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Marya D Zilberberg,1 Brian H Nathanson,2 Kate Sulham,3 John F Mohr,3 Matthew Goodwin,3 Andrew F Shorr4 1EviMed Research Group, LLC, Goshen, MA, USA; 2OptiStatim, LLC, Longmeadow, MA, USA; 3scPharmaceuticals, Burlington, MA, USA; 4Washington Hospital Center, Washington, DC, USACorrespondence: Marya D Zilberberg, Department of Health Services Research, EviMed Research Group, LLC, PO Box 303, Goshen, MA, 01032, USA, Email evimedgroup@gmail.comBackground: Two-thirds of the 1 million annual US CHF hospitalizations are for diuresis only; some may be avoidable. We describe a population of low-severity short-stay ( 2. We compared baseline characteristics, processes of care, and outcomes in low-severity (CHF-L) to CHF-H.Results: Among 301,672 short-stay CHF patients, 135,304 (44.8%) were CHF-L. Compared to CHF-H, CHF-L was younger (70.5 ± 14.1 vs 72.1 ± 13.6 years, p < 0.001), more commonly female (48.6% vs 45.8%, p < 0.001), and more likely to receive IV ACE-I/ARB agents (0.5% vs 0.4%, p = 0.003). Most other IV medications were more common in CHF-H, and anticoagulation was the most prevalent non-diuretic IV therapy in both groups (23.8% vs 33.3%, p < 0.001). Hospital mortality (0.2% vs 1.5%, p < 0.001) and CHF-related 30-day readmissions (8.1% vs 10.5%, p < 0.001) were lower in CHF-L than CHF-H.Conclusion: Among short-stay CHF patients, nearly &half; meet criteria for CHF-L, and are mainly admitted for fluid management. Avoiding these admissions could result in substantial savings.Keywords: congestive heart failure, epidemiology, outcomes, hospital, costs

Marya D Zilberberg,1 Brian H Nathanson,2 Katherine Sulham,3 John F Mohr,3 Matthew M Goodwin,3 Andrew F Shorr4 1EviMed Research Group, LLC, Goshen, MA, USA; 2Optistatim, LLC, Longmeadow, MA, USA; 3scPharmaceuticals, Burlington, MA, USA; 4Washington Hospital Center, Washington, DC, USACorrespondence: Marya D Zilberberg, EviMed Research Group, LLC, PO Box 303, Goshen, MA, 01032, USA, Email evimedgroup@gmail.comBackground: Congestive heart failure (CHF) hospitalizations cost the US &dollar;35 billion annually. Two-thirds of these admissions, generally requiring /=65 years: 68.3% vs 71.9%), less likely covered by Medicare (71.9% vs 75.4%), and had a lower comorbidity burden (Charlson: 3.9 [2.1] vs 4.5 [2.2) than patients with LLOS; they less frequently developed acute kidney injury (0.4% vs 2.9%) or a need for mechanical ventilation (0.7% vs 2.8%). A higher proportion with SLOS than with LLOS underwent no procedures (70.4% vs 48.4%). Mean LOS (2.2 [0.8] vs 7.7 [6.5]), direct hospital costs (&dollar;6150 [&dollar;4413]) vs &dollar;17,127 [&dollar;26,936]), and aggregate annual hospital costs &dollar;3,131,560,372 vs &dollar;11,359,002,072) were all lower with SLOS than LLOS. All comparisons reached alpha = 0.001.Conclusion: Among patients admitted for CHF, nearly &half; have LOS

OBJECTIVES:. Nosocomial pneumonia (NP) remains a costly complication of hospitalization fraught with subsequent complications and augmented resource utilization. Consisting of ventilated hospital-acquired bacterial pneumonia (vHABP), nonventilated hospital-acquired bacterial pneumonia (nvHABP), and ventilator-associated bacterial pneumonia (VABP), each may respond differently to inappropriate empiric treatment (IET). We explored whether IET affects the three pneumonia types differently. DESIGN:. A multicenter, retrospective cohort study within the Premier Research database. SETTING:. Acute care hospitals in the United States. PATIENTS:. Patients with three types of NP were identified based on a previously published International Classification of Diseases, 9th Edition/International Classification of Diseases, 10th Edition Clinical Modification algorithm. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We compared the impact of IET on hospital costs, length of stay (LOS), and development of Clostridium difficile infection (CDI), extubation failure (EF), and reintubation (RT). Marginal effects were derived from multivariable regression analyses. IET was present if no drug covering the organism recovered from the index culture was administered within 2 days of the culture date. Among 17,819 patients who met the enrollment criteria, 26.5% had nvHABP, 25.6% vHABP, and 47.9% VABP. Compared with non-IET, IET was associated with increased mean unadjusted hospital LOS across all NP types: nvHABP 12.5 versus 21.1, vHABP 16.7 versus 19.2, and VABP 18.6 versus 21.4 days. The adjusted marginal hospital LOS (4.9 d) and costs ($13,147) with IET were the highest in nvHABP. Incident CDI was rare and similar across NP types (2.4% nvHABP to 3.6% VABP). Both EF and RT were more common with IET in VABP (EF, 15.4% vs 19.2%; RT, 6.2% vs 10.4%), but not vHABP (EF, 15.1% vs 17.7%; RT, 8.1% vs 9.1%). CONCLUSIONS:. Although IET is relatively uncommon, it affects resource utilization and the risk of complications differently across NP types. The impact of IET is greatest on both LOS and costs in nvHABP and is greater on VABP than vHABP in terms of EF and RT.

Alcohol abuse and dependence, referred to as alcohol-use disorders (AUDs), affect 76.3 million people worldwide and account for 1.8 million deaths per year. AUDs affect 18.3 million Americans (7.3% of the population), and up to 40% of hospitalized patients have AUDs. This review discusses the development and progression of critical illness in patients with AUDs. In contrast to acute intoxication, AUDs have been linked to increased severity of illness in a number of studies. In particular, surgical patients with AUDs experience higher rates of postoperative hemorrhage, cardiac complications, sepsis, and need for repeat surgery. Outcomes from trauma are worse for patients with chronic alcohol abuse, whereas burn patients who are acutely intoxicated may not have worse outcomes. AUDs are linked to not only a higher likelihood of community-acquired pneumonia and sepsis but also a higher severity of illness and higher rates of nosocomial pneumonia and sepsis. The management of sedation in patients with AUDs may be particularly challenging because of the increased need for sedatives and opioids and the difficulty in diagnosing withdrawal syndrome. The health-care provider also must be watchful for the development of dangerous agitation and violence, as these problems are not uncommonly seen in hospital ICUs. Despite studies showing that up to 40% of hospitalized patients have AUDs, relatively few guidelines exist on the specific management of the critically ill patient with AUDs. AUDs are underdiagnosed, and a first step to improving patient outcomes may lie in systematically and accurately identifying AUDs. [ABSTRACT FROM AUTHOR]

