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We sought to assess the characteristics and outcomes of neutropenic hematologic patients with Pseudomonas aeruginosa (PA) bloodstream infection (BSI) treated with ceftolozane-tazobactam (C/T). We conducted a multicenter, international, matched-cohort study of PA BSI episodes in neutropenic hematologic patients who received C/T. Controls were patients with PA BSI treated with other antibiotics. Risk factors for overall 7-day and 30-day case fatality rates were analyzed. We compared 44 cases with 88 controls. Overall, 91% of episodes were caused by multidrug-resistant (MDR) strains. An endogenous source was the most frequent BSI origin (35.6%), followed by pneumonia (25.8%). There were no significant differences in patient characteristics between groups. C/T was given empirically in 11 patients and as definitive therapy in 41 patients. Treatment with C/T was associated with less need for mechanical ventilation (13.6% versus 33.3%; P = 0.021) and reduced 7-day (6.8% versus 34.1%; P = 0.001) and 30-day (22.7% versus 48.9%; P = 0.005) mortality. In the multivariate analysis, pneumonia, profound neutropenia, and persistent BSI were independent risk factors for 30-day mortality, whereas lower mortality was found among patients treated with C/T (adjusted OR [aOR] of 0.19; confidence interval [CI] 95% of 0.07 to 0.55; P = 0.002). Therapy with C/T was associated with less need for mechanical ventilation and reduced 7-day and 30-day case fatality rates compared to alternative agents in neutropenic hematologic patients with PA BSI. IMPORTANCE Ceftolozane-tazobactam (C/T) has been shown to be a safe and effective alternative for the treatment of difficult to treat infections due to Pseudomonas aeruginosa (PA) in the general nonimmunocompromised population. However, the experience of this agent in immunosuppressed neutropenic patients is very limited. Our study is unique because it is focused on extremely immunosuppressed hematological patients with neutropenia and bloodstream infection (BSI) due to PA (mainly multidrug resistant [MDR]), a scenario which is often associated with very high mortality rates. In our study, we found that the use of C/T for the treatment of MDR PA BSI in hematological neutropenic patients was significantly associated with improved outcomes, and, in addition, it was found to be an independent risk factor associated with increased survival. To date, this is the largest series involving neutropenic hematologic patients with PA BSI treated with C/T. Ceftolozane-tazobactam (C/T) has been shown to be a safe and effective alternative for the treatment of difficult to treat infections due to Pseudomonas aeruginosa (PA) in the general nonimmunocompromised population. However, the experience of this agent in immunosuppressed neutropenic patients is very limited.

Background: Medically vulnerable individuals are at increased risk of acquiring multidrug-resistant Enterobacterales (MDR-E) infections. People with HIV (PWH) experience a greater burden of comorbidities and may be more susceptible to MDR-E due to HIV-specific factors. Methods: We performed an observational study of PWH participating in an HIV clinical cohort and engaged in care at a tertiary care center in the Southeastern United States from 2000 to 2018. We evaluated demographic and clinical predictors of MDR-E by estimating prevalence ratios (PRs) and employing machine learning classification algorithms. In addition, we created a predictive model to estimate risk of MDR-E among PWH using a machine learning approach. Results: Among 4734 study participants, MDR-E was isolated from 1.6% (95% CI, 1.2%-2.1%). In unadjusted analyses, MDR-E was strongly associated with nadir CD4 cell count ≤200 cells/mm3 (PR, 4.0; 95% CI, 2.3-7.4), history of an AIDS-defining clinical condition (PR, 3.7; 95% CI, 2.3-6.2), and hospital admission in the prior 12 months (PR, 5.0; 95% CI, 3.2-7.9). With all variables included in machine learning algorithms, the most important clinical predictors of MDR-E were hospitalization, history of renal disease, history of an AIDS-defining clinical condition, CD4 cell count nadir ≤200 cells/mm3, and current CD4 cell count 201-500 cells/mm3. Female gender was the most important demographic predictor. Conclusions: PWH are at risk for MDR-E infection due to HIV-specific factors, in addition to established risk factors. Early HIV diagnosis, linkage to care, and antiretroviral therapy to prevent immunosuppression, comorbidities, and coinfections protect against antimicrobial-resistant bacterial infections.

