Background: To examine the clinical and economic burdens associated with delayed receipt of appropriate therapy among patients with Gram-negative bacteria (GNB) infections, stratified by antibiotic resistance status. Materials and Methods: Retrospective analysis using the Premier Hospital Database. Adult admissions (July 2011-September 2014) with evidence of complicated urinary tract infection, complicated intra-abdominal infection, hospital-associated pneumonia, or bloodstream infection, length of stay (LOS) ≥1 days and a positive GNB culture from a site consistent with infection type (culture draw date = index date) were identified and stratified by antibiotic susceptibility to index pathogens. Delayed appropriate therapy was defined as no receipt of antibiotic(s) with relevant microbiological activity on or within 2 days of index date. Inverse probability weighting and multivariate regression analyses were used to estimate the association between delayed appropriate therapy and outcomes. Generalized linear models were used to evaluate postindex duration of antibiotic therapy, LOS and total in-hospital costs. Logistic models were used to evaluate discharge destination and in-hospital mortality/discharge to hospice. Results: A total of 56,357 patients with GNB infections were identified (resistant, n = 6,055; susceptible, n = 50,302). Delayed appropriate therapy was received by 2,800 (46.2%) patients with resistant and 16,585 (33.0%) patients with susceptible infections. Using multivariate analysis, delayed appropriate therapy was associated with worse outcomes including »70% increase in LOS, »65% increase in total in-hospital costs and »20% increase in the risk of in-hospital mortality/discharge to hospice, regardless of susceptibility status. Conclusions: Our results suggest that outcomes in patients with GNB infections, regardless of resistance status, significantly improve if timely appropriate therapy can be provided.

A large proportion of patients on insulin-based therapy fail to reach glycemic goals. More education of clinicians may improve insulin intensification rates and increase the proportion of patients reaching glycemic targets.

Background The relative contribution of antimicrobial resistance versus delayed appropriate treatment to the clinical and economic burden of Enterobacteriaceae infections is not well understood. Methods Using a large US hospital database, we identified all admissions between July 2011 and September 2014 with evidence of serious Enterobacteriaceae infection. The “index date” was the earliest date on which a culture positive for Enterobacteriaceae was drawn. Infections were classified as carbapenem-resistant (CRE) or carbapenem-susceptible (CSE). Receipt of antimicrobials with activity against all index pathogens on the index date or ≤2 days thereafter was deemed as “timely”; all other instances were “delayed.” Associations between CRE status and delayed appropriate therapy on outcomes were estimated using inverse probability weighting and multivariate regression models (ie, logistic model for discharge destination and composite mortality [in-hospital death or discharge to hospice] or generalized linear model for duration of antibiotic therapy, hospital length of stay [LOS], and costs). Results A total of 50 069 patients met selection criteria; 514 patients (1.0%) had CRE. Overall, 67.5% of CSE patients (vs 44.6%, CRE) received timely appropriate therapy (P < .01). Irrespective of CRE status, patients who received delayed appropriate therapy had longer durations of antibiotic therapy and LOS, higher costs, lower likelihood of discharge to home, and greater likelihood of the composite mortality outcome (P for trend < .01). Conclusions Delayed appropriate therapy is a more important driver of outcomes than CRE, although the 2 factors are somewhat synergistic. Better methods of early CRE identification may improve outcomes in this patient population.