Background: Hospital performance measures rely on aggregate outcomes. For patients receiving mechanical ventilation (MV), outcomes depend on severity of illness, hospital MV volume, and case mix. Patients requiring prolonged acute MV (PAMV) [MV for >or= 96 h] comprise a resource-intensive group, but the impact of its volume on aggregate outcomes is unknown. We investigated whether observed outcomes differed from those predicted by APACHE (acute physiology and chronic health evaluation) IV risk adjustment and the relationship between hospital MV volume and outcomes among patients receiving PAMV.Methods: We conducted a retrospective cohort study using the APACHE IV database between the years 2001 and 2005.Results: Of the 94,553 patients receiving MV at 45 hospitals, 24,366 (25.8%) were receiving PAMV. Unadjusted mortality was 32.3% for patients receiving PAMV and 22.9% for patients receiving short-term MV (STMV) [< 96 h]. Although mortality predictions were accurate in both groups, the length-of-stay (LOS) predictions underestimated duration of MV, ICU LOS, and hospital LOS by 5.2, 4.6, and 5.4 days, respectively, in the PAMV group. After stratifying the PAMV group by hospital MV volume, except for quintile 1, the standardized mortality ratio (SMR) was found to be inversely related to the volume quintile. The difference between actual and predicted MV durations, however, exhibited a consistent direct relationship with the MV volume.Conclusions: In patients requiring PAMV, the SMR is inversely proportional to hospital MV volume. Conversely, the PAMV group had a disproportionate effect on durations of MV, ICU LOS, and hospital LOS, and these marginal excesses increased with the hospital MV volume quintile. Development of specific predictive equations for patients receiving PAMV is recommended. Benchmarking measures must consider the case mix of patients receiving STMV vs those receiving PAMV. [ABSTRACT FROM AUTHOR]

Background: Patients with health-care-associated pneumonia (HCAP) are frequently infected with a resistant pathogen and receive inappropriate empiric antibiotics (ie, pathogens resistant to administered treatment). Initial inappropriate treatment has been shown to increase hospital mortality. It is not known whether escalation in response to culture results mitigates this risk.Methods: We identified patients admitted with a culture-positive pneumonia between January 2003 and December 2005. HCAP patients met one or more of the following criteria indicating ongoing contact with the health-care system: recent hospitalization (< or = 12 months), admission from a nursing home, immunosuppression, or long-term dialysis. We compared survivors to nonsurvivors among those patients with HCAP still hospitalized beyond 48 h.Results: Of 431 HCAP patients, 396 patients (92%) were alive and still hospitalized beyond 48 h. The crude mortality rate was 21.5%. Compared to survivors, nonsurvivors were significantly more likely to be treated with inappropriate empiric antibiotics (37.6% vs 24.1%, p = 0.013). Although mortality was higher among patients receiving inappropriate than appropriate therapy (30.0% vs 18.3%, p = 0.013), this difference was more pronounced among nonbacteremic patients (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.26 to 4.75) than bacteremic patients (OR, 1.25; 95% CI, 0.41 to 3.57). In a logistic regression, inappropriate empiric antibiotic treatment among nonbacteremic patients was independently associated with mortality (OR, 2.88; 95% CI, 1.46 to 5.67); treatment escalation did not attenuate the risk of death.Conclusion: Among HCAP patients alive and hospitalized beyond 48 h, hospital mortality was high and, in the absence of bacteremia, greater with initial inappropriate antibiotic treatment. Despite subsequent escalation, initial inappropriate antibiotic choice nearly tripled the risk of hospital death. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hyponatremia, the most frequent electrolyte derangement identified among hospitalized patients, is associated with worsened outcomes in patients with pneumonia, heart failure and other disorders. RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study of hospitalized patients to quantify the attributable influence of admission hyponatremia on hospital costs and outcomes. Data were derived from a large administrative database with laboratory components, representing 198,281 discharges from 39 US hospitals from January 2004 to December 2005. Hyponatremia was defined as admission serum [Na(+)]<135 mEq/L. RESULTS: The incidence of hyponatremia at admission was 5.5% (n=10,899). Patients with hyponatremia were older (65.7+/-19.6 vs. 61.5+/-21.8, p<0.001) and had a higher Deyo-Charlson Comorbidity Index score (1.8+/-2.1 vs. 1.3+/-1.8, p<0.001) than those with normal [Na(+)]. A higher proportion of hyponatremic patients required intensive care unit (ICU) (17.3% vs. 10.9%, p<0.001) and mechanical ventilation (MV) (5.0% vs. 2.8%, p<0.001) within 48 hours of hospitalization. Hospital mortality (5.9% vs. 3.0%, p<0.001), mean length of stay (HLOS, 8.6+/-8.0 vs. 7.2+/-8.2 days, p<0.001) and costs ($16,502+/-$28,984 vs. $13,558+/-$24,640, p<0.001) were significantly greater among patients with hyponatremia than those without. After adjusting for confounders, hyponatremia was independently associated with an increased need for ICU (OR 1.64, 95% CI 1.56-1.73) and MV (OR 1.68, 95% CI 1.53-1.84), and higher hospital mortality (OR 1.55, 95% CI 1.42-1.69). Hyponatremia also contributed an increase in HLOS of 1.0 day and total hospital costs of $2,289. CONCLUSIONS: Hyponatremia is common at admission among hospitalized patients and is independently associated with a 55% increase in the risk of death, substantial hospital resource utilization and costs. Potential for bias inherent in the retrospective cohort design is the main limitation of our study. Studies are warranted to explore how prompt normalization of [Na(+)] may impact these outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: Adjusted costs of mechanical ventilation (MV) are $1,500 per patient-day. We compared the prevalence, characteristics, and outcomes of MV <96 hrs (MV<96) and prolonged acute MV (PAMV) of >/=96 hrs' duration in a representative sample of U.S. hospital discharges. DESIGN:: A multicenter cross-sectional study. SETTING:: Nationally representative sample of U.S. hospital discharges. PATIENTS:: Adult hospital discharges were identified from the 2003 Nationwide Inpatient Sample, Healthcare Cost and Utilization Project from the Agency for Healthcare Research and Quality (AHRQ). PAMV was based on the presence of ICD-9 code 96.72, and MV <96 hrs based on ICD-9 codes 96.70 and 96.71. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Of 31,340,578 discharges for adults (>/=18 yrs), 2.4% had any MV, of which 469,168 (61%) had MV<96, and 294,333 (39%) had PAMV. Patient demographics were similar for MV<96 and PAMV. With the exception of acute myocardial infarction and chronic and end-stage renal disease without dialysis, the prevalence of coexisting conditions was higher in the PAMV group. Median length of stay (17 vs. 6 days) and hospital costs ($40,903 vs. $13,434) also were higher with PAMV vs. MV<96. Although Agency for Healthcare Research and Quality disease severity and mortality probability were higher in the PAMV than MV<96 group, actual mortality was similar between the two groups (34% vs. 35%). CONCLUSIONS:: There were nearly 300,000 PAMV discharges in the United States in 2003 at an annual aggregated hospital cost of >$16 billion, or nearly two thirds of the cost for all of the MV discharges. Despite a higher predicted mortality, patients requiring PAMV had the same likelihood of being discharged alive as those on shorter-term MV. These analyses will help inform health care decision-making and resource planning in the face of an aging population. [ABSTRACT FROM AUTHOR]

