Race Does Not Impact Sepsis Outcomes When Considering Socioeconomic Factors in Multilevel Modeling.

OBJECTIVES: To determine whether race is a major determinant of sepsis outcomes when controlling for socioeconomic factors. DESIGN: Retrospective cohort study. SETTING: Barnes-Jewish Hospital a 1,350 bed academic medical center. PATIENTS: Eleven-thousand four-hundred thirty-two patients hospitalized between January 2010 and April 2017 with sepsis and septic shock. INTERVENTIONS: Multilevel random effects modeling was employed whereby patients were nested within ZIP codes. Individual patient characteristics and socioeconomic variables aggregated at the ZIP code level (education, employment status, income, poverty level, access to healthcare) were included in the model. MEASUREMENTS AND MAIN RESULTS: In hospital mortality, length of stay, need for vasopressors, and mechanical ventilation were the main endpoints. Black patients had more comorbidities than White patients except for cirrhosis and malignancy. In unadjusted comparisons, White individuals were more likely to require mechanical ventilation and had higher mortality rates and longer hospital stays for both low- and high-income groups. When nesting within ZIP codes and accounting for socioeconomic variables, race did not have a significant effect on mortality. Non-White races had lower odds ratio for mechanical ventilation. CONCLUSIONS: Our study demonstrates that race is not an independent risk factor for sepsis mortality, as well as sepsis-related length of stay. We should expand our inquiry into determinants of sepsis outcomes by including socioeconomic variables.

Assessment of Antibiotic De-escalation by Spectrum Score in Patients With Nosocomial Pneumonia: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant mortality. Guidelines recommend empiric broad-spectrum antibiotics followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure. METHODS: This single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016 to 2019. Patients were enrolled if they met predefined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with no de-escalation (NDE). The primary outcome was composite treatment failure, defined as all-cause mortality or readmission for pneumonia within 30 days of diagnosis. RESULTS: Of 11860 admissions screened, 1812 unique patient-admissions were included (1102 HAP, 710 VAP). Fewer patients received DE (876 DE vs 1026 NDE). Groups were well matched at baseline, although more patients receiving DE had respiratory cultures ordered (56.6% vs 50.6%, P = .011). There was no difference in composite treatment failure (35.0% DE vs 33.8% NDE, P = .604). De-escalation was not associated with treatment failure on multivariable Cox regression analysis (hazard ratio, 1.13; 95% confidence interval, 0.96-1.33). Patients receiving DE had fewer antibiotic days (median 9 vs 11, P < .0001), episodes of Clostridioides difficile infection (2.2% vs 3.8%, P = .046), and hospital days (median 20 vs 22 days, P = .006). CONCLUSIONS: De-escalation and NDE resulted in similar rates of 30-day treatment failure; however, DE was associated with fewer antibiotic days, episodes of C difficile infection, and days of hospitalization.

Racial Disparities in Readmissions Following Initial Hospitalization for Sepsis.

OBJECTIVES: To assess whether Black race is associated with a higher rate of all-cause readmission compared with White race following community-onset sepsis. DESIGN: Retrospective cohort study. SETTING: One-thousand three-hundred bed urban academic medical centers. PATIENTS: Three-thousand three-hundred ninety patients hospitalized with community-onset sepsis between January 1, 2010, and December 31, 2017. INTERVENTIONS: Community-onset sepsis was defined as patients admitted through the emergency department with an International Classification of Disease, ninth revision, Clinical Modification code for either severe sepsis (995.92) or septic shock (785.52). Beginning in 2015, we used International Classification of Disease, Tenth Revision, Clinical Modification codes R65.20 (severe sepsis) and R65.21 (septic shock). We excluded those individuals hospitalized at another acute care facility that were transferred to our facility. Race was abstracted electronically, and patients who expired or self-identified as a race other than Black or White race were excluded. Patients who experienced a subsequent hospitalization at our facility were considered to be readmitted. MEASUREMENTS AND MAIN RESULTS: Compared with White race, Black race demonstrated a significantly higher rate of all-cause readmission (60.8% vs 71.1%; p < 0.001), including a higher rate of readmission for sepsis (14.0% vs 19.8%; p < 0.001). Black patients also resided in zip codes with a lower median household income and were more likely to use public insurance compared with White race. Similar rates of comorbid diseases and disease burden were observed between the two groups, but vasopressors were less likely to be administered to Black patients. Multivariable analysis showed that Black race was associated with a 50% increased odds (odds ratio, 1.52, 99% CI, 1.25-1.84) in all-cause readmission risk compared with White race. CONCLUSIONS: Black race was associated with a higher rate of all-cause and sepsis readmission, possibly as a result of unaddressed health disparities, compared with White race. Programs addressing healthcare disparities should use readmission as another marker of equity.

