The determinants of hospital mortality among patients with septic shock receiving appropriate initial antibiotic treatment*.

OBJECTIVE: To identify the determinants of hospital mortality among patients with septic shock receiving appropriate initial antibiotic treatment. DESIGN: A retrospective cohort study of hospitalized patients with blood culture positive septic shock (January 2002-December 2007). SETTING: Barnes-Jewish Hospital, a 1,250-bed urban teaching hospital. PATIENTS: Four hundred thirty-six consecutive patients with septic shock and a positive blood culture. INTERVENTIONS: Data abstraction from computerized medical records. MEASUREMENTS AND MAIN RESULTS: Septic shock was associated with bloodstream infection due to Gram-negative bacteria (59.2%) and Gram-positive bacteria (40.8%). Two hundred twenty-four patients (51.4%) died during their hospitalization. The presence of infection attributed to antibiotic-resistant bacteria was similar for patients who survived and expired (22.6% vs. 20.1%; p = .516). Multivariate logistic regression analysis demonstrated that infection acquired in the intensive care unit (adjusted odds ratio 1.99; 95% confidence interval 1.52-2.60; p = .011) and increasing Acute Physiology and Chronic Health Evaluation II scores (one-point increments) (adjusted odds ratio 1.11; 95% confidence interval 1.09-1.14; p < .001) were independently associated with a greater risk of hospital mortality, whereas infection with methicillin-susceptible Staphylococcus aureus (adjusted odds ratio 0.32; 95% confidence interval 0.20-0.52; p = .017) was independently associated with a lower risk of hospital mortality. Patients infected with methicillin-susceptible Staphylococcus aureus infections were statistically younger and had lower Charlson comorbidity and Acute Physiology and Chronic Health Evaluation II scores compared to patients with non-methicillin-susceptible Staphylococcus aureus infections. CONCLUSIONS: Among patients with septic shock who receive appropriate initial antibiotic treatment, acquisition of infection in the intensive care unit and severity of illness appear to be the most important determinants of clinical outcome.

Implementation of a real-time computerized sepsis alert in nonintensive care unit patients.

OBJECTIVE: Early therapy of sepsis involving fluid resuscitation and antibiotic administration has been shown to improve patient outcomes. A proactive tool to identify patients at risk for developing sepsis may decrease time to interventions and improve patient outcomes. The objective of this study was to evaluate whether the implementation of an automated sepsis screening and alert system facilitated early appropriate interventions. DESIGN: Prospective, observational, pilot study. SETTING: Six medicine wards in Barnes-Jewish Hospital, a 1250-bed academic medical center. PATIENTS: Patients identified by the sepsis screen while admitted to a medicine ward were included in the study. A total of 300 consecutive patients were identified comprising the nonintervention group (n=200) and the intervention group (n=100). INTERVENTIONS: A real-time sepsis alert was implemented for the intervention group, which notified the charge nurse on the patient's hospital ward by text page. MEASUREMENTS AND MAIN RESULTS: Within 12 hrs of the sepsis alert, interventions by the treating physicians were assessed, including new or escalated antibiotics, intravenous fluid administration, oxygen therapy, vasopressors, and diagnostic tests. After exclusion of patients without commitment to aggressive management, 181 patients in the nonintervention group and 89 patients in the intervention group were analyzed. Within 12 hrs of the sepsis alert, 70.8% of patients in the intervention group had received≥1 intervention vs. 55.8% in the nonintervention group (p=.018). Antibiotic escalation, intravenous fluid administration, oxygen therapy, and diagnostic tests were all increased in the intervention group. This was a single-center, institution- and patient-specific algorithm. CONCLUSIONS: The sepsis alert developed at Barnes-Jewish Hospital was shown to increase early therapeutic and diagnostic interventions among nonintensive care unit patients at risk for 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.

Treatment-related risk factors for hospital mortality in Candida bloodstream infections.

