive review of cirrhotic cardiomyopathy to date. AIMS: To comprehensively review the literature on the definition, pathogenic mechanisms, diagnostic criteria, prevalence, management and influence on liver transplantation including reversibility of cirrhotic cardiomyopathy. METHODS: Electronic searches of the EMBASE, MEDLINE, EBM Reviews-Cochrane Central Register of Controlled Trials, EBM Reviews-Cochrane Database of Systematic Reviews and Google Scholar databases were conducted. MeSH terms focused on cirrhosis, cardiomyopathy, medication classes and epidemiology. Literature up to August 2020 was reviewed. RESULTS: New diagnostic criteria for the definition of cirrhotic cardiomyopathy have recently been published, consisting of systolic and diastolic dysfunction parameters as assessed by echocardiographic methods. The roles of electrocardiographic disturbances and biomarkers in the definition criteria remain unclear. Pathogenic mechanisms underlying cirrhotic cardiomyopathy are likely related to the inflammatory phenotype of cirrhosis. Prevalence rates of 26%-81% in cirrhotic patients are reported. Several medical therapies have been proposed, but none with clear evidence of efficacy. The presence of cirrhotic cardiomyopathy complicates the liver transplantation process with a higher risk of adverse cardiovascular events post-transplant. Complete reversibility of the syndrome after transplantation remains controversial but most studies suggest that it does not occur at least within the first post-operative year. CONCLUSIONS: Cirrhotic cardiomyopathy is a clinically relevant syndrome that affects morbidity and mortality in patients with cirrhosis.

Neither Blood Culture Positivity nor Time to Positivity Is Associated With Mortality Among Patients Presenting With Severe Manifestations of Sepsis: The FABLED Cohort Study.

BACKGROUND: Sepsis is a leading cause of morbidity, mortality, and health care costs worldwide. METHODS: We conducted a multicenter, prospective cohort study evaluating the yield of blood cultures drawn before and after empiric antimicrobial administration among adults presenting to the emergency department with severe manifestations of sepsis. Enrolled patients who had the requisite blood cultures drawn were followed for 90 days. We explored the independent association between blood culture positivity and its time to positivity in relation to 90-day mortality. RESULTS: Three hundred twenty-five participants were enrolled; 90-day mortality among the 315 subjects followed up was 25.4% (80/315). Mortality was associated with age (mean age [standard deviation] in those who died was 72.5 [15.8] compared with 62.9 [17.7] years among survivors; P < .0001), greater Charlson Comorbidity Index (2 [interquartile range {IQR}, 1-3] vs 1 [IQR, 0-3]; P = .008), dementia (13/80 [16.2%] vs 18/235 [7.7%]; P = .03), cancer (27/80 [33.8%] vs 47/235 [20.0%]; P = .015), positive quick Sequential Organ Failure Assessment score (57/80 [71.2%] vs 129/235 [54.9%]; P = .009), and normal white blood cell count (25/80 [31.2%] vs 42/235 [17.9%]; P = .02). The presence of bacteremia, persistent bacteremia after antimicrobial infusion, and shorter time to blood culture positivity were not associated with mortality. Neither the source of infection nor pathogen affected mortality. CONCLUSIONS: Although severe sepsis is an inflammatory condition triggered by infection, its 90-day survival is not influenced by blood culture positivity nor its time to positivity. CLINICAL TRIALS REGISTRATION: NCT01867905.

The impact of primary sclerosing cholangitis or inflammatory bowel disease on cholangiocarcinoma phenotype, therapy, and survival.