Evaluating the Value of the Respiratory Therapist: Where Is the Evidence? Focus on the Barnes-Jewish Hospital Experience.

Currently, >20 million people in the United States have asthma, and approximately 15 million adults have been diagnosed with COPD, with approximately the same number not yet having been diagnosed with this condition. Moreover, the overall burden of respiratory diseases is still increasing, in part due to environmental factors, such as air pollution. At the same time, the number of patients requiring hospitalization as well as the number of individuals admitted to ICUs from emergency departments has been on the rise over the last decade. Because of the cost to the health-care system, the burden of respiratory diseases, hospitalizations, and ICU admissions also falls on society; it is paid for with tax dollars, higher health insurance rates, and lost productivity. Respiratory therapists (RTs) are in a unique position to influence health-care delivery in a number of settings that include acutely ill hospitalized patients and those with chronic conditions in ambulatory settings. Clinical studies have demonstrated the value of RTs in specific areas, including the performance of medical procedures, the development and implementation of protocols aimed at weaning patients from mechanical ventilation and providing lung-protective ventilation, optimal delivery of in-patient respiratory treatments, the application of disease management programs for COPD, and as part of rapid response teams. However, due to increasing scrutiny of health-care expenditures and limited resources, there is a growing need to document the impact of health-care providers in terms of clinical outcomes. As a profession, RTs should continue to describe the impact they have on patient outcomes and the value they bring to our health-care system. Promoting such investigative outcomes research, along with enhancing the professional aspects of the field of respiratory care, will ensure that the value of RTs does not go unappreciated.

HDQLIFE: development and assessment of health-related quality of life in Huntington disease (HD).

PURPOSE: Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL-Quality of Life in Neurological Disorders and PROMIS-Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS methodology to develop new, HD-specific content. METHODS: New item pools were developed using cognitive debriefing with individuals with HD, and expert, literacy, and translatability reviews. Existing item banks and new item pools were field tested in 536 individuals with prodromal, early-, or late-stage HD. RESULTS: Moderate to strong relationships between Neuro-QoL/PROMIS measures and generic self-report measures of HRQOL, and moderate relationships between Neuro-QoL/PROMIS and clinician-rated measures of similar constructs supported the validity of Neuro-QoL/PROMIS in individuals with HD. Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses were utilized to develop new item banks for Chorea, Speech Difficulties, Swallowing Difficulties, and Concern with Death and Dying, with corresponding six-item short forms. A four-item short form was developed for Meaning and Purpose. CONCLUSIONS: HDQLIFE encompasses both validated Neuro-QoL/PROMIS measures, as well as five new scales in order to provide a comprehensive assessment of HRQOL in HD.

Use of a Shared Canister Protocol for the Delivery of Metered-Dose Inhalers in Mechanically Ventilated Subjects.