Objective: To understand the impact of anemia on health-related quality of life (HRQOL) and healthcare resource utilization (HRU) in patients with HIV/AIDS.Methods: In 2003, adults with HIV/AIDS were recruited through 114 US STD/HIV clinics to complete self-administered questionnaires. Adults reporting anemia as a side-effect of antiretroviral therapy (ART) during the past month were considered anemic. HRU was evaluated by emergency room (ER) visits, days of hospitalization, and healthcare provider visits in the past 6 months. The SF-8 was used to measure HRQOL. Linear regression was used to evaluate independent effects of anemia on HRQOL and HRU controlling for demographics, years since HIV diagnosis, HIV viral load, CD4 + count, and ART use.Results: 2044 patients were enrolled, with 498 (24%) experiencing anemia. Anemic patients had lower SF-8 summary scores (mental: 38.2 +/- 11.6 vs. 42.9 +/- 11.9, p < 0.001; physical: 40.1 +/- 10.0 vs. 45.5 +/- 10.4, p < 0.001) than nonanemic patients. HRU in the anemic group was significantly higher (p < 0.05), with respect to percentage of patients visiting ER, mean number of ER visits, mean number of days hospitalized, and mean number of total visits to providers. In linear regression models, anemic patients had mental and physical HRQOL scores more than 4 points lower than nonanemic patients (p < 0.001 for both). Additionally, anemic patients had 2.7 more visits to healthcare providers (p < 0.001).Limitations: Data were cross-sectional, self-reported by patients, and did not include clinical measures of anemia.Conclusion: Based on this survey, self-reported anemia appears to be associated with worsened HRQOL and greater HRU among HIV/AIDS patients using ART. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess patient preferences across two attributes--effectiveness and convenience--in the selection of an erythropoietic agent to treat chemotherapy-related anemia. METHODS: During 2004, 500 adults with solid tumors and anemia were recruited through 50 oncologists' offices across the USA. Data were collected through self-administered questionnaires, divided into two parts. The first, completed by the provider, captured clinical information and providers' perceptions of patient preferences. The second, completed by the patient, recorded knowledge, experiences, and preferences regarding anemia and its treatments. Patient preferences, the relative importance of effectiveness (time to noticeable relief of fatigue) and convenience (number of provider visits required in an 8-week period), were measured using a choice-based conjoint (CBC) analysis. Each attribute was assessed at three levels (4, 6, or 8 weeks/visits). RESULTS: 467 providers (93%) and 438 patients (88%) completed the preference sections. When choosing a medication to treat anemia, 77% of providers viewed effectiveness as more important to patients than convenience. Similarly, patients had a greater preference for effectiveness than convenience. Relative preference weights were significantly higher for 4- versus 6-week effectiveness (0.61 vs. 0.09, p < 0.001) and 6- versus 8-week effectiveness (0.09 vs. -0.70, p = 0.004). Overall, time to effectiveness was twice as important to patients as the number of visits. LIMITATIONS: Only two attributes were included in the CBC, which did not control for bias from respondent characteristics or experiences. CONCLUSION: When evaluating an erythropoietic agent to treat chemotherapy-related anemia, both providers and patients view effectiveness as more important than convenience. [ABSTRACT FROM AUTHOR]

OBJECTIVES: : Patients requiring prolonged acute mechanical ventilation (mechanical ventilation >=96 hrs) have hospital survival rates similar to those requiring <96 hrs of mechanical ventilation and consume approximately two-thirds of hospital resources devoted to mechanical ventilation care. Using 2000-2005 data, we previously estimated that their volume will go from approximately 250,000 cases in 2000 to 605,898 by year 2020. With 2006-2008 data becoming available, we explored the precision of our previous formulas and estimates. DESIGN: : We utilized National Inpatient Sample/Health Care Utilization Project of the Agency for Healthcare Research and Quality data from 2000 to 2008 to calculate historic annual age-adjusted prolonged acute mechanical ventilation incidence rates using estimated population statistics from the U.S. Census Bureau. To predict future growth by age group, we fit linear regression models to the historic incidence rate changes. Age-adjusted estimates were computed using population projections obtained from the U.S. Census Bureau. SETTING: : U.S. hospitals. PATIENTS: : Nationally representative sample of U.S. hospital discharges with prolonged acute mechanical ventilation (International Classification of Diseases version 9 code 96.72). INTERVENTIONS: : None. MEASUREMENTS AND MAIN RESULTS: : Formulas based on the 2000-2005 data predicted the 2008 prolonged acute mechanical ventilation volume within a 1.9% margin. The historic annualized increase in adult prolonged acute mechanical ventilation increased from 5.0% to 5.2% after incorporating the 2006-2008 data. Factoring in the 2006-2008 data altered our 2020 prolonged acute mechanical ventilation estimates from 605,898 (95% confidence interval 456,695-779,806) to 625,298 (95% confidence interval 552,168-698,838), an upward revision of 3.2%. CONCLUSION: : Our original projections for growth of the adult prolonged acute mechanical ventilation population in the U.S. hospitals by the year 2020 are altered only slightly by adding the 2006-2008 data. Relatively precise prediction of the 2008 prolonged acute mechanical ventilation numbers by the original formulas lends internal validity to the methodology. By virtue of being a large, resource-intensive, and rapidly increasing population, this group of mechanical ventilation patients requires continued close monitoring over time to optimize our preparedness to meet their growing healthcare needs. [ABSTRACT FROM AUTHOR]

The article presents abstracts on allergy which include the efficacy, safety, and onset of action of azelastine nasal spray 0.15%, azelastine nasal spray 0.10% and placebo in patients with seasonal allergic rhinitis (SAR), the efficacy and safety of olopatadine hydrochloride nasal spray, 0.6% in patients with nonallergic vasomotor rhinitis (VMR) and the annual rate and resource use of hospitalizations in the U.S. with hereditary angioedema (HAE).

Background: Community-acquired (CAP) and nosocomial pneumonias contribute substantially to morbidity and hospital resource utilization. Hyponatremia, occurring in >1/4 of patients with CAP, is associated with greater disease severity and worsened outcomes.Methods: To explore how hyponatremia is associated with outcomes in hospitalized patients with pneumonia, we analyzed a large administrative database with laboratory component from January 2004 to December 2005. Hyponatremia was defined as at least two [Na+] < 135 mEq/L within 24 hours of admission value.Results: Of 7,965 patients with pneumonia, 649 (8.1%) with hyponatremia were older (72.4 +/- 15.7 vs. 68.0 +/- 22.0, p < 0.01), had a higher mean Deyo-Charlson Comorbidity Index Score (1.7 +/- 1.7 vs. 1.6 +/- 1.6, p = 0.02), and higher rates of ICU (10.0% vs. 6.3%, p < 0.001) and MV (3.9% vs. 2.3%, p = 0.01) in the first 48 hours of hospitalization than patients with normal sodium. Hyponatremia was associated with an increased ICU (6.3 +/- 5.6 vs. 5.3 +/- 5.1 days, p = 0.07) and hospital lengths of stay (LOS, 7.6 +/- 5.3 vs. 7.0 +/- 5.2 days, p < 0.001) and a trend toward increased hospital mortality (5.4% vs. 4.0%, p = 0.1). After adjusting for confounders, hyponatremia was associated with an increased risk of ICU (OR 1.58, 95% CI 1.20-2.08), MV (OR 1.75 95% CI 1.13-2.69), and hospital death (OR 1.3, 95% CI 0.90-1.87) and with increases of 0.8 day to ICU and 0.3 day to hospital LOS, and over $1,300 to total hospital costs.Conclusion: Hyponatremia is common among hospitalized patients with pneumonia and is associated with worsened clinical and economic outcomes. Studies in this large population are needed to explore whether prompt correction of [Na+] may impact these outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Do-not-resuscitate ( DNR) orders are used to express patient preferences for cardiopulmonary resuscitation. This study examined whether early DNR orders are associated with differences in treatments and outcomes among patients hospitalized with pneumonia., Methods: This is a retrospective cohort study of 768,015 adult patients hospitalized with pneumonia from 2010 to 2015 in 646 US hospitals. The exposure was DNR orders present on admission. Secondary analyses stratified patients by predicted in-hospital mortality. Main outcomes included in-hospital mortality, length of stay, cost, intensive care admission, invasive mechanical ventilation, noninvasive ventilation, vasopressors, and dialysis initiation., Results: Of 768,015 patients, 94,155 (12.3%) had an early DNR order. Compared with those without, patients with DNR orders were older (mean age 80.1 ± 10.6 years vs 67.8 ± 16.4 years), with higher comorbidity burden, intensive care use (31.6% vs 30.6%), and in-hospital mortality (28.2% vs 8.5%). After adjustment via propensity score weighting, these patients had higher mortality (odds ratio [OR] 2.39, 95% confidence interval [CI] 2.33-2.45) and lower use of intensive therapies such as vasopressors (OR 0.83, 95% CI 0.81-0.85) and invasive mechanical ventilation (OR 0.68, 95% CI 0.66-0.70). Although there was little relationship between predicted mortality and DNR orders, among those with highest predicted mortality, DNR orders were associated with lower intensive care use compared with those without (66.7% vs 80.8%)., Conclusions: Patients with early DNR orders have higher in-hospital mortality rates than those without, but often receive intensive care. These orders have the most impact on the care of patients with the highest mortality risk.

