Microbiome Compositions and Resistome Levels after Antibiotic Treatment of Critically Ill Patients: An Observational Cohort Study

Hospitalization and treatment with antibiotics increase the risk of acquiring multidrug-resistant bacteria due to antibiotic-mediated changes in patient microbiota. This study aimed to investigate how broad- and narrow-spectrum antibiotics affect the gut microbiome and the resistome in antibiotic naïve patients during neurointensive care. Patients admitted to the neurointensive care unit were treated with broad-spectrum (meropenem or piperacillin/tazobactam) or narrow-spectrum antibiotic treatment (including ciprofloxacin, cefuroxime, vancomycin and dicloxacillin) according to clinical indications. A rectal swab was collected from each patient before and after 5–7 days of antibiotic therapy (N = 34), respectively. Shotgun metagenomic sequencing was performed and the composition of metagenomic species (MGS) was determined. The resistome was characterized with CARD RGI software and the CARD database. As a measure for selection pressure in the patient, we used the sum of the number of days with each antibiotic (antibiotic days). We observed a significant increase in richness and a tendency for an increase in the Shannon index after narrow-spectrum treatment. For broad-spectrum treatment the effect was more diverse, with some patients increasing and some decreasing in richness and Shannon index. This was studied further by comparison of patients who had gained or lost >10 MGS, respectively. Selection pressure was significantly higher in patients with decreased richness and a decreased Shannon index who received the broad treatment. A decrease in MGS richness was significantly correlated to the number of drugs administered and the selection pressure in the patient. Bray–Curtis dissimilarities were significant between the pre- and post-treatment of samples in the narrow group, indicating that the longer the narrow-spectrum treatment, the higher the differences between the pre- and the post-treatment microbial composition. We did not find significant differences between pre- and post-treatment for both antibiotic spectrum treatments; however, we observed that most of the antibiotic class resistance genes were higher in abundance in post-treatment after broad-spectrum treatment.

Neurointensive care of traumatic brain injury in the elderly—age-specific secondary insult levels and optimal physiological levels to target need to be defined

Background Elderly patients with traumatic brain injury increase. Current targets and secondary insult definitions during neurointensive care (NIC) are mostly based on younger patients. The aim was therefore to study the occurrence of predefined secondary insults and the impact on outcome in different ages with particular focus on elderly. Methods Patients admitted to Uppsala 2008–2014 were included. Patient characteristics, NIC management, monitoring data, and outcome were analyzed. The percentage of monitoring time for ICP, CPP, MAP, and SBP above-/below-predefined thresholds was calculated. Results Five hundred seventy patients were included, 151 elderly ≥ 65 years and 419 younger 16–64 years. Age ≥ 65 had significantly higher percentage of CPP > 100, MAP > 120, and SBP > 180 and age 16–64 had higher percentage of ICP ≥ 20, CPP ≤ 60, and MAP ≤ 80. Age ≥ 65 contributed independently to the different secondary insult patterens. When patients in all ages were analyzed, low percentage of CPP > 100 and SBP > 180, respectively, was significant predictors of favorable outcome and high percentage of ICP ≥ 20, CPP > 100, SBP ≤ 100, and SBP > 180, respectively, was predictors of death. Analysis of age interaction showed that patients ≥ 65 differed and had a higher odds for favorable outcome with large proportion of good monitoring time with SBP > 180. Conclusions Elderly ≥ 65 have different patterns of secondary insults/physiological variables, which is independently associated to age. The finding that SBP > 180 increased the odds of favorable outcome in the elderly but decreased the odds in younger patients may indicate that blood pressure should be treated differently depending on age.

Effect of Therapeutic Plasma Exchange on Plasma Constituents in Neurointensive Care Unit Patients: A Retrospective Study

Purpose Plasma exchange is one of the recommended therapeutic procedures for autoimmune neurological conditions and involves removal of plasma over multiple sessions for exclusion of autoantibodies responsible for the disease process. This study aimed to evaluate the changes in the concentration of plasma constituents with five cycles of alternate day therapeutic plasma exchange (TPE), identify contributing factors for hypoproteinemia, and examine its impact on clinical outcomes. Methods This was a single-center, retrospective cohort study involving patients with autoimmune neurological diseases who underwent at least five cycles of TPE in the neurointensive care unit (NICU). Data regarding plasma protein concentrations, serum electrolytes, fluid input/output before and after every TPE cycle and clinical outcomes in terms of duration of ventilation, and NICU and hospital stay were collected from the medical records over a 1-year period. Results The levels of plasma proteins (total protein, albumin and globulin) (p < 0.001), sodium (p < 0.001), calcium (p < 0.001), and hemoglobin (p = 0.002) declined significantly after TPE. Difference in plasma protein levels before and after TPE did not correlate with durations of mechanical ventilation and hospital and NICU stay. Difference in total protein and globulin correlated negatively with fluid balance and positively with daily protein intake (p < 0.05 for both). Conclusion A significant decrease in plasma proteins and other plasma constituents is seen with TPE. Changes in plasma proteins are related to hemodilution and protein intake. Decrease in plasma proteins did not affect duration of hospital or NICU stay and duration of mechanical ventilation.

Upstream/Downstream

Withdrawal of life-sustaining treatment is the leading factor in deaths after brain injuries: 64 to 92 percent of neurointensive care deaths occur after treatment withdrawal, most within the first 72 hours after injury. There is risk inversion in the way the upstream and downstream ethical risks are weighed for comatose patients. The inversion occurs when more certain risks are undertaken upstream (in neurointensive care) to avoid less certain, more speculative risks downstream. These are ethical risks—the upstream risk is that withdrawing life-sustaining treatment soon after a brain injury will result in death, and a lost opportunity to survive and live a good and flourishing life. The downstream risk is that the patient will survive, but in a condition that is unacceptable to them. The upstream/downstream problem is a wicked problem, where each solution can create new problems. Whether the risks can, and should, be reinverted is the question.