Ref: Cotoia et al. J Anesth Analg Crit Care (2022) 2:41, https://doi.org/10.1186/s44158-022-00068-1

Glutamine (GLN) is classified as a non-essential amino acid and it is released from skeletal muscle to be a constituent of proteins . Furthermore, GLN acts as an immune stimulator as an essential component for lymphocyte proliferation and cytokine production, macrophage phagocytic and secretory activities, and neutrophil bacterial killing . Under stable conditions, GLN can be produced in suffcient amounts and stored in the muscle tissue. Tese stores actually represent greater than 50% of the total free amino acid pool in the body.

However, GLN levels normally decrease in intensive care unit (ICU) patients both due to a hypercatabolic status, especially in trauma and sepsis, and an increased requirement by the gut, the immune system, liver and kidneys which exceeds the individual’s ability to produce it in sufficient amounts. In critically ill patients, GLN may even become a “conditionally essential” amino acid : it is considered a “fuel for the immune system”, where a low blood concentration may impair immune cell function, resulting in poor clinical outcomes and increased risk of mortality, and so its supplementation is recommended in ICU patients . Interestingly, some authors showed that GLN supplements of 10–20 g/day (or with a high dose >0.2g/kg/day) plus standard enteral nutrition (EN) formulas reduced the rates of pneumonia, sepsis and bacteraemia in ICU patients with shortened hospital stays, better immune function and lower hospital costs .

It is important to note that humoral immunity is a process of adaptive immunity mediated by immunoglobulins such as IgA secreted by B lymphocytes . Cell-mediated immunity is responsible for destroying the intracellular pathogens with T lymphocytes, which consequently produce inflammatory mediators such as interleukin. More clinical trial and new studies on these topics are necessary to focus on cell-mediated and humoral immune responses in severely injured trauma patients and rule on GLN depletion on immune functioning . We hypothesize that GLN could enhance both humoral and cell-mediated immunity. The aim of our study is to investigate the effect of GLN-enriched EN on the cell mediated and humoral immune system in ICU polytrauma patients.

Methods:

All consecutive patients with polytrauma who required mechanical ventilation and enteral nutrition (EN) provided within 24 h since the admission in ICU at the University Hospital of Foggia from September 2016 to February 2017 were included.

Thereafter, two groups were identifed: patients treated by conventional EN (25 kcal/kg/die) and patients who have received conventional EN enriched with 50 mg/kg/ideal body weight of alanyl-GLN 20% intravenously.

We analysed the plasmatic concentration of IgA, CD3+/CD4+ T helper lymphocytes, CD3+/CD8+ T suppressor lymphocytes, CD3+/CD19+ B lymphocytes, IL-4 and IL-2 at admission and at 4 and 8 days.

Results:

IgA levels in control and glutamine (GLN) groups. Data are presented as mean ± SD. °, * and  ^ indicate a significant difference in GLN vs control at T0 (p < 0.05), at T4 (p < 0.05), and at T8 (p < 0.01); • indicates a significant difference (p < 0.05) in the GLN group between T4 and T8

CD3+/CD4+ T helper lymphocyte levels in control and glutamine (GLN) groups. Data are presented as mean ± SD. *, °, and ^ indicate a significant difference in GLN vs control at T4 (p < 0.01) and T8 (p < 0.001); ˅, ”, and • indicate statistically highly significant (p < 0.001) in the GLN group

CD3+/CD8+ T suppressor lymphocyte levels in control and glutamine (GLN) groups. Data are presented as mean ± SD. * and °indicate a significant difference in GLN vs control at T4 (p < 0.05) and at T8 (p < 0.001); ˅, ”, and • indicate statistically significant (p < 0.001) in the GLN group; x and ∩ indicate a significant difference in the control group between T0 and T4 (p < 0.001) and T4 and T8 (p = 0.002)

B lymphocyte CD3+/CD19+ levels in control and glutamine (GLN) groups. Data are presented as mean ± SD. “indicate a significant difference in GLN vs control at T8 (p = 0.01); *, ˅, and ” indicate statistically highly significant (p < 0.001) in the GLN group