Background: Multidrug-resistant Enterobacterales (MDR-E) are important pathogens. People living with human immunodeficiency virus (HIV; PLWH) may be at greater risk for MDR-E infection given relatively high antibiotic exposure and burden of comorbidities. Methods: We analyzed data from 36 521 patients in a healthcare system in North Carolina who had a clinical culture with growth of an Enterobacterales species from 2000 to 2018; 440 were PLWH. We used generalized linear models to estimate prevalence ratios and differences, contrasting PLWH and people not living with HIV (PNLWH) for resistance to individual antibiotic classes, as well as MDR-E. We assessed trends in prevalence over time by calculating the 5-year moving average and fitting restricted cubic spline models. Results: The overall prevalence of MDR-E was higher among PLWH (21.5%; 95% confidence interval [CI], 18.2%-25.1%) vs PNLWH (16.5%; 95% CI, 16.2%-16.9%), with an adjusted prevalence ratio of 1.38 (95% CI, 1.14-1.65). PLWH had higher rates of antimicrobial resistance than PNLWH for all antibiotic classes analyzed, including penicillins, penicillin/beta lactamase inhibitor combinations, and sulfonamides. MDR-E prevalence was 3 to 10 percentage points higher among PLWH than PNLWH throughout the study period based on the 5-year moving average. Conclusions: In a large clinical study population in the southeastern United States from 2000 to 2018, the prevalence of antibacterial resistance among Enterobacterales was consistently higher among PLWH than PNLWH. These data highlight the importance of identifying and mitigating the factors that contribute to antimicrobial resistance in PLWH, given the potential clinical consequences of these resistant pathogens.

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p&nbsp

Background: Among burn patients, research is conflicted, but may suggest that females are at increased risk of mortality, despite the opposite being true in non-burn trauma. Our objective was to determine whether sex-based differences in burn mortality exist, and assess whether patient demographics, comorbid conditions, and injury characteristics explain said differences. Methods: Adult patients admitted with burn injury—including inhalation injury only—between 2004 and 2013 were included. Inverse probability of treatment weights (IPTW) and inverse probability of censor weights (IPCW) were calculated using admit year, patient demographics, comorbid conditions, and injury characteristics to adjust for potential confounding and informative censoring. Standardized Kaplan–Meier survival curves, weighted by both IPTW and IPCW, were used to estimate the 30-day and 60-day risk of inpatient mortality across sex. Results: Females were older (median age 44 vs. 41 years old, p < 0.0001) and more likely to be Black (32% vs. 25%, p < 0.0001), have diabetes (14% vs. 10%, p < 0.0001), pulmonary disease (14% vs. 7%, p < 0.0001), heart failure (4% vs. 2%, p = 0.001), scald burns (45% vs. 26%, p < 0.0001), and inhalational injuries (10% vs. 8%, p = 0.04). Even after weighting, females were still over twice as likely to die after 60 days (RR 2.87, 95% CI 1.09, 7.51). Conclusion: Female burn patients have a significantly higher risk of 60-day mortality, even after accounting for demographics, comorbid conditions, burn size, and inhalational injury. Future research efforts and treatments to attenuate mortality should account for these sex-based differences. The project was supported by the National Institutes of Health, Grant Number UL1TR001111.

