Quantitative SARS-CoV-2 RT-PCR and Bronchoalveolar Cytokine Concentrations Redefine the COVID-19 Phenotypes in Critically Ill Patients.

RATIONALE: Recent studies suggest that both hypo- and hyperinflammatory acute respiratory distress syndrome (ARDS) phenotypes characterize severe COVID-19-related pneumonia. The role of lung Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) viral load in contributing to these phenotypes remains unknown. OBJECTIVES: To redefine COVID-19 ARDS phenotypes when considering quantitative SARS-CoV-2 RT-PCR in the bronchoalveolar lavage of intubated patients. To compare the relevance of deep respiratory samples versus plasma in linking the immune response and the quantitative viral loads. METHODS: Eligible subjects were adults diagnosed with COVID-19 ARDS who required mechanical ventilation and underwent bronchoscopy. We recorded the immune response in the bronchoalveolar lavage and plasma and the quantitative SARS-CoV-2 RT-PCR in the bronchoalveolar lavage. Hierarchical clustering on principal components was applied separately on the 2 compartments' datasets. Baseline characteristics were compared between clusters. MEASUREMENTS AND RESULTS: Twenty subjects were enrolled between August 2020 and March 2021. Subjects underwent bronchoscopy on average 3.6 days after intubation. All subjects were treated with dexamethasone prior to bronchoscopy, 11 of 20 (55.6%) received remdesivir and 1 of 20 (5%) received tocilizumab. Adding viral load information to the classic 2-cluster model of ARDS revealed a new cluster characterized by hypoinflammatory responses and high viral load in 23.1% of the cohort. Hyperinflammatory ARDS was noted in 15.4% of subjects. Bronchoalveolar lavage clusters were more stable compared to plasma. CONCLUSIONS: We identified a unique group of critically ill subjects with COVID-19 ARDS who exhibit hypoinflammatory responses but high viral loads in the lower airways. These clusters may warrant different treatment approaches to improve clinical outcomes.

Addition of aminoglycosides reduces recurrence of infections with multidrug-resistant Gram-negative bacilli in patients with sepsis and septic shock.

OBJECTIVES: Aminoglycosides and ß-lactams have been recommended for treatment of sepsis/septic shock despite a lack of mortality benefit. Previous studies have examined resistance emergence for the same bacterial isolate using old dosing regimens and during a narrow follow-up window. We hypothesised that combination regimens employing aminoglycosides will decrease the cumulative incidence of infections due to multidrug-resistant (MDR) Gram-negative bacilli (GNB) compared with ß-lactams alone. METHODS: All adult patients admitted to Barnes Jewish Hospital between 2010 and 2017 with a diagnosis of sepsis/septic shock were included in this retrospective cohort study. Patients were divided into two treatment groups, with and without aminoglycosides. Patient demographics, severity of presentation, administered antibiotics, follow-up cultures with susceptibility results for a period of 4-60 days, and mortality were extracted. After propensity score matching, a Fine-Gray subdistribution proportional hazards model summarised the estimated incidence of subsequent infections with MDR-GNB in the presence of all-cause death as a competing risk. RESULTS: A total of 10 212 septic patients were included, with 1996 (19.5%) treated with at least two antimicrobials including one aminoglycoside. After propensity score matching, the cumulative incidence of MDR-GNB infections between 4-60 days was lower in the combination group (incidence at 60 days 0.073, 95% CI 0.062-0.085) versus patients not receiving aminoglycosides (0.116, 95% CI 0.102-0.130). Patients aged ≤65 years and with haematological malignancies had a larger treatment effect in subgroup analyses. CONCLUSION: Addition of aminoglycosides to ß-lactams may protect against subsequent infections due to MDR-GNB in patients with sepsis/septic shock.

Clinician Perspectives on Barriers and Enablers to Implementing an Inpatient Oncology Early Warning System: A Mixed-Methods Study.

