Full-Time Cardiac Intensive Care Unit Staffing by Heart Failure Specialists and its Association with Mortality Rates.

BACKGROUND: Cardiac intensive care units (CICUs) serve medically complex patients with multiorgan dysfunction. Whether a CICU that is staffed full time by heart failure (HF) specialists is associated with decreased mortality is unclear. METHODS AND RESULTS: A retrospective review of consecutive CICU admissions from January 1, 2012, to December 31, 2016, was performed. In January 2014, the CICU changed from an open unit staffed by any cardiologist to a closed unit managed by HF specialists. Patients' baseline characteristics were determined, and a multivariate regression analysis was performed to ascertain mortality rates in the CICU. Baseline severity of illness was higher in the closed/HF specialist CICU model (P< 0.001). Death occurred in 101 of 1185 patients admitted to the CICU (8.5%) in the open-unit model and in 139 of 2163 patients (6.4%) admitted to the closed/HF specialist model (absolute risk reduction 2.1%, 95% confidence interval [CI] 0.1-4.0%; P = 0.01). The transition from an open to a closed/HF specialist model was associated with a lower overall CICU mortality rate (odds ratio [OR] 0.63; 95% CI 0.43-0.93). Prespecified interaction with a mechanical circulatory support device and unit model showed that treatment with such a device was associated with lower mortality rates in the closed/HF specialist model of a CICU (OR 0.6; 95% CI 0.18-0.78; P for interaction <0.01). CONCLUSION: Transition to a closed unit model staffed by a dedicated HF specialist is associated with lower CICU mortality rates.

Derivation of a Model to Guide Empiric Therapy for Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infection in an Endemic Area.

BACKGROUND: Appropriate therapy for carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) is often given late in the course of infection, and strategies for identifying CRKP BSI earlier are needed. METHODS: A retrospective case-control study was performed at a tertiary care hospital, university hospital, and community hospital in Bronx, New York. All participants had a blood culture sent and received an antibiotic within 48 hours of the culture. The case group (n = 163) had a blood culture with CRKP. The control group (n = 178) had a blood culture with carbapenem-susceptible Klebsiella. Data were obtained by electronic or conventional medical record abstraction. A multiple logistic regression model was built to identify associated factors and develop a clinical model for CRKP BSI. Model performance characteristics were estimated using a 10-fold cross-validation analysis. RESULTS: A prior nonblood culture with carbapenem-resistant Enterobacteriaceae, skilled nursing facility (SNF) residence, mechanical ventilation, and admission >3 days were strongly associated risk factors. A significant interaction led to development of separate clinical models for subjects admitted <3 days at the time of positive blood culture from those admitted at least 3 days. The derived models had a good ability to discriminate between subjects with and without CRKP BSI. A clinical classification rule to guide therapy can prioritize sensitivity or specificity. CONCLUSIONS: Prior nonblood cultures showing resistance and exposure to SNF and health care settings are factors associated with carbapenem resistance. The clinical classification rules derived in this work should be validated for ability to guide therapy.

A new means to identify type 3 secreted effectors: functionally interchangeable class IB chaperones recognize a conserved sequence.

UNLABELLED: Many Gram-negative bacteria utilize specialized secretion systems to inject proteins (effectors) directly into host cells. Little is known regarding how bacteria ensure that only small subsets of the thousands of proteins they encode are recognized as substrates of the secretion systems, limiting their identification through bioinformatic analyses. Many of these proteins require chaperones to direct their secretion. Here, using the newly described protein interaction platform assay, we demonstrate that type 3 secretion system class IB chaperones from one bacterium directly bind their own effectors as well as those from other species. In addition, we observe that expression of class IB homologs from seven species, including pathogens and endosymbionts, mediate the translocation of effectors from Shigella directly into host cells, demonstrating that class IB chaperones are often functionally interchangeable. Notably, class IB chaperones bind numerous effectors. However, as previously proposed, they are not promiscuous; rather they recognize a defined sequence that we designate the conserved chaperone-binding domain (CCBD) sequence [(LMIF)(1)XXX(IV)(5)XX(IV)(8)X(N)(10)]. This sequence is the first defined amino acid sequence to be identified for any interspecies bacterial secretion system, i.e., a system that delivers proteins directly into eukaryotic cells. This sequence provides a new means to identify substrates of type III secretion systems. Indeed, using a pattern search algorithm for the CCBD sequence, we have identified the first two probable effectors from an endosymbiont, Sodalis glossinidius. IMPORTANCE: Many Gram-negative pathogens utilize type 3 secretion systems to deliver tens of effectors into host cells. In order to understand the diverse ways that these organisms cause disease, it is necessary to identify their effectors, many of which require chaperones to be secreted. Here we establish that class IB chaperones are not promiscuous, as previously proposed, but rather recognize a conserved effector sequence. We demonstrate that pattern search algorithms based on this defined sequence can be used to identify previously unknown effectors. Furthermore, we observe that class IB chaperones from at least seven bacterial species are functionally interchangeable. Not only do they bind and mediate the delivery of their own set of effectors into host cells but they also bind to type 3 substrates from other bacteria, suggesting that inhibitors that block chaperone-effector interactions could provide a novel means to effectively treat infections due to Gram-negative pathogens, including organisms resistant to currently available antibiotics.