Safety, feasibility, and impact on the gut microbiome of kefir administration in critically ill adults.

BACKGROUND: Dysbiosis of the gut microbiome is frequent in the intensive care unit (ICU), potentially leading to a heightened risk of nosocomial infections. Enhancing the gut microbiome has been proposed as a strategic approach to mitigate potential adverse outcomes. While prior research on select probiotic supplements has not successfully shown to improve gut microbial diversity, fermented foods offer a promising alternative. In this open-label phase I safety and feasibility study, we examined the safety and feasibility of kefir as an initial step towards utilizing fermented foods to mitigate gut dysbiosis in critically ill patients. METHODS: We administered kefir in escalating doses (60 mL, followed by 120 mL after 12 h, then 240 mL daily) to 54 critically ill patients with an intact gastrointestinal tract. To evaluate kefir's safety, we monitored for gastrointestinal symptoms. Feasibility was determined by whether patients received a minimum of 75% of their assigned kefir doses. To assess changes in the gut microbiome composition following kefir administration, we collected two stool samples from 13 patients: one within 72 h of admission to the ICU and another at least 72 h after the first stool sample. RESULTS: After administering kefir, none of the 54 critically ill patients exhibited signs of kefir-related bacteremia. No side effects like bloating, vomiting, or aspiration were noted, except for diarrhea in two patients concurrently on laxatives. Out of the 393 kefir doses prescribed for all participants, 359 (91%) were successfully administered. We were able to collect an initial stool sample from 29 (54%) patients and a follow-up sample from 13 (24%) patients. Analysis of the 26 paired samples revealed no increase in gut microbial α-diversity between the two timepoints. However, there was a significant improvement in the Gut Microbiome Wellness Index (GMWI) by the second timepoint (P = 0.034, one-sided Wilcoxon signed-rank test); this finding supports our hypothesis that kefir administration can improve gut health in critically ill patients. Additionally, the known microbial species in kefir were found to exhibit varying levels of engraftment in patients' guts. CONCLUSIONS: Providing kefir to critically ill individuals is safe and feasible. Our findings warrant a larger evaluation of kefir's safety, tolerability, and impact on gut microbiome dysbiosis in patients admitted to the ICU. TRIAL REGISTRATION: NCT05416814; trial registered on June 13, 2022.

The human gut microbiome in critical illness: disruptions, consequences, and therapeutic frontiers.

With approximately 39 trillion cells and over 20 million genes, the human gut microbiome plays an integral role in both health and disease. Modern living has brought a widespread use of processed food and beverages, antimicrobial and immunomodulatory drugs, and invasive procedures, all of which profoundly disrupt the delicate homeostasis between the host and its microbiome. Of particular interest is the human gut microbiome, which is progressively being recognized as an important contributing factor in many aspects of critical illness, from predisposition to recovery. Herein, we describe the current understanding of the adverse impacts of standard intensive care interventions on the human gut microbiome and delve into how these microbial alterations can influence patient outcomes. Additionally, we explore the potential association between the gut microbiome and post-intensive care syndrome, shedding light on a previously underappreciated avenue that may enhance patient recuperation following critical illness. There is an impending need for future epidemiological studies to encompass detailed phenotypic analyses of gut microbiome perturbations. Interventions aimed at restoring the gut microbiome represent a promising therapeutic frontier in the quest to prevent and treat critical illnesses.

Clonidine use during dexmedetomidine weaning: A systematic review.