Background: Diabetes mellitus (DM) is a major cause of illness and death in the United States, and diabetic patients are at increased risk for burn injury. We therefore sought to examine the impact of pre-existing DM on the risk of inpatient mortality and hospital acquired infections (HAI) among burn patients. Methods: Adult patients (≥18 years old) admitted from 2004 to 2013 were analyzed. Weighted Kaplan–Meier survival curves – adjusting for patient demographics, burn mechanism, presence of inhalation injury, total body surface area, additional comorbidities, and differential lengths of stay – were used to estimate the 30-day and 60-day risk of mortality and HAIs. Results: A total of 5539 adult patients were admitted and included in this study during the study period. 655 (11.8%) had a pre-existing DM. The crude incidence of HAIs and in-hospital mortality for the whole burn cohort was 8.5% (n = 378) and 4.4% (n = 243), respectively. Diabetic patients were more likely to be older, female, have additional comorbidities, inhalational injury, and contact burns. After adjusting for patient and burn characteristics, the 60-day risk of HAI among patients with DM was significantly higher, compared to non-diabetic patients (RR 2.07, 95% CI 1.28, 6.79). However, no significant difference was seen in the 60-day risk of mortality (RR 1.34, 95% CI 0.44, 3.10). Conclusions: Pre-existing DM significantly increases the risk of developing an HAI in patients following burn injury, but does not significantly impact the risk of inpatient mortality. Further understanding of the immune modulatory mechanism of burn injury and DM is imperative to better attenuate the acquisition of HAIs.

The endemic mycoses are a group of thermally dimorphic fungal pathogens occupying a specific geographic range. In North America, the chief endemic mycoses are histoplasmosis, coccidioidomycosis, and blastomycosis. Endemic fungi can cause serious infections in solid organ transplant recipients from primary infection, reactivation of latent disease, or donor-derived infection.

Enrolling severely burn injured patients into prospective research studies poses specific challenges to investigators. The authors describe their experience of recruiting adults with ≥20% TBSA burns or inhalation injury admitted to a single academic burn unit into observational research with minimally invasive specimen collection. The authors outline iterative changes that they made to their recruitment processes in response to perceived weaknesses leading to delays in enrollment. The primary outcome was the change in days to consent for enrolled patients or cessation of recruitment for nonenrolled patients before and after the interventional modifications. The authors assessed change in overall enrollment as a secondary outcome. Study enrollment was approximately 70% in both 4-month study periods before and after the intervention. Following the intervention, time to consent by surrogate decision maker decreased from a median of 26.5 days (interquartile range [IQR] 14-41) to 3 days (IQR 3-6) (P =.004). Time to initial consent by patient changed from a median of 15 days (IQR 2-30) to 3 days (IQR 2-6) (P =.27). Time to decline for nonenrolled patients decreased from a median of 12 days (IQR 6.5-27) to 1.5 days (IQR 1-3.5) (P =.026). Both the findings of the study and a brief literature review suggest that careful design of the recruitment protocol, increased experience of the study team, and broad time windows for both approach and enrollment improve the efficiency of recruiting critically injured burn patients into research.

OBJECTIVE Burn patients are particularly vulnerable to infection, and an estimated half of all burn deaths are due to infections. This study explored risk factors for healthcare-Associated infections (HAIs) in adult burn patients. DESIGN Retrospective cohort study. SETTING Tertiary-care burn center. PATIENTS Adults (≥18 years old) admitted with burn injury for at least 2 days between 2004 and 2013. METHODS HAIs were determined in real-Time by infection preventionists using Centers for Disease Control and Prevention criteria. Multivariable Cox proportional hazards regression was used to estimate the direct effect of each risk factor on time to HAI, with inverse probability of censor weights to address potentially informative censoring. Effect measure modification by burn size was also assessed. RESULTS Overall, 4,426 patients met inclusion criteria, and 349 (7.9%) patients had at least 1 HAI within 60 days of admission. Compared to 6 times as likely to acquire an HAI (HR, 6.38; 95% CI, 3.64-11.17); and patients with >20% TBSA were >10 times as likely to acquire an HAI (HR, 10.33; 95% CI, 5.74-18.60). Patients with inhalational injury were 1.5 times as likely to acquire an HAI (HR, 1.61; 95% CI, 1.17-2.22). The effect of inhalational injury (P=.09) appeared to be larger among patients with ≤20% TBSA. CONCLUSIONS Larger burns and inhalational injury were associated with increased incidence of HAIs. Future research should use these risk factors to identify potential interventions.

Ventilator-associated pneumonia (VAP) is a frequent complication of severe burn injury. Comparing the current ventilator-associated event-possible VAP definition to the pre-2013 VAP definition, we identified considerably fewer VAP cases in our burn ICU. The new definition does not capture many VAP cases that would have been reported using the pre-2013 definition.