BACKGROUND: Mechanically ventilated patients often need bronchodilators administered via a metered-dose inhaler (MDI). Unfortunately, there are no data examining the impact of shared canister delivery of MDI therapy in mechanically ventilated patients. METHODS: A prospective trial was conducted with subjects assigned to shared canister MDI therapy or single-patient canister MDI therapy. Outcomes assessed were occurrence of ventilator-associated pneumonia (VAP), hospital mortality, length of stay, ventilator-associated events, and MDI costs. RESULTS: Among 486 screened patients, 353 were included for analysis of which 201 (56.9%) received shared canister MDI therapy and 152 (43.1%) received single-patient canister therapy. VAP (7.0% vs 4.6%, P = .35), hospital mortality (21.9% vs 20.4%, P = .73), and ventilator days (median [interquartile range] 3.1 [0.9-7.5] d vs 2.7 [1.2-7.1] d, P = .62) were similar between the shared canister and single-patient canister groups. We did not observe clinically important differences for ventilator-associated events between study groups in our logistic regression analysis (P = .07). There was a savings of $217/subject in the shared canister group due to the use of 299 fewer MDIs. CONCLUSIONS: Our study found that shared canister MDI therapy compared with single-patient MDI use was associated with a significant cost savings and similar rates of VAP, hospital mortality, and length of stay but a greater prevalence of ventilator-associated events. This finding suggests that shared canister delivery of MDIs may be a cost-effective practice in mechanically ventilated patients. Based on our findings, further studies examining the overall safety of shared canister use in mechanically ventilated patients seem warranted before recommending their routine use. (ClinicalTrials.gov registration NCT01935388.).

Ventilator-associated complications, including infection-related complications: the way forward.

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

An institutional perspective on the impact of recent antibiotic exposure on length of stay and hospital costs for patients with gram-negative sepsis.

BACKGROUND: Prior antibiotic exposure has been associated with the emergence of antibiotic resistance in subsequent bacterial infections, whose outcomes are typically worse than similar infections with more antibiotic susceptible infections. The influence of prior antibiotic exposure on hospital length of stay (LOS) and costs in patients with severe sepsis or septic shock attributed to Gram-negative bacteremia has not been previously examined. METHODS: A retrospective cohort study of hospitalized patients (January 2002-December 2007) was performed at Barnes-Jewish Hospital, a 1200-bed urban teaching hospital. Patients with Gram-negative bacteremia complicated by severe sepsis or septic shock had data abstraction from computerized medical records. We examined a consecutive cohort of 754 subjects (mean age 59.3 ± 16.3 yrs, mean APACHE II 23.7 ± 6.7). RESULTS: Escherichia coli (30.8%), Klebsiella pneumoniae (23.2%), and Pseudomonas aeruginosa (17.6%) were the most common organisms isolated from blood cultures. 310 patients (41.1%) had exposure to antimicrobial agents in the previous 90 days. Patients with recent antibiotic exposure had greater inappropriate initial antimicrobial therapy (45.4% v. 21.2%; p < 0.001) and hospital mortality (51.3% v. 34.0%; p < 0.001) compared to patients without recent antibiotic exposure. The unadjusted median LOS (25th percentile, 75th percentile) following sepsis onset in patients with prior antimicrobial exposure was 13.0 days (5.0 days, 24.0 days) compared to 8.0 days (5.0 days, 14.0 days) in those without prior antimicrobial exposure (p < 0.001). In a Cox model controlling for multiple confounders, prior antibiotic exposure independently correlated with remaining hospitalized (Adjusted hazard ratio: 1.473, 95% CI: 1.297-1.672, p < 0.001). Adjusting for potential confounders indicated that prior antibiotic exposure independently increased median attributable LOS by 5.0 days. Similarly, total hospital costs following sepsis onset was significantly greater among patients with prior antimicrobial exposure (median values: $94,737 v. $21,329; p < 0.001). CONCLUSIONS: Recent antibiotic exposure is associated with increased LOS and hospital costs in Gram-negative bacteremia complicated by severe sepsis or septic shock. Clinicians and hospital administrators should consider the potential impact of recent antibiotic exposure when formulating empiric treatment decisions for patients with serious infections attributed to Gram-negative bacteria.

Economic impact of ventilator-associated pneumonia in a large matched cohort.