IL-2 levels in control and glutamine (GLN) groups. Data are presented as mean ± SD. ^, •, and ˅ indicate a significant difference in the GLN group (p < 0.05); * and ° indicate a significant difference in the control group between T0 and T4 (p = 0.002) and T4 and T8 (p = 0.002)

IL-4 levels in control and glutamine (GLN) groups. Data are presented as mean ± SD. °, ”, and ^ indicate a significant difference (p < 0.004) in the GLN group

Results:

We identified 30 patients, with 15 subjects per group. IgA levels increased significantly in GLN vs the control group at T0, T4 and T8. CD3+/CD4+ T helper lymphocyte and CD3+/CD8+ T suppressor lymphocyte levels significantly increased in GLN vs the control group at T4 and T8. CD3+/CD19+ B lymphocyte levels increased significantly in GLN vs the control group only at T8. IL-2 and IL-4 levels showed no significant differences when comparing GLN with the control group.

Conclusions:

Our study showed that there was an improvement in humoral and cell-mediated immunity with GLN supplementation in polytrauma ICU patients using recommended doses.

The post Immunological effects of glutamine supplementation in polytrauma patients in intensive care unit first appeared on Serene.

Ref: A. Ma, M. Dong, J. Cheng et al, Journal of Intensive Medicine 3 (2023) 65–72, https://doi.org/10.1016/j.jointm.2022.05.006

The intensive care unit (ICU) is the “hardest hit” department for hospital-acquired infections, where a range of traumatic procedures can lead to fatal infections. Ventilator-related pneumonia, catheter-related bloodstream infections caused by an arterial or venous puncture, and skin and soft tissue infections (SSTIs) secondary to tracheotomy and surgical wounds are the main types of hospital-acquired infections. Nearly half of these infections are caused by Gram-positive bacteria. The increasing prevalence of multidrug-resistant Gram positive pathogens poses a significant challenge in the ICU. Methicillin-resistant Staphylococcus aureus (MRSA), methicillin susceptible Staphylococcus aureus (MSSA), and vancomycin resistant Enterococci (VRE), which are extremely common in the ICU, are regarded as priority pathogens that cause morbidity and mortality in countless cases. Therefore, it is essential for ICU clinicians to identify resistance patterns in Gram-positive bacteria and use antibiotics that are effective against these resistant phenotypes. Linezolid, a synthetic oxazolidinone antibiotic, has been approved for the treatment of infections caused by VRE, hospital acquired pneumonia caused by MRSA and MSSA, complicated SSTIs caused by Staphylococcus aureus or Streptococcus pneumoniae, and uncomplicated SSTIs caused by Staphylococcus aureus (methicillin-resistant only) or Streptococcus pyogenes. The drug has favorable in vitro and in vivo activity against the mentioned organismsy.

As advanced antibiotics commonly used in the ICU, linezolid and vancomycin are often compared. Although vancomycin is often used as the first choice, side effects pertaining to liver and kidney function, and especially renal injury, lead to certain limitations in its use in ICU patients. Linezolid is more useful than vancomycin in SSTIs and MRSA pneumonia, and is more effective and cost-effective for hospital-acquired MRSA infections. It is also the only antibiotic that is more effective than daptomycin and quinopidine (among others) for vancomycin resistant Enterococcus faecalis infection. Considering the role of linezolid in the treatment of Gram positive bacteria, this real-world study was conducted to characterize the population of critically ill patients in the ICU and infections treated with linezolid in the ICU. It also aimed to evaluate the clinical efficacy of linezolid therapy and to assess the safety of Chinese-made linezolid in ICU patients. This study collected data from 52 hospitals and conducted a retrospective analysis to guide better antibiotic prescribing among clinicians.

Clinical outcome by infecting pathogen. MRSA: Methicillin-resistant Staphylococcus aureus; MSSA: Methicillin-susceptible Staphylococcus aureus; SSTI: Skin and soft tissue infections; VRE: Vancomycin-resistant Enterococci; VSE: Vancomycin-susceptible Enterococci.

Methods:

This multi-center, observational, real-world study was conducted across 52 hospitals between June 9, 2018, and December 28, 2019. Patients who met the following inclusion criteria were included: (1) admitted to the ICU, (2) of any age group, and (3) having a clinical or laboratory diagnosis of a Gram-positive bacterial infection. Clinical efficacy was categorized as success (cured or improved), failed, or non-evaluable. Adverse events and serious adverse events were recorded during treatment.

Results:

A total of 366 ICU patients who met the inclusion criteria were evaluated. Linezolid was used as second and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (methicillin-resistant Staphylococcus aureus: n=37/119, 31.1%; methicillin-susceptible Staphylococcus aureus: n=15/119, 12.6%); this was followed by Enterococci (vancomycin-resistant Enterococci: n=8/119, 6.7%; vancomycin-susceptible Enterococci: n=11/119, 9.2%) and Streptococcus pneumoniae (multi drug resistant: n=4/119, 3.4%; non-multidrug resistant: n=2/119, 1.7%). The main infection sites where pathogens were detected included the lung (n=216/366, 59.6%), skin and soft tissue (n=104/366, 28.4%), and blood (n=50/366, 13.7%). Clinical success was achieved in 301 (82.2%) patients; 34 (9.3%) were cured and 267 (73.0%) improved; treatment failure and non-evaluable outcomes were observed in 29 (7.9%) in 36 (9.8%) patients, respectively. Linezolid-related adverse events were reported in 8 (2.2%) patients. No treatment-related serious adverse events were reported.

Conclusions:

The treatment of Gram-positive bacterial infections in the ICU is extremely important, and the selection of appropriate antibiotics based on patients’ clinical characteristics is the key to prognosis. Based on real-world results, linezolid has been found to be effective and safe in the treatment of Gram-positive bacterial infections in critically ill patients. Linezolid showed better clinical success in pulmonary infections or SSTIs caused by Staphylococcus aureus. Our results will provide intensivists with a reference for the selection of medication. However, due to the limitations of this study including those pertaining to sample size, clinicians will need to individually evaluate patient conditions before using linezolid in the clinic. In addition, they will need to be vigilant regarding possible side effects during administration.

The post Clinical efficacy and safety of linezolid in intensive care unit patients first appeared on Serene.

Ref: Bussini L., et al, J Emerg Crit Care Med 2022;6:25 | https://dx.doi.org/10.21037/jeccm-22-32

Hospital-acquired pneumonia (HAP) and ventilator associated pneumonia (VAP) remain leading causes of morbidity and mortality despite recent advances in prevention, diagnosis, and treatment. HAP is a lung infection occurring in the nosocomial setting which develops after 48 hours of hospitalization and does not appear in incubation at the hospital admission. Among nosocomial pneumonia, VAP is an infection developing in patients admitted to intensive care unit (ICU) after 48 hours of endotracheal intubation.

Indeed, the definition of VAE/VAC—that is an increase in the daily minimum positive end expiratory pressure (PEEP) of ≥3 cmH2O sustained for ≥2 days after ≥2 days of stable or decreasing daily minimum PEEP, or an increase in the fraction of inspired oxygen (FiO2) of ≥20 points sustained for ≥2 days after ≥2 days of stable or decreasing daily minimum FiO2 level—was created to frame the wide spectrum of complications related to mechanical ventilation (MV). Among them, infection-related ventilator associated complications (IVAC) are considered VAE/ VAC associated with possible pulmonary infection or nonpulmonary infection leading to respiratory deterioration (i.e., an abnormal temperature—38 ℃—and/ or white blood cell count—≤4,000 or ≥12,000 cells/mm3 —and administration of 1 or more new antibiotic for ≥4 days). Possible VAP (PVAP) refers to an IVAC with presumable lung infection supported by positive respiratory secretion or pleural fluid cultures for potentially pathogenic organisms, positive assays for respiratory viruses or Legionella, or suggestive histopathology concurrent with the IVAC.

Epidemiology

Though it is one of the most common nosocomial infections, epidemiologic data on HAP in non-ICU patients are limited and fragmented. Estimated incidence ranges from 5 to more than 20 cases per 1,000 admissions and from 2.5 to more than 6.1 cases per 1,000 non-ICU patients.

In the US, various formalized systems for ongoing national surveillance provide systematized information concerning infection rates, including pneumonia. One of the most recent large experience comes from a multicenter retrospective cohort study of 17,819 hospitalized patients from 253 US hospitals in 2012–2019 period. Among all patients enrolled, 26.5% had NVHAP, 25.6% ventilated HAP (V-HAP), and 47.9% VAP.

In Europe and incoming countries, no such reporting systems exist, and epidemiology of VAP/HAP in ICUs is inferred from national and international studies. A more recent report on pneumonia in European ICUs comes from the EU-VAP/CAP study on 2,436 patients from 27 ICUs. Among all patients enrolled, 34% developed pneumonia during ICU stay, with 18.3 VAP episodes per 1,000 ventilator-days.

The INICC is an international research network comprising centers from Latin America, Eastern Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific aimed to measure and prevent nosocomial infection. The Consortium collected prospective data on nosocomial infections from 861,284 patients hospitalized in 703 ICUs in a 6-year period from January 2010 to December 2015.

The overall rate of VAP was 13.1 per 1,000 ventilator-days, higher than rates from hospitals in North America, Western Europe in the same period (0.9 per 1,000 ventilator-days). Such higher rates could be due to the extremely low nurse-to-patient staffing ratios, the hospital overcrowding, the lack of medical supplies, and an insufficient number of experienced nurses or trained healthcare workers .

Overall, prevalence of VAP has decreased in the last decades, principally as a result of implementation of prevention protocols. Main novel strategies have been priority use of high-flow nasal oxygen or non-invasive positive pressure ventilation (NIPPV) in place of intubation/ reintubation, reduced duration of sedation and MV, daily oral care, early enteral feeding, correct in-bed positioning and early mobilization.

# , not indicated in case of VAP; *, the choice of drugs with antiCRE activity should be made upon the presence of specific risk factors, rectal carriage status and taking into account the local or center-specific epidemiology (i.e., prevalence of infections caused by CRE and most common type of carbapenemase between OXA-48, KPC and MBLs); § , consider combination treatment when ceftazidime-avibactam is used in case of VAP; °, mainly based on center-specific epidemiology, previous colonization or infection. HAP, hospital-acquired pneumonia; VAP, ventilator-associated pneumonia; MDR, multi-drug resistant; MSSA, methicillin-susceptible S. aureus; MRSA, methicillinresistant S. aureus; CRE, carbapenem-resistant Enterobacterales.

Conclusions:

HAP/VAP still represents one of the most challenging complications affecting hospitalized patients. This narrative review may provide to clinicians a complete and updated summary on prevention, diagnosis and management of HAP/VAP.

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Ref: William Durante, Nutrients 2019, 11, 2092; doi:10.3390/nu11092092

Cardiovascular disease is the primary cause of morbidity and mortality in the world, accounting  for nearly one-third of all deaths . Although the age-adjusted mortality rate for cardiovascular disease has diminished in industrialized countries owing to life- style changes, smoking cessation, advances in biomedical research, and improvements in medical care and technologies, the aging population and burgeoning epidemic of cardiometabolic disease characterized by obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, and hypertension, threatens to reverse this progress, underscoring the requirement for additional therapeutic options that target this deadly disease.

Substantial evidence indicate that amino acids play a fundamental role in the cardiovascular system. While amino acids serve as basic building blocks for protein synthesis and constitute an important energy source, a select group has been widely studied in the context of cardiovascular disease. Decades of research have established the importance of l-arginine in promoting cardiovascular health through the generation of the gas nitric oxide (NO) by the enzyme NO synthase (NOS). The release of NO by endothelial cells (ECs) regulates blood flow and blood pressure by inhibiting arterial tone. Furthermore, NO maintains blood fluidity and prevents thrombosis by limiting platelet aggregation and adhesion.

NO also protects against intimal thickening by blocking smooth muscle cell (SMC) proliferation, migration, and collagen synthesis. Moreover, NO mitigates the development of atherosclerosis by blocking the inflammatory response within the vessel wall. Interestingly, l-homoarginine, a derivative of l-arginine, also elicits beneficial effects in the circulation

l-Glutamine Metabolism

Figure-1: Overview of l-glutamine (Gln) transport and metabolism. Gln is transported into cells by various transporters and preferentially metabolized to l-glutamate (Glu) and ammonia (NH3) by the mitochondrial enzyme glutaminase (GLS). In contrast, the enzyme glutamine synthetase (GS) condenses NH3 to Glu to form Gln while the enzyme glutamine:fructose-6-phosphate amidotransferase (GFAT) transfers Gln’s amino group to fructose-6-phosphate to generate glucosamine-6-phosphate. Gln and Glu can be converted to a number of important molecules, including amino acids, fatty acids, nucleotides, adenosine triphosphate (ATP), glutathione, and Krebs cycle intermediates. Asn, asparagine; ASNS, asparagine synthetase; Asp, aspartate; ASS, argininosuccinate synthetase; ASL, argininosuccinate lyase; Cit, citrate; GLUD, glutamate dehydrogenase; _KG, _-ketoglutarate; Mal, malate; ME, malic enzyme; mTOR, mammalian target of rapamycin; NEAA, nonessential amino acids; NO, nitric oxide; OAA, oxaloacetate; Pyr, pyruvate; TAs, transaminases.

Emerging evidence indicates that l-glutamine (Gln) plays a fundamental role in cardiovascular physiology and pathology. By serving as a substrate for the synthesis of DNA, ATP, proteins, and lipids, Gln drives critical processes in vascular cells, including proliferation, migration, apoptosis, senescence, and extracellular matrix deposition. Furthermore, Gln exerts potent antioxidant and anti-inflammatory effects in the circulation by inducing the expression of hemeoxygenase-1, heat shock proteins, and glutathione. Gln also promotes cardiovascular health by serving as an l-arginine precursor to optimize nitric oxide synthesis. Importantly, Gln mitigates numerous risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, glucose intolerance, obesity, and diabetes. Many studies demonstrate that Gln supplementation protects against cardiometabolic disease, ischemia-reperfusion injury, sickle cell disease, cardiac injury by inimical stimuli, and may be beneficial in patients with heart failure. However, excessive shunting of Gln to the Krebs cycle can precipitate aberrant angiogenic responses and the development of pulmonary arterial hypertension. In these instances, therapeutic targeting of the enzymes involved in glutaminolysis such as glutaminase-1, Gln synthetase, glutamate dehydrogenase, and amino acid transaminase has shown promise in preclinical models. Future translation studies employing Gln delivery approaches and/or glutaminolysis inhibitors will determine the success of targeting Gln in cardiovascular disease.

Figure-2: Role of l-glutamine (Gln)-derived ammonia (NH3) in stimulating endothelial cell heme oxygenase-1 (HO-1) gene expression and maintaining vascular homeostasis. Gln is metabolized by glutaminase-1 (GLS1) to form the gas NH3. NH3 stimulates the production of mitochondrial reactive oxygen species (ROS) which causes the activation and translocation of NF-E2-related factor-2 transcription factor (Nrf2) into the nucleus, where it binds to the antioxidant responsive element (ARE)in the promoter region of the gene to trigger HO-1 transcription. HO-1 catalyzes the conversion of heme to carbon monoxide (CO) and biliverdin, the latter being rapidly metabolized to bilirubin by biliverdin reductase (BR). CO and the bile pigments (biliverdin and bilirubin) promote vascular homeostasis by inhibiting apoptosis, oxidative stress, inflammation, arterial tone, and vascular smooth muscle cell (SMC) proliferation and migration.

The post The Emerging Role of l-Glutamine in Cardiovascular Health and Disease first appeared on Serene.

Ref: Raman S.,etal, The SPLYT-P Randomized Clinical Trial, JAMA Pediatr. Published online December 19, 2022. doi:10.1001/jamapediatrics.2022.4912 

Importance  Most children admitted to pediatric intensive care units (PICUs) receive intravenous fluids. A recent systematic review suggested mortality benefit in critically ill adults treated with balanced solutions compared with sodium chloride, 0.9% (saline). There is a lack of clinically directive data on optimal fluid choice in critically ill children.

Objective  To determine if balanced solutions decrease the rise of plasma chloride compared with saline, 0.9%, in critically ill children.

Design, Setting, and Participants  This single-center, 3-arm, open-label randomized clinical trial took place in a 36-bed PICU. Children younger than 16 years admitted to the PICU and considered to require intravenous fluid therapy by the treating clinician were eligible. Children were screened from November 2019 to April 2021.

Interventions  Enrolled children were 1:1:1 allocated to gluconate/acetate–buffered solution, lactate-buffered solution, or saline as intravenous fluids.

Main Outcomes and Measures  The primary outcome was an increase in serum chloride of 5 mEq/L or more within 48 hours from randomization. New-onset acute kidney injury, length of hospital and intensive care stay, and intensive care–free survival  were secondary outcomes.

Results  A total of 516 patients with a median (IQR) age of 3.8 (1.0-10.4) years were randomized with 178, 171, and 167 allocated to gluconate/acetate–buffered solution, lactate-buffered solution, and saline, respectively. The serum chloride level increased 5 mEq/L or more in 37 patients (25.2%), 34 patients (23.9%), and 58 patients (40.0%) in the gluconate/acetate–buffered solution, lactate-buffered solution, and saline groups. The odds of a rise in plasma chloride 5 mEq/L or more was halved with the use of gluconate/acetate–buffered solution compared with saline (odds ratio, 0.50 [95% CI, 0.31-0.83]; P = .007) and with the use of lactate-buffered solution compared with saline (odds ratio, 0.47 [95% CI, 0.28-0.79]; P = .004). New-onset acute kidney injury was observed in 10 patients (6.1%), 6 patients (3.7%), and 5 patients (3.2%) in the gluconate/acetate–buffered solution, lactate-buffered solution, and saline groups, respectively.

Conclusions and Relevance  Balanced solutions (gluconate/acetate–buffered solution and lactate-buffered solution) administered as intravenous fluid therapy reduced the incidence of rise in plasma chloride compared with saline in children in PICU.

The post Effect of Saline vs Gluconate/Acetate–Buffered Solution vs Lactate-Buffered Solution on Serum Chloride Among Children in the Paediatric Intensive Care Unit first appeared on Serene.

Ref: Einav L. etal. Risk Factors for Malnutrition among IBD Patients, Nutrients 2021, 13, 4098. https:// doi.org/10.3390/nu13114098

The prevalence of malnutrition in inflammatory bowel diseases (IBD) is estimated to be between 6.1% and 69.7% depending on the definition used, the type of IBD, the clinical setting and disease activity. Malnutrition and sarcopenia are associated with poor clinical outcomes, hospital admissions, response to therapy and quality of life. Among hospitalized patients, malnutrition is an independent risk factor for venous thromboembolism, non-elective surgery, longer admission and increased mortality. Due to its high prevalence and associated risks, early detection of IBD patients at risk of malnutrition development is of high importance. Malnutrition is a target for primary and secondary prevention, and patients with IBD are advised to be screened for malnutrition at diagnosis and annually. The most common screening tool for malnutrition risk, and one of the most common tools used in practice, is the Malnutrition Universal Screening Tool (MUST), incorporating body mass index (BMI), recent weight loss and inadequate nutritional intake. Other screening tools, such as the Malnutrition Screening Tool (MST) used for hospitalized patients, the Mini Nutritional Assessment—Short Form (MNA-SF) for geriatric patients, and the Nutrition Risk Screening (NRS-2002) for assessment of severely ill patients , all use relatively similar parameters and provide a numerical score to categorize risk of malnutrition. Additional etiologies for impaired nutritional status among IBD patients include reduced intake due to disease symptoms, malabsorption, enteric nutrient loss, increased basal energy expenditure and certain medications. Further, a patient’s avoidance of eating may be due to fasting during medical procedures, and from prolonged restrictive diets. Therefore, malnutrition and sarcopenia are also prevalent among IBD patients in clinical remission. These IBD-specific malnutrition risk factors are not incorporated into any of the current malnutrition screening tools. Therefore, we aimed to identify IBD-related risk factors of malnutrition development, in the general IBD clinic setting.

Methods: A retrospective case-control study among IBD patients attending the IBD clinic of the Tel-Aviv Medical Center for ≥2 consecutive physician consultations per year during 2017–2020. Cases who had normal nutritional status and developed malnutrition between visits were compared to matched controls who maintained normal nutritional status. Detailed information was gathered from medical files, including: demographics, disease phenotype, characteristics and activity, diet altering symptoms and comorbidities, medical and surgical history, annual healthcare utility, nutritional intake and the Malnutrition Universal Screening Tool (MUST) score. Univariate and multivariate analyses were used to identify malnutrition risk factors. The independent risk factors identified were summed up to calculate the IBD malnutrition risk score (IBD-MR).

Results: Data of 1596 IBD patients met the initial criteria for the study. Of these, 59 patients developed malnutrition and were defined as cases (n = 59) and matched to controls (n = 59). The interval between the physician consultations was 6.2 ± 3.0 months, during which cases lost 5.3 ± 2.3 kg of body weight and controls gained 0.2 ± 2.3 kg (p < 0.001). Cases and controls did not differ in demographics, disease duration, disease phenotype or medical history. Independent IBD-related malnutrition risk factors were: 18.5 ≤ BMI ≤ 22 kg/m2 (OR = 4.71, 95%CI 1.13–19.54), high annual healthcare utility (OR = 5.67, 95%CI 1.02–31.30) and endoscopic disease activity (OR = 5.49, 95%CI 1.28–23.56). The IBD-MR was positively associated with malnutrition development independently of the MUST score (OR = 7.39, 95%CI 2.60–20.94). Among patients with low MUST scores determined during the index visit, identification of ≥2 IBD-MR factors was strongly associated with malnutrition development (OR = 8.65, 95%CI 2.21–33.82, p = 0.002). (4)

Conclusions: We identified IBD-related risk factors for malnutrition, highlighting the need for a disease-specific malnutrition screening tool, which may increase malnutrition risk detection.

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Ref: https://www.pharmacypracticenews.com/Online-First/Article/05-22/Reluctance-to-Prescribe-Supplemental-Nutrition-to-COVID-19-ICU-Patients/67144

Despite the benefits of providing early enteral nutrition (EN) and parenteral nutrition (PN) to critically ill COVID-19 patients, many physicians remain reluctant to do so, according to a survey highlighted at the American Society for Parenteral and Enteral Nutrition (ASPEN) 2022 Nutrition Science and Practice Conference.

Beth Taylor, DCN, a research scientist at Barnes-Jewish Hospital in St. Louis, and her colleagues surveyed 199 physicians and dietitians about their COVID-19 ICU nutrition practices and found that only 9% thought they had met their patients’ energy and protein requirements.

However, this feeding shortfall “was not a result of patients not absorbing nutrients; it was due to the fact that they were not being fed” for a number of reasons, Dr. Taylor noted. 

For example, 75% of respondents said they could not meet their patients’ nutritional needs because the course of their illness was unpredictable and uncertain. Even patients who “seemed to be stable” and were given “some nutrition support suddenly underwent an abrupt and profound deterioration, leading to excessive deficits of energy and protein,” she said. When this happens, the impulse is to remove enteral feeds, but she said that instead, the nutrition should be adjusted accordingly.

Much of the reluctance to use PN is linked to concerns that doing so will worsen outcomes. But as a large randomized controlled trial conducted in the pre–COVID-19 era found, there is no difference in the risk for infection or other complications between early EN and early PN in ICU patients with sepsis (Lancet 2018;391[10116]:133-143), according to Dr. Taylor.

“There are significant misconceptions or personal biases about the risks and benefits associated with use of PN, such as concern about hyperglycemia, which we have learned to manage by not providing excessive calories and practicing early glycemic control,” Dr. Taylor said. “We need to address these beliefs and prejudices and encourage aggressive EN and earlier use of supplemental PN.” 

She stressed that “a more methodical approach to nutrition support for COVID-19 patients in the ICU” is needed, along with “updated consensus guidelines on nutrition management to ensure  optimal care.”

Given the pressures of the ongoing pandemic, Dr. Taylor acknowledged, this is no easy task. “Since the very beginning of the COVID-19 pandemic, we have had to roll with the punches and learn as we go as to how to best treat our COVID-19 patients in the ICU,” she said.

During those early days, Dr. Taylor and her colleagues realized that COVID-19 patients may require nutritional assistance soon after being admitted to the ICU. “With this virus, the disease process can last a long time, so we need to think about supplemental parenteral nutrition earlier than we normally would in patients who might have a shorter course of illness,” she said.

Indeed, recommendations published in early 2020 (J Parenter Enteral Nutr 2020;44[7]:1174-1184)—and updates issued since then—urge that EN be started within 24 to 36 hours of ICU admission and PN be administered immediately if EN is not tolerated. Those guide-lines reflect what is known about the importance of early nutrition in the ICU population, where the strategy can reduce the risk for death by up to 55%, compared with when EN is delayed (Crit Care Med 2018;46[7]:1049-1056).

The post Reluctance to Prescribe Supplemental Nutrition to COVID-19 ICU Patients By David Wild first appeared on Serene.

Ref: https://www.pharmacypracticenews.com/Online-First/Article/03-22/Conservative-Dextrose-Administration-Reduces-PN-Related-Hyperglycemia-Risk/66550

Conservative rates of dextrose infusion can mitigate the risk for hyperglycemia in hospitalized adults with obesity who are receiving parenteral nutrition (PN), as shown in findings presented at the ASPEN 2022 Nutrition Science and Practice Conference. Moreover, obesity alone does not predict the likelihood of hyperglycemia during PN administration.

“Hyperglycemia is a well-described metabolic complication of parenteral nutrition in any patient, but obese adult hospitalized patients may be at an elevated risk, given the higher prevalence of insulin resistance and glucose intolerance in these individuals,” said Angela Bingham, PharmD, the vice chair and an associate professor of clinical pharmacy at Philadelphia College of Pharmacy.

To determine the effect of obesity on glycemic control in adult hospitalized patients started on PN, Dr. Bingham and her colleagues retrospectively studied 646 adult patients hospitalized from 2013 to 2021, who received at least two consecutive days of PN. The group included 205 obese patients with a body mass index (BMI) of at least 30 kg/m²; the median BMI for obese and nonobese patients was 35.55 and 23.85 kg/m², respectively. The researchers defined a hyperglycemic episode as a blood glucose level above 200 mg/dL.

According to Dr. Bingham, obese patients were younger than nonobese patients (median age, 58 vs. 62 years), more likely to have critical illness (42% vs. 29.7%) and diabetes mellitus (35.6% vs. 18.1%), and had higher serum creatinine levels (median, 0.84 vs. 0.76 mg/dL) (P<0.05 for all). Nearly all patients received PN through a central line.

Dextrose infusion rates for obese patients were lower than for nonobese patients, at 1.66 and 1.92 mg/kg per minute, on day 1 of PN (P<0.0001) and 2.62 and 2.79 mg/kg per minute on day 2 (P=0.0003).

Dr. Bingham told meeting attendees that hyperglycemic episodes were infrequent in both groups on days 1 and 2 of PN, but occurred significantly more commonly in obese patients (0.89 vs. 0.52; P<0.05).

However, multivariate analyses that adjusted for potential confounders