Search

Objective:To develop and implement an objective, reliable approach to surveillance for ventilator-associated events in adult patients.Design:The Centers for Disease Control and Prevention (CDC) convened a Ventilator-Associated Pneumonia (VAP) Surveillance Definition Working Group in September 2011.

Background One aim of antimicrobial stewardship programs is to combat climbing rates of antibiotic resistance. Typically coordinated by Infectious Diseases (ID) physicians, such programs have decreased costs, resistance rates and secondary infections. A point of contention is whether ID or Critical Care (CC) physicians should manage the antibiotics prescribed to critically ill patients in the Intensive Care Unit (ICU). We surveyed ID and CC physicians regarding their perspectives on ICU antimicrobial stewardship and collaborations. Methods In 2017, CC and ID fellows and attendings completed an online survey that included 17 Likert-scaled items (1 = strongly disagree to 5 = strongly agree) measuring views on ICU antibiotic stewardship. Principal components analysis (PCA) was used for data reduction. Multivariable linear regression models explored variables associated with outcomes measuring physicians’ views on which specialty should guide antibiotic stewardship and the value of clinical collaborations in the ICU. Results Of 334 physicians, 71% were attendings (vs. fellows) and 61% were ID (vs. CC) specialists. From the PCA, 3 factors emerged measuring views about: (1) the specialty that should serve as ICU antibiotic stewards (Cronbach’s α = 0.71; higher scores indicate ID physicians should be stewards); (2) ICU clinical collaborations (α = 0.60; higher scores indicate greater value of collaboration); and (3) ICU decision-making insecurity (α = 0.45; higher scores indicate greater insecurity). In the regression models (n = 309), CC physicians and those placing lower value on ICU collaborations reported greater agreement that ID physicians should be the primary ICU stewards; women and physicians reporting greater ICU decision-making insecurity and less agreement that ID physicians should be ICU antibiotic stewards reported greater value of clinical collaborations. Conclusion CC physicians favor ID specialists to assume ICU antibiotic stewardship. Disclosures All authors: No reported disclosures.

Background Prospectively identifying patients at highest risk for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) by implementing a risk assessment scoring tool may help focus prevention efforts, optimize the screening process to improve clinical trial feasibility, and enhance development of new antibacterial agents. Methods Within the intensive care units (ICU) of 28 US hospitals, between February 6, 2016 and October 7, 2016, patients hospitalized >48 hours and receiving high levels of respiratory support were prospectively followed for meeting the definition of HABP/VABP recommended in US FDA draft guidance. Patient demographics, medical comorbidities, and treatment exposures were recorded. The association between candidate risk factors and odds of developing HABP/VABP was evaluated with a multivariable logistic regression model. Risk factors were selected using backward selection with α = 0.1 for model inclusion. A web-based scoring system was developed to estimate the risk of HABP/VABP from the risk factors identified. Results A total of 5,101 patients were enrolled, of whom 1,005 (20%) developed HABP/VABp. 4,613 patients were included in the model, excluding 488 (10%) with HABP/VABP at or before enrollment. There are 15 variables included in the model. APACHE II admission score >20 (P < 0.001, OR 2.14, 95% CI 2.00–2.29), admission diagnosis of trauma (P < 0.001, OR 3.31, 95% CI 1.90–5.74), frequent oral or lower respiratory tract suctioning (P < 0.001, OR 2.33, 95% CI 1.81–2.99), and receipt of enteral nutrition (P < 0.001, OR 2.31, 95% CI 1.69–3.16) were the key drivers of increased pneumonia risk. The model demonstrated excellent discrimination (bias-corrected C-statistic 0.861, 95% CI 0.843–0.880). The web-based scoring system can be accessed via this link: https://ctti-habpvabp.shinyapps.io/web_based_tool/. Conclusion Using a web-based scoring system, ICU patients at highest risk for developing HABP/VABP can be accurately identified. Prospective implementation of this tool may assist in focusing additional prevention efforts on the highest risk patients and enhance new drug development for HABP/VABP. Disclosures S. P. Bergin, CTTI: Investigator and Scientific Advisor, Research support and Travel to study related meetings. A. Coles, CTTI: Investigator and Scientific Advisor, Salary. S. B. Calvert, CTTI: Employee, Salary. M. J. Zervos, CTTI: Investigator, Research support. A. C. Bardossy, CTTI: Investigator, Research support. M. Kollef, CTTI: Investigator, Research support. M. J. Durkin, CTTI: Investigator, Research support. M. Sims, CTTI: Investigator, Research support. C. Greenshields, CTTI: Investigator, Research support. B. A. Kabchi, CTTI: Investigator, Research support. H. K. Donnelly, CTTI: Collaborator and Scientific Advisor, Research support and Salary. P. Tenaerts, CTTI: Employee, Salary. P. Gu, CTTI: Collaborator, Research support and Salary. V. G. Fowler Jr., CTTI: Investigator and Scientific Advisor, Research support and Salary. Merck: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Grant recipient and Research support. Cerexa/Actavis/Allegan: Grant Investigator, Grant recipient. Pfizer: Consultant and Grant Investigator, Consulting fee and Grant recipient. Advanced Liquid Logics: Grant Investigator, Grant recipient. NIH: Investigator, Grant recipient, Research support and Salary. MedImmune: Consultant and Grant Investigator, Consulting fee and Grant recipient. Basilea: Consultant and Grant Investigator, Consulting fee and Grant recipient. Karius: Grant Investigator, Grant recipient. Contrafect: Consultant and Grant Investigator, Consulting fee and Grant recipient. Regeneron: Grant Investigator, Grant recipient. Genentech: Consultant and Grant Investigator, Consulting fee and Grant recipient. Achaogen: Consultant, Consulting fee. Astellas: Consultant, Consulting fee. Arsanis: Consultant, Consulting fee. Affinergy: Consultant, Consulting fee. Bayer: Consultant, Consulting fee. Cerexa: Consultant, Consulting fee. Cubist: Consultant, Consulting fee. Debiopharm: Consultant, Consulting fee. Durata: Consultant, Consulting fee. Grifols: Consultant, Consulting fee. Medicines Co.: Consultant, Consulting fee. Novartis: Consultant, Consulting fee. Novadigm: Consultant, Consulting fee. Theravance: Consultant, Consulting fee and Speaker honorarium. xBiotech: Consultant, Consulting fee. Green Cross: Consultant, Speaker honorarium. T. L. Holland, CTTI: Investigator and Scientific Advisor, Research support and Salary.