OBJECTIVE: To evaluate the economic impact of ventilator-associated pneumonia (VAP) on length of stay and hospital costs. Design. Retrospective matched cohort study. SETTING: Premier database of hospitals in the United States. PATIENTS: Eligible patients were admitted to intensive care units (ICUs), received mechanical ventilation for ≥2 calendar-days, and were discharged between October 1, 2008, and December 31, 2009. METHODS: VAP was defined by International Classification of Diseases, Ninth Revision (ICD-9), code 997.31 and ventilation charges for ≥2 calendar-days. We matched patients with VAP to patients without VAP by propensity score on the basis of demographics, administrative data, and severity of illness. Cost was based on provider perspective and procedural cost accounting methods. RESULTS: Of 88,689 eligible patients, 2,238 (2.5%) had VAP; the incidence rate was 1.27 per 1,000 ventilation-days. In the matched cohort, patients with VAP ([Formula: see text]) had longer mean durations of mechanical ventilation (21.8 vs 10.3 days), ICU stay (20.5 vs 11.6 days), and hospitalization (32.6 vs 19.5 days; all [Formula: see text]) than patients without VAP ([Formula: see text]). Mean hospitalization costs were $99,598 for patients with VAP and $59,770 for patients without VAP ([Formula: see text]), resulting in an absolute difference of $39,828. Patients with VAP had a lower in-hospital mortality rate than patients without VAP (482/2,144 [22.5%] vs 630/2,144 [29.4%]; [Formula: see text]). CONCLUSIONS: Our findings suggest that VAP continues to occur as defined by the new specific ICD-9 code and is associated with a statistically significant resource utilization burden, which underscores the need for cost-effective interventions to minimize the occurrence of this complication.

Institutional perspective on the impact of positive blood cultures on the economic and clinical outcomes of patients with complicated skin and skin structure infections: focus on gram-positive infections.

BACKGROUND: Traditionally, skin and skin structure infections (SSSIs) have been viewed as having a lower risk of mortality, morbidity, and cost compared with other types of infection. The influence of secondary bacteremia on the medicoeconomic outcomes of patients with SSSIs has not been well described. OBJECTIVE: The goal of this study was to evaluate the impact of bacteremia complicating SSSIs on length of hospital stay and costs. METHODS: This was a retrospective cohort study involving 579 patients with culture-positive SSSIs who were admitted to Barnes-Jewish Hospital, a major academic medical center, between April 1, 2005, and December 31, 2007. The outcomes evaluated in this analysis included hospital mortality, length of stay, hospital costs, and hospital readmission. RESULTS: Secondary bacteremia was present in 277 (47.8%) patients. Hospital mortality was statistically greater among patients with bacteremia (7.9% vs 1.0%; P < 0.001). The unadjusted median length of stay in bacteremic patients was 7.1 days compared with 2.8 days in those without bacteremia (P < 0.001 by log-rank test). This finding correlated with total hospital costs, which were greater in patients with bacteremia (median values: $14,623 vs $5841.50; P < 0.001). In a Cox model controlling for multiple confounders, bacteremia independently correlated with hospital duration (adjusted hazard ratio [HR], 1.820; 95% CI, 1.654-2.003; P < 0.001) and hospital costs (adjusted HR, 1.895; 95% CI, 1.723-2.083; P < 0.001). Hospital readmission within 30 days of discharge was also significantly more common among patients with SSSIs complicated by bacteremia (24.5% vs 12.9%; P < 0.001). CONCLUSIONS: Bacteremia complicating SSSIs occurred in almost 50% of patients infected with gram-positive bacteria in our institution. Beyond its impact on mortality, bacteremia is associated with increased length of stay, hospital costs, and readmission. However, these data are from a single academic medical center and may not be adjusted for all applicable confounders.

Cost and mortality prediction using polymerase chain reaction pathogen detection in sepsis: evidence from three observational trials.

