Nicholas Hampton

Septic Shock Attributed to Candida Infection: Importance of Empiric Therapy and Source Control

BACKGROUND Delayed treatment of candidemia has previously been shown to be an important determinant of patient outcome. However, septic shock attributed to Candida infection and its determinants of outcome have not been previously evaluated in a large patient population. METHODS A retrospective cohort study of hospitalized patients with septic shock and blood cultures positive for Candida species was conducted at Barnes-Jewish Hospital, a 1250-bed urban teaching hospital (January 2002-December 2010). RESULTS Two hundred twenty-four consecutive patients with septic shock and a positive blood culture for Candida species were identified. Death during hospitalization occurred among 155 (63.5%) patients. The hospital mortality rate for patients having adequate source control and antifungal therapy administered within 24 hours of the onset of shock was 52.8% (n = 142), compared to a mortality rate of 97.6% (n = 82) in patients who did not have these goals attained (P < .001). Multivariate logistic regression analysis demonstrated that delayed antifungal treatment (adjusted odds ratio [AOR], 33.75; 95% confidence interval [CI], 9.65-118.04; P = .005) and failure to achieve timely source control (AOR, 77.40; 95% CI, 21.52-278.38; P = .001) were independently associated with a greater risk of hospital mortality. CONCLUSIONS The risk of death is exceptionally high among patients with septic shock attributed to Candida infection. Efforts aimed at timely source control and antifungal treatment are likely to be associated with improved clinical outcomes.

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.

Clostridium difficile infection: a multicenter study of epidemiology and outcomes in mechanically ventilated patients.

Objectives:Clostridium difficile is a leading cause of hospital-associated infection in the United States. The purpose of this study is to assess the prevalence of C. difficile infection among mechanically ventilated patients within the ICUs of three academic hospitals and secondarily describe the influence of C. difficile infection on the outcomes of these patients. Design:A retrospective cohort study. Setting:ICUs at three teaching hospitals: Barnes-Jewish Hospital, Mayo Clinic, and Creighton University Medical Center over a 2-year period. Patients:All hospitalized patients requiring mechanical ventilation for greater than 48 hours within an ICU were eligible for inclusion. Interventions:None. Measurements and Main Results:A total of 5,852 consecutive patients admitted to the ICU were included. Three hundred eighty-six (6.6%) patients with development of C. difficile infection while in the hospital (5.39 cases/1,000 patient days). Septic shock complicating C. difficile infection occurred in 34.7% of patients. Compared with patients without C. difficile infection (n = 5,466), patients with C. difficile infection had a similar hospital mortality rate (25.1% vs 26.3%, p = 0.638). Patients with C. difficile infection were significantly more likely to be discharged to a skilled nursing or rehabilitation facility (42.4% vs 31.9%, p < 0.001), and the median hospital (23 d vs 15 d, p < 0.001) and ICU length of stay (12 d vs 8 d, p < 0.001) were found to be significantly longer in patients with C. difficile infection. Conclusions:Clostridium difficile infection is a relatively common nosocomial infection in mechanically ventilated patients and is associated with prolonged length of hospital and ICU stay, and increased need for skilled nursing care or rehabilitation following hospital discharge.

Epidemiology, co-infections, and outcomes of viral pneumonia in adults an observational cohort study

AbstractAdvanced technologies using polymerase-chain reaction have allowed for increased recognition of viral respiratory infections including pneumonia. Co-infections have been described for several respiratory viruses, especially with influenza. Outcomes of viral pneumonia, including cases with co-infections, have not been well described.This was observational cohort study conducted to describe hospitalized patients with viral pneumonia including co-infections, clinical outcomes, and predictors of mortality. Patients admitted from March 2013 to November 2014 with a positive respiratory virus panel (RVP) and radiographic findings of pneumonia within 48 h of the index RVP were included. Co-respiratory infection (CRI) was defined as any organism identification from a respiratory specimen within 3 days of the index RVP. Predictors of in-hospital mortality on univariate analysis were evaluated in a multivariate model.Of 284 patients with viral pneumonia, a majority (51.8%) were immunocompromised. A total of 84 patients (29.6%) were found to have a CRI with 48 (57.6%) having a bacterial CRI. Viral CRI with HSV, CMV, or both occurred in 28 patients (33.3%). Fungal (16.7%) and other CRIs (7.1%) were less common. Many patients required mechanical ventilation (54%) and vasopressor support (36%). Overall in-hospital mortality was high (23.2%) and readmissions were common with several patients re-hospitalized within 30 (21.1%) and 90 days (36.7%) of discharge. Predictors of in-hospital mortality on multivariate regression included severity of illness factors, stem-cell transplant, and identification of multiple respiratory viruses. In conclusion, hospital mortality is high among adult patients with viral pneumonia and patients with multiple respiratory viruses identified may be at a higher risk.

Impact of antibacterials on subsequent resistance and clinical outcomes in adult patients with viral pneumonia: An opportunity for stewardship

IntroductionRespiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use.MethodThis was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy.ResultsA total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027).ConclusionThis study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization.

