Extended-spectrum ␤-lactamase (ESBL)-producing Enterobacteriaceae are pathogens that may lead to a spectrum of clinical syndromes. We aimed to identify predictors and outcomes of ESBL bacteremia upon hospital admission (UHA) in a nationwide prospective study. Thus, a multicenter prospective study was conducted in 10 Israeli hospitals. Adult patients with bacteremia due to Enterobacteriaceae diagnosed within 72 h of hospitalization were included. Patients with ESBL producers (cases) were compared to those with non-ESBL producers (controls), and a 1:1 ratio was attempted in each center. A case-control study to identify predictors and a cohort study to identify outcomes were conducted. Bivariate and multivariate logistic regressions were used for analyses. Overall, 447 patients with bacteremia due to Enterobacteriaceae were recruited: 205 cases and 242 controls. Independent predictors of ESBL were increased age, multiple comorbid conditions, poor functional status, recent contact with health care settings, invasive procedures, and prior receipt of antimicrobial therapy. In addition, patients presenting with septic shock and/or multiorgan failure were more likely to have ESBL infections. Patients with ESBL producers suffered more frequently from a delay in appropriate antimicrobial therapy (odds ratio [OR], 4.7; P, <0.001) and had a higher mortality rate (OR, 3.5; P, <0.001). After controlling for confounding variables, both ESBL production (OR, 2.3; P, 9.1) and a delay in adequate therapy (OR, 0.05; P, 0.001) were significant predictors for mortality and other adverse outcomes. We conclude that among patients with bacteremia due to Enterobacteriaceae UHA, those with ESBL producers tend to be older and chronically ill and to have a delay in effective therapy and severe adverse outcomes. Efforts should be directed to improving the detection of patients with ESBL bacteremia UHA and to providing immediate appropriate therapy.Enterobacteriaceae producing extended-spectrum ␤-lactameses (ESBL) pose a major worldwide threat (27). These pathogens are resistant to all penicillins and cephalosporins and often are coresistant to multiple other classes of antibiotics (2). Thus, therapeutic options to treat infections with these pathogens are limited (27). The Infectious Diseases Society of America has listed ESBL-producing Enterobacteriaceae as pathogens necessitating the urgent development of new and novel therapeutics (37). While infections caused by ESBLproducing strains have been acquired primarily in hospitals and health care institutions, recent reports from multiple parts of the world show that these pathogens now have a role in community-acquired infections as well (2,3,5,6,8,9,12,15,19,27,29,30,32,38). The burden of these infections is enormous, and compared to bacteremia caused by non-ESBL-producing Enterobacteriaceae, infections caused by ESBL producers are associated with a significantly higher mortality rate, 6 additional days of hospitalization, and approximately $10,000 in additional costs per case (35,36).There ...

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Background Treatment of severely ill COVID-19 patients requires simultaneous management of oxygenation and inflammation without compromising viral clearance. While multiple tools are available to aid oxygenation, data supporting immune biomarkers for monitoring the host-pathogen interaction across disease stages and for titrating immunomodulatory therapy is lacking. Methods In this single-center cohort study, we used an immunoassay platform that enables rapid and quantitative measurement of interferon γ-induced protein 10 (IP-10), a host protein involved in lung injury from virus-induced hyperinflammation. A dynamic clinical decision support protocol was followed to manage patients infected with severe acute respiratory syndrome coronavirus 2 and examine the potential utility of timely and serial measurements of IP-10 as tool in regulating inflammation. Results Overall, 502 IP-10 measurements were performed on 52 patients between 7 April and 10 May 2020, with 12 patients admitted to the intensive care unit. IP-10 levels correlated with COVID-19 severity scores and admission to the intensive care unit. Among patients in the intensive care unit, the number of days with IP-10 levels exceeding 1,000 pg/mL was associated with mortality. Administration of corticosteroid immunomodulatory therapy decreased IP-10 levels significantly. Only two patients presented with subsequent IP-10 flare-ups exceeding 1,000 pg/mL and died of COVID-19-related complications. Conclusions Serial and readily available IP-10 measurements potentially represent an actionable aid in managing inflammation in COVID-19 patients and therapeutic decision-making. Trial registration Clinicaltrials.gov, NCT04389645, retrospectively registered on May 15, 2020.