INTRODUCTION: Delays in adequate antimicrobial treatment contribute to high cost and mortality in sepsis. Polymerase chain reaction (PCR) assays are used alongside conventional cultures to accelerate the identification of microorganisms. We analyze the impact on medical outcomes and healthcare costs if improved adequacy of antimicrobial therapy is achieved by providing immediate coverage after positive PCR reports. METHODS: A mathematical prediction model describes the impact of PCR-based rapid adjustment of antimicrobial treatment. The model is applied to predict cost and medical outcomes for 221 sepsis episodes of 189 post-surgical and intensive care unit (ICU) sepsis patients with available PCR data from a prospective, observational trial of a multiplex PCR assay in five hospitals. While this trial demonstrated reduction of inadequate treatment days, data on outcomes associated with reduced inadequate initial antimicrobial treatment had to be obtained from two other, bigger, studies which involved 1,147 (thereof 316 inadequately treated) medical or surgical ICU patients. Our results are reported with the (5% to 95%) percentile ranges from Monte Carlo simulation in which the input parameters were randomly and independently varied according to their statistical characterization in the three underlying studies. The model allows predictions also for different patient groups or PCR assays. RESULTS: A total of 13.1% of PCR tests enabled earlier adequate treatment. We predict that cost for PCR testing (300 €/test) can be fully recovered for patients above 717 € (605 € to 1,710 €) daily treatment cost. A 2.6% (2.0 to 3.2%) absolute reduction of mortality is expected. Cost per incremental survivor calculates to 11,477 € (9,321 € to 14,977 €) and incremental cost-effectiveness ratio to 3,107 € (2,523 € to 4,055 €) per quality-adjusted life-year. Generally, for ICU patients with >25% incidence of inadequate empiric antimicrobial treatment, and at least 15% with a positive blood culture, PCR represents a cost-neutral adjunct method. CONCLUSIONS: Rapid PCR identification of microorganisms has the potential to become a cost-effective component for managing sepsis. The prediction model tested with data from three observational trials should be utilized as a framework to deepen insights when integrating more complementary data associated with utilization of molecular assays in the management of sepsis.

Inappropriate empiric antifungal therapy for candidemia in the ICU and hospital resource utilization: a retrospective cohort study.

BACKGROUND: Candida represents the most common cause of invasive fungal disease, and candidal blood stream infections (CBSI) are prevalent in the ICU. Inappropriate antifungal therapy (IAT) is known to increase a patient's risk for death. We hypothesized that in an ICU cohort it would also adversely affect resource utilization. METHODS: We retrospectively identified all patients with candidemia on or before hospital day 14 and requiring an ICU stay at Barnes-Jewish Hospital between 2004 and 2007. Hospital length of stay following culture-proven onset of CBSI (post-CBSI HLOS) was primary and hospital costs secondary endpoints. IAT was defined as treatment delay of > or =24 hours from candidemia onset or inadequate dose of antifungal agent active against the pathogen. We developed generalized linear models (GLM) to assess independent impact of inappropriate therapy on LOS and costs. RESULTS: Ninety patients met inclusion criteria. IAT was frequent (88.9%). In the IAT group antifungal delay > or =24 hours occurred in 95.0% and inappropriate dosage in 26.3%. Unadjusted hospital mortality was greater among IAT (28.8%) than non-IAT (0%) patients, p = 0.059. Both crude post-CBSI HLOS (18.4 +/- 17.0 vs. 10.7 +/- 9.4, p = 0.062) and total costs ($66,584 +/- $49,120 vs. $33,526 +/- $27,244, p = 0.006) were higher in IAT than in non-IAT. In GLMs adjusting for confounders IAT-attributable excess post-CBSI HLOS was 7.7 days (95% CI 0.6-13.5) and attributable total costs were $13,398 (95% CI $1,060-$26,736). CONCLUSIONS: IAT of CBSI, such as delays and incorrect dosing, occurs commonly. In addition to its adverse impact on clinical outcomes, IAT results in substantial prolongation of hospital LOS and increase in hospital costs. Efforts to enhance rates of appropriate therapy for candidemia may improve resource use.