BACKGROUND AND AIM: Primary sclerosing cholangitis (PSC), with or without inflammatory bowel disease (IBD), confers the risk of cholangiocarcinoma. Isolated IBD may be an independent risk factor for cholangiocarcinoma. We sought to compare cholangiocarcinoma phenotype and outcomes between patients with PSC, IBD, and neither. METHODS: Patients with malignancy were separated into cohorts by the presence of PSC and IBD. Data regarding demographics, clinical presentation, therapeutic regimens, and survival were collected. Statistical analysis was carried out using GraphPad and R-Studio. RESULTS: Of 946 patients, 22 had PSC, and 18 had isolated IBD. PSC and IBD patients were younger than controls (P < 0.001, P = 0.01). Cholangiocarcinoma prevalence was estimated at 0.01% for IBD patients, 0.6% for PSC patients, and 0.002% for all other patients. All cohorts most often presented at stage 4. PSC patients presented more often at stage 3 (P = 0.04) and with perihilar disease (P = 0.001). Patients with PSC or IBD received less chemotherapy (P = 0.004, 0.01). Median overall survivals were 15 months (PSC), 11 months (IBD), and 10 months (controls) (P = 0.79). Patients with intrahepatic tumors had longer survival (P < 0.001). Curative intent resection improved survival in all cohorts (P < 0.001). Multivariate regression identified resection as a predictor of improved survival. Extrahepatic, perihilar, gallbladder, and unspecified biliary tumors were predictors of death. CONCLUSIONS: Cholangiocarcinoma presents at a late stage and portends dismal survival regardless of PSC or IBD status. Survival was dependent on tumor location and surgical resection. These data suggest that efforts should focus on developing protocols that are able to detect and treat cholangiocarcinoma in high-risk populations (PSC) at an early stage.

Ischemic Colitis after Colonoscopy with Bisacodyl Bowel Preparation: A Report of Two Cases.

BACKGROUND: Colonoscopy is widely used for the diagnosis and management of colorectal disease and requires adequate bowel preparation. Ischemic colitis is a form of intestinal ischemia that presents with abdominal pain, diarrhea, and hematochezia. Risk factors include advanced age, cardiovascular disease, and diabetes. Both colonoscopy and bisacodyl bowel preparation have been described as rare causes of ischemic colitis with less than 35 cases collectively in the literature. Our review found that of these cases, there exists significant heterogeneity within individual patient characteristics. The majority of the cases are managed conservatively without complications or sequela. Due to the risk of ischemic colitis, the FDA has withdrawn bisacodyl bowel preparations from use in the USA. Bisacodyl bowel preparations are still used in Canada. CASES: Here, we present two cases of ischemic colitis in previously healthy women aged 57 and 69 who underwent screening colonoscopy using bisacodyl bowel preparation. Both were treated conservatively without complications. CONCLUSION: Thus far, there has been one documented case of ischemic colitis following colonoscopy with bisacodyl bowel preparation; here, we present two additional cases with one case occurring without the presence of known risk factors for ischemic colitis. Our literature review finds that there is limited evidence surrounding bisacodyl as a causative agent of ischemic colitis. Cases often contain confounding variables such as the presence of known risk factors for ischemic colitis. Our report aims to highlight the need for a more comprehensive analysis evaluating the safety of bowel preparations as well as increasing the clinical awareness surrounding the rare risk of colonoscopy-induced ischemic colitis.

Real-world Time to Positivity of 2 Widely Used Commercial Blood Culture Systems in Patients With Severe Manifestations of Sepsis: An Analysis of the FABLED Study.

BACKGROUND: Of all microbiological tests performed, blood cultures have the most impact on patient care. Timely results are essential, especially in the management of sepsis. While there are multiple available blood culture systems on the market, they have never been compared in a prospective study in a critically ill population. METHODS: We performed an analysis of the FABLED study cohort to compare culture results and time to positivity (TTP) of 2 widely used blood culture systems: BacT/Alert and BACTEC. In this multisite prospective study, patients with severe manifestations of sepsis had cultures drawn before antibiotics using systematic enrollment criteria and blood drawing methodology allowing for minimization of pre-analytical biases. RESULTS: We enrolled 315 patients; 144 had blood cultures (47 positive) with BacT/Alert and 171 with BACTEC (53 positive). Patients whose blood cultures were processed using the BacT/Alert system were younger (median, 64 vs 70 years; P = .003), had a higher proportion of HIV (9.03% vs 1.75%; P = .008) and a lower qSOFA (P = .003). There were no statistically significant differences in the most commonly identified bacterial species. TTP was shorter for BACTEC (median [interquartile range {IQR}], 12.5 [10-14] hours) compared with BacT/Alert (median [IQR], 17 [14-21] hours; P < .0001). CONCLUSIONS: In this large prospective multi-centre study comparing the two blood culture systems among patients with severe manifestations of sepsis, and using a rigorous pre-analytical methodology, the BACTEC system yielded positive culture results 4.5 hours earlier than BacT/Alert. These results apply to commonly isolated bacteria. However, our study design did not allow direct comparison of TTP for unusual pathogens nor of clinical sensitivity between systems. More research is needed to determine the clinical implications of this finding.