PURPOSE: To elicit end-user and stakeholder perceptions regarding design and implementation of an inpatient clinical deterioration early warning system (EWS) for oncology patients to better fit routine clinical practices and enhance clinical impact. METHODS: In an explanatory-sequential mixed-methods study, we evaluated a stakeholder-informed oncology early warning system (OncEWS) using surveys and semistructured interviews. Stakeholders were physicians, advanced practice providers (APPs), and nurses. For qualitative data, we used grounded theory and thematic content analysis via the constant comparative method to identify determinants of OncEWS implementation. RESULTS: Survey respondents generally agreed that an oncology-focused EWS could add value beyond clinical judgment, with nurses endorsing this notion significantly more strongly than other clinicians (nurse: median 5 on a 6-point scale [6 = strongly agree], interquartile range 4-5; doctors/advanced practice providers: 4 [4-5]; P = .005). However, some respondents would not trust an EWS to identify risk accurately (n = 36 [42%] somewhat or very concerned), while others were concerned that institutional culture would not embrace such an EWS (n = 17 [28%]).Interviews highlighted important aspects of the EWS and the local context that might facilitate implementation, including (1) a model tailored to the subtleties of oncology patients, (2) transparent model information, and (3) nursing-centric workflows. Interviewees raised the importance of sepsis as a common and high-risk deterioration syndrome. CONCLUSION: Stakeholders prioritized maximizing the degree to which the OncEWS is understandable, informative, actionable, and workflow-complementary, and perceived these factors to be key for translation into clinical benefit.

The importance of viruses in ventilator-associated pneumonia.

OBJECTIVE: Ventilator-associated pneumonia (VAP) remains a challenge. The importance of viruses in VAP is not established. We sought to determine the prevalence of viruses in VAP and the outcomes of viral VAP. DESIGN: Retrospective study of VAP over 3 years. The frequency of a viral process represented the primary endpoint. Clinical outcomes served as secondary endpoints. We identified variables independently associated with a virus and conducted sensitivity analyses to assess the interaction between type of infection and patient characteristics. SETTING: Tertiary-care referral center. PATIENTS: The final cohort consisted of 710 patients and a virus was isolated in 5.1%. INTERVENTIONS: None. RESULTS: The most common viruses included: rhinovirus, influenza A, and cytomegalovirus. Baseline characteristics were similar between those with and without viral infections. In logistic regression, immunosuppression (adjusted odds ratio [aOR], 2.97; 95% confidence interval [CI], 1.44-6.14) and stem-cell transplantation (SCT, aOR, 3.58; 95% CI, 1.17-10.99) were independently associated with a virus. The presence of either variable performed poorly as a screening test for a virus. In-hospital (22.4% vs 21.6%; P = .869) and 30-day (32.8% vs 27.9%; P = .448) mortality rates were similar between the cohorts, respectively. Sensitivity analyses restricted to patients without a mixed viral and bacterial infection or those who were immunocompetent yielded similar results. CONCLUSION: Although infrequent, a range of viruses may cause VAP. Viruses more often complicate SCT and immunosuppression, but one can isolate viruses in immunocompetent subjects. Viral VAP produces severe infection and results in high mortality rates. Clinical features do not differentiate viral from nonviral VAP.

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.

The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update.

Pseudomonas aeruginosa is a Gram-negative bacterial pathogen that is a common cause of nosocomial infections, particularly pneumonia, infection in immunocompromised hosts, and in those with structural lung disease such as cystic fibrosis. Epidemiological studies have identified increasing trends of antimicrobial resistance, including multi-drug resistant (MDR) isolates in recent years. P. aeruginosa has several virulence mechanisms that increase its ability to cause severe infections, such as secreted toxins, quorum sensing and biofilm formation. Management of P. aeruginosa infections focuses on prevention when possible, obtaining cultures, and prompt initiation of antimicrobial therapy, occasionally with combination therapy depending on the clinical scenario to ensure activity against P. aeruginosa. Newer anti-pseudomonal antibiotics are available and are increasingly being used in the management of MDR P. aeruginosa.