OBJECTIVES/SPECIFIC AIMS: Afebrile septic patients are twice as likely to die and develop nosocomial infections as compared with those with fever; the reason for these differences is unknown. One hypothesis is that elevated temperatures directly boost immunity and inhibit microorganism growth. However, there is little data examining the clinical effects of warming septic patients. The goal of this study was to determine whether warming afebrile septic patients to fever-range hyperthermia with noninvasive forced air warmers is feasible and safe. METHODS/STUDY POPULATION: This is an ongoing randomized trial on afebrile mechanically ventilated patients with severe sepsis. The intervention consisted of 48 hours of external warming with a forced air warming device to a goal core temperature of 1.5°C higher than the lowest recorded temperature within the 24 hours preceding enrollment. Efficacy of the intervention and adverse event data (i.e., increases in heart rate and vasopressor doses) were collected. Clinical outcomes included 28-day mortality and acquisition of secondary infections. RESULTS/ANTICIPATED RESULTS: In total, 18 patients were randomized to the control and warming groups, respectively. Baseline characteristics (including demographics, comorbidities, and illness severity scores) were similar among the 2 groups, except the control group had more males (61% vs. 28%, p=0.04). Median (IQR) body temperature averaged over the 48-hour intervention period was higher in the warming group [38.2 (37.6, 38.6) vs. 37.1 (36.4, 37.4) °C, pp=0.07). DISCUSSION/SIGNIFICANCE OF IMPACT: Externally warming severe septic patients with forced air warming devices effectively raises core body temperature and is safe. Additional research will focus on cellular and immunological changes seen in warmed Versus control patients.

Background The National Healthcare Safety Network (NHSN) has recently supported efforts to shift surveillance away from ventilator-associated pneumonia to ventilator-associated events (VAEs) to decrease subjectivity in surveillance and minimize concerns over clinical correlation. The goals of this study were to compare the results of an automated surveillance strategy using the new VAE definition with a prospectively performed clinical application of the definition. Methods All patients ventilated for ≥2 days in a medical and surgical intensive care unit were evaluated by 2 methods: retrospective surveillance using an automated algorithm combined with manual chart review after the NHSN's VAE methodology and prospective surveillance by pulmonary physicians in collaboration with the clinical team administering care to the patient at the bedside. Results Overall, a similar number of events were called by each method (69 vs 67). Of the 1,209 patients, 56 were determined to have VAEs by both methods (κ = .81, P = .04). There were 24 patients considered to be a VAE by only 1 of the methods. Most discrepancies were the result of clinical disagreement with the NHSN’s VAE methodology. Conclusions There was good agreement between the study teams. Awareness of the limitations of the surveillance definition for VAE can help infection prevention personnel in discussions with critical care partners about optimal use of these data.

Septic shock affects 750,000 people annually, and accounts for 10 % of all deaths annually in the US. In recent years, outcomes in patients with septic shock have improved; however, mortality still remains high at 40 - 50 %. The use of early protocolized resuscitation goals have been associated with reduced mortality in septic shock. However, strong evidenced-based recommendations for the continued management of patients with septic shock in the ICU setting are currently lacking. Appropriate antibiotic therapy is the cornerstone of management in septic shock. Inappropriate antibiotic therapy can lead to treatment failures and adverse outcomes, including high risk of mortality. This article outlines other key factors that contribute to outcome in septic shock. It is challenging for physicians to optimize therapy when fixed patient features such as age and underlying comorbidity can negatively influence mortality. However, outcomes can also potentially be affected by physician management decisions including fluid balance, corticosteroid use, glucose control and adherence to protocols including early goal-directed therapy and infection-control measures. Certain pathogen virulence characteristics also adversely affect outcomes. We give an overview of the determinants of outcome in septic shock in the setting of appropriate antibiotic use.

Clostridium difficile is a leading cause of hospital-associated infection in the United States. The purpose of this study is to assess the prevalence of C. difficile infection among mechanically ventilated patients within the ICUs of three academic hospitals and secondarily describe the influence of C. difficile infection on the outcomes of these patients.A retrospective cohort study.ICUs at three teaching hospitals: Barnes-Jewish Hospital, Mayo Clinic, and Creighton University Medical Center over a 2-year period.All hospitalized patients requiring mechanical ventilation for greater than 48 hours within an ICU were eligible for inclusion.None.A total of 5,852 consecutive patients admitted to the ICU were included. Three hundred eighty-six (6.6%) patients with development of C. difficile infection while in the hospital (5.39 cases/1,000 patient days). Septic shock complicating C. difficile infection occurred in 34.7% of patients. Compared with patients without C. difficile infection (n = 5,466), patients with C. difficile infection had a similar hospital mortality rate (25.1% vs 26.3%, p = 0.638). Patients with C. difficile infection were significantly more likely to be discharged to a skilled nursing or rehabilitation facility (42.4% vs 31.9%, p0.001), and the median hospital (23 d vs 15 d, p0.001) and ICU length of stay (12 d vs 8 d, p0.001) were found to be significantly longer in patients with C. difficile infection.Clostridium difficile infection is a relatively common nosocomial infection in mechanically ventilated patients and is associated with prolonged length of hospital and ICU stay, and increased need for skilled nursing care or rehabilitation following hospital discharge.

Ceftaroline fosamil resulted in higher cure rates than ceftriaxone in patients with community-acquired bacterial pneumonia in 2 randomized trials (FOCUS 1 and FOCUS 2). The present analysis examines the subgroup of patients with Streptococcus pneumoniae infection to determine whether the apparent difference in cure rates persists after adjusting for potential covariates. We retrospectively pooled subjects with S. pneumoniae isolated at baseline in the original studies and employed logistic regression to evaluate the independent relationship between clinical cure and treatment with ceftaroline. Covariates evaluated included demographics, severity of illness, bacteremia, and pathogen characteristics. The final cohort included 139 subjects (69 ceftaroline, 70 ceftriaxone). Unadjusted cure rates were 85.5% and 68.6% (P = 0.009) in the ceftaroline and ceftriaxone groups, respectively. After logistic regression, ceftaroline remained associated with higher cure rates. Our findings indicate that ceftaroline may result in improved outcomes of S. pneumoniae pneumonia. Formal clinical trials are warranted to confirm this hypothesis.

BACKGROUND With limited numbers of intensive care unit (ICU) beds available, increasing patient acuity is expected to contribute to episodes of inpatient deterioration on general wards. OBJECTIVE To prospectively validate a predictive algorithm for clinical deterioration in general–medical ward patients, and to conduct a trial of real-time alerts based on this algorithm. DESIGN Randomized, controlled crossover study. SETTING/PATIENTS Academic center with patients hospitalized on 8 general wards between July 2007 and December 2011. INTERVENTIONS Real-time alerts were generated by an algorithm designed to predict the need for ICU transfer using electronically available data. The alerts were sent by text page to the nurse manager on intervention wards. MEASUREMENTS Intensive care unit transfer, hospital mortality, and hospital length of stay. RESULTS Patients meeting the alert threshold were at nearly 5.3-fold greater risk of ICU transfer (95% confidence interval [CI]: 4.6-6.0) than those not satisfying the alert threshold (358 of 2353 [15.2%] vs 512 of 17678 [2.9%]). Patients with alerts were at 8.9-fold greater risk of death (95% CI: 7.4-10.7) than those without alerts (244 of 2353 [10.4%] vs 206 of 17678 [1.2%]). Among patients identified by the early warning system, there were no differences in the proportion of patients who were transferred to the ICU or who died in the intervention group as compared with the control group. CONCLUSIONS Real-time alerts were highly specific for clinical deterioration resulting in ICU transfer and death, and were associated with longer hospital length of stay. However, an intervention notifying a nurse of the risk did not result in improvement in these outcomes. Journal of Hospital Medicine 2013;8:236–242. © 2013 Society of Hospital Medicine