OBJECTIVE: To examine the relationship between treatment-related variables for Candida bloodstream infection and hospital mortality. DESIGN: Retrospective cohort analysis. SETTING: Thousand two hundred-bed academic medical center. PATIENTS: A total of 245 consecutive patients with Candida bloodstream infections who received antifungal therapy. INTERVENTIONS: Identification of treatment-related risk factors: central vein catheter retention, inadequate initial fluconazole dosing, and delayed administration of antifungal therapy. MEASUREMENTS AND MAIN RESULTS: A total of 245 patients with Candida bloodstream infections who received antifungal therapy were identified. One hundred eleven (45.3%) patients were managed in an intensive care unit and analyzed as a separate subgroup. In the hospital cohort, 72 (29.4%) patients died during hospitalization and 40 (36.0%) patients died in the intensive care unit cohort. In the hospital cohort, logistic regression analysis identified Acute Physiology and Chronic Health Evaluation II scores (1-point increments) (adjusted odds ratio [AOR], 1.18; 95% confidence interval [CI], 1.11-1.25; p = 0.003), corticosteroid use at the time a positive blood culture was drawn (AOR, 3.41; 95% CI, 1.96-5.93; p = 0.027), inadequate initial fluconazole dosing (AOR, 3.31; 95% CI, 1.83-6.00; p = 0.044), and retention of a central vein catheter (AOR, 4.85; 95% CI, 2.54-9.29; p = 0.015) as independent determinants of hospital mortality. In the intensive care unit cohort, logistic regression analysis identified Acute Physiology and Chronic Health Evaluation II scores (1-point increments) (AOR, 1.21; 95% CI, 1.14-1.29; p = 0.001), inadequate initial fluconazole dosing (AOR, 9.22; 95% CI, 2.15-19.79; p = 0.004), and retention of a central vein catheter (AOR, 6.21; 95% CI, 3.02-12.77; p = 0.011), as independent determinants of hospital mortality. For both cohorts the incremental presence of treatment-related risk factors was statistically associated with greater hospital mortality. CONCLUSIONS: Treatment-related factors, including retention of central vein catheters and inadequate initial fluconazole dosing, were associated with increased hospital mortality in patients with Candida bloodstream infections. These data suggest that optimization of initial antifungal therapy and removal of central vein catheters may improve the outcomes of patients with Candida bloodstream infections.

Healthcare-associated pneumonia: approach to management.

Healthcare-associated pneumonia patients have worse outcomes and a different microbiologic profile than those with community-acquired pneumonia, including a greater risk for multidrug-resistant (MDR) organism infection. Risks include hospitalization for 2 or more days within 90 days, presentation from a nursing home or long-term care facility, attending a hospital or hemodialysis clinic, receiving intravenous therapy within 30 days, and immunosuppression. Ability to predict infection with MDR organisms varies, and the relative frequency of MDR organisms varies by geographic region. Initial treatment is broad-spectrum empiric antibiotics.

A comparison of culture-positive and culture-negative health-care-associated pneumonia.

OBJECTIVE: The aim of this study is to describe the initial antibiotic treatment regimens, severity of illness, and in-hospital mortality among culture-negative (CN) and culture-positive (CP) patients with health-care-associated pneumonia (HCAP). METHODS: We used a retrospective cohort study, examining adult patients with HCAP from Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital. RESULTS: Eight hundred seventy patients with HCAP were identified over a 3-year period (January 2003 through December 2005) of whom 431 (49.5%) were CP. Among the non-CP patients, 290 (66.1%) had no respiratory cultures obtained, and 149 (33.9%) had no growth or nonpathogenic oral flora identified and were classified as CN. CN patients were more likely to have received an initial antibiotic regimen (ceftriaxone +/- azithromycin or moxifloxacin) targeting community-acquired pneumonia pathogens compared with CP patients (71.8% vs 25.5%, P < .001). Severity of illness as assessed by ICU admission and mechanical ventilation (MV) was statistically lower in CN compared with CP patients (ICU admittance 12.1% vs 48.7%, P < .001; MV: 6.7% vs 44.5%, P < .001). In-hospital mortality and hospital length of stay were also statistically lower for CN patients (mortality: 7.4% vs 24.6%, P < .001; hospital length of stay: 6.7 +/- 7.4 days vs 12.1 +/- 11.7 days, P < .001). CONCLUSIONS: In this analysis, patients with CN HCAP had lower severity of illness, hospital mortality, and hospital length of stay compared with CP patients. These data suggest that patients with CN HCAP differ substantially from patients with HCAP with positive microbiologic cultures.

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.