Time to Clinical Stability in Patients with Ventilator-Associated Pneumonia due to Methicillin-Resistant Staphylococcus aureus Treated with Linezolid versus Vancomycin: Results from the IMPACT-HAP Study

Background: Time to clinical stability is a well-defined early clinical outcome in hospitalized patients with community-acquired pneumonia, but it has not been evaluated in patients with ventilator-associated pneumonia (VAP). The objective of this study was to compare time to clinical stability in patients with MRSA VAP treated with linezolid versus vancomycin. Methods: This was a secondary analysis of the IMPACT-HAP study database. VAP was defined according to CDC criteria. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. A patient was considered to reach clinical stability the day that the following four criteria were met: 1) Afebrile for 24 hours, 2) Decrease in WBC \u3e10% or WBC within normal range, 3) Improving of PaO2/FiO2 ratio of \u3e 20%, or PaO2/FiO2 ratio \u3e 250, or extubation, or FiO2 ≤ 30% if extubated, and 4) Systolic blood pressure \u3e90 mmHg. Time to clinical stability for linezolid and vancomycin were compared using the Chi-Squared and Student’s t-tests. Results: A total of 89 patients treated with linezolid and 75 patients treated with vancomycin met study criteria. From the population of linezolid treated patients, 79% reached clinical stability, compared to 75% of the population of vancomycin treated patients (P=0.463). Median time to clinical stability was 6 days (IQR 8) for patients treated with linezolid, versus 7 days (IQR 12) for patients treated with vancomycin (P=0.490). Conclusions: This study failed to demonstrate a statistically significant difference in time to clinical stability in patients with MRSA VAP treated with linezolid or vancomycin. The number of days for patients to reach clinical stability can be used as an early clinical outcome in patients with VAP

Anidulafungin compared with fluconazole for treatment of candidemia and other forms of invasive candidiasis caused by Candida albicans: a multivariate analysis of factors associated with improved outcome

<p>Abstract</p> <p>Background</p> <p><it>Candida albicans </it>is the most common cause of candidemia and other forms of invasive candidiasis. Systemic infections due to <it>C. albicans </it>exhibit good susceptibility to fluconazole and echinocandins. However, the echinocandin anidulafungin was recently demonstrated to be more effective than fluconazole for systemic <it>Candida </it>infections in a randomized, double-blind trial among 245 patients. In that trial, most infections were caused by <it>C. albicans</it>, and all respective isolates were susceptible to randomized study drug. We sought to better understand the factors associated with the enhanced efficacy of anidulafungin and hypothesized that intrinsic properties of the antifungal agents contributed to the treatment differences.</p> <p>Methods</p> <p>Global responses at end of intravenous study treatment in patients with <it>C. albicans </it>infection were compared post-hoc. Multivariate logistic regression analyses were performed to predict response and to adjust for differences in independent baseline characteristics. Analyses focused on time to negative blood cultures, persistent infection at end of intravenous study treatment, and 6-week survival.</p> <p>Results</p> <p>In total, 135 patients with <it>C. albicans </it>infections were identified. Among these, baseline APACHE II scores were similar between treatment arms. In these patients, global response was significantly better for anidulafungin than fluconazole (81.1% vs 62.3%; 95% confidence interval [CI] for difference, 3.7-33.9). After adjusting for baseline characteristics, the odds ratio for global response was 2.36 (95% CI, 1.06-5.25). Study treatment and APACHE II score were significant predictors of outcome. The most predictive logistic regression model found that the odds ratio for study treatment was 2.60 (95% CI, 1.14-5.91) in favor of anidulafungin, and the odds ratio for APACHE II score was 0.935 (95% CI, 0.885-0.987), with poorer responses associated with higher baseline APACHE II scores. Anidulafungin was associated with significantly faster clearance of blood cultures (log-rank <it>p </it>< 0.05) and significantly fewer persistent infections (2.7% vs 13.1%; <it>p </it>< 0.05). Survival through 6 weeks did not differ between treatment groups.</p> <p>Conclusions</p> <p>In patients with <it>C. albicans </it>infection, anidulafungin was more effective than fluconazole, with more rapid clearance of positive blood cultures. This suggests that the fungicidal activity of echinocandins may have important clinical implications.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00058682">NCT00058682</a></p