BACKGROUND: β-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results. OBJECTIVE: To determine whether prolonged infusion of β-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection. METHODS: We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011). RESULTS: A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329). CONCLUSIONS: Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

Acute respiratory failure represents the most common condition requiring admission to an adult intensive care unit. Ventilator-associated pneumonia (VAP) has been used as a marker of quality for patients with respiratory failure. Hospital-based process-improvement initiatives to prevent VAP have been successfully used. The use of ventilator-associated complications (VACs) has been proposed as an objective marker to assess the quality of care for this patient population. The use of evidence-based bundles targeting the reduction of VACs, as well as the conduct of prospective studies showing that VACs are preventable complications, are reasonable first-steps in addressing this important clinical problem.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of pneumonia in ventilated patients. Our objective was to evaluate the GeneXpert MRSA/SA SSTI Assay (Xpert MRSA/SA) (Cepheid, Sunnyvale, CA) for use in lower respiratory tract (LRT) specimens for rapid MRSA detection and to determine the potentially saved antibiotic-days if a culture-based identification method was replaced by this assay. Remnant LRT samples from ventilated patients submitted to the microbiology laboratory for routine culture were tested using conventional culture and Xpert MRSA/SA. One hundred of 310 LRT specimens met the inclusion criteria. Ten samples were positive for MRSA by Xpert MRSA/SA, while six were positive by routine culture methods. Xpert MRSA/SA correctly identified 5/6 positive and 89/94 negative MRSA specimens, for a sensitivity of 83.3%, specificity of 94.7%, positive predictive value of 45.6%, and negative predictive value of 98.9%. The assay also correctly detected 3/3 positive and 90/97 negative methicillin-susceptible S. aureus (MSSA) specimens, for a sensitivity of 100%, specificity of 92.8%, positive predictive value of 30%, and negative predictive value of 100%. A total of 748 vancomycin and 305 linezolid antibiotic-days were associated with the enrolled specimens. Vancomycin and linezolid utilization could decrease by 68.4% and 83%, respectively, if discontinued 1 day after negative polymerase chain reaction (PCR) results. The Xpert MRSA/SA SSTI rapid MRSA PCR assay performed well in respiratory samples from ventilated patients with suspected pneumonia and has the potential to facilitate stewardship efforts such as reducing empiric vancomycin and linezolid therapy.

Despite the increasing incidence of vancomycin-intermediate Staphylococcus aureus (VISA) infections, few studies have examined the impact of delay in receipt of appropriate antimicrobial therapy on outcomes in VISA patients. We examined the effects of timing of appropriate antimicrobial therapy in a cohort of patients with sterile-site methicillin-resistant S. aureus (MRSA) and VISA infections. In this single-center, retrospective cohort study, we identified all patients with MRSA or VISA sterile-site infections from June 2009 to February 2015. Clinical outcomes were compared according to MRSA/VISA classification, demographics, comorbidities, and antimicrobial treatment. Thirty-day all-cause mortality was modeled with Kaplan-Meier curves. Multivariate logistic regression analysis (MVLRA) was used to determine odds ratios for mortality. We identified 354 patients with MRSA ( n = 267) or VISA ( n = 87) sterile-site infection. Fifty-five patients (15.5%) were nonsurvivors. Factors associated with mortality in MVLRA included pneumonia, unknown source of infection, acute physiology and chronic health evaluation (APACHE) II score, solid-organ malignancy, and admission from skilled care facilities. Time to appropriate antimicrobial therapy was not significantly associated with outcome. Presence of a VISA infection compared to that of a non-VISA S. aureus infection did not result in excess mortality. Linezolid use was a risk for mortality in patients with APACHE II scores of ≥14. Our results suggest that empirical vancomycin use in patients with VISA infections does not result in excess mortality. Future studies should (i) include larger numbers of patients with VISA infections to confirm the findings presented here and (ii) determine the optimal antibiotic therapy for critically ill patients with MRSA and VISA infections.

Over the last few decades, machine learning and data mining have been increasingly used for clinical prediction in ICUs. However, there is still a huge gap in making full use of the time-series data generated from ICUs. Aiming at filling this gap, we propose a novel approach entitled Time Slicing Cox regression (TS-Cox), which extends the classical Cox regression into a classification method on multi-dimensional time-series. Unlike traditional classifiers such as logistic regression and support vector machines, our model not only incorporates the discriminative features derived from the time-series, but also naturally exploits the temporal orders of these features based on a Cox-like function. Empirical evaluation on MIMIC-II database demonstrates the efficacy of the TS-Cox model. Our TS-Cox model outperforms all other baseline models by a good margin in terms of AUC_PR, sensitivity and PPV, which indicates that TS-Cox may be a promising tool for mortality prediction in ICUs.

The “golden era” of antibiotics started with the discovery of penicillin, streptomycin, chloramphenicol, and tetracycline [1]. However, their introduction into medical practice was associated with rapid appearance of resistance: 50 % of hospital Staphylococcus aureus isolates were resistant within 7 years of penicillin’s first use [1]. During the following years a huge number of newer antibiotics have been released but simultaneously more and more pathogenic bacteria developed resistance to nearly all antibiotic classes through intrinsic or acquired resistance mechanisms; this has created a global public health problem that affects all parts of the world (in 2004, more than 70 % of pathogenic bacteria were resistant to at least one of the currently used antibiotics) [2, 3]. Bacterial resistance mechanisms to antibiotics include their inactivation via hydrolysis, alteration or bypassing the drug target, preventing access of the drug to the target sites making the cells unrecognizable to the antibiotic, and active efflux out of the cell via membrane-bound efflux transporters. These resistance mechanisms primarily occur as a result of mutations of endogenous genes and/or lateral gene transfer of resistance genes from other pathogens [4]. Studies on genomics and metagenomics recently reported that diverse natural ecosystems (human gut, soil, etc.), the so-called resistomes, contain genes able to confer resistance to antimicrobials, in addition to some pathogens being considered as disseminated multicellular organisms having interactions mediated by complex cell–cell signaling [5]. These interactions lead to the formation of complex matrices of polysaccharide/ extracellular DNA and biofilm development, especially in the ICU setting where many devices are used. The biofilm promotes cellular resistance due to a high mutation rate (up to 100 times higher than planktonic cells) leading to faster development of antibiotic-resistant mutants while the various pathogens within biofilm facilitate horizontal gene transfer and acquisition and spread of resistance determinants [6]. From all the above it appears that bacteria are involved in a continuous effort to “find” new pathways and to develop newer and newer mechanisms of resistance in order to overcome antibiotics usage. We still use antibiotics and will do so for the foreseeable future so antibiotic resistance will continue to emerge to existing as well as to new agents, and it will probably escalate over time. Even when antibiotic restriction practices are applied to sizable urban communities like Shanghai, large-scale consumption of antibiotics continues to occur [7]. The consumption patterns of antibiotics seem to favor the use of parenteral agents and specifically cephalosporins, macrolides, and quinolones, classes of antibiotics already having some of the highest rates of resistance. Moreover, the demographic characteristics of both developing and developed countries favor increasing utilization rates of antibiotics. For example, of the 7.7 million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents [8]. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905,059 deaths) and diarrheal diseases among older children (38,325 deaths) [8]. These patterns of disease would suggest that pressures on antibiotic utilization will continue to occur unless the causes of disease and death are altered on a global scale. It is very likely that the newly available antibiotics will see increased utilization over time, as they have been specifically developed to treat existing antibiotic-resistant *Correspondence: gdimop@med.uoa.gr 1 Department of Critical Care, Attikon University Hospital, University of Athens, Medical School, Athens, Greece Full author information is available at the end of the article