Bloodstream infections (BSIs) arising in the intensive care unit (ICUs) present a significant challenge and we completed a narrative review of the emerging literature on this issue. Multiple reports document that these infections are associated with substantial morbidity and mortality. Also, they can be caused by a variety of pathogens. Generally classified as either community or hospital in onset, or as either primary or secondary in origin, the microbiology of ICU BSIs varies across the globe. Gram-positive pathogens predominate in certain regions such as the United States while Gram-negative organisms occur more frequently in Europe, Asia, and Latin America. The incidence of ICU BSIs climbed during the recent pandemic. BSIs complicating the care of persons suffering from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection significantly heighten the risk for death compared to patients who develop ICU BSIs but who are not infected with SARS-CoV-2. Furthermore, rates of antimicrobial resistance are generally increasing in ICU BSIs. This fact complicates attempts to ensure that the patient receives initially appropriate antimicrobial therapy and is of particular concern in Methicillin-resistant Staphylococcus aureus , Carbapenem-resistant Enterobacterales, and Acinetobacter baumannii . Fortunately, with respect to clinical application, preventive measures exist, and recent analyses suggest that increased collaboration between infectious disease specialists and intensivists can improve patient outcomes.

Background: Community-acquired pneumonia (CAP) is a leading cause of hospital admissions and antimicrobial use. Clinical practice guidelines recommend switching from intravenous (IV) to oral antibiotics once patients are clinically stable., Methods: We conducted a retrospective cohort study of adults admitted with CAP and initially treated with IV antibiotics at 642 US hospitals from 2010 through 2015. Switching was defined as discontinuation of IV and initiation of oral antibiotics without interrupting therapy. Patients switched by hospital day 3 were considered early switchers. We compared length of stay (LOS), in-hospital 14-day mortality, late deterioration (intensive care unit [ICU] transfer), and hospital costs between early switchers and others, controlling for hospital characteristics, patient demographics, comorbidities, initial treatments, and predicted mortality., Results: Of 378 041 CAP patients, 21 784 (6%) were switched early, most frequently to fluoroquinolones. Patients switched early had fewer days on IV antibiotics, shorter duration of inpatient antibiotic treatment, shorter LOS, and lower hospitalization costs, but no significant excesses in 14-day in-hospital mortality or late ICU admission. Patients at a higher mortality risk were less likely to be switched. However, even in hospitals with relatively high switch rates, <15% of very low-risk patients were switched early., Conclusions: Although early switching was not associated with worse outcomes and was associated with shorter LOS and fewer days on antibiotics, it occurred infrequently. Even in hospitals with high switch rates, <15% of very low-risk patients were switched early. Our findings suggest that many more patients could be switched early without compromising outcomes., Competing Interests: Conflict of interest. A. D. reports research funding (to institution) from the Clorox Company, consultant fees from Merck, and grants or contracts to institution, unrelated to the current study, from Seres Therapeutics. M. K. reports royalties from UpToDate and grants or contracts to institution from the Centers for Disease Control and Prevention and the Agency for Healthcare Research and Quality. M. D. Z. reports research support from Tetraphase Pharmaceuticals, Astellas, Lungpacer, Merck, Spero, Medicines Co, Melinta, scPharma, Shionogi, and Pfizer; consulting fees from Paratek, Arasanis, Shionogi, Pfizer, Nabriva, scPharma, and Melinta; and stock or stock options from Johnson & Johnson. T. H. reports consulting fees from the Cerner Corporation. P. B. I. reports consulting fees from Colgate-Palmolive. S. H. reports a role with the Society for Health Epidemiology of America (councilor, board of trustees, volunteer; no compensation). All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To derive and validate a model for risk of resistance to first-line community-acquired pneumonia (CAP) therapy., Design: We developed a logistic regression prediction model from a large multihospital discharge database and validated it versus the Drug Resistance in Pneumonia (DRIP) score in a holdout sample and another hospital system outside that database. Resistance to first-line CAP therapy (quinolone or third generation cephalosporin plus macrolide) was based on blood or respiratory cultures., Setting: This study was conducted using data from 177 Premier Healthcare database hospitals and 11 Cleveland Clinic hospitals., Participants: Adults hospitalized for CAP., Exposure: Risk factors for resistant infection., Results: Among 138,762 eligible patients in the Premier database, 12,181 (8.8%) had positive cultures and 5,200 (3.8%) had organisms resistant to CAP therapy. Infection with a resistant organism in the previous year was the strongest predictor of resistance; markers of acute illness (eg, receipt of mechanical ventilation or vasopressors) and chronic illness (eg, pressure ulcer, paralysis) were also associated with resistant infections. Our model outperformed the DRIP score with a C-statistic of 0.71 versus 0.63 for the DRIP score ( P < .001) in the Premier holdout sample, and 0.65 versus 0.58 ( P < .001) in Cleveland Clinic hospitals. Clinicians at Premier facilities used broad-spectrum antibiotics for 20%-30% of patients. In discriminating between patients with and without resistant infections, physician judgment slightly outperformed the DRIP instrument but not our model., Conclusions: Our model predicting infection with a resistant pathogen outperformed both the DRIP score and physician practice in an external validation set. Its integration into practice could reduce unnecessary use of broad-spectrum antibiotics.

