Multidimensional Assessment of the Host Response in Mechanically Ventilated Patients with Suspected Pneumonia.

Rationale: The identification of informative elements of the host response to infection may improve the diagnosis and management of bacterial pneumonia. Objectives: To determine whether the absence of alveolar neutrophilia can exclude bacterial pneumonia in critically ill patients with suspected infection and to test whether signatures of bacterial pneumonia can be identified in the alveolar macrophage transcriptome. Methods: We determined the test characteristics of alveolar neutrophilia for the diagnosis of bacterial pneumonia in three cohorts of mechanically ventilated patients. In one cohort, we also isolated macrophages from alveolar lavage fluid and used the transcriptome to identify signatures of bacterial pneumonia. Finally, we developed a humanized mouse model of Pseudomonas aeruginosa pneumonia to determine if pathogen-specific signatures can be identified in human alveolar macrophages. Measurements and Main Results: An alveolar neutrophil percentage less than 50% had a negative predictive value of greater than 90% for bacterial pneumonia in both the retrospective (n = 851) and validation cohorts (n = 76 and n = 79). A transcriptional signature of bacterial pneumonia was present in both resident and recruited macrophages. Gene signatures from both cell types identified patients with bacterial pneumonia with test characteristics similar to alveolar neutrophilia. Conclusions: The absence of alveolar neutrophilia has a high negative predictive value for bacterial pneumonia in critically ill patients with suspected infection. Macrophages can be isolated from alveolar lavage fluid obtained during routine care and used for RNA-Seq analysis. This novel approach may facilitate a longitudinal and multidimensional assessment of the host response to bacterial pneumonia.

The Influence of Surrogate Decision Makers on Clinical Decision Making for Critically Ill Adults.

PURPOSE: Intensive care unit patients rarely have decisional capacity and often surrogates make clinical decisions on their behalf. Little is known about how surrogate characteristics may influence end-of-life decision making for these patients. This study sought to determine how surrogate characteristics impact physicians' approach to end-of-life decision making. METHODS: From March 2011 to August 2011, a survey was fielded to 1000 randomly sampled critical care physicians using a modified Dillman approach. The survey included a hypothetical vignette to examine how physicians' approach varied based on patient age, patient-surrogate relationship, surrogate-staff relationship, basis for surrogate's stated preferences, and surrogate's understanding of patient's condition. Outcomes included physicians' beliefs regarding (1) appropriateness of cardiopulmonary resuscitation (CPR); (2) appropriate locus of decision making for the patient; (3) degree to which a physician would try to influence a surrogate if disagreement was present; and (4) physician strategies to discussing end-of-life with surrogates. RESULTS: Of 922 eligible physicians, 608 (66%) participated. Across all vignettes, CPR was felt to be less appropriate and surrogates less likely to be given priority with an older rather than younger patient (15% vs 63% and 50% vs 65%, both P values <.001). Cardiopulmonary resuscitation was considered less appropriate when the surrogate-patient relationship was not close (34% vs 44%, P = .03) and the surrogate's understanding was poor (34% vs 43%, P = .05). No other surrogate characteristics examined yielded statistically significant associations. CONCLUSION: Some surrogate characteristics may modify clinicians' beliefs and practices regarding end-of-life care, suggesting the nuances of the surrogate-physician relationship and clinical decision making for critically ill patients.

Rapid Detection of Methicillin-Resistant Staphylococcus aureus in BAL: A Pilot Randomized Controlled Trial.

BACKGROUND: Guidelines recommend empirical vancomycin or linezolid for patients with suspected pneumonia at risk for methicillin-resistant Staphylococcus aureus (MRSA). Unneeded vancomycin or linezolid use may unnecessarily alter host flora and expose patients to toxicity. We therefore sought to determine if rapid testing for MRSA in BAL can safely decrease use of vancomycin or linezolid for suspected MRSA pneumonia. METHODS: Operating characteristics of the assay were initially validated against culture on residual BAL. A prospective, unblinded, randomized clinical trial to assess the effect of antibiotic management made on the basis of rapid diagnostic testing (RDT) compared with usual care was subsequently conducted, with primary outcome of duration of vancomycin or linezolid administration. Secondary end points focused on safety. RESULTS: Sensitivity of RPCR was 95.7%, with a negative likelihood ratio of 0.04 for MRSA. The clinical trial randomized 45 patients: 22 to antibiotic management made on the basis of RDT and 23 to usual care. Duration of vancomycin or linezolid administration was significantly reduced in the intervention group (32 h [interquartile range, 22-48] vs 72 h [interquartile range, 50-113], P < .001). Proportions with complications and length of stay trended lower in the intervention group. Hospital mortality was 13.6% in the intervention group and 39.1% for usual care (95% CI of difference, -3.3 to 50.3, P = .06). Standardized mortality ratio was 0.48 for the intervention group and 1.18 for usual care. CONCLUSIONS: A highly sensitive BAL RDT for MRSA significantly reduced use of vancomycin and linezolid in ventilated patients with suspected pneumonia. Management made on the basis of RDT had no adverse effects, with a trend to lower hospital mortality. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT02660554; URL: www.clinicaltrials.gov.

Viral Pneumonia and Acute Respiratory Distress Syndrome.

Respiratory viruses are a common cause of severe pneumonia and acute respiratory distress syndrome (ARDS) in adults. The advent of new diagnostic technologies, particularly multiplex reverse transcription polymerase chain reaction, have increased the recognition of viral respiratory infections in critically ill adults. Supportive care for adults with ARDS caused by respiratory viruses is similar to the care of patients with ARDS from other causes. Although antiviral therapy is available for some respiratory viral infections, further research is needed to determine which groups of patients would benefit.