This article describes the strategies for stratifying patients with skin and soft tissue infections (SSTIs) according to their risk for infection with multidrug-resistant (MDR) pathogens.Methicillin-resistant Staphylococcus aureus (MRSA) now represents the main cause in a variety of serious SSTIs. Risk factors for MRSA are constantly evolving and the distinction between community-acquired MRSA and hospital-acquired MRSA is becoming less clear from a therapeutic standpoint because of overlapping susceptibility patterns. Given these observations, physicians should be aware that directed empirical coverage of MRSA for serious SSTIs should be required in communities where this resistant pathogen is recognized to be a prevalent cause of infection. Similarly, other MDR bacteria are demonstrating alarming trends as causative pathogens in SSTIs. Pseudomonas aeruginosa, Acinetobacter species, and vancomycin-resistant Enterococcus can play an important role in polymicrobial long-standing infections such as diabetic foot infection and decubiti, but are also increasingly recognized in monomicrobial SSTIs.SSTIs caused by MDR bacteria, both Gram-positive and Gram-negative bacteria, are on the rise especially in patients with long-standing infections and those with prior antibiotic exposure. Recognition of risk factors for infection with MDR bacteria should assist clinicians in targeting appropriate antibiotic therapy to at-risk individuals.

The optimal approach for the prevention of ventilator-associated complications (VACs) is currently unknown. A retrospective pre–post intervention analysis was conducted to assess a multifaceted educational intervention targeting the most common causes for VACs and VAC risk factors. Results indicated that the addition of this intervention to existing infection control and treatment protocols did not demonstrate a decrease in VAC occurrence or duration of mechanical ventilation.

Adjunctive aerosolized antibiotics (AAA) have been recommended in the setting of Gram-negative ventilator-associated pneumonia (VAP), but little is known about their influence on clinical outcomes.To assess outcomes associated with AAA for the treatment of Pseudomonas aeruginosa (PA) and Acinetobacter baumannii (AB) VAP.A retrospective, single-center cohort study at Barnes-Jewish Hospital in St Louis, Missouri. Consecutive subjects treated for bronchoalveolar lavage-confirmed PA or AB VAP between January 1, 2004 and December 31, 2009 were enrolled. Records of subjects treated with AAA were compared to those who did not receive AAAs (NAAA).Ninety-three patients were evaluated (NAAA n = 74, AAA n = 19, inhaled colistin n = 9, inhaled tobramycin n = 10). Patients receiving AAA were significantly more likely to be infected with multidrug-resistant bacteria (52.6% vs 14.9%, P.001) and had greater Acute Physiology and Chronic Health Evaluation II scores (21.4 ± 5.7 vs 17.5 ± 5.3, P = .004) compared to patients receiving NAAA. NAAA subjects experienced a shorter time from VAP onset to appropriate intravenous antibiotic initiation (0.5 ± 0.9 d vs 2.6 ± 5.4 d, P = .038), but length of intravenous therapy was similar between groups (12.8 ± 8.5 d vs 17.8 ± 13.3 d, P = .16). The NAAA group demonstrated significantly shorter mechanical ventilation duration (18.9 ± 15.9 d vs 38.4 ± 32.4 days, P.001), intensive care unit stay (37.5 ± 42.5 d vs 56.3 ± 31.3 d, P = .001), and hospital stay (39.0 ± 42.5 d vs 58.3 ± 33.4 d, P = .001). However, Kaplan-Meier curves for the probability of 30-day survival from VAP onset demonstrated that patients receiving AAA had statistically greater survival (P = .030 by the log rank test).Patients with PA and AB VAP may experience favorable survival when treated with AAA, despite greater severity of illness and a greater incidence of multidrug-resistant infection. Large randomized trials are needed to further explore this therapy.

Background: Delayed treatment of candidemia has previously been shown to be an important determinant of patient outcome. However, septic shock attributed to Candida infection and its determinants of outcome have not been previously evaluated in a large patient population. Methods: A retrospective cohort study of hospitalized patients with septic shock and blood cultures positive for Candida species was conducted at Barnes-Jewish Hospital, a 1250-bed urban teaching hospital (January 2002-December 2010). Results: Two hundred twenty-four consecutive patients with septic shock and a positive blood culture for Candida species were identified. Death during hospitalization occurred among 155 (63.5%) patients. The hospital mortality rate for patients having adequate source control and antifungal therapy administered within 24 hours of the onset of shock was 52.8% (n = 142), compared to a mortality rate of 97.6% (n = 82) in patients who did not have these goals attained (P < .001). Multivariate logistic regression analysis demonstrated that delayed antifungal treatment (adjusted odds ratio [AOR], 33.75; 95% confidence interval [CI], 9.65-118.04; P = .005) and failure to achieve timely source control (AOR, 77.40; 95% CI, 21.52-278.38; P = .001) were independently associated with a greater risk of hospital mortality. Conclusions: The risk of death is exceptionally high among patients with septic shock attributed to Candida infection. Efforts aimed at timely source control and antifungal treatment are likely to be associated with improved clinical outcomes.

BACKGROUND: Conventional chest physical therapy (CCPT), applied by therapists using cupped hands to perform percussion, is commonly used in hospitalized adults. However, increased work load demands and occupational health concerns (eg, carpal tunnel syndrome) limit the overall utilization of this therapy. Therefore, we conducted a study to compare the overall effectiveness of CCPT to high-frequency chest wall compressions (HFCWC) applied via a vibratory vest. METHODS: A single-center, randomized trial among hospitalized intubated and non-intubated adult patients requiring chest physical therapy comparing CCPT and HFCWC. The primary outcome measure was hospital stay. RESULTS: A total of 280 per-protocol patients (out of an a priori estimated 320 patients required to demonstrate a 20% relative reduction in hospital stay) were randomly assigned to receive CCPT (no. = 146, 52.1%) or HFCWC (no. = 134, 47.9%). The hospital stay was 12.5 ± 8.8 days for patients randomized to CCPT and 13.0 ± 8.9 days for patients randomized to HFCWC ( P = .62). Patient comfort was assessed using a visual analog scale (increasing score reflects greater discomfort) and was statistically greater for patients randomized to CCPT compared to HFCWC (2.2 ± 0.8 vs 1.9 ± 0.8, P = .009). The duration of time until radiographic resolution of lobar atelectasis trended less for CCPT compared to HFCWC (5.2 ± 4.3 d vs 6.5 ± 5.2 d, P = .051). All other secondary outcomes, including hospital mortality and nosocomial pneumonia, were similar for both treatment groups. CONCLUSIONS: This study was inadequately powered for the primary outcome of interest and hence we cannot make recommendations on the preferential use of HFCWC or CCPT for intubated and non-intubated adult patients. HFCWC was associated with statistically better comfort scores. (ClinicalTrials.gov registration [NCT00717873][1].) [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00717873&atom=%2Frespcare%2F57%2F2%2F221.atom