BACKGROUND: Dexmedetomidine is a centrally acting alpha-2A adrenergic agonist that is commonly used as a sedative and anxiolytic in the intensive care unit (ICU), with prolonged use increasing risk of withdrawal symptoms upon sudden discontinuation. As clonidine is an enterally available alpha-2A adrenergic agonist, it may be a suitable agent to taper off dexmedetomidine and reduce withdrawal syndromes. The appropriate dosing and conversion strategies for using enteral clonidine in this context are not known. The objective of this systematic review is to summarize the evidence of enteral clonidine application during dexmedetomidine weaning for prevention of withdrawal symptoms. AIM: To systematically review the practice, dosing schema, and outcomes of enteral clonidine use during dexmedetomidine weaning in critically ill adults. METHODS: This was a systematic review of enteral clonidine used during dexmedetomidine weaning in critically ill adults (≥ 18 years). Randomized controlled trials, prospective cohorts, and retrospective cohorts evaluating the use of clonidine to wean patients from dexmedetomidine in the critically ill were included. The primary outcomes of interest were dosing and titration schema of enteral clonidine and dexmedetomidine and risk factors for dexmedetomidine withdrawal. Other secondary outcomes included prevalence of adverse events associated with enteral clonidine use, re-initiation of dexmedetomidine, duration of mechanical ventilation, and ICU length of stay. RESULTS: A total of 3427 studies were screened for inclusion with three meeting inclusion criteria with a total of 88 patients. All three studies were observational, two being prospective and one retrospective. In all included studies, the choice to start enteral clonidine to wean off dexmedetomidine was made at the discretion of the physician. Weaning time ranged from 13 to 167 h on average. Enteral clonidine was started in the prospective studies in a similar protocolized method, with 0.3 mg every 6 h. After starting clonidine, patients remained on dexmedetomidine for a median of 1-28 h. Following the termination of dexmedetomidine, two trials tapered enteral clonidine by increasing the interval every 24 h from 6 h to 8h, 12h, and 24 h, followed by clonidine discontinuation. For indicators of enteral clonidine withdrawal, the previously tolerable dosage was reinstated for several days before resuming the taper on the same protocol. The adverse events associated with enteral clonidine use were higher than patients on dexmedetomidine taper alone with increased agitation. The re-initiation of dexmedetomidine was not documented in any study. Only 17 (37%) patients were mechanically ventilated with median duration of 3.5 d for 13 patients in one of the 2 studies. ICU lengths of stay were similar. CONCLUSION: Enteral clonidine is a strategy to wean critically ill patients from dexmedetomidine. There is an association of increased withdrawal symptoms and agitation with the use of a clonidine taper.

Fatal Case of Burkholderia gladioli Pneumonia in a Patient With COVID-19.

Background: Burkholderia gladioli (B gladioli) is a rare, gram-negative rod that was initially regarded as a plant pathogen. However, B gladioli has been reported as the primary pathogen causing pneumonia in organ transplant recipients and in patients with cystic fibrosis. We report a case of bacterial pneumonia caused by B gladioli in a patient hospitalized for coronavirus disease 2019 (COVID-19). Case Report: A 68-year-old male was admitted for acute hypoxic respiratory failure secondary to COVID-19 pneumonia. He was treated with dexamethasone and convalescent plasma, resulting in improvement in the hypoxemia. However, during the latter part of his inpatient stay, the patient developed pneumonia caused by B gladioli. The isolate of B gladioli was sensitive to meropenem, levofloxacin, and trimethoprim/sulfamethoxazole and intermediate to ceftazidime. He was treated with meropenem and levofloxacin. Despite treatment, the patient developed acute respiratory distress syndrome with multiorgan failure, suffered cardiac arrest, and died. Conclusion: To the best of our knowledge, this case is the first report of B gladioli coinfection in a patient hospitalized for COVID-19 and provides insight into the possible detrimental outcome of B gladioli and COVID-19 coinfection.

Readmissions among People Living with HIV Admitted for Hypertensive Emergency.

