Drug resistance among gram-negative pathogens is a risk factor for inappropriate empiric treatment (IET), which in turn increases the risk for mortality. We explored the impact of carbapenem-resistant Enterobacteriaceae (CRE) on the risk of IET and of IET on outcomes in patients with Enterobacteriaceae infections. We conducted a retrospective cohort study in Premier Perspective database (2009–2013) of 175 US hospitals. We included all adult patients with community-onset culture-positive urinary tract infection (UTI), pneumonia, or sepsis as a principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, treated with antibiotics within 2 days of admission. We employed regression modeling to compute adjusted association of presence of CRE with risk of receiving IET, and of IET on hospital mortality, length of stay (LOS) and costs. Among 40,137 patients presenting to the hospital with an Enterobacteriaceae UTI, pneumonia or sepsis, 1227 (3.1%) were CRE. In both groups, the majority of the cases were UTI (51.4% CRE and 54.3% non-CRE). Those with CRE were younger (66.6+/−15.3 vs. 69.1+/−15.9 years, p < 0.001), and more likely to be African-American (19.7% vs. 14.0%, p < 0.001) than those with non-CRE. Both chronic (Charlson score 2.0+/−2.0 vs. 1.9+/−2.1, p = 0.009) and acute (by day 2: ICU 56.3% vs. 30.4%, p < 0.001, and mechanical ventilation 35.8% vs. 11.7%, p < 0.001) illness burdens were higher among CRE than non-CRE subjects, respectively. CRE patients were 3× more likely to receive IET than non-CRE (46.5% vs. 11.8%, p < 0.001). In a regression model CRE was a strong predictor of receiving IET (adjusted relative risk ratio 3.95, 95% confidence interval 3.5 to 4.5, p < 0.001). In turn, IET was associated with an adjusted rise in mortality of 12% (95% confidence interval 3% to 23%), and an excess of 5.2 days (95% confidence interval 4.8, 5.6, p < 0.001) LOS and $10,312 (95% confidence interval $9497, $11,126, p < 0.001) in costs. In this large US database, the prevalence of CRE among patients with Enterobacteriaceae UTI, pneumonia or sepsis was comparable to other national estimates. Infection with CRE was associated with a four-fold increased risk of receiving IET, which in turn increased mortality, LOS and costs.

The relationship between multidrug resistance (MDR), inappropriate empiric therapy (IET), and mortality among patients with Acinetobacter baumannii (AB) remains unclear. We examined it using a large U.S. database. We conducted a retrospective cohort study using the Premier Research database (2009–2013) of 175 U.S. hospitals. We included all adult patients admitted with pneumonia or sepsis as their principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, along with antibiotic administration within 2 days of admission. Only culture-confirmed infections were included. Resistance to at least three classes of antibiotics defined multidrug-resistant AB (MDR-AB). We used logistic regression to compute the adjusted relative risk ratio (RRR) of patients with MDR-AB receiving IET and IET’s impact on mortality. Among 1423 patients with AB infection, 1171 (82.3 %) had MDR-AB. Those with MDR-AB were older (63.7 ± 15.4 vs. 61.0 ± 16.9 years, p = 0.014). Although chronic disease burden did not differ between groups, the MDR-AB group had higher illness severity than those in the non-MDR-AB group (intensive care unit 68.0 % vs. 59.5 %, p < 0.001; mechanical ventilation 56.2 % vs. 42.1 %, p < 0.001). Patients with MDR-AB were more likely to receive IET than those in the non-MDR-AB group (76.2 % MDR-AB vs. 13.8 % non-MDR-AB, p < 0.001). In a regression model, MDR-AB strongly predicted receipt of IET (adjusted RRR 5.5, 95 % CI 4.0–7.7, p < 0.001). IET exposure was associated with higher hospital mortality (adjusted RRR 1.8, 95 % CI 1.4–2.3, p < 0.001). In this large U.S. database, the prevalence of MDR-AB among patients with AB infection was > 80 %. Harboring MDR-AB increased the risk of receiving IET more than fivefold, and IET nearly doubled hospital mortality.