Ventilator-associated pneumonia is a difficult diagnosis to establish in the critically ill patient because of the presence of underlying cardiopulmonary disorders (e.g., pulmonary contusion, acute respiratory distress syndrome, atelectasis) and the nonspecific radiographic and clinical signs associated with this infection. However, the escalating antimicrobial resistance of the bacterial pathogens associated with ventilator-associated pneumonia, as well as with other nosocomial infections, has created an imperative to reduce their occurrence and the unnecessary use of antibiotics. Hospital-based process improvement initiatives aimed at the prevention of ventilator-associated pneumonia, and other ventilator-associated complications, have been successfully used despite the limitations of clinical criteria for establishing the diagnosis of ventilator-associated pneumonia. Given current restrictions in hospital resources, absence of available new antimicrobial agents, and potential lack of reimbursement for patients with development of ventilator-associated pneumonia, hospitals need to develop and successfully implement programs aimed at reducing ventilator-associated pneumonia. The use of evidence-based bundles targeting ventilator-associated pneumonia seems to be a reasonable first step in addressing this important clinical problem.

The objective of this study was to compare the observed rates of ventilator-associated pneumonia when using the National Healthcare Safety Network vs. the American College of Chest Physicians criteria.Prospective, observational cohort study.A 1250-bed academic tertiary care medical center.Adult medical and surgical intensive care unit patients requiring mechanical ventilation for48 hrs.None.Patients were prospectively and independently screened for ventilator-associated pneumonia from January 2009 to January 2010 using the National Healthcare Safety Network and American College of Chest Physicians criteria. All American College of Chest Physicians classifications, including the corresponding radiographs and laboratory data, were prospectively reviewed by one of the investigators (JD) and confirmed by a second investigator (MHK). All National Healthcare Safety Network classifications were administratively determined using the hospital's infection prevention surveillance system. Over 1 yr, 2060 patients met the inclusion criteria. Of these, 83 patients (4%) had ventilator-associated pneumonia according to the American College of Chest Physicians criteria as compared with 12 patients (0.6%) using the National Healthcare Safety Network criteria. The corresponding rates of ventilator-associated pneumonia were 8.5 vs. 1.2 cases per 1,000 ventilator days, respectively. Agreement of the two sets of criteria was marginal (κ statistic, 0.26). Cultures were positive in 88% of ventilator-associated pneumonias in the American College of Chest Physicians group as compared to 92% in the National Healthcare Safety Network group.There is poor agreement between clinical and administrative surveillance methods for the diagnosis of ventilator-associated pneumonia. Although there may be some benefit to using more stringent criteria for surveillance of ventilator-associated pneumonia, use of the administratively applied National Healthcare Safety Network criteria may significantly underestimate the scope of the clinical problem.

In 2013, a before-and-after intervention study was conducted to evaluate the effect 24-hour intensivist coverage on length of stay and rates of catheter-associated urinary tract infection, central-line associated blood stream infection, and ventilator-associated events. Intensivist coverage for 24 hours did not decrease length of stay or result in a decrease in any specific infection rate.Infect. Control Hosp. Epidemiol. 2016;37(3):352–354

Introduction Randomized controlled trials suggest clinical outcomes may be improved with dexmedetomidine as compared with benzodiazepines; however, further study and validation are needed. The objective of this study was to determine the clinical effectiveness of a sedation protocol minimizing benzodiazepine use in favor of early dexmedetomidine. Methods We conducted a before-after study including adult surgical and medical intensive care unit (ICU) patients requiring mechanical ventilation and continuous sedation for at least 24 hours. The before phase included consecutive patients admitted between 1 April 2011 and 31 August 31 2011. Subsequently, the protocol was modified to minimize use of benzodiazepines in favor of early dexmedetomidine through a multidisciplinary approach, and staff education was provided. The after phase included consecutive eligible patients between 1 May 2012 and 31 October 2012. Results A total of 199 patients were included, with 97 patients in the before phase and 102 in the after phase. Baseline characteristics were well balanced between groups. Use of midazolam as initial sedation (58% versus 27%, P P P P P =0.013) and median percentage of days with delirium (55% (interquartile range (IQR), 18 to 83) versus 71% (IQR, 45 to 100), P =0.001) were increased in the after phase. The median duration of mechanical ventilation was significantly reduced in the after phase (110 (IQR, 59 to 192) hours versus 74.5 (IQR, 42 to 148) hours, P =0.029), and significantly fewer patients required tracheostomy (20% versus 9%, P =0.040). The median ICU length of stay was 8 (IQR, 4 to 12) days in the before phase and 6 (IQR, 3 to 11) days in the after phase (P =0.252). Conclusions Implementing a sedation protocol that targeted light sedation and reduced benzodiazepine use led to significant improvements in the duration of mechanical ventilation and the requirement for tracheostomy, despite increases in the prevalence and duration of ICU delirium.

Advanced technologies using polymerase-chain reaction have allowed for increased recognition of viral respiratory infections including pneumonia. Co-infections have been described for several respiratory viruses, especially with influenza. Outcomes of viral pneumonia, including cases with co-infections, have not been well described. This was observational cohort study conducted to describe hospitalized patients with viral pneumonia including co-infections, clinical outcomes, and predictors of mortality. Patients admitted from March 2013 to November 2014 with a positive respiratory virus panel (RVP) and radiographic findings of pneumonia within 48 h of the index RVP were included. Co-respiratory infection (CRI) was defined as any organism identification from a respiratory specimen within 3 days of the index RVP. Predictors of in-hospital mortality on univariate analysis were evaluated in a multivariate model. Of 284 patients with viral pneumonia, a majority (51.8%) were immunocompromised. A total of 84 patients (29.6%) were found to have a CRI with 48 (57.6%) having a bacterial CRI. Viral CRI with HSV, CMV, or both occurred in 28 patients (33.3%). Fungal (16.7%) and other CRIs (7.1%) were less common. Many patients required mechanical ventilation (54%) and vasopressor support (36%). Overall in-hospital mortality was high (23.2%) and readmissions were common with several patients re-hospitalized within 30 (21.1%) and 90 days (36.7%) of discharge. Predictors of in-hospital mortality on multivariate regression included severity of illness factors, stem-cell transplant, and identification of multiple respiratory viruses. In conclusion, hospital mortality is high among adult patients with viral pneumonia and patients with multiple respiratory viruses identified may be at a higher risk.

Introduction Respiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use. Method This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy. Results A total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027). Conclusion This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization.

A study was performed to determine the potential influence of a rapid response system (RRS) employing real-time clinical deterioration alerts (RTCDAs) on patient outcomes involving 8 general medicine units. Introduction of the RRS occurred in 2006 with staged addition of the RTCDAs in 2009. Statistically significant year-to-year decreases in mortality were observed through 2014 ( r = −.794; P = .002). Similarly, year-to-year decreases in the number of cardiopulmonary arrests (CPAs; r = −.792; P = .006) and median lengths of stay ( r = −.841; P = .001) were observed. There was a statistically significant year-to-year increase in the number of RRS activations for these units ( r = .939; P < .001) that was inversely correlated with the occurrence of CPAs ( r = −.784; P = .007). In this single-institution retrospective study, introduction of a RRS employing RTCDAs was associated with lower hospital mortality, CPAs, and hospital length of stay.