Medical resource utilization among patients with ventilator-associated pneumonia: pooled analysis of randomized studies of doripenem versus comparators.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is associated with increased medical resource utilization, but few randomized studies have been conducted to evaluate the effect of initial antibiotic therapy. To assess medical resource utilization in patients with VAP, we conducted a pooled analysis of two prospective, randomized, open-label, multicenter, phase III studies, which also showed that doripenem was clinically noninferior to comparators. METHODS: We assessed durations of mechanical ventilation, intensive care unit (ICU) stay, and hospitalization in patients with VAP who received at least 1 dose of doripenem or a comparator in the phase III studies. Comparators were piperacillin/tazobactam (study 1) and imipenem (study 2). We analyzed between-group differences in medical resource utilization endpoints by comparison of Kaplan-Meier curves with generalized Wilcoxon test and in microbiologic eradication rates by two-sided Fisher's exact test. RESULTS: 625 patients with VAP were evaluated and received at least 1 dose of doripenem (n = 312) or a comparator (n = 313). Median durations of mechanical ventilation (7 versus 10 days; P = 0.008) and hospitalization (22 versus 26 days; P = 0.010) were shorter for doripenem than comparators; corresponding ICU stays were 12 and 13 days (P = 0.065). All-cause, overall mortality rates were similar (51/312 [16%] versus 47/313 [15%]; P = 0.648). MIC90 values against Pseudomonas aeruginosa for doripenem versus imipenem were 4 versus 16 microg/mL in study 2. P. aeruginosa was eradicated from 16/24 (67%) doripenem recipients and 10/24 (42%) comparator recipients (P = 0.147). In patients with P. aeruginosa at baseline, median durations of mechanical ventilation (7 versus 13 days; P = 0.031) and ICU stay (13 versus 21 days; P = 0.027) were shorter for doripenem; corresponding hospital stays were 24 and 35 days (P = 0.129). CONCLUSIONS: Doripenem was associated with lower medical resource utilization than comparators. Differences in antipseudomonal activity may have contributed to these findings. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00211003 (study 1) and NCT00211016 (study 2).

Economic burden of ventilator-associated pneumonia based on total resource utilization.

OBJECTIVES: To characterize the current economic burden of ventilator-associated pneumonia (VAP) and to determine which services increase the cost of VAP in North American hospitals. DESIGN AND SETTING: We performed a retrospective, matched cohort analysis of mechanically ventilated patients enrolled in the North American Silver-Coated Endotracheal Tube (NASCENT) study, a prospective, randomized study conducted from 2002 to 2006 in 54 medical centers, including 45 teaching institutions (83.3%). METHODS: Case patients with microbiologically confirmed VAP (n = 30)were identified from 542 study participants with claims data and were matched by use of a primary diagnostic code, and subsequently by the Acute Physiology and Chronic Health Evaluation II score, to control patients without VAP (n = 90). Costs were estimated by applying hospital-specific cost-to-charge ratios based on all-payer inpatient costs associated with VAP diagnosis-related groups. RESULTS: Median total charges per patient were $198,200 for case patients and $96,540 for matched control patients (P < .001); corresponding median hospital costs were $76,730 for case patients and $41,250 for control patients (P = .001). After adjusting for diagnosis-related group payments, median losses to hospitals were $32,140 for case patients and $19,360 for control patients (P = .151). The median duration of intubation was longer for case patients than for control patients (10.1 days vs 4.7 days; P < .001), as were the median duration of intensive care unit stay (18.5 days vs 8.0 days; P < .001) and the median duration of hospitalization (26.5 days vs 14.0 days; P < .001). Examples of services likely to be directly related to VAP and having higher median costs for case patients were hospital care (P < .05) and respiratory therapy (P < .05). CONCLUSIONS: VAP was associated with increased hospital costs, longer duration of hospital stay, and a higher number of hospital services being affected, which underscores the need for bundled measures to prevent VAP. TRIAL REGISTRATION: NASCENT study ClinicalTrials.gov Identifier: NCT00148642.

Hospital resource utilization and costs of inappropriate treatment of candidemia.