Objective: Clostridioides difficile infection (CDI) is the most common cause of gastroenteritis, and community-acquired pneumonia (CAP) is the most common infection treated in hospitals. American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) CAP guidelines recommend empiric therapy with a respiratory fluoroquinolone or cephalosporin plus macrolide combination, but the CDI risk of these regimens is unknown. We examined the association between each antibiotic regimen and the development of hospital-onset CDI., Methods: We conducted a retrospective cohort study using data from 638 US hospitals contributing administrative including 177 also contributing microbiologic data to Premier, Inc. We included adults admitted with pneumonia and discharged from July 2010 through June 2015 with a pneumonia diagnosis code who received ≥3 days of either empiric regimen. Hospital-onset CDI was defined by a diagnosis code not present on admission and positive laboratory test on day 4 or later or readmission for CDI. Mixed propensity-weighted multiple logistic regression was used to estimate the associations of CDI with antibiotic regimens., Results: Our sample included 58,060 patients treated with either cephalosporin plus macrolide (36,796 patients) or a fluoroquinolone alone (21,264 patients) and with microbiological data; 127 (0.35%) patients who received cephalosporin plus macrolide and 65 (0.31%) who received a fluoroquinolone developed CDI. After adjustment for patient demographics, comorbidities, risk factors for antimicrobial resistance, and hospital characteristics, CDI risks were similar for fluoroquinolones versus cephalosporin plus macrolide (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.70-1.38)., Conclusion: Among patients with CAP at US hospitals, CDI was uncommon, occurring in ∼0.33% of patients. We did not detect a significant association between the choice of empiric guideline recommended antibiotic therapy and the development of CDI.

Introduction: Nosocomial pneumonia (NP) remains associated with excess morbidity and mortality. The effect of NP on measures such as re-admission at 30 days remains unclear. Moreover, differing types of NP may have varying impacts on re-admissions., Methods: We conducted a multicenter retrospective cohort study within the Premier Research database, a source containing administrative, pharmacy, and microbiology data. We compared NP patients readmitted with pneumonia (RaP) as the principal diagnosis to those readmitted for other reasons (RaO) with respect to the type of NP (ventilator-associated bacterial pneumonia [VABP], ventilated hospital-acquired bacterial pneumonia [vHABP], and non-ventilated HABP [nvHABP]), and characteristics and outcomes of the index hospitalization., Results: Among 17,819 patients with NP, 14,123 (79.3%) survived to discharge, of whom 2,151 (15.2%) required an acute readmission within 30 days of index discharge. Of these, 106 (4.9%) were RaP, and the remainder were RaO. At index hospitalization, RaP patients were older (mean age [SD] 67.4 (13.9] vs. 63.0 [15.2] years), more likely medical (44.3% vs. 36.7%), and less chronically ill (median [IQR] Charlson scores (3 [2-5] vs. 4 [2-5]) than persons with RaO. Bacteremia (10.4% vs. 17.5%), need for vasopressors (15.1% vs. 20.0%), dialysis (9.4% vs. 16.5%), and/or sepsis (9.4% vs. 16.5%) or septic shock 14.2% vs. 17.1%) occurred less frequently in the RaP group. With respect to NP type, nvHABP was most common in RaP (47.2%) and VABP in RaO (38.1%)., Conclusions: One in seven survivors of a hospitalization complicated by NP requires an acute rehospitalization within 30 days. However, few of these readmissions had a principal diagnosis of pneumonia, irrespective of NP type. Of the 5% of NP subjects with RaP, the plurality initially suffered from nvHABP., Competing Interests: I have read the journal’s policy. In addition to funding statement above, the following potential competing interest exist: •MDZ and AFS have received grant support and/or have served as consultants to Lungpacer, Melinta, Tetraphase, Pfizer, Astellas, Shionogi, The Medicines Company, Spero, and Theravance., (Copyright: © 2022 Zilberberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Inappropriate empiric antimicrobial treatment (IET) contributes to worsened outcomes. While IET's differential impact across types of nosocomial pneumonia (NP: non-ventilated [nvHABP], ventilated [vHABP] hospital-acquired and ventilator-associated [VABP] bacterial pneumonia) is established, its potential interaction with the bacterial etiology is less clear., Methods: We conducted a multicenter retrospective cohort study in the Premier Healthcare Database using an administrative algorithm to identify NP. We paired respective pathogens with empiric treatments. Antimicrobial coverage was appropriate if a drug administered within 2 days of infection onset covered the recovered organism(s). All other treatment was IET., Results: Among 17,819 patients with NP, 26.5% had nvHABP, 25.6% vHABP, and 47.9% VABP. Gram-negative (GN) organisms accounted for > 50% of all infections. GN pathogens were ~ 2 × as likely (7.4% vHABP to 10.7% nvHABP) to engender IET than Gram-positive (GP, 2.9% vHABP to 4.9% nvHABP) pathogens. Although rare (5.6% nvHABP to 8.3% VABP), GN + GP infections had the highest rates of IET (6.7% vHABP to 12.9% nvHABP). Carbapenem-resistant GNs were highly likely to receive IET (33.8% nvHABP to 40.2% VABP). Hospital mortality trended higher in the IET group, reaching statistical significance in GN + GP vHABP (47.8% IET vs. 29.3% non-IET, p = 0.016). 30-day readmission was more common with IET (16.0%) than non-IET (12.6%, p = 0.024) in GN VABP. Generally post-infection onset hospital length of stay and costs were higher with IET than non-IET., Conclusions: IET is ~ 2 × more common in GN than GP infections. Although the magnitude of its impact varies by NP type, IET contributes to worsened clinical and economic outcomes., (© 2022. The Author(s).)