Background Inappropriate initial antibiotic therapy (IIAT) for sepsis increases mortality. Fast diagnostic tests providing earlier identification (ID) of pathogens and antimicrobial susceptibility testing (AST) have the potential to improve mortality and antimicrobial stewardship. The Accelerate Pheno™ system (AXDX) is a newly FDA cleared fast diagnostic testing system that provides ID and AST for Gram-positive and Gram-negative bacteria (GNB) and ID for Candida bloodstream isolates. Methods From April 14, 2016 to March 13, 2017, blood cultures from unique patients in the emergency department or medical intensive care units at Barnes-Jewish Hospital signaling positive and Gram-stain positive for GNB or yeast were eligible for inclusion. Standard-of-care (SOC) diagnostics were conducted in parallel with AXDX, though AXDX could be delayed up to 8 hours depending on research technician availability. Differences in time to ID and AST between SOC and AXDX were determined. Clinical outcomes included appropriateness of initial empiric antimicrobial therapy, potential for early antimicrobial de-escalation with AXDX, and mortality. Results Of 341 screened blood cultures, 123 met inclusion criteria; 101 had organisms that were on-panel for AXDX, 88 GNB and 13 C. glabrata or C. albicans. For GNB, mean time from blood culture positivity to ID and AST using SOC was 19.8 and 53.5 hours, respectively, and 1.4 and 6.7 hours using AXDX (from time AXDX started). For Candida spp., mean time to ID was 33.1 hours for SOC, 1.4 hours for AXDX. Antimicrobial de-escalation was possible based on AXDX testing in 52.9% of patients with GNB infections. A total of 27 (27.3%) patients received IIAT. In-hospital mortality was higher (48.1%) in the IIAT group than in those receiving appropriate initial antibiotics (12.5%), P < 0.001. AXDX could have improved antimicrobial therapy in 89.8% of GNB and 92.3% of Candida spp. cases. Conclusion The Accelerate Pheno™ system is a novel fast diagnostic that significantly reduces the time to ID and AST for GNB and ID of Candida spp. bloodstream infections, with the potential to impact clinical outcomes. Prospective clinical trials are needed to evaluate the impact of this new system on clinical outcomes and antimicrobial stewardship. Disclosures C. A. D. Burnham, Accelerate Diagnostics: Investigator, Research support; M. Kollef, Accelerate Diagnostics: Consultant, Research support

Clostridium difficile infection (CDI) management has become more daunting over the past decade because of alarming increases in CDI incidence and severity both in the hospital and in the community. This increase has concomitantly caused significant escalation of the health-care economic burden caused by CDI, and it will likely be translated to increased ICU admission and attributable mortality. Some possible causes for difficulty in management of CDI are as follows: (1) inability to predict and prevent development of severe/complicated or relapsing CDI in patients who initially present with mild symptoms; (2) lack of a method to determine who would have benefited a priori from initiating vancomycin treatment first instead of treatment with metronidazole; (3) lack of sensitive and specific CDI diagnostics; (4) changing epidemiology of CDI, including the emergence of a hypervirulent, epidemic C difficile strain associated with increased morbidity and mortality; (5) association of certain high-usage nonantimicrobial medications with CDI; and (6) lack of treatment regimens that leave the normal intestinal flora undisturbed while treating the primary infection. The objective of this article is to present current management and prevention guidelines for CDI based on recommendations by the Society for Healthcare Epidemiology of America and Infectious Diseases Society of America and potential new clinical management strategies on the horizon.

Background Resistant organisms (ROs) are increasingly implicated in pneumonia in patients presenting to the emergency department (ED). The concept of healthcare-associated pneumonia (HCAP) exists to help identify patients infected with ROs but may be overly broad. We sought to validate a previously developed score for determining the risk for an RO and to compare it with the HCAP definition. Methods We evaluated adult patients admitted via the ED with bacterial pneumonia (January-December 2010). We defined methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and extended-spectrum β-lactamases as ROs. The risk score was as follows: 4, recent hospitalization; 3, nursing home; 2, chronic hemodialysis; 1, critically ill. We evaluated the screening value of the score and of HCAP by determining their areas under the receiver-operating characteristic (AUROC) curves for predicting ROs. Results The cohort included 977 patients, and ROs were isolated in 46.7%. The most common organisms included MRSA (22.7%), P. aeruginosa (19.1%), and Streptococcus pneumoniae (19.1%). The risk score was higher in those with an RO (median score, 4 vs 1; P 0 had a high negative predictive value (84.5%) and could lead to fewer patients unnecessarily receiving broad-spectrum antibiotics. Conclusions ROs are common in patients presenting to the ED with pneumonia. A simple clinical risk score performs moderately well at classifying patients regarding their risk for an RO.

The emerging problem of antibiotic resistance, especially among Gram-negative bacteria (GNB), has become a serious threat to global public health. Very few new antibacterial classes with activity against antibiotic-resistant GNB have been brought to market. Renewed and growing attention to the development of novel compounds targeting antibiotic-resistant GNB, as well as a better understanding of strategies aimed at preventing the spread of resistant bacterial strains and preserving the efficacy of existing antibiotic agents, has occurred. The Gram-Negative Resistance Summit convened national opinion leaders for the purpose of analyzing current literature, epidemiologic trends, clinical trial data, therapeutic options, and treatment guidelines related to the management of antibiotic-resistant GNB infections. After an in-depth analysis, the Summit investigators were surveyed with regard to 4 clinical practice statements. The results then were compared with the same survey completed by 138 infectious disease and critical care physicians and are the basis of this article.

BACKGROUND: Gram-negative bacteria are an important cause of severe sepsis. Recent studies have demonstrated reduced susceptibility of Gram-negative bacteria to currently available antimicrobial agents. METHODS: We performed a retrospective cohort study of patients with severe sepsis who were bacteremic with Pseudomonas aeruginosa, Acinetobacter species, or Enterobacteriaceae from 2002 to 2007. Patients were identified by the hospital informatics database and pertinent clinical data (demographics, baseline severity of illness, source of bacteremia, and therapy) were retrieved from electronic medical records. All patients were treated with antimicrobial agents within 12 hours of having blood cultures drawn that were subsequently positive for bacterial pathogens. The primary outcome was hospital mortality. RESULTS: A total of 535 patients with severe sepsis and Gram-negative bacteremia were identified. Hospital mortality was 43.6%, and 82 (15.3%) patients were treated with an antimicrobial regimen to which the causative pathogen was resistant. Patients infected with a resistant pathogen had significantly greater risk of hospital mortality (63.4% vs 40.0%; P < 0.001). In a multivariate analysis, infection with a pathogen that was resistant to the empiric antibiotic regimen, increasing APACHE II scores, infection with Pseudomonas aeruginosa, healthcare-associated hospital-onset infection, mechanical ventilation, and use of vasopressors were independently associated with hospital mortality. CONCLUSIONS: In severe sepsis attributed to Gram-negative bacteremia, initial treatment with an antibiotic regimen to which the causative pathogen is resistant was associated with increased hospital mortality. This finding suggests that rapid determination of bacterial susceptibility could influence treatment choices in patients with severe sepsis potentially improving their clinical outcomes. Journal of Hospital Medicine 2011. © 2011 Society of Hospital Medicine