Objective.: Urinary tract infections (UTIs) are common among hospitalized patients. Selection of an appropriate antibiotic for this infection requires knowledge of both its general microbiology and the epidemiology of drug-resistant organisms. We sought to determine secular trends in UTI hospitalizations that involve gram-negative (GN) multidrug-resistant Pseudomonas aeruginosa (MDR-PA), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (EC) and Klebsiella pneumoniae(KP), and carbapenem-resistant Enterobacteriaceae (CRE).Design.: Survey.Patients.: Patients with UTI in US hospitals between 2000 and 2009.Methods.: We first derived the total number of UTI hospitalizations in the United States from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database years 2000–2009. Based on a literature review, we then determined what proportion of all UTIs arise due to each of the organisms of interest, irrespective of resistance pattern. Finally, we assessed the prevalence of resistance within each pathogen based on the Eurofins Surveillance Network database 2000–2009. Susceptibility patterns served as phenotypic surrogates for resistance.Results.: Between 2000 and 2009, the frequency of UTI hospitalizations increased by approximately 50%, from 53 to 77 cases per 1,000 hospitalizations. Infections due to all GN bacteria followed a similar trajectory, whereas those caused by resistant GN pathogens increased by approximately 50% (MDR-PA) to approximately 300% (ESBL). CRE emerged and reached 0.5 cases per 1,000 hospitalizations in this 10-year period.Conclusions.: The epidemiology and microbiology of GN UTI hospitalizations has shifted over the past decade. The proportion of all hospitalizations involving this infection has climbed. Resistant GN bacteria are becoming more prevalent and are implicated in an increasing proportion of UTIs among hospitalized patients.

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.

Objectives: Most patients requiring mechanical ventilation only require it for a short term (< 4 d of mechanical ventilation). Those undergoing prolonged acute mechanical ventilation (≥ 4 d mechanical ventilation) represent a select cohort who face significant morbidity, mortality, and resource utilization. Using administrative codes, we identified prolonged acute mechanical ventilation and short-term mechanical ventilation patients and compared their baseline characteristics, hospital events, and hospital outcomes. Design: Retrospective cohort. Setting: Seven-hundred eighty-seven acute care hospitals, United States, contributing data to Premier database, 2014–2018. Patients: Patients on mechanical ventilation. Interventions: None. Measurements and Main Results: Among 691,961 patients meeting the enrollment criteria, 266,374 (38.5%) received prolonged acute mechanical ventilation. At baseline, patients on prolonged acute mechanical ventilation were similar to short-term mechanical ventilation in age (years: 62.0 ± 15.8 prolonged acute mechanical ventilation vs 61.7 ± 17.2 short-term mechanical ventilation), gender (males: 55.6% prolonged acute mechanical ventilation vs 53.9% short-term mechanical ventilation), and race (white: 69.1% prolonged acute mechanical ventilation vs 72.4% short-term mechanical ventilation). The prolonged acute mechanical ventilation group had a higher comorbidity burden than short-term mechanical ventilation (mean Charlson Score 3.5 ± 2.7 vs 3.1 ± 2.7). The prevalence of vasopressors (50.3% vs 36.9%), dialysis (19.4% vs 10.3%), severe sepsis (20.3% vs 10.3%), and septic shock (33.5% vs 15.9%) was higher in prolonged acute mechanical ventilation than short-term mechanical ventilation. Hospital mortality (29.75% vs 21.1%), combined mortality, or discharge to hospice (37.2% vs 25.3%), extubation failure (12.3% vs 6.1%), tracheostomy (21.6% vs 4.5%), development of Clostridium difficile (4.5% vs 1.7%), and incidence density of ventilator-associated pneumonia (2.4/1,000 patient-days vs 0.6/1,000 patient-days) were all higher in the setting of prolonged acute mechanical ventilation than short-term mechanical ventilation. Median (interquartile range) post mechanical ventilation onset length of stay (13 [8–20] vs 4 d [1–8 d]) and hospital costs ($55,014 [$35,051–$88,007] vs $20,120 [$12,071–$34,915] were higher in prolonged acute mechanical ventilation than short-term mechanical ventilation. Conclusions: Over one-third of all hospitalized patients on mechanical ventilation require it for greater than or equal to 4 days. Prolonged acute mechanical ventilation patients exhibit a higher burden of both chronic and acute illness and experience higher rates than those on short-term mechanical ventilation of hospital-acquired complications and worse clinical and economic outcomes.