Background: Influenza is a leading cause of community-acquired pneumonia (CAP), and results of influenza tests can direct therapy. However, among adults hospitalized with CAP, little is known about the frequency and timing of influenza testing, treatment, and their associations with outcomes., Research Question: In patients with CAP, is testing for influenza associated with antiviral treatment and shorter antibiotic courses, and is early treatment associated with better clinical outcomes?, Study Design and Methods: This study included adults admitted with pneumonia in 2010 to 2015 to 179 US hospitals contributing to the Premier database. We assessed influenza testing and compared antimicrobial utilization and the outcomes of test-positive, test-negative, and untested patients. Associations of early antiviral treatment (oseltamivir) with 14-day in-hospital mortality, hospital length of stay, and cost were studied., Results: Among 166,268 patients with CAP, 38,703 (23.3%) were tested for influenza, of whom 11.5% tested positive. Testing increased from 15.4% to 35.6% from 2010 to 2015 and was 28.9% during flu season (October-May) vs 8.2% in June to September. Patients testing positive for influenza received antiviral agents more often and antibacterial agents less often and for shorter courses than patients testing negative (5.3 vs 6.4 days; P < .001). Influenza-positive patients receiving oseltamivir on hospital day 1 (n = 2,585) experienced lower 14-day in-hospital mortality (adjusted OR, 0.75; 95% CI, 0.59-0.96), lower costs (adjusted ratio of means, 0.88; 95% CI, 0.81-0.95), and shorter length of stay (adjusted ratio of means, 0.88; 95% CI, 0.84-0.93) vs patients receiving oseltamivir later or not at all (n = 1,742)., Interpretation: Even during flu season, most patients with CAP in this study went untested for influenza. A positive influenza test result was associated with antiviral treatment, and early treatment was associated with lower mortality, suggesting that more widespread testing might improve patient outcomes., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: Compare the clinical practice and outcomes in severe community-acquired pneumonia (sCAP) patients to those in non-sCAP patients using guideline-defined criteria for sCAP., Design: Retrospective observational cohort study., Setting: One hundred seventy-seven U.S. hospitals within the Premier Healthcare Database., Patients: Hospitalized adult (≥ 18 yr old) patients with pneumonia., Measurements and Main Results: Adult patients (≥ 18 yr old) with a principal diagnosis of pneumonia or a secondary diagnosis of pneumonia paired with a principal diagnosis of sepsis or respiratory failure were included. Patients with at least one guideline-defined major criterion for severe pneumonia were compared with patients with nonsevere disease. Among 154,799 patients with pneumonia, 21,805 (14.1%) met criteria for sCAP. They had higher organ failure scores (1.9 vs 0.63; p < 0.001) and inpatient mortality (22.0 vs 5.0%; p < 0.001), longer lengths of stay (8 vs 5 d; p < 0.001), and higher costs ($20,046 vs $7,543; p < 0.001) than those with nonsevere disease. Patients with sCAP had twice the rate of positive blood cultures (10.0% vs 4.5%; p < 0.001) and respiratory cultures (34.2 vs 21.1%; p < 0.001) and more often had isolates resistant to first-line community-acquired pneumonia antibiotics (10% of severe vs 3.1% of nonsevere; p < 0.001). Regardless of disease severity, Streptococcus pneumoniae was the most common pathogen recovered from blood cultures and Staphylococcus aureus and Pseudomonas species were the most common pathogens recovered from the respiratory tract. Although few patients with sCAP had cultures positive for a resistant organism, 65% received vancomycin and 42.8% received piperacillin-tazobactam., Conclusions: sCAP patients had worse outcomes and twice the rate of culture positivity. S. aureus and S. pneumoniae were the most common organisms in respiratory and blood specimens, respectively. Although only recommended for sCAP patients, nearly all pneumonia patients received blood cultures, a quarter of nonsevere patients received sputum cultures, and treatment with broad-spectrum agents was widespread, indicating fertile ground for antimicrobial and diagnostic stewardship programs., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Nosocomial pneumonia (NP) remains a costly complication of hospitalization fraught with subsequent complications and augmented resource utilization. Consisting of ventilated hospital-acquired bacterial pneumonia (vHABP), nonventilated hospital-acquired bacterial pneumonia (nvHABP), and ventilator-associated bacterial pneumonia (VABP), each may respond differently to inappropriate empiric treatment (IET). We explored whether IET affects the three pneumonia types differently., Design: A multicenter, retrospective cohort study within the Premier Research database., Setting: Acute care hospitals in the United States., Patients: Patients with three types of NP were identified based on a previously published International Classification of Diseases , 9th Edition/ International Classification of Diseases , 10th Edition Clinical Modification algorithm., Interventions: None., Measurements and Main Results: We compared the impact of IET on hospital costs, length of stay (LOS), and development of Clostridium difficile infection (CDI), extubation failure (EF), and reintubation (RT). Marginal effects were derived from multivariable regression analyses. IET was present if no drug covering the organism recovered from the index culture was administered within 2 days of the culture date. Among 17,819 patients who met the enrollment criteria, 26.5% had nvHABP, 25.6% vHABP, and 47.9% VABP. Compared with non-IET, IET was associated with increased mean unadjusted hospital LOS across all NP types: nvHABP 12.5 versus 21.1, vHABP 16.7 versus 19.2, and VABP 18.6 versus 21.4 days. The adjusted marginal hospital LOS (4.9 d) and costs ($13,147) with IET were the highest in nvHABP. Incident CDI was rare and similar across NP types (2.4% nvHABP to 3.6% VABP). Both EF and RT were more common with IET in VABP (EF, 15.4% vs 19.2%; RT, 6.2% vs 10.4%), but not vHABP (EF, 15.1% vs 17.7%; RT, 8.1% vs 9.1%)., Conclusions: Although IET is relatively uncommon, it affects resource utilization and the risk of complications differently across NP types. The impact of IET is greatest on both LOS and costs in nvHABP and is greater on VABP than vHABP in terms of EF and RT., Competing Interests: Dr. M. D. Zilberberg’s employer, EviMed Research Group, LLC, has received research grant support from Merck Sharp & Dohme, a subsidiary of Merck, Kenilworth, NJ. Dr. Nathanson’s employer, OptiStatim, LLC, has received support from EviMed Research Group, LLC, Goshen, MA. Dr. Puzniak is an employee of Merck Sharp & Dohme, a subsidiary of Merck, and a stockholder in Merck. Dr. Zilberberg has no conflicts to report. Dr. Shorr is a consultant to and has received research grant support from of Merck Sharp & Dohme, a subsidiary of Merck. Drs. M. D. Zilberberg and Shorr have received grant support and/or have served as consultants to Lungpacer, Melinta, Tetraphase, Pfizer, Astellas, Shionogi, The Medicines Company, Spero, and Theravance., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objective: There are >1 million emergency department visits and 100,000 admissions with urinary tract infection (UTI) annually in the United States. A fraction of total UTI volume, complicated (cUTI) costs the health care system over $3.5 billion per year. We evaluated the contemporary annual burden of emergency department (ED) visits with cUTI., Methods: We conducted a cross-sectional multicenter study within the National Emergency Department database, a 20% stratified sample of all US hospital-based EDs, 2016-2018, to explore characteristics of visits with a cUTI. We compared cUTI as the principal (PD) versus secondary diagnosis (non-PD). We applied survey methods to develop national estimates., Results: Among 2,379,448 ED cUTI visits (44.8% PD), 40.1% were female (45.1% PD; 36.9% non-PD) and 62.2% were ≥ 65 years (52.5% PD; 70.2% non-PD). Mean Charlson score was 2.3 (3.0 PD; 2.1 non-PD); end-stage renal disease prevalence was 2.3% (1.4% PD; 3.0% non-PD). Whereas pyelonephritis occurred in ∼10% of both groups, severe sepsis (7.2% vs 2.0%) and septic shock (7.1% vs 1.8%) were ∼4 times more prevalent among those with cUTI-non-PD than cUTI-PD. Overall, two thirds of all visits ended in hospitalization (44.9% PD; 85.5% non-PD). Despite similar numbers of visits, the annual national ED bill for cUTI rose from $2.8 billion in 2016 to $3.2 billion in 2018., Conclusion: There were over 2 million ED visits with cUTI in 2016-2018. Although <10% met criteria for severe sepsis/septic shock, ∼two thirds were admitted. The aggregate cost for cUTI visits rose by 15% without a substantial increase in volume., Competing Interests: Marya D. Zilberberg is a consultant to Spero Therapeutics. Her employer, EviMed Research Group, LLC, has received research grant support from Spero Therapeutics. Brian H. Nathanson's employer, OptiStatim, LLC, has received support from EviMed Research Group, LLC. Kate Sulham was an employee of and stockholder in Spero Therapeutics during the conduct of this study. She currently serves as a consultant to Spero. Andrew F. Shorr is a consultant to and has received research grant support from Spero Therapeutics. Marya D. Zilberberg and Andrew F. Shorr have received grant support and/or have served as consultants to Merck, Melinta, Tetraphase, Pfizer, Astellas, Shionogi, The Medicines Company, Lungpacer, and Theravance., (© 2022 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Objectives: Multiple randomized controlled trials exploring the outcomes of patients with ventilator-associated bacterial pneumonia and hospital-acquired bacterial pneumonia have noted that hospital-acquired bacterial pneumonia patients who require subsequent ventilated hospital-acquired bacterial pneumonia suffered higher mortality than either those who did not (nonventilated hospital-acquired bacterial pneumonia) or had ventilator-associated bacterial pneumonia. We examined the epidemiology and outcomes of all three conditions in a large U.S. database., Design: Retrospective cohort., Setting: Two hundred fifty-three acute-care hospitals, United States, contributing data (including microbiology) to Premier database, 2012-2019., Patients: Patients with hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia identified based on a slightly modified previously published International Classification of Diseases, 9th Edition/International Classification of Diseases, 10th Edition-Clinical Modification algorithm., Interventions: None., Measurements and Main Results: Among 17,819 patients who met enrollment criteria, 26.5% had nonventilated hospital-acquired bacterial pneumonia, 25.6% vHAPB, and 47.9% ventilator-associated bacterial pneumonia. Ventilator-associated bacterial pneumonia predominated in the Northeastern United States and in large urban teaching hospitals. Patients with nonventilated hospital-acquired bacterial pneumonia were oldest (mean 66.7 ± 15.1 yr) and most likely White (76.9%), whereas those with ventilator-associated bacterial pneumonia were youngest (59.7 ± 16.6 yr) and least likely White (70.3%). Ventilated hospital-acquired bacterial pneumonia was associated with the highest comorbidity burden (mean Charlson score 4.1 ± 2.8) and ventilator-associated bacterial pneumonia with the lowest (3.2 ± 2.5). Similarly, hospital mortality was highest among patients with ventilated hospital-acquired bacterial pneumonia (29.2%) and lowest in nonventilated hospital-acquired bacterial pneumonia (11.7%), with ventilator-associated bacterial pneumonia in-between (21.3%). Among survivors, 24.5% of nonventilated hospital-acquired bacterial pneumonia required a rehospitalization within 30 days of discharge, compared with 22.5% among ventilated hospital-acquired bacterial pneumonia and 18.8% ventilator-associated bacterial pneumonia. Unadjusted hospital length of stay after infection onset was longest among ventilator-associated bacterial pneumonia and shortest among nonventilated hospital-acquired bacterial pneumonia patients. Median total hospital costs mirrored length of stay: ventilator-associated bacterial pneumonia $77,657, ventilated hospital-acquired bacterial pneumonia $62,464, and nonventilated hospital-acquired bacterial pneumonia $39,911., Conclusions: Both hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia remain associated with significant mortality and cost in the United States. Our analyses confirm that of all three conditions, ventilated hospital-acquired bacterial pneumonia carries the highest risk of death. In contrast, ventilator-associated bacterial pneumonia remains most costly. Nonventilated hospital-acquired bacterial pneumonia survivors were most likely to require a readmission within 30 days of discharge., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Objective: To explore whether microbiology profiles and the impact of inappropriate empiric treatment differ in the setting of hospital-acquired bacterial pneumonia that requires subsequent mechanical ventilation (vHABP) versus one that does not (nvHABP) versus ventilator-associated bacterial pneumonia (VABP)., Design: Multicenter retrospective cohort study within Premier Research database, 2014-2019., Methods: We identified cases based on a previously published International Classification of Disease, Ninth Revision/Tenth Revision Clinical Modification (ICD-9/ICD-10-CM) algorithm, and we compared the 3 groups with respect to the bacterial pathogens isolated from their blood, sputum, or lower airway samples, and their respective rates of exposure to inappropriate empiric treatment. Using regression modeling we computed the effect of inappropriate empiric treatment on outcomes., Results: Among 17,819 patients who met enrollment criteria, 26.5% had nvHABP, 25.6% vHAPB, and 47.9% VABP. S. aureus (majority methicillin-susceptible) was the most frequently isolated organism, followed P. aeruginosa, K. pneumoniae, and E. coli with variations across the conditions. Rates of carbapenem resistance were highest in VABP (9.1%) and to third-generation cephalosporins in vHABP (14.9%). Patients with nvHABP were most likely to receive inappropriate empiric treatment (8.5%). Although inappropriate empiric treatment was associated with an increase in adjusted postinfection-onset hospital length of stay (2.3 days) and cost ($12,142), its greatest magnitude was in the nvHABP group (4.9 days, $13,147)., Conclusions: Substantial microbiologic differences exist among populations who suffer nvHABP, vHABP, and VABP, and inappropriate empiric treatment significantly worsens utilization outcomes. Given the moderate rates of carbapenem resistance and third-generation cephalosporin resistance, all patients require empiric coverage for a range of bacteria, including those targeting extended-spectrum β-lactamase and carbapenem resistance where appropriate.