Sepsis in Patients with Ventilator Associated Pneumonia due to Methicillin- Resistant Staphylococcus aureus: Incidence and Impact on Clinical outcomes

Background: Sepsis is a clinical syndrome associated with organ dysfunction due to a dysregulated host response to infection. Methicillin-resistant Staphylococcus aureus (MRSA) Ventilator-associated pneumonia (VAP) is a serious infection frequently associated with sepsis. The objectives of this study were to define the incidence of sepsis and clinical failure in patients with MRSA VAP. Methods: This was a secondary analysis of the Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) study database. VAP was defined according to CDC criteria. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. We used the 3rd International Consensus Definitions for sepsis. The presence of clinical failure was evaluated at the 14-day follow-up and defined as: 1) progression of baseline signs and symptoms of pneumonia, or 2) death. The Chi- Square Trend Test was utilized to determine the association between the level of organ dysfunction and clinical failure. Results: MRSA VAP was diagnosed in 205 patients with 138 (67%) presenting with sepsis. Clinical failure occurred in 14% (8/57) of patients without sepsis. Clinical failure occurred in 18% (13/73) of patients with sepsis and 1 organ dysfunction, in 28% (12/43) of patients with sepsis and 2 organ dysfunction, in 28% (5/18) of patients with sepsis and 3 organ dysfunction, and in 100% (4/4) of patients with sepsis and 4 organ dysfunction (p= 0.01). Conclusions: Sepsis is a frequent complication of MRSA VAP and the number of organ dysfunction correlates with clinical failure in these patients. Effective prevention and treatment of sepsis and associated organ dysfunction is essential to avoid cumulative burden of disease in MRSA VAP

Assessment of Disparities Associated with a Crisis Standards of Care Resource Allocation Algorithm for Patients in 2 US Hospitals during the COVID-19 Pandemic

Importance: Significant concern has been raised that crisis standards of care policies aimed at guiding resource allocation may be biased against people based on race/ethnicity. Objective: To evaluate whether unanticipated disparities by race or ethnicity arise from a single institution\u27s resource allocation policy. Design, Setting, and Participants: This cohort study included adults (aged ≥18 years) who were cared for on a coronavirus disease 2019 (COVID-19) ward or in a monitored unit requiring invasive or noninvasive ventilation or high-flow nasal cannula between May 26 and July 14, 2020, at 2 academic hospitals in Miami, Florida. Exposures: Race (ie, White, Black, Asian, multiracial) and ethnicity (ie, non-Hispanic, Hispanic). Main Outcomes and Measures: The primary outcome was based on a resource allocation priority score (range, 1-8, with 1 indicating highest and 8 indicating lowest priority) that was assigned daily based on both estimated short-term (using Sequential Organ Failure Assessment score) and longer-term (using comorbidities) mortality. There were 2 coprimary outcomes: maximum and minimum score for each patient over all eligible patient-days. Standard summary statistics were used to describe the cohort, and multivariable Poisson regression was used to identify associations of race and ethnicity with each outcome. Results: The cohort consisted of 5613 patient-days of data from 1127 patients (median [interquartile range {IQR}] age, 62.7 [51.7-73.7]; 607 [53.9%] men). Of these, 711 (63.1%) were White patients, 323 (28.7%) were Black patients, 8 (0.7%) were Asian patients, and 31 (2.8%) were multiracial patients; 480 (42.6%) were non-Hispanic patients, and 611 (54.2%) were Hispanic patients. The median (IQR) maximum priority score for the cohort was 3 (1-4); the median (IQR) minimum score was 2 (1-3). After adjustment, there was no association of race with maximum priority score using White patients as the reference group (Black patients: incidence rate ratio [IRR], 1.00; 95% CI, 0.89-1.12; Asian patients: IRR, 0.95; 95% CI. 0.62-1.45; multiracial patients: IRR, 0.93; 95% CI, 0.72-1.19) or of ethnicity using non-Hispanic patients as the reference group (Hispanic patients: IRR, 0.98; 95% CI, 0.88-1.10); similarly, no association was found with minimum score for race, again with White patients as the reference group (Black patients: IRR, 1.01; 95% CI, 0.90-1.14; Asian patients: IRR, 0.96; 95% CI, 0.62-1.49; multiracial patients: IRR, 0.81; 95% CI, 0.61-1.07) or ethnicity, again with non-Hispanic patients as the reference group (Hispanic patients: IRR, 1.00; 95% CI, 0.89-1.13). Conclusions and Relevance: In this cohort study of adult patients admitted to a COVID-19 unit at 2 US hospitals, there was no association of race or ethnicity with the priority score underpinning the resource allocation policy. Despite this finding, any policy to guide altered standards of care during a crisis should be monitored to ensure equitable distribution of resources