Ceftolozane/tazobactam probability of target attainment and outcomes in participants with augmented renal clearance from the randomized phase 3 ASPECT-NP trial.

BACKGROUND: The randomized, double-blind, phase 3 ASPECT-NP trial evaluated the efficacy of 3 g of ceftolozane/tazobactam (C/T) versus 1 g of meropenem infused every 8 h for 8 to 14 days for treatment of adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). We assessed the probability of target attainment and compared efficacy outcomes from ASPECT-NP in participants with augmented renal clearance (ARC) versus those with normal renal function. METHODS: Baseline renal function was categorized as normal renal function (creatinine clearance 80-130 mL/min) or ARC (creatinine clearance > 130 mL/min). Population pharmacokinetic models informed Monte Carlo simulations to assess probability of target attainment in plasma and pulmonary epithelial lining fluid. Outcomes included 28-day all-cause mortality and clinical cure and per-participant microbiologic cure rates at the test-of-cure visit. RESULTS: A > 99% and > 80% probability of target attainment was demonstrated for ceftolozane and tazobactam, respectively, in simulated plasma and epithelial lining fluid. Within treatment arms, 28-day all-cause mortality rates in participants with normal renal function (C/T, n = 131; meropenem, n = 123) and ARC (C/T, n = 96; meropenem, n = 113) were comparable (data comparisons presented as rate; treatment difference [95% CI]) (C/T: normal renal function, 17.6%; ARC, 17.7%; 0.2 [- 9.6 to 10.6]; meropenem: normal renal function, 20.3%; ARC, 17.7%; - 2.6 [- 12.6 to 7.5]). Clinical cure rates at test-of-cure were also comparable across renal function groups within treatment arms (C/T: normal renal function, 57.3%; ARC, 59.4%; - 2.1 [- 14.8 to 10.8]; meropenem: normal renal function, 59.3%; ARC, 57.5%; 1.8 [- 10.6 to 14.2]). Per-participant microbiologic cure rates at test-of-cure were consistent across renal function groups within treatment arms (C/T: normal renal function, 72.2% [n/N = 70/97]; ARC, 71.4% [n/N = 55/77]; 0.7 [- 12.4 to 14.2]; meropenem: normal renal function, 75.0% [n/N = 66/88]; ARC, 70.0% [n/N = 49/70]; 5.0 [- 8.7 to 19.0]). CONCLUSIONS: C/T and meropenem resulted in 28-day all-cause mortality, clinical cure, and microbiologic cure rates that were comparable between participants with ARC or normal renal function. In conjunction with high probability of target attainment, these results confirm that C/T (3 g) every 8 h is appropriate in patients with HABP/VABP and ARC. Trial registration ClinicalTrials.gov identifier: NCT02070757, registered February 25, 2014; EudraCT: 2012-002862-11.

A Pragmatic Machine Learning Model To Predict Carbapenem Resistance.

Infection caused by carbapenem-resistant (CR) organisms is a rising problem in the United States. While the risk factors for antibiotic resistance are well known, there remains a large need for the early identification of antibiotic-resistant infections. Using machine learning (ML), we sought to develop a prediction model for carbapenem resistance. All patients >18 years of age admitted to a tertiary-care academic medical center between 1 January 2012 and 10 October 2017 with ≥1 bacterial culture were eligible for inclusion. All demographic, medication, vital sign, procedure, laboratory, and culture/sensitivity data were extracted from the electronic health record. Organisms were considered CR if a single isolate was reported as intermediate or resistant. Patients with CR and non-CR organisms were temporally matched to maintain the positive/negative case ratio. Extreme gradient boosting was used for model development. In total, 68,472 patients met inclusion criteria, with 1,088 patients identified as having CR organisms. Sixty-seven features were used for predictive modeling. The most important features were number of prior antibiotic days, recent central venous catheter placement, and inpatient surgery. After model training, the area under the receiver operating characteristic curve was 0.846. The sensitivity of the model was 30%, with a positive predictive value (PPV) of 30% and a negative predictive value of 99%. Using readily available clinical data, we were able to create a ML model capable of predicting CR infections at the time of culture collection with a high PPV.