Sepsis and septic shock represent important infection-related medical emergencies that result in significant morbidity and mortality. The prevalence and microbiology of these processes are evolving. Nonetheless, timely and appropriate antibiotic therapy continues to represent the most important determinant of survival. Recent trials have clarified that crystalloids are preferred for initial resuscitation, and balanced crystalloids appear superior to 0.9% saline. Controversy remains regarding not only the rate and rapidity of fluid resuscitation but also about the timing and use of vasopressors to maintain blood pressure. While some newer alternative vasopressors may have a role in sepsis, more evidence supporting their use is required. Conflicting data exist regarding the impact of corticosteroids on mortality in septic shock. However, these reports indicate that adjunctive hydrocortisone can lead to more rapid shock reversal., Competing Interests: A.F.S. has served as a consultant to or received grant support from Entasis, Merck, Shionogi, Spero, and Tetraphase., (Thieme. All rights reserved.)

Background: Evidence from pandemics suggests that influenza is often associated with bacterial coinfection. Among patients hospitalized for influenza pneumonia, we report the rate of coinfection and distribution of pathogens, and we compare outcomes of patients with and without bacterial coinfection., Methods: We included adults admitted with community-acquired pneumonia (CAP) and tested for influenza from 2010 to 2015 at 179 US hospitals participating in the Premier database. Pneumonia was identified using an International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) algorithm. We used multiple logistic and gamma-generalized linear mixed models to assess the relationships between coinfection and inpatient mortality, intensive care unit (ICU) admission, length of stay, and cost., Results: Among 38,665 patients hospitalized with CAP and tested for influenza, 4,313 (11.2%) were positive. In the first 3 hospital days, patients with influenza were less likely than those without to have a positive culture (10.3% vs 16.2%; P < .001), and cultures were more likely to contain Staphylococcus aureus (34.2% vs 28.2%; P = .007) and less likely to contain Streptococcus pneumoniae (24.9% vs 31.0%; P = .008). Of S. aureus isolates, 42.8% were methicillin resistant among influenza patients versus 53.2% among those without influenza (P = .01). After hospital day 3, pathogens for both groups were similar. Bacterial coinfection was associated with increased odds of in-hospital mortality (aOR, 3.00; 95% CI, 2.17-4.16), late ICU transfer (aOR, 2.83; 95% CI, 1.98-4.04), and higher cost (risk-adjusted mean multiplier, 1.77; 95% CI, 1.59-1.96)., Conclusions: In a large US inpatient sample hospitalized with influenza and CAP, S. aureus was the most frequent cause of bacterial coinfection. Coinfection was associated with worse outcomes and higher costs.