OBJECTIVES: People with human immunodeficiency virus (HIV) are at an increased risk of developing cardiovascular diseases. Hypertensive emergency (HTNE), a complication of hypertension with potentially serious health implications, has high healthcare utilization. We attempted to determine the association between HIV status and risk for 30-day readmission after index hospitalization for HTNE. METHODS: We used the Nationwide Readmissions Database to identify all of the admissions during 2010-2017 with a primary discharge diagnosis of HTNE. Admissions were stratified by HIV status and comparisons were made with the χ2 test. We investigated predictors of all-cause 30-day readmission via multivariable logistic regression. RESULTS: A total of 612,854 hospitalizations with a primary discharge diagnosis of HTNE were identified, and 4115 (0.7%) were HIV positive. There was a total of 43,937 (7.16%) 30-day readmissions, and the rate was higher in regard to positive HIV status (29.8% vs 15.0%; P < 0.001). Renal failure was the most frequent reason for HIV readmissions and the second most frequent reason for non-HIV readmissions (15.6% vs 10.3%; P < 0.001). In contrast, heart failure was the most frequent reason for non-HIV readmissions and the second most frequent reason for HIV readmissions (10.3% vs 11.9%; P = 0.234). There was a higher median cost for HIV readmissions in comparison to non-HIV readmissions ($7660 vs $7490; P < 0.001). Finally, HIV was attributed to 40.6% increased odds of readmission after adjusting for pertinent clinical and demographic factors (P < 0.001). CONCLUSIONS: HIV-positive status is associated with an increased risk for 30-day readmission after index hospitalization for HTNE.

Challenges in the Management of Gram-Negative Bacterial Infections in Patients With Ventriculoperitoneal Shunt.

Gram-negative bacterial infections of the central nervous system (CNS) have worse clinical outcomes. The most common bacteria include Escherichia Coli, Citrobacter species, Enterobacter species, Serratia species, and Pseudomonas aeruginosa. There are multiple risk factors for CNS infection after shunt insertion, including younger age, obstructive hydrocephalus, shunt revision surgery, and trauma. The clinical presentation of a ventriculoperitoneal (VP) shunt infection includes the signs and symptoms of meningitis to fever with abdominal pain and peritonitis. Apart from cerebrospinal fluid (CSF) analysis, microbiological cultures and radiological studies are key diagnostic tools. Initial empirical intravenous antimicrobial therapy is preferably broad spectrum with appropriate coverage for resistant Gram-negative pathogens and the duration of treatment depends upon pathogenesis, host factors, and clinical response to the therapy. Considering the importance of this disease and associated clinical outcomes, in this review article, we have summarized the epidemiology, clinical features, management, and prevention of Gram-negative VP shunt infections in adults.

Mycobacterium Avium Complex Genitourinary Infections: Case Report and Literature Review.

Nontuberculous mycobacterial (NTM) genitourinary (GU) infections are relatively rare, and there is frequently a delay in diagnosis. Mycobacterium avium-intracellulare complex (MAC) cases seem to be less frequent than other NTM as a cause of these infections. In addition, there are no set treatment guidelines for these organisms in the GU tract. Given the limitations of data this review summarizes a case presentation of this infection and the literature available on the topic. Many different antimicrobial regimens and durations have been used in the published literature. While the infrequency of these infections suggests that there will not be randomized controlled trials to determine optimal therapy, our case suggests that a brief course of amikacin may play a useful role in those who cannot tolerate other antibiotics.

Multisystem inflammatory syndrome in adults: A rare sequela of SARS-CoV-2 infection.

Multisystem inflammatory syndrome in adults (MIS-A) came to attention back in June 2020, when the United States Center for Disease Control and Prevention (CDC) received initial reports regarding patients who had presented delayed and multisystem involvement of the disease, with clinical course resembling multisystem inflammatory syndrome in children (MIS-C). This study introduces a case of MIS-A, where the patient presented 3 weeks after initial COVID-19 exposure. His clinical course was consistent with the working definition of MIS-A as specified by the CDC. Aggressive supportive care in the intensive care unit, utilization of advanced heart failure devices, and immunomodulatory therapeutics (high-dose steroids, anakinra, intravenous immunoglobulin) led to clinical recovery. Management of MIS-A is a topic of ongoing research and needs more studies to elaborate on treatment modalities and clinical predictors.