New Perspectives on Antimicrobial Agents: Ceftolozane-Tazobactam.

Ceftolozane-tazobactam (C/T) is a new fifth-generation cephalosporin/beta-lactamase inhibitor combination approved by the Food and Drug Administration and the European Medicines Agency for treatment of complicated intraabdominal infections, complicated urinary tract infections, and hospital-acquired pneumonia in adult patients. This review will briefly describe the pharmacology of C/T and focus on the emerging clinical trial and real-world data supporting its current utilization. Additionally, our synthesis of these data over time has set our current usage of C/T at Barnes-Jewish Hospital (BJH). C/T is primarily employed as directed monotherapy at BJH when Pseudomonas aeruginosa isolates are identified with resistance to other beta-lactams. C/T can also be used empirically in specific clinical situations at BJH prior to microbiological detection of an antibiotic-resistant P. aeruginosa isolate. These situations include critically ill patients in the intensive care unit (ICU) setting, where there is a high likelihood of infection with multidrug-resistant (MDR) P. aeruginosa; patients failing therapy with a carbapenem; specific patient populations known to be at high risk for infection with MDR P. aeruginosa (e.g., lung transplant and cystic fibrosis patients); and patients know to have previous infection or colonization with MDR P. aeruginosa.

Bloodstream Infections and Delayed Antibiotic Coverage Are Associated With Negative Hospital Outcomes in Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Bloodstream infections (BSIs) are common after hematopoietic stem cell transplantation (HSCT) and are associated with increased long-term morbidity and mortality. However, short-term outcomes related to BSI in this population remain unknown. More specifically, it is unclear whether choices related to empiric antimicrobials for potentially infected patients are associated with patient outcomes. RESEARCH QUESTION: Are potential delays in appropriate antibiotics associated with hospital outcomes among HSCT recipients with BSI? STUDY DESIGN AND METHODS: We conducted a retrospective cohort study at a large comprehensive inpatient academic cancer center between January 2014 and June 2017. We identified all admissions for HSCT and prior recipients of HSCT. We defined potential delay in appropriate antibiotics as > 24 h between positive blood culture results and the initial dose of an antimicrobial with activity against the pathogen. RESULTS: We evaluated 2,751 hospital admissions from 1,086 patients. Of these admissions, 395 (14.4%) involved one or more BSIs. Of these 395 hospitalizations, 44 (11.1%) involved potential delays in appropriate antibiotics. The incidence of mortality was higher in BSI hospitalizations than in those without BSI (23% vs 4.5%; P < .001). In multivariable analysis, BSI was an independent predictor of mortality (OR, 8.14; 95% CI, 5.06-13.1; P < .001). Mortality was higher for admissions with potentially delayed appropriate antibiotics than for those with appropriate antibiotics (48% vs 20%; P < .001). Potential delay in antibiotics was also an independent predictor of mortality in multivariable analysis (OR, 13.8; 95% CI, 5.27-35.9; P < .001). INTERPRETATION: BSIs were common and independently associated with increased morbidity and mortality. Delays in administration of appropriate antimicrobials were identified as an important factor in hospital morbidity and mortality. These findings may have important implications for our current practice of empiric antibiotic treatment in HSCT patients.

Early Palliative Care Consultation in the Medical ICU: A Cluster Randomized Crossover Trial.