Anidulafungin in the treatment of patients with invasive candidiasis

Echinocandins have emerged as important agents for the treatment of invasive candidiasis. Forthcoming guidelines are expected to recommend an echinocandin agent as initial primary therapy in patients who are severely ill and/or have risk factors for azole resistance. Amphotericin B deoxycholate and fluconazole should be considered for initial therapy in specific populations. The echinocandin, anidulafungin, has been shown to have higher response rates compared with fluconazole in patients with invasive candidiasis. Additionally, patients treated with anidulafungin compared with patients receiving fluconazole have exhibited a trend toward improved survival. The three echinocandins (anidulafungin, caspofungin and micafungin) offer proven efficacy along with excellent side-effect profiles. While these three drugs have important differences, the empirical selection of an echinocandin should be based on the specific patient population, including clinical status, the suspected pathogen, and the susceptibility pattern at the institution. Once the Candida species is identified and its susceptibility is determined, clinicians should consider step-down therapy to either fluconazole or voriconazole, with possible conversion from intravenous to oral therapy

Defining standards of CARE for invasive fungal diseases in the ICU

The aim of this article is to review the current recommendations for the diagnosis and treatment of invasive fungal infection in the ICU setting and to explore whether there are standards of care for this patient population. The text focuses mainly on the two most common invasive fungal diseases that afflict non-neutropenic patients: candidaemia and invasive candidosis (IC), and invasive pulmonary aspergillosis (IPA).status: publishe

Candida prophylaxis and therapy in the ICU

The incidence of invasive candidiasis in critically ill patients has increased over the past decade and is associated with considerable morbidity and mortality. CANDIDA is identified in up to 17% of ICU patients, with candidemia occurring in ∼1%. CANDIDA ALBICANS continues to account for approximately half of the invasive candidiasis cases, with non- ALBICANS CANDIDA species, such CANDIDA GLABRATA, increasing in frequency. Diagnosis of invasive candidiasis is commonly based on blood culture results; however, the sensitivity of blood culture to identify CANDIDA is low. Because early, appropriate therapy has been associated with improved outcomes, antifungal therapy is being implemented in critically ill patients with risk factors for candidemia (prophylaxis). Systemic antifungal therapy is also being utilized in patients at increased risk for invasive candidiasis based on surrogate markers of infection such as colonization (preemptive therapy), or in patients with unresolving sepsis despite appropriate management (empirical therapy). Recent guidelines on the use of antifungal therapy have better identified patients who can be treated with azole derivatives and those who may benefit from echinocandins or polyenes. However, prospective trials are still needed to better identify appropriate therapy for patients at risk for, or with, confirmed invasive CANDIDA infections