STUDY OBJECTIVES: To evaluate the impact of inappropriate therapy--defined as delayed antifungal therapy beyond 24 hours from culture collection, inadequate antifungal dosage, or administration of an antifungal to which an isolate was considered resistant--on postculture hospital length of stay and costs, and to evaluate the relationship between modifiable risk factors, including failure to remove a central venous catheter, antifungal delay, and inadequate dosage, for an additive effect on hospital length of stay and costs. DESIGN: Single-center retrospective cohort study. SETTING: 1250-bed academic medical center. PATIENTS: One hundred sixty-seven consecutive adult patients admitted between January 2004 and May 2006 with culture-confirmed Candida bloodstream infections that occurred within 14 days of hospital admission and who received at least one dose of antifungal treatment. MEASUREMENTS AND MAIN RESULTS: Patients were stratified according to appropriateness of antifungal therapy. Appropriate therapy was defined as initiation of an antifungal to which the isolated pathogen was sensitive in vitro within 24 hours of positive culture collection, in addition to receipt of an adequate dose as recommended by the Infectious Diseases Society of America and the antifungal package insert. Postculture length of stay was the primary outcome and hospital costs the secondary outcome. An evaluation of modifiable risk factors was performed separately. Data were analyzed for 167 patients (22 in the appropriate therapy group and 145 in the inappropriate therapy group). Postculture length of stay was shorter in the appropriate therapy group (mean 7 vs 10.4 days, p=0.037). This correlated with total hospital costs that were lower in the appropriate therapy group (mean $15,832 vs $33,021, p<0.001.) A graded increase in costs was noted with increasing number of modifiable risk factors (p=0.001). CONCLUSION: Inappropriate therapy for Candida bloodstream infection occurring within 14 days of hospitalization was associated with prolonged postculture length of stay and increased costs. A rise in costs, but not length of stay, was noted with increasing modifiable risk factors.

Epidemiology and outcomes of clostridium difficile-associated disease among patients on prolonged acute mechanical ventilation.

PURPOSES: Patients receiving prolonged acute mechanical ventilation (PAMV), although comprising a third of all mechanical ventilation (MV) patients, consume two-thirds of all the resources allocated to MV, and their numbers are projected to double by 2020. By virtue of their prolonged hospital length of stay (median LOS, 17 days), they are subject to such nosocomial infections as Clostridium difficile-associated disease (CDAD), the incidence and age-adjusted case fatality rate of which doubled between 2000 and 2005. We examined the rates and outcomes of CDAD among adult PAMV patients. METHODS: We analyzed 2005 data from the Health Care Utilization Project/Nationwide Inpatient Sample from the Agency for Healthcare Research and Quality. PAMV and CDAD were identified using the International Classification of Diseases, ninth revision, clinical modification codes 96.72 and 008.45, respectively. RESULTS: Among 64,910 adult PAMV patients who were discharged in 2005, 3,468 patients (5.34%) had a concurrent diagnosis of CDAD (PAMV patients who were discharged with concomitant diagnosis of CDAD [CDAD+]). CDAD+ patients who were discharged were older (mean [+/- SD] age, 66.7 +/- 15.9 vs 63.7 +/- 16.9 years, respectively; p < 0.001) and were more likely to have been admitted to the hospital from a long-term care facility (5.7% vs 2.9%, respectively; p < 0.001) than PAMV patients who were discharged without CDAD (CDAD-). Although crude hospital mortality rates did not differ among PAMV patients who were discharged from the hospital by CDAD status (CDAD+, 32.6%; CDAD-, 33.0%; p = 0.598), both unadjusted calculations and propensity-score adjustment showed a substantial increase in LOS (6.1 days; 95% confidence interval [CI], 4.9 to 7.4) and total costs ($10,355; 95% CI, $7,540 to $13,170) among CDAD+ patients. CONCLUSIONS: PAMV patients have an order of magnitude higher risk of having CDAD than other hospitalized patients. Concurrent CDAD infection is associated with increased hospital LOS and costs. The PAMV population is an attractive target for aggressive measures aimed at CDAD prevention.

Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria.