Pneumonia Pathogen Characterization Is an Independent Determinant of Hospital Readmission

BACKGROUND Hospital readmissions for pneumonia occur often and are difficult to predict. For fiscal year 2013, the Centers for Medicare & Medicaid Services readmission penalties have been applied to acute myocardial infarction, heart failure, and pneumonia. However, the overall impact of pneumonia pathogen characterization on hospital readmission is undefined. METHODS This was a retrospective 6-year cohort study (August 2007 to September 2013). RESULTS We evaluated 9,624 patients with a discharge diagnosis of pneumonia. Among these patients, 4,432 (46.1%) were classified as having culture-negative pneumonia, 1,940 (20.2%) as having pneumonia caused by antibiotic-susceptible bacteria, 2,991 (31.1%) as having pneumonia caused by potentially antibiotic-resistant bacteria, and 261 (2.7%) as having viral pneumonia. The 90-day hospital readmission rate for survivors (n = 7,637, 79.4%) was greatest for patients with pneumonia attributed to potentially antibiotic-resistant bacteria (11.4%) followed by viral pneumonia (8.3%), pneumonia attributed to antibiotic-susceptible bacteria (6.6%), and culture-negative pneumonia (5.8%) (P < .001). Multiple logistic regression analysis identified pneumonia attributed to potentially antibiotic-resistant bacteria to be independently associated with 90-day readmission (OR, 1.75; 95% CI, 1.56-1.97; P < .001). Other independent predictors of 90-day readmission were Charlson comorbidity score > 4, cirrhosis, and chronic kidney disease. Culture-negative pneumonia was independently associated with lower risk for 90-day readmission. CONCLUSIONS Readmission after hospitalization for pneumonia is relatively common and is related to pneumonia pathogen characterization. Pneumonia attributed to potentially antibiotic-resistant bacteria is associated with an increased risk for 90-day readmission, whereas culture-negative pneumonia is associated with lower risk for 90-day readmission.

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

Effects of Empiric Antifungal Therapy for Septic Shock on Time to Appropriate Therapy for Candida Infection: A Pilot Study

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.)

Outcomes associated with de-escalating anti-MRSA therapy in culture-negative nosocomial pneumonia

PURPOSE Inappropriate initial therapy for Candida-related septic shock is common and associated with a high mortality rate. This before-after pilot study was conducted to determine the feasibility of using empiric therapy for reducing the time to appropriate antifungal therapy in patients with Candida-related septic shock. METHODS Patients aged 18-99 years with septic shock presenting to Barnes-Jewish Hospital, St. Louis, Missouri, in 2012-2013 were assigned to 1 of 2 groups. Patients presenting between January 1, 2012, and December 31, 2012, were managed according to local standard of care for patients with septic shock, to include antifungal therapy at the discretion of the treating physician (standard therapy group). Patients presenting between January 1, 2013, and December 31, 2013, received empiric antifungal therapy (primarily micafungin 100 mg/d or fluconazole 800 mg on day 1, followed by 400 mg/d), facilitated by a clinical pharmacist in the medical intensive care unit, until microbiologic cultures were available to determine the cause of septic shock (empiric therapy group). The primary outcome was time to appropriate therapy after shock onset. FINDINGS A total of 28 patients were enrolled (mean age, 56.3 [15.1] years [range, 30-92 years]; 16 [57.1%] men). The time to appropriate therapy after shock onset was statistically shorter with empiric therapy (n = 13) compared with standard therapy (n = 15) (10.6 [15.8] vs 40.5 [26.0] hours; P = 0.001). Patients receiving empiric therapy were more likely to have received appropriate therapy within 12 hours (69.2% vs 6.7%; P = 0.001) and within 24 hours (76.9% vs 40.0%; P = NS) of shock onset. In an analysis to determine the number of septic shock patients needed to be treated with empiric antifungal therapy for 1 patient with Candida-related septic shock to receive appropriate treatment, 256 patients without Candida infection received a total of 687 doses of empiric antifungal therapy (mean, 2.7 doses per patient) compared with 136 patients who received 382 doses of standard antifungal therapy (mean, 2.8 doses per patient); the number needed to treat was 19.6. IMPLICATIONS The present pilot study demonstrated that the use of empiric antifungal therapy for Candida-related septic shock was associated with a statistically shorter time to administration of appropriate treatment. ClinicalTrials.gov identifier.

Importance of Site of Infection and Antibiotic Selection in the Treatment of Carbapenem-Resistant Pseudomonas aeruginosa Sepsis

BACKGROUND: In culture‐positive nosocomial pneumonia, de‐escalation (DE) from broad‐spectrum empirical antimicrobials to narrower‐spectrum agents has shown to decrease broad‐spectrum antibiotic use without compromising patient outcomes. However, uncertainty exists regarding the safety of anti‐methicillin‐resistant Staphylococcus aureus (MRSA) agent DE in culture‐negative nosocomial pneumonia. This study aimed to determine if anti‐MRSA agent DE in culture‐negative nosocomial pneumonia affects 28‐day and hospital mortality, ICU and hospital length of stay (LOS), treatment failure, and safety. METHODS: This single‐center retrospective cohort study included adult patients admitted from 2012 to 2017 with nosocomial pneumonia and a negative respiratory culture. DE was defined as anti‐MRSA agent discontinuation within 4 days of initiation. Secondary outcomes included hospital mortality, hospital and ICU LOS, treatment failure, and occurrence of acute kidney injury (AKI). RESULTS: Of 279 patients included, 92 were in the DE group and 187 were in the no DE (NDE) group. Patients who were not de‐escalated received 5 more days of MRSA coverage than patients who were de‐escalated; however, there was no difference in 28‐day mortality (NDE group, 28% vs DE group, 23%; difference, −5.5%; 95% CI, −16.1 to 6.5). Patients who were de‐escalated had shorter hospital (DE group, 15 days vs NDE group, 20 days; difference, 3.2 days; 95% CI, 0.1‐6.4) and ICU (DE group, 10 days vs NDE group, 13 days; difference, 2.2 days; 95% CI, −0.3 to 4.9) LOSs after the index date. The incidence of AKI was significantly higher in patients who were not de‐escalated (DE group, 36% vs NDE group, 50%; difference, −13.8%; 95% CI, −26.9 to −0.4). CONCLUSIONS: Although anti‐MRSA agent DE in culture‐negative nosocomial pneumonia did not affect 28‐day mortality, it was associated with a shorter hospital LOS and lower incidence of AKI.