Patients who are admitted to the hospital after sustaining a large burn injury are at high risk for developing hospital-associated infections. If patients survive the initial 72 hours after a burn injury, infections are the most common cause of death. Ventilator-associated pneumonia is the most important infection in this patient population. The risk of infections caused by multidrug-resistant bacterial pathogens increases with hospital length of stay in burn patients. In the first days of the postburn hospitalization, more susceptible, Gram-positive organisms predominate, whereas later more resistant Gram-negative organisms are found. These findings impact the choice of empiric antibiotics in critically ill burn patients. A proactive infection control approach is essential in burn units. Furthermore, a multidisciplinary approach to burn patients with a team that includes an infectious disease specialist and a pharmacist in addition to the burn surgeon is highly recommended.

Purpose Case reports of treatment failure with standard-dose daptomycin (6 mg/kg) have recently surfaced in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) episodes with daptomycin MICs of 3 to 4 mg/L. The clinical implications of daptomycin MICs of 3 to 4 mg/L in VRE BSIs have not been elucidated. Methods We performed a single institutional retrospective analysis of adult stem cell transplant recipients and patients with hematologic malignancies diagnosed with VRE BSI from 2006 to 2014 and compared outcomes between those with daptomycin MICs of 3 to 4 mg/L those with 2 mg/L, as determined by Etest. Findings Forty-two daptomycin-treated VRE BSI episodes, all due to Enterococcus faecium were identified; 19 episodes with daptomycin MICs of 3 to 4 mg/L and 23 episodes with a daptomycin MIC of 2 mg/L. Patients in the higher daptomycin MIC group were more likely to be male, to be stem cell transplant recipients, and to have received high-dose daptomycin treatment (>6 mg/kg). In unadjusted analyses, microbiological failure in the daptomycin MICs 3 to 4 mg/L versus 2 mg/L groups (odds ratio = 1.79, 95% CI, 0.52–6.11; P = 0.35), the median duration of bacteremia (4 days in daptomycin MICs 3–4 mg/L vs 3 days in daptomycin MIC 2 mg/L; P = 0.18) and all-cause 30-day mortality (21% in daptomycin MICs 3–4 mg/L vs 35% in daptomycin MIC 2 mg/L group; P = 0.49) were not different. In adjusted analyses, the association between higher Pitt bacteremia scores and all-cause 30-day mortality was statistically significant (P = 0.0006), whereas the association between daptomycin MICs of 3 to 4 mg/L and all-cause 30-day mortality approached statistical significance (P = 0.06). Implications Duration of bacteremia and microbiological failure rates did not differ by daptomycin MICs in VRE BSI episodes in our patients, composed of adult stem cell transplant recipients and patients with hematologic malignancies. There was a nonsignificant trend in multivariable analysis suggesting that all-cause 30-day mortality was lower in patients whose VRE bloodstream isolates were with daptomycin MICs of 3 to 4 mg/L.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important healthcare-associated pathogen. We evaluated the impact of CRKP strain type and treatment on outcomes of patients with CRKP bacteriuria.

Bij de ontwikkeling van multidisciplinaire evidence based richtlijnen voor de geestelijke gezondheidszorg is het afgelopen jaar voor het eerst ervaring opgedaan met een nieuwe methode om de kracht van het wetenschappelijk bewijs te beoordelen en de sterkte van de aanbevelingen voor behandeling te bepalen: GRADE. We tonen met twee voorbeelden hoe GRADE is toegepasta in de conceptrichtlijn ASS bij volwassen. Het eerste is cognitieve gedragstherapie (CGT), waarvoor slechts één relevante studie gevonden werd, het andere is een behandeling met antidepressiva, waarvoor we meer relevante studies vonden.

Background: When developing clinical guidelines, every country summarizes the international literature itself. To save time and to develop guidelines with a broader scope, countries could join forces. In 2010 and 2011, the Netherlands Institute of Mental Health and Addiction (Trimbos Institute) and [for full text, please go to the a.m. URL], G-I-N Conference 2012