OBJECTIVE: To identify predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia (VAP) attributed to potentially antibiotic-resistant Gram-negative bacteria (PARGNB) [Pseudomonas aeruginosa, Acinetobacter species, and Stenotrophomonas maltophilia]. DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital. PATIENTS: Adult patients requiring hospitalization with microbiologically confirmed VAP attributed to PARGNB. INTERVENTIONS: Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: Seventy-six patients with VAP attributed to PARGNB were identified over a 5-year period. Nineteen patients (25.0%) died during hospitalization. Patients receiving their first dose of appropriate antibiotic therapy within 24 h of BAL sampling had a statistically lower 30-day mortality rate compared to patients receiving the first dose of appropriate therapy >24 h after BAL (17.2% vs 50.0%; p = 0.005). VAP due to Acinetobacter species was most often initially treated with an inappropriate antibiotic regimen, followed by S maltophilia and P aeruginosa (66.7% vs 33.3% vs 17.2%; p = 0.017). Overall, total hospitalization costs were statistically similar in patients initially treated with an inappropriate antibiotic regimen compared to an appropriate regimen ($68,597 +/- $55,466 vs $86,644 +/- $64,433; p = 0.390). CONCLUSIONS: These data suggest that inappropriate initial antibiotic therapy of microbiologically confirmed VAP attributed to PARGNB is associated with greater 30-day mortality. High rates of VAP attributed to antibiotic-resistant bacteria (eg, Acinetobacter species) may require changes in the local empiric antibiotic treatment of VAP in order to optimize the prescription of appropriate initial therapy.

Inappropriate therapy for methicillin-resistant Staphylococcus aureus: resource utilization and cost implications.

BACKGROUND: Methicillin-resistant Staphylococcus aureus causes significant morbidity and mortality. Initially inappropriate antibiotic therapy for methicillin-resistant S. aureus increases the risk for mortality. The impact of initially inappropriate antibiotic therapy on hospital length of stay and costs remains unknown. METHODS: We identified patients admitted with nonnosocomial methicillin-resistant S. aureus sterile-site infections during a 3 yr period and compared those given appropriate antibiotic therapy with those given initially inappropriate antibiotic therapy. Appropriate therapy was defined based on timely administration of an anti-infective to which the pathogen was in vitro susceptible. Hospital length of stay served as the primary end point whereas total hospital costs represented a secondary end point. We attempted to adjust for multiple potential confounders including demographics, comorbid illnesses, infection characteristics, and severity of illness. We conducted subgroup analyses in patients who survived their hospital stay and in those requiring admission to the intensive care unit. RESULTS: The cohort included 291 patients and 77% received initially inappropriate antibiotic therapy. Approximately one in five patients died during their hospitalization. The median length of stay among the appropriately treated population was 2 days shorter than those given initially inappropriate antibiotic therapy (7.1 vs. 9.3 days, p = .050). After adjusting for covariates in a Cox proportional hazards model, initially appropriate therapy remained associated with a reduced length of stay (hazard ratio: 0.69, 95% confidence interval: 0.51-0.92, p = .013). Median crude costs in those treated appropriately were $13,688 compared with $19,427 (p = .019). Restricting the analysis to either hospital survivors or to those needing intensive care did not alter our observations. CONCLUSION: Initially inappropriate antibiotic therapy for methicillin-resistant S. aureus prolongs length of stay and increases hospital costs. Efforts to lower rates of initially inappropriate antibiotic therapy for methicillin-resistant S. aureus sterile-site infections will likely improve outcomes for both patients and for healthcare institutions.

Health care-associated pneumonia (HCAP): a critical appraisal to improve identification, management, and outcomes--proceedings of the HCAP Summit.

Increasingly, patients are receiving treatment at facilities other than hospitals, including long-term-health care facilities, assisted-living environments, rehabilitation facilities, and dialysis centers. As with hospital environments, nonhospital settings present their own unique risks of pneumonia. Traditionally, pneumonia in these facilities has been categorized as community-acquired pneumonia (CAP). However, the new designation for pneumonias acquired in these settings is health care-associated pneumonia (HCAP), which covers pneumonias acquired in health care environments outside of the traditional hospital setting and excludes hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and CAP. Although HCAP is currently treated with the same protocols as CAP, recent evidence indicates that HCAP differs from CAP with respect to pathogens and prognosis and, in fact, more closely resembles HAP and VAP. The HCAP Summit convened national infectious disease opinion leaders for the purpose of analyzing current literature, clinical trial data, diagnostic considerations, therapeutic options, and treatment guidelines related to HCAP. After an in-depth analysis of these areas, the infectious disease investigators participating in the summit were surveyed with regard to 10 clinical practice statements. The results were then compared with results of the same survey as completed by 744 Infectious Diseases Society of America members. The similarities and differences between those survey results are the basis of this publication.