OBJECTIVES: To assess the impact of early triggered palliative care consultation on the outcomes of high-risk ICU patients. DESIGN: Single-center cluster randomized crossover trial. SETTING: Two medical ICUs at Barnes Jewish Hospital. PATIENTS: Patients (n = 199) admitted to the medical ICUs from August 2017 to May 2018 with a positive palliative care screen indicating high risk for morbidity or mortality. INTERVENTIONS: The medical ICUs were randomized to intervention or usual care followed by washout and crossover, with independent assignment of patients to each ICU at admission. Intervention arm patients received a palliative care consultation from an interprofessional team led by board-certified palliative care providers within 48 hours of ICU admission. MEASUREMENTS AND MAIN RESULTS: Ninety-seven patients (48.7%) were assigned to the intervention and 102 (51.3%) to usual care. Transition to do-not-resuscitate/do-not-intubate occurred earlier and significantly more often in the intervention group than the control group (50.5% vs 23.4%; p < 0.0001). The intervention group had significantly more transfers to hospice care (18.6% vs 4.9%; p < 0.01) with fewer ventilator days (median 4 vs 6 d; p < 0.05), tracheostomies performed (1% vs 7.8%; p < 0.05), and postdischarge emergency department visits and/or readmissions (17.3% vs 38.9%; p < 0.01). Although total operating cost was not significantly different, medical ICU (p < 0.01) and pharmacy (p < 0.05) operating costs were significantly lower in the intervention group. There was no significant difference in ICU length of stay (median 5 vs 5.5 d), hospital length of stay (median 10 vs 11 d), in-hospital mortality (22.6% vs 29.4%), or 30-day mortality between groups (35.1% vs 36.3%) (p > 0.05). CONCLUSIONS: Early triggered palliative care consultation was associated with greater transition to do-not-resuscitate/do-not-intubate and to hospice care, as well as decreased ICU and post-ICU healthcare resource utilization. Our study suggests that routine palliative care consultation may positively impact the care of high risk, critically ill patients.

Factors Associated With Clinical Deterioration Among Patients Hospitalized on the Wards at a Tertiary Cancer Hospital.

PURPOSE: Patients hospitalized outside the intensive care unit (ICU) frequently experience clinical deterioration. Little has been done to describe the landscape of clinical deterioration among inpatients with cancer. We aimed to describe the frequency of clinical deterioration among patients with cancer hospitalized on the wards at a major academic hospital and to identify independent risk factors for clinical deterioration among these patients. METHODS: This was a retrospective cohort study at a 1,300-bed urban academic hospital with a 138-bed inpatient cancer center. We included consecutive admissions to the oncology wards between January 1, 2014, and June 30, 2017. We defined clinical deterioration as the composite of ward death and transfer to the ICU. RESULTS: We evaluated 21,219 admissions from 9,058 patients. The composite outcome occurred during 1,945 admissions (9.2%): 1,365 (6.4%) had at least one ICU transfer, and 580 (2.7%) involved ward death. Logistic regression identified several independent risk factors for clinical deterioration, including the following: age (odds ratio [OR], 1.33 per decade; 95% CI, 1.07 to 1.67), male sex (OR, 1.15; 95% CI, 1.05 to 1.33), comorbidities, illness severity (OR, 1.11; 95% CI, 1.10 to 1.13), emergency admission (OR, 1.45; 95% CI, 1.26 to 1.67), hospitalization on particular wards (OR, 1.525; 95% CI, 1.326 to 1.67), bacteremia (OR, 1.24; 95% CI, 1.01 to 1.52), fungemia (OR, 3.76; 95% CI, 1.90 to 7.41), tumor lysis syndrome (OR, 3.01; 95% CI, 2.41 to 3.76), and receipt of antimicrobials (OR, 2.04; 95% CI, 1.72 to 2.42) and transfusions (OR, 1.65; 95% CI, 1.42 to 1.92). CONCLUSION: Clinical deterioration was common; it occurred in more than 9% of admissions. Factors independently associated with deterioration included comorbidities, admission source, infections, and blood product transfusion.

Postoperative Pneumonia Prevention in Pulmonary Resections: A Feasibility Pilot Study.

BACKGROUND: Pneumonia after pulmonary resection occurs in 5% to 12% of patients and causes substantial morbidity. Oral hygiene regimens lower the incidence of ventilator-associated pneumonias; however, the impact in patients undergoing elective pulmonary resection is unknown. We conducted a prospective pilot study to assess the feasibility of an oral hygiene intervention in this patient cohort. METHODS: Patients undergoing elective pulmonary resection were prospectively enrolled in a single-arm interventional study with time-matched controls. Participants were asked to brush their teeth with 0.12% chlorhexidine three times daily for 5 days before their operations and 5 days or until the time of discharge after their operations. Patients were eligible if they had known or suspected lung cancer and were undergoing (1) any anatomic lung resection or (2) a wedge resection with forced expiratory volume in 1 second or diffusing capacity of lung for carbon monoxide less than 50% predicted. RESULTS: Sixty-two patients were enrolled in the pilot intervention group and compared with a contemporaneous cohort of 611 patients who met surgical inclusion criteria. Preoperative adherence to the chlorhexidine toothbrushing regimen was high: median 100% (interquartile range: 87% to 100%). Postoperatively, 80% of patients continued toothbrushing, whereas 20% declined further participation. Among those who participated postoperatively, median adherence was 86% (interquartile range: 53% to 100%). There was a trend toward reduction in postoperative pneumonia: 1.6% (1 of 62) in the intervention cohort versus 4.9% (30 of 611) in the time-matched cohort (p = 0.35). The number needed to treat to prevent one case of pneumonia was 30 patients. CONCLUSIONS: This pilot study demonstrated patients can comply with an inexpensive perioperative oral hygiene regimen that may be promising for reducing morbidity (Clinical Trials Registry: NCT01446874).

Clinical epidemiology of carbapenem-resistant gram-negative sepsis among hospitalized patients: Shifting burden of disease?

BACKGROUND: Infections caused by carbapenem-resistant gram-negative bacilli are an emerging public health threat. However, there is a paucity of data examining comparative incidence rates, risk factors, and outcomes in this population. METHODS: This single-center retrospective cohort study was conducted at an urban tertiary-care academic medical center. We included patients admitted from 2012 to 2015 who met the following criteria: i) age ≥ 18 years; and ii) culture positive for carbapenem-resistant Enterobacteriaceae (CRE) or carbapenem-resistant non-Enterobacteriaceae (CRNE) from any site. Exclusion criteria were: i) < 2 systemic inflammatory response criteria; ii) cystic fibrosis; and iii) no targeted treatment. We evaluated hospital survival by Cox regression and year-by-year differences in the distribution of cases by the Cochran-Armitage test. RESULTS: 448 patients were analyzed (CRE, n = 111 [24.8%]; CRNE, n = 337 [75.2%]). CRE sepsis cases increased significantly over the study period (P <.001), driven primarily by increasing incidence of Enterobacter spp. infection (P = .004). No difference was observed in hospital survival between patients with CRE versus CRNE sepsis (hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.83-2.02; P = .285), even after adjusting for confounding factors (adjusted HR, 1.08; 95% CI, 0.62-1.87; P = .799). CONCLUSIONS: Clinical outcomes did not differ between patients with CRE versus CRNE sepsis. Dramatic increases in CRE, particularly Enterobacter spp., appear to be causing a shift in the burden of clinically significant carbapenem-resistant gram-negative infection.

Sepsis-Associated Coagulopathy Severity Predicts Hospital Mortality.

OBJECTIVES: To assess whether sepsis-associated coagulopathy predicts hospital mortality. DESIGN: Retrospective cohort study. SETTING: One-thousand three-hundred beds urban academic medical center. PATIENTS: Six-thousand one-hundred forty-eight consecutive patients hospitalized between January 1, 2010, and December 31, 2015. INTERVENTIONS: Mild sepsis-associated coagulopathy was defined as an international normalized ratio greater than or equal to 1.2 and less than 1.4 plus platelet count less than or equal to 150,000/µL but greater than 100,000/µL; moderate sepsis-associated coagulopathy was defined with either an international normalized ratio greater than or equal to 1.4 but less than 1.6 or platelets less than or equal to 100,000/µL but greater than 80,000/µL; severe sepsis-associated coagulopathy was defined as an international normalized ratio greater than or equal to 1.6 and platelets less than or equal to 80,000/µL. MEASUREMENTS AND MAIN RESULTS: Hospital mortality increased progressively from 25.4% in patients without sepsis-associated coagulopathy to 56.1% in patients with severe sepsis-associated coagulopathy. Similarly, duration of hospitalization and ICU care increased progressively as sepsis-associated coagulopathy severity increased. Multivariable analyses showed that the presence of sepsis-associated coagulopathy, as well as sepsis-associated coagulopathy severity, was independently associated with hospital mortality regardless of adjustments made for baseline patient characteristics, hospitalization variables, and the sepsis-associated coagulopathy-cancer interaction. Odds ratios ranged from 1.33 to 2.14 for the presence of sepsis-associated coagulopathy and from 1.18 to 1.51 for sepsis-associated coagulopathy severity for predicting hospital mortality (p < 0.001 for all comparisons). CONCLUSIONS: The presence of sepsis-associated coagulopathy identifies a group of patients with sepsis at higher risk for mortality. Furthermore, there is an incremental risk of mortality as the severity of sepsis-associated coagulopathy increases.

The Burden of Viruses in Pneumonia Associated With Acute Respiratory Failure: An Underappreciated Issue.

BACKGROUND: Pneumonia associated with mechanical ventilation (MV) results in substantial mortality and represents a leading reason for the use of antibiotics. The role of viruses in this setting is unclear. Identifying a viral cause in such instances could facilitate antibiotic stewardship. METHODS: We performed a secondary analysis of a prospective cohort with pneumonia requiring MV. We included both cases occurring in the community and hospital-onset cases and classified patients according to the cause of the pneumonia. The prevalence of viral pathogens represented the primary end point. We identified variables independently associated with isolation of a viral organism as the sole pathogen. RESULTS: The cohort included 364 patients, and a virus was the sole pathogen in 79 cases (21.7%). The most common viruses included rhinovirus/enterovirus (n = 20), influenza A (n = 12), and respiratory syncytial virus (n = 11). The rate of in-hospital death was high (37.2%) and did not differ from that seen in other patients (36.5%). The duration of MV, hospital length of stay, and 30-day readmission rates also did not differ based on the cause of pneumonia. Two variables were independently associated with recovery of a virus: an Acute Physiology and Health Evaluation II score of < 26 (adjusted odds ratio [AOR], 0.51; 95% CI, 0.28-0.93; P = .027) and stem cell transplantation (SCT) (AOR, 4.39; 95% CI, 2.03-9.50; P = .001). A sensitivity analysis excluding patients who underwent SCT did not substantially alter our observations. CONCLUSIONS: Viruses represent a major cause of pneumonia in critically ill patients requiring MV. Identifying such subjects presents an opportunity for discontinuing antibiotics. Clinicians should consider systematically evaluating patients with pneumonia requiring MV for viral pathogens.

Treatment of severe skin and soft tissue infections: a review.

PURPOSE OF REVIEW: To review the salient features of the management of severe skin and soft tissue infections (SSTIs), including toxic shock syndrome, myonecrosis/gas gangrene, and necrotizing fasciitis. RECENT FINDINGS: For severe SSTIs, intensive care, source control, and broad-spectrum antimicrobials are required for the initial phase of illness. There is an increasing focus on the utility of rapid diagnostic tests to help in selection and de-escalation of antimicrobials for SSTIs. In addition, clinical prediction scores have shown promise in helping predict patients who do not require antimicrobials directed against methicillin-resistant Staphylococcus aureus. Immune status has been shown to be important in clinical outcomes of some, but not all types of SSTIs. The debate for benefits of intravenous immunoglobulin continues to be waged in the recent literature. SUMMARY: Severe SSTIs are common and their management complex due to regional variation in predominant pathogens and antimicrobial resistance patterns, as well variations in host immune responses. Unique aspects of care for severe SSTIs are discussed including the role of surgical consultation and source control. The unique features of SSTIs in immunocompromised hosts are also described.