Background: Hospitalizations with complicated urinary tract infection (cUTI) in the United States have increased. Though most often studied as a subset of cUTI, catheter-associated UTI (CAUTI) afflicts a different population of patients and carries outcomes distinct from non-CA cUTI (nCAcUTI). We examined the epidemiology and outcomes of hospitalizations in these groups., Methods: We conducted a cross-sectional multicenter study within the 2018 National Inpatient Sample (NIS) database, a 20% stratified sample of discharges from US community hospitals, to explore characteristics and outcomes of patients discharged with a UTI diagnosis. We divided cUTI into mutually exclusive categories of nCAcUTI and CAUTI. We applied survey methods to develop national estimates., Results: Among 2   837   385 discharges with a UTI code, 500   400 (17.6%, 19.8% principal diagnosis [PD]) were nCAcUTI and 126   120 (4.4%, 63.8% PD) were CAUTI. Though similar in age (CAUTI, 70.1 years; and nCAcUTI, 69.7 years), patients with nCAcUTI had lower comorbidity (mean Charlson, 4.3) than those with CAUTI (mean Charlson, 4.6). Median (interquartile range [IQR]) length of stay (LOS) was 5 (3-8) days in nCAcUTI and 5 (3-9) days in CAUTI. Overall median (IQR) hospital costs were similar in nCAcUTI ($9713 [$5923-$17   423]) and CAUTI ($9711 [$5969-$17   420]). Though low in both groups, hospital mortality was lower in nCAcUTI (2.8%) than in CAUTI (3.4%). Routine discharges home were higher in nCAcUTI (41.5%) than CAUTI (22.1%)., Conclusions: There are >626   000 hospital admissions with a cUTI, comprising ~1.8% of all annual admissions in the United States; 4/5 are nCAcUTI. Because CAUTI is frequently the reason for admission, preventive efforts are needed beyond the acute care setting., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Viruses are more common than bacteria in patients hospitalized with community-acquired pneumonia. Little is known, however, about the frequency of respiratory viral testing and its associations with antimicrobial utilization., Design: Retrospective cohort study., Setting: The study included 179 US hospitals., Patients: Adults admitted with pneumonia between July 2010 and June 2015., Methods: We assessed the frequency of respiratory virus testing and compared antimicrobial utilization, mortality, length of stay, and costs between tested versus untested patients, and between virus-positive versus virus-negative patients., Results: Among 166,273 patients with pneumonia on admission, 40,787 patients (24.5%) were tested for respiratory viruses, 94.8% were tested for influenza, and 20.7% were tested for other viruses. Viral assays were positive in 5,133 of 40,787 tested patients (12.6%), typically for influenza and rhinovirus. Tested patients were younger and had fewer comorbidities than untested patients, but patients with positive viral assays were older and had more comorbidities than those with negative assays. Blood cultures were positive for bacterial pathogens in 2.7% of patients with positive viral assays versus 5.3% of patients with negative viral tests (P < .001). Antibacterial courses were shorter for virus-positive versus -negative patients overall (mean 5.5 vs 6.4 days; P < .001) but varied by bacterial testing: 8.1 versus 8.0 days (P = .60) if bacterial tests were positive; 5.3 versus 6.1 days (P < .001) if bacterial tests were negative; and 3.3 versus 5.2 days (P < .001) if bacterial tests were not obtained (interaction P < .001)., Conclusions: A minority of patients hospitalized with pneumonia were tested for respiratory viruses; only a fraction of potential viral pathogens were assayed; and patients with positive viral tests often received long antibacterial courses.

Background: The Pareto principle states that the majority of any effect comes from a minority of the causes. This property is widely used in quality improvement science., Research Question: Among patients requiring mechanical ventilation (MV), are there subgroups according to MV duration that may serve as potential nodes for high-value interventions aimed at reducing costs without compromising quality?, Study Design and Methods: This multicenter retrospective cohort study included approximately 780 hospitals in the Premier Research Database (2014-2018). Patients receiving MV were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification, and International Classification of Diseases, Tenth Revision, codes. They were then divided into quintiles according to MV duration; their hospital costs, post-MV onset length of stay (LOS), ICU LOS, and cumulative post-MV onset hospital days per quintile were compared., Results: A total of 691,961 patients were included in the analysis. Median [interquartile range] duration of MV in days by quintile was as follows: quintile 1 (Q1), 1 [1, 1]; Q2, 2 [2, 2]; Q3, 3 [3, 3]; Q4, 6 [6, 7]; and Q5, 13 [10, 19]. Median [interquartile range] post-MV onset LOS (Q1, 2 [0, 5]; Q5, 17 [12, 26]) and hospital costs (Q1, $15,671 [$9,180, $27,901]; Q5, $70,133 [$47,136, $108,032]) rose from Q1 through Q5. Patients in Q5 consumed 47.7% of all post-MV initiation hospital days among all patients requiring MV, and the mean per-patient hospital costs in Q5 exceeded the sum of costs incurred by Q1 to Q3. Adjusted marginal mean (95% CI) hospital costs rose exponentially from Q1 through Q5: Q2 vs Q1, $3,976 ($3,354, $4,598); Q3 vs Q2, $5,532 ($5,103, $5,961); Q4 vs Q3, $11,705 ($11,071, $12,339); and Q5 vs Q4, $26,416 ($25,215, $27,616)., Interpretation: Patients undergoing MV in the highest quintiles according to duration of MV consume a disproportionate amount of resources, as evidenced by MV duration, hospital LOS, and costs, making them a potential target for streamlining MV care., (Copyright © 2020. Published by Elsevier Inc.)

Background: For patients at risk for multidrug-resistant organisms, IDSA/ATS guidelines recommend empiric therapy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. Following negative cultures, the guidelines recommend antimicrobial de-escalation. We assessed antibiotic de-escalation practices across hospitals and their associations with outcomes in hospitalized patients with pneumonia with negative cultures., Methods: We included adults admitted with pneumonia in 2010-2015 to 164 US hospitals if they had negative blood and/or respiratory cultures and received both anti-MRSA and antipseudomonal agents other than quinolones. De-escalation was defined as stopping both empiric drugs on day 4 while continuing another antibiotic. Patients were propensity adjusted for de-escalation and compared on in-hospital 14-day mortality, late deterioration (ICU transfer), length-of-stay (LOS), and costs. We also compared adjusted outcomes across hospital de-escalation rate quartiles., Results: Of 14 170 patients, 1924 (13%) had both initial empiric drugs stopped by hospital day 4. Hospital de-escalation rates ranged from 2-35% and hospital de-escalation rate quartile was not significantly associated with outcomes. At hospitals in the top quartile of de-escalation, even among patients at lowest risk for mortality, the de-escalation rates were <50%. In propensity-adjusted analysis, patients with de-escalation had lower odds of subsequent transfer to ICU (adjusted odds ratio, .38; 95% CI, .18-.79), LOS (adjusted ratio of means, .76; .75-.78), and costs (.74; .72-.76)., Conclusions: A minority of eligible patients with pneumonia had antibiotics de-escalated by hospital day 4 following negative cultures and de-escalation rates varied widely between hospitals. To adhere to recent guidelines will require substantial changes in practice., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose of Review: To describe the increasing burden of multidrug resistant (MDR) Gram-negative pathogens in severe pneumonia and to examine the clinical trials supporting a role for novel agents for the treatment of this infection., Recent Findings: MDR Gram-negative bacteria cause an increasing proportion of severe pneumonias. Although the epidemiology of resistance varies across the globe, all regions have seen an evolution in resistance, especially among Enterobacterales spp, Pseudomonas aeruginosa, and Acinetobacter bumannii. Fortunately, several clinical trials have established the role for multiple new antibiotics in pneumonia. Although these drugs all have different ranges of in vitro activity and potency, each helps to address the problem of MDR. These studies have varied based on the proportion of subjects undergoing mechanical ventilation and the comparator agents employed. Although all these trials have demonstrated noninferiority to the comparator, the mortality rates across the analyses ranged from <% to >20%. None of the recent investigations included immunocompromised subjects., Summary: Multiple new agents exist for treating MDR Gram-negative pneumonia. These agents are not interchangeable. Thus, one must approach their adoption with a nuanced eye., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)