To determine whether exposure to antimicrobial agents in the previous 90 days resulted in decreased bacterial susceptibility and increased hospital mortality in patients with severe sepsis or septic shock attributed to Gram-negative bacteremia.A retrospective cohort study of hospitalized patients (January 2002 to December 2007).Barnes-Jewish Hospital, a 1200-bed urban teaching hospital.Seven hundred fifty-four consecutive patients with Gram-negative bacteremia complicated by severe sepsis or septic shock.Data abstraction from computerized medical records.Escherichia coli (30.8%), Klebsiella pneumoniae (23.2%), and Pseudomonas aeruginosa (17.6%) were the most common isolates from blood cultures. Three hundred ten patients (41.1%) had recent antibiotic exposure. Cefepime was the most common agent with previous exposure (50.0%) followed by ciprofloxacin (32.6%) and imipenem or meropenem (28.7%). Patients with prior antibiotic exposure had significantly higher rates of resistance to cefepime (29.0% vs. 7.0%), piperacillin/tazobactam (31.9% vs. 11.5%), carbapenems (20.0% vs. 2.5%), ciprofloxacin (39.7% vs. 17.6%), and gentamicin (26.1% vs. 7.9%) (p.001 for all comparisons). Patients with recent antibiotic exposure had greater inappropriate initial antimicrobial therapy (45.4% vs. 21.2%; p.001) and hospital mortality (51.3% vs. 34.0%; p.001) compared with patients without recent antibiotic exposure. Multivariate logistic regression analysis demonstrated that recent antibiotic exposure was independently associated with hospital mortality (adjusted odds ratio, 1.70; 95% confidence interval, 1.41-2.06; p = .005). Other variables independently associated with hospital mortality included use of vasopressors, infection resulting from P. aeruginosa, inappropriate initial antimicrobial therapy, increasing Acute Physiology and Chronic Health Evaluation II scores, and the number of acquired organ failures.Recent antibiotic exposure is associated with increased hospital mortality in Gram-negative bacteremia complicated by severe sepsis or septic shock. Clinicians caring for patients with severe sepsis or septic shock should consider recent antibiotic exposure when formulating empiric antimicrobial regimens for suspected Gram-negative bacterial infection.

Summary Background: Traditionally, pneumonia developing in patients who receive healthcare services in the outpatient environment has been classified as community-acquired pneumonia (CAP). However, recent investigations suggest that this type of infection, known as healthcare-associated pneumonia (HCAP), is distinct from CAP in terms of its epidemiology, etiology, and risk for infection with multidrug-resistant (MDR) pathogens. Methods: A Medline literature review of available clinical studies using the term HCAP was conducted to determine outcomes compared to CAP and effective empiric treatment strategies. Results: Analysis of multi-institutional clinical data showed that mortality in hospitalized patients with HCAP is greater than that in CAP, and patients with HCAP received inappropriate initial empiric antibiotic treatment more frequently than CAP patients. The bacterial pathogens associated with HCAP also differed from CAP with potentially MDR Gram-positive and Gram-negative bacteria being more common in HCAP. Conclusions: All patients hospitalized with suspected HCAP should be evaluated for their underlying risk of infection with MDR pathogens. Because HCAP is similar to hospital-acquired pneumonia (HAP), both clinically and etiologically, it should be treated as HAP until culture data become available.

Pneumonia associated with mechanical ventilation in the intensive care unit (ICU) setting is one of the most common infections managed by intensivists. The current classification of nosocomial pneumonia includes hospital-acquired pneumonia, ventilator-associated pneumonia (VAP), and nursing home

Data mining on medical data has great potential to improve the treatment quality of hospitals and increase the survival rate of patients. Every year, 4-17% of patients undergo cardiopulmonary or respiratory arrest while in hospitals. Clinical study has found early detection and intervention to be essential for preventing clinical deterioration in patients at general hospital units. This paper proposes an early warning system (EWS) designed to identify the signs of clinical deterioration and provide early warning for serious clinical events. The EWS is designed to provide reliable early alarms for patients at the general hospital wards (GHWs). The main task of EWS is a challenging classification problem on high-dimensional stream data with irregular, multi-scale data gaps, measurement errors, outliers, and class imbalance. This paper proposes a novel data mining framework for analyzing such medical data streams. The authors assess the feasibility of the proposed EWS approach through retrospective study that includes data from 41,503 visits at a major hospital. Finally, the system is applied in a clinical trial at a major hospital and obtains promising results. This project is an example of multidisciplinary cyber-physical systems involving researchers in clinical science, data mining, and nursing staff.

Background: The occurrence of nosocomial pneumonia (NP) in the hospital setting is especially problematic, as it is associated with a greater risk of in-hospital death, longer stays on mechanical ventilation and in the intensive care unit (ICU), more need for tracheostomy, and significantly higher medical care costs. Methods: Review of the pertinent English-language literature. Results: The adverse effect of NP on healthcare outcomes has increased pressure on clinicians and hospital systems to prevent this infection. This brief review provides an overview of the current approaches to the prevention of NP, focusing primarily on ventilator-associated pneumonia (VAP). Conclusion: Clinicians working in ICUs should consider the following recommendations: (1) Develop a VAP prevention bundle based on evidence-based guidelines; (2) monitor the rates of VAP prior to and during implementation of the program; (3) make adjustments according to VAP occurrence; and (4) integrate VAP prevention with other quali...

Nosocomial pneumonia is a difficult diagnosis to establish in the intensive care unit setting, due to the non-specific nature of the clinical and radiographic findings. Procalcitonin is a circulating biomarker that may become elevated in the presence of bacterial infection.We conducted a prospective single-center cohort study at Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital in St Louis, Missouri. In medical and surgical intensive care unit patients with suspected nosocomial pneumonia we measured plasma procalcitonin with an enzyme-linked fluorescent assay.We evaluated 104 consecutive patients with suspected nosocomial pneumonia, 67 (64%) of whom met our predefined clinical and microbiologic criteria for definite nosocomial pneumonia. Though the mean procalcitonin concentration was greater in the 67 patients with definite nosocomial pneumonia (18.3 ± 99.1 ng/mL, median 0.8 ng/mL, 5th percentile 0.0 ng/mL, 95th percentile 43.1 ng/mL) than in the 12 patients with definite absence of nosocomial pneumonia (1.7 ± 2.0 ng/mL, median 1.0 ng/mL, 5th percentile 0.0 ng/mL, 95th percentile 6.7 ng/mL), this difference was not statistically significant (P = .66). A procalcitonin cutoff value of1 ng/mL yielded a diagnostic sensitivity of 50% and a specificity of 49% for definite nosocomial pneumonia. Receiver operating curve and multivariate logistic regression analyses demonstrated that procalcitonin is inferior to clinical variables for diagnosing nosocomial pneumonia. However, compared to patients with an initial procalcitonin1 ng/mL, those with lower procalcitonin had fewer total antibiotic days (13.0 ± 10.3 d vs 19.7 ± 12.0 d, P.001) and fewer antibiotic days for treatment of nosocomial pneumonia (10.0 ± 5.9 d vs 14.7 ± 7.4 d, P.001).Plasma procalcitonin has minimal diagnostic value for nosocomial pneumonia.

Hospital-acquired pneumonia (HAP) is the second most common nosocomial infection and the leading cause of mortality attributable to these critical infections [ 1– 3]. Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is now a major cause of HAP [ 4– 6]. Rates of clinical failure in patients with HAP due to MRSA are high [ 7, 8]. Currently, only vancomycin and linezolid are recommended for treatment of HAP due to MRSA [ 9]. Results from recent pneumonia trials with new antibiotics active against MRSA have not been encouraging [ 10– 12]. Therefore, additional antistaphylococcal agents for treatment of HAP are urgently needed. Telavancin is a lipoglycopeptide antibacterial agent exhibiting potent, concentration-dependent bactericidal effects via a dual mechanism of action that combines inhibition of cell wall synthesis and disruption of membrane barrier function [ 13– 15]. In vitro, telavancin is rapidly bactericidal against clinically important gram-positive bacteria, including MRSA, vancomycin-intermediate S. aureus, and penicillin-resistant S. pneumoniae [ 13, 16, 17]. Telavancin penetrates well into the epithelial lining fluid and alveolar macrophages of healthy subjects, achieving concentrations up to 8-fold and 85-fold, respectively, above telavancin's minimum inhibitory concentration (MIC) for 90% (MIC90) of MRSA strains (.5 μg/mL) [ 16, 18]. Unlike daptomycin (a cyclic lipopeptide), telavancin remains active in vitro in the presence of pulmonary surfactant [ 16]. Telavancin is approved in the United States and Canada for the treatment of adult patients with complicated skin and skin-structure infections due to susceptible gram-positive pathogens. The current studies were designed to assess the clinical efficacy and safety of telavancin compared with vancomycin in the treatment of HAP due to gram-positive organisms, with a focus on infections due to MRSA. Partial results of these studies have been previously reported.

Central-line-associated bloodstream infections (CLABSIs) are responsible for ∼1/3 of all deaths from healthcare-associated infections in the United States. Of these, multidrug-resistant organisms (MDROs) are responsible for 20% to 67%. However, whether catheter removal affects clinical outcomes for MDRO CLABSIs has not been studied. Our objective was to determine the relationship between failure to remove a central venous catheter (CVC) and 30-day all-cause mortality in patients with MDRO CLABSIs. We used a retrospective cohort from Barnes-Jewish Hospital (1/1/2009–10/1/2015) to study patients with a multidrug-resistant Staphylococcus aureus, Enterococcus species, Enterobacteriaceae, Acinetobacter species, or Pseudomonas aeruginosa CLABSI. Risk factors for 30-day mortality, including catheter removal, were assessed for association with 30-day mortality using Cox proportional hazards models. The CLABSIs were assessed prospectively at the time of occurrence by infection prevention specialists. A total of 430 patients met inclusion criteria, 173 (40.2%) with Enterococcus, 116 (27.0%) Enterobacteriaceae, 81 (18.8%) S aureus, 44 (10.2%) polymicrobial, 11 (2.6%) P aeruginosa, and 5 (1.2%) Acinetobacter CLABSIs. Removal of a CVC occurred in 50.2% of patients, of which 4.2% died by 30 days (n = 9). For patients whose CVC remained in place, 45.3% died (n = 97). Failure to remove a CVC was strongly associated with 30-day all-cause mortality with a hazard ratio of 13.5 (6.8–26.7), P

Ultrasound (US) greatly facilitates cannulation of the internal jugular vein. Despite the ability to visualize the needle and anatomy, adverse events still occur. We hypothesized that the technique has limitations among certain patients and clinical scenarios. Objective: The purpose of our study was to identify characteristics of adverse events surrounding US-guided central venous cannulation (CVC). Methods: We assembled a prospective observational cohort of emergency department (ED) patients undergoing consecutive CVC under US. The primary outcome of interest was a composite of acute mechanical adverse events including hematoma, arterial cannulation, pneumothorax, and unsuccessful placement. Physicians performing the CVC recorded anatomical site, reason for insertion, and acute complications. We followed the catheters until they were removed based on radiographic evidence hospital nursing records. ED charts and pharmacy records contributed variables of interest. A self reported online survey provided physician experience information. Logistic regression was used to calculate the odds of an adverse outcome. Results: Physicians attempted 289 CVC on 282 patients. An adverse outcome occurred in 57 attempts (19.7%, 95%CI 15.5–24.7) the most common being 31 unsuccessful placements (11%, 95% CI 7.7–14.8). Patients with a history of end stage renal disease (OR 3.54, 95%CI 1.59–7.89) and central lines placed by operators with intermediate experience (OR 2.26, 95% CI 1.19–4.32) were most likely to encounter adverse events. Previously cited predictors such as BMI, coagulopathy, and pulmonary hyperinflation were not significant in our final model. Conclusions: Acute adverse events occurred in approximately 20% of US guided central line attempts. We identified both patient (history of end stage renal disease) and physician (intermediate experience level) factors that are associated with acute adverse events.

OBJECTIVE: Inappropriate empiric therapy worsens outcomes in certain healthcare-associated infections (HCAI). We studied the association of inappropriate empiric therapy with outcomes in patients with HCA complicated skin and skin structure infections (cSSSI). DESIGN: A single-center retrospective cohort study. PATIENTS: Hospitalized with a culture-positive cSSSI. MEASUREMENTS: We defined HCA-cSSSI as having ≥1 of these risk factors: (1) recent hospitalization, (2) recent antibiotics, (3) hemodialysis, (4) transfer from a nursing home, and inappropriate treatment as no antimicrobial therapy active against the pathogen(s) within 24 hours of obtaining culture specimen. We performed descriptive and multivariate statistics to compute the impact of inappropriate empiric therapy on outcomes. Hospital length of stay (LOS) served as primary and mortality as secondary outcomes. RESULTS: Of the 717 patients with culture-positive cSSSI, 527 (73.5%) had HCAI, of whom 405 (76.9%) received appropriate treatment. A higher proportion of those receiving inappropriate than appropriate treatment had a decubitus ulcer (29.5% vs. 10.9%, P < 0.001), a device-associated infection (42.6% vs. 28.6%, P = 0.004), or bacteremia (68.9% vs. 57.8%, P = 0.028). The frequency of methicillin-resistant Staphylococcus aureus (MRSA) did not differ between the groups. The low overall unadjusted mortality rate did not vary based on initial treatment. In a multivariable analysis adjusting for potential confounders inappropriate therapy had an attributable increase in hospital LOS of 1.8 days (95% CI, 1.4–2.3). CONCLUSION: Similar to other populations with HCAI, HCA-cSSSI patients are likely to receive inappropriate empiric therapy for their infection. This early exposure is associated with a significant prolongation of the hospitalization by nearly 2 days. Journal of Hospital Medicine 2010;. © 2010 Society of Hospital Medicine.