Background We developed a clinical bedside tool to simultaneously estimate the probabilities of third-generation cephalosporin-resistant Enterobacteriaceae (3GC-R), carbapenem-resistant Enterobacteriaceae (CRE), and multidrug-resistant Pseudomonas aeruginosa (MDRP) among hospitalized adult patients with Gram-negative infections. Methods Data were obtained from a retrospective observational study of the Premier Hospital that included hospitalized adult patients with a complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), hospital-acquired/ventilator-associated pneumonia (HAP/VAP), or bloodstream infection (BSI) due to Gram-negative bacteria between 2011 and 2015. Risk factors for 3GC-R, CRE, and MDRP were ascertained by multivariate logistic regression, and separate models were developed for patients with community-acquired versus hospital-acquired infections for each resistance phenotype ( N = 6). Models were converted to a singular user-friendly interface to estimate the probabilities of a patient having an infection due to 3GC-R, CRE, or MDRP when ≥ 1 risk factor was present. Results Overall, 124,068 patients contributed to the dataset. Percentages of patients admitted for cUTI, cIAI, HAP/VAP, and BSI were 61.6, 4.6, 16.5, and 26.4%, respectively (some patients contributed > 1 infection type). Resistant infection rates were 1.90% for CRE, 12.09% for 3GC-R, and 3.91% for MDRP. A greater percentage of the resistant infections were community-acquired relative to hospital-acquired (CRE, 1.30% vs 0.62% of 1.90%; 3GC-R, 9.27% vs 3.42% of 12.09%; MDRP, 2.39% vs 1.59% of 3.91%). The most important predictors of having an 3GC-R, CRE or MDRP infection were prior number of antibiotics; infection site; infection during the previous 3 months; and hospital prevalence of 3GC-R, CRE, or MDRP. To enable application of the six predictive multivariate logistic regression models to real-world clinical practice, we developed a user-friendly interface that estimates the risk of 3GC-R, CRE, and MDRP simultaneously in a given patient with a Gram-negative infection based on their risk (Additional file 1). Conclusions We developed a clinical prediction tool to estimate the probabilities of 3GC-R, CRE, and MDRP among hospitalized adult patients with confirmed community- and hospital-acquired Gram-negative infections. Our predictive model has been implemented as a user-friendly bedside tool for use by clinicians/healthcare professionals to predict the probability of resistant infections in individual patients, to guide early appropriate therapy. Electronic supplementary material The online version of this article (10.1186/s12879-019-4363-y) contains supplementary material, which is available to authorized users.

Introduction:We sought to assess adherence to and persistence with ocrelizumab (OCR) compared with other disease-modifying treatments (DMTs), by route of administration (RoA), for multiple sclerosis (MS) after 24 months in the United States. Methods: This retrospective claims analysis of MS patients initiating a new DMT was conducted using the IBM MarketScan Commercial and Medicare Supplemental databases between April 2016 and December 2019. Continuous enrollment of C 12 months before and up to 24 months after initiating the index DMT was required. Adherence was assessed based on proportion of days covered (PDC) in the followup period with values C 80% considered adherent. Persistence was defined as no evidence of switching to another DMT or no gap C 60 days in DMT coverage.Results: A total of 1710 patients with C 24 months of follow-up (OCR, n = 524; oral, n = 701; injectable, n = 365; other intravenous [IV], n = 120) were included. Patients initiating OCR had higher adherence (80% vs. 55%, 35%, and 54% for oral, injectable, and other IV, respectively) and persistence (75% vs. 54%, 33%, and 55%, respectively) at 24 months. Relative risks (RRs) of 24-month non-adherence for those initiating orals, injectables, and other IVs were 2.2 (95% CI, 1.7-2.9), 3.0 (95% CI, 2.2-4.0), and 2.2 (95% CI, 1.5-3.3), respectively, compared to those initiating OCR. Similarly, patients receiving orals, injectables, and other IVs had RR of 1.9 (95% CI, 1.4-2.4), 2.5 (95% CI, 1.9-3.4), and 1.8 (95% CI, 1.2-2.6) for 24-month discontinuation, respectively. Similar patterns were observed at 12 and 18 months. Conclusions: Patients initiating OCR in a realworld setting achieved higher rates of adherence and persistence at 24 months compared with those initiating other DMTs, consistent with published literature showing similar results at 12 and 18 months. Optimizing medication adherence and persistence is fundamental to MS care, so clinicians should consider all elements of DMTs that may improve compliance.