Associations between Present-on-Admission Do-Not-Resuscitate Orders and Short-Term Outcomes in Patients with Pneumonia.

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.

Intravenous to Oral Antibiotic Switch Therapy Among Patients Hospitalized With Community-Acquired Pneumonia.

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.

Descriptive Epidemiology and Outcomes of Nonventilated Hospital-Acquired, Ventilated Hospital-Acquired, and Ventilator-Associated Bacterial Pneumonia in the United States, 2012-2019.

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.

Etiology, Treatments, and Outcomes of Patients With Severe Community-Acquired Pneumonia in a Large U.S. Sample.

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.

The risk of inappropriate empiric treatment and its outcomes based on pathogens in non-ventilated (nvHABP), ventilated (vHABP) hospital-acquired and ventilator-associated (VABP) bacterial pneumonia in the US, 2012-2019.

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.

Sepsis and Septic Shock: Evolving Evidence, Evolving Paradigms.

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.

De-escalation of Empiric Antibiotics Following Negative Cultures in Hospitalized Patients With Pneumonia: Rates and Outcomes.

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.

Novelty and nuance in the intensive care unit: new options to combat multidrug resistant pneumonia.

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.

Multiple antimicrobial resistance and outcomes among hospitalized patients with complicated urinary tract infections in the US, 2013-2018: a retrospective cohort study.

BACKGROUND: Complicated urinary tract infection (cUTI) is common among hospitalized patients. Though carbapenems are an effective treatment in the face of rising resistance, overuse drives carbapenem resistance (CR). We hypothesized that resistance to routinely used antimicrobials is common, and, despite frequent use of carbapenems, associated with an increased risk of inappropriate empiric treatment (IET), which in turn worsens clinical outcomes. METHODS: We conducted a retrospective cohort study of patients hospitalized with a culture-positive non-CR cUTI. Triple resistance (TR) was defined as resistance to > 3 of the following: 3rd generation cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin. Multivariable models quantified the impact of TR and inappropriate empiric therapy (IET) on mortality, hospital LOS, and costs. RESULTS: Among 23,331 patients with cUTI, 3040 (13.0%) had a TR pathogen. Compared to patients with non-TR, those with TR were more likely male (57.6% vs. 47.7%, p < 0.001), black (17.9% vs. 13.6%, p < 0.001), and in the South (46.3% vs. 41.5%, p < 0.001). Patients with TR had higher chronic (median [IQR] Charlson score 3 [2, 4] vs. 2 [1, 4], p < 0.001) and acute (mechanical ventilation 7.0% vs. 5.0%, p < 0.001; ICU admission 22.3% vs. 18.6%, p < 0.001) disease burden. Despite greater prevalence of empiric carbapenem exposure (43.3% vs. 16.2%, p < 0.001), patient with TR were also more likely to receive IET (19.6% vs. 5.4%, p < 0.001) than those with non-TR. Although mortality was similar between groups, TR added 0.38 (95% CI 0.18, 0.49) days to LOS, and $754 (95% CI $406, $1103) to hospital costs. Both TR and IET impacted the outcomes among cUTI patients whose UTI was not catheter-associated (CAUTI), but had no effect on outcomes in CAUTI. CONCLUSIONS: TR occurs in 1 in 8 patients hospitalized with cUTI. It is associated with an increase in the risk of IET exposure, as well as a modest attributable prolongation of LOS and increase in total costs, particularly in the setting of non-CAUTI.

Blood Cultures Versus Respiratory Cultures: 2 Different Views of Pneumonia.

BACKGROUND: Choice of empiric therapy for pneumonia depends on risk for antimicrobial resistance. Models to predict resistance are derived from blood and respiratory culture results. We compared these results to understand if organisms and resistance patterns differed by site. We also compared characteristics and outcomes of patients with positive cultures by site. METHODS: We studied adult patients discharged from 177 US hospitals from July 2010 through June 2015, with principal diagnoses of pneumonia, or principal diagnoses of respiratory failure, acute respiratory distress syndrome, respiratory arrest, or sepsis with a secondary diagnosis of pneumonia, and who had blood or respiratory cultures performed. Demographics, treatment, microbiologic results, and outcomes were examined. RESULTS: Among 138 561 hospitalizations of patients with pneumonia who had blood or respiratory cultures obtained at admission, 12 888 (9.3%) yielded positive cultures: 6438 respiratory cultures, 5992 blood cultures, and 458 both respiratory and blood cultures. Forty-two percent had isolates resistant to first-line therapy for community-acquired pneumonia. Isolates from respiratory samples were more often resistant than were isolates from blood (54.2% vs 26.6%; P < .001). Patients with both culture sites positive had higher case-fatality, longer lengths of stay, and higher costs than patients who had only blood or respiratory cultures positive. Among respiratory cultures, the most common pathogens were Staphylococcus aureus (34%) and Pseudomonas aeruginosa (17%), whereas blood cultures most commonly grew Streptococcus pneumoniae (33%), followed by S. aureus (22%). CONCLUSIONS: Patients with positive respiratory tract cultures are clinically different from those with positive blood cultures, and resistance patterns differ by source. Models of antibiotic resistance should account for culture source.

Antimicrobial Susceptibility and Cross-Resistance Patterns among Common Complicated Urinary Tract Infections in U.S. Hospitals, 2013 to 2018.

In the face of increasing rates of antimicrobial resistance in complicated urinary tract infections (cUTIs), clinicians need to understand cross-resistance patterns among commonly encountered pathogens. We performed a multicenter, retrospective cohort study in the Premier database of approximately 180 hospitals, from 2013 to 2018. Using an ICD-9/10-based algorithm, we identified all adult patients hospitalized with cUTIs and included those with a positive blood or urine culture. We examined the microbiology and susceptibilities to common cUTI antimicrobials (3rd-generation cephalosporin [C3], fluoroquinolones [FQ], trimethoprim-sulfamethoxazole [TMP/SMZ], fosfomycin [FFM], and nitrofurantoin [NFT]) singly and in groups of two. Among 28,057 organisms from 23,331 patients, the 3 most common pathogens were Escherichia coli (41.0%; C3r, 15.1%), Klebsiella pneumoniae (12.1%; C3r, 13.2%), and Pseudomonas aeruginosa (11.0%; C3r, 12.0%). E. coli was most frequently resistant to FQ (43.5%) and least to NFT (6.7%). K. pneumoniae was most frequently resistant to NFT (60.8%) and least to FFM (0.1%). P. aeruginosa was most frequently resistant to FQ (34.4%) and least to TMP/SMZ (4.2%). Of the C3rE. coli isolates, 87.1% were also FQr, 63.7% were TMP/SMZr, and 13.3% were NFTr C3rK. pneumoniae isolates had a 76.5% chance of being FQr, 78.1% were TMP/SMZr, and 77.6% were NFTr C3rP. aeruginosa coexisted with FQr in 47.3%, TMP/SMZr in 18.9%, and NFTr in 28.7%. Among the most common pathogens isolated from hospitalized patients with cUTIs, the rates of single resistance to common treatments and of cross-resistance to these regimens are substantial. Knowing the patterns of cross-resistance may help clinicians tailor empirical therapy more precisely.

Characteristics, Hospital Course, and Outcomes of Patients Requiring Prolonged Acute Versus Short-Term Mechanical Ventilation in the United States, 2014-2018.

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.

Current Epidemiology, Etiology, and Burden of Acute Skin Infections in the United States.

The US burden of acute skin infections is substantial. While Staphylococcus aureus and Streptococcus spp. are the most common causes, gram-negative bacteria and mixed infections can occur in some settings. These mixed infections are more likely to result in inappropriate empiric antibiotic therapy. Important challenges remain in diagnosing and treating acute skin infections.

Burden of hospitalizations over time with invasive aspergillosis in the United States, 2004-2013.

BACKGROUND: Using aggregated data available on the interactive website from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Network (HCUPnet), we examined the annual volume of invasive aspergillosis (IA)-related hospitalizations in the US. METHODS: This was a population study. Age-adjusted volumes were derived through population incidence calculated using year-specific censal and intercensal US population estimates available from the US Census Bureau. We additionally examined IA as the principal diagnosis and its associated outcomes in patients with ICD-9-CM codes 117.3, 117.9 and 484.6. RESULTS: The age-adjusted number of annual hospitalizations with IA grew from 35,968 cases in 2004 to 51,870 in 2013, a 44.2% overall increase, 4.4% per annum. Regionally, the South contributed the plurality of the cases (40%), and the Northeast the fewest (17%). While IA as principal diagnosis dropped, from 14.4 to 9.3%, mortality rose from 10 to 12%. Despite mean hospital length of stay decreasing from 13.3 (standard error [SE] 0.07) to 11.5 (SE 0.6) days, the corresponding mean hospital charges rose from $71,164 (SE $5248) to $123,005 (SE $9738). The aggregate US inflation-adjusted hospital charges for IA principal diagnosis rose from $436,074,445 in 2004 to $592,358,369 in 2013. CONCLUSIONS: Given the substantial volume and rate of growth in IA-related hospitalizations in the US between 2004 and 2013, an increase in mortality and high costs, IA may represent an attractive target for intensive preventive efforts.

Epidemiology and Outcomes of Hospitalizations With Invasive Aspergillosis in the United States, 2009-2013.

Background: Though invasive aspergillosis (IA) complicates care of up to 13% of patients with immunocompromise, little is known about its morbidity and mortality burden in the United States. Methods: We analyzed the Health Care Utilization Project's data from the Agency for Healthcare Research and Quality for 2009-2013. Among subjects with high-risk conditions for IA, IA was identified via International Classification of Diseases, Ninth Revision, Clinical Modification codes 117.3, 117.9, and 484.6. We compared characteristics and outcomes between those with (IA) and without IA (non-IA). Using propensity score matching, we calculated the IA-associated excess mortality and 30-day readmission rates, length of stay, and costs. Results: Of the 66634683 discharged patients meeting study inclusion criteria, 154888 (0.2%) had a diagnosis of IA. The most common high-risk conditions were major surgery (50.1%) in the non-IA and critical illness (41.0%) in the IA group. After propensity score matching, both mortality (odds ratio, 1.43; 95% confidence interval, 1.36-1.51) and 30-day readmission (1.39; 1.34-1.45) rates were higher in the IA group. IA was associated with 6.0 (95% confidence interval, 5.7-6.4) excess days in the hospital and $15542 ($13869-$17215) in excess costs per hospitalization. Conclusions: Although rare even among high-risk groups, IA is associated with increased hospital mortality and 30-day readmission rates, excess duration of hospitalization, and costs. Given nearly 40000 annual admissions for IA in the United States, the aggregate IA-attributable excess costs may reach $600 million annually.

Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Association Between Initial Route of Fluoroquinolone Administration and Outcomes in Patients Hospitalized for Community-acquired Pneumonia.

BACKGROUND: Fluoroquinolones have equivalent oral and intravenous bioavailability, but hospitalized patients with community-acquired pneumonia (CAP) generally are treated intravenously. Our objectives were to compare outcomes of hospitalized CAP patients initially receiving intravenous vs oral respiratory fluoroquinolones. METHODS: This was a retrospective cohort study utilizing data from 340 hospitals involving CAP patients admitted to a non-intensive care unit (ICU) setting from 2007 to 2010, who received intravenous or oral levofloxacin or moxifloxacin. The primary outcome was in-hospital mortality. Secondary outcomes included clinical deterioration (transfer to ICU, initiation of vasopressors, or invasive mechanical ventilation [IMV] initiated after the second hospital day), antibiotic escalation, length of stay (LOS), and cost. RESULTS: Of 36 405 patients who met inclusion criteria, 34 200 (94%) initially received intravenous treatment and 2205 (6%) received oral treatment. Patients who received oral fluoroquinolones had lower unadjusted mortality (1.4% vs 2.5%; P = .002), and shorter mean LOS (5.0 vs 5.3; P < .001). Multivariable models using stabilized inverse propensity treatment weighting revealed lower rates of antibiotic escalation for oral vs intravenous therapy (odds ratio [OR], 0.84; 95% confidence interval [CI], .74-.96) but no differences in hospital mortality (OR, 0.82; 95% CI, .58-1.15), LOS (difference in days 0.03; 95% CI, -.09-.15), cost (difference in $-7.7; 95% CI, -197.4-182.0), late ICU admission (OR, 1.04; 95% CI, .80-1.36), late IMV (OR, 1.17; 95% CI, .87-1.56), or late vasopressor use (OR, 0.94; 95% CI, .68-1.30). CONCLUSIONS: Among hospitalized patients who received fluoroquinolones for CAP, there was no association between initial route of administration and outcomes. More patients may be treated orally without worsening outcomes.

Multidrug resistance, inappropriate empiric therapy, and hospital mortality in Acinetobacter baumannii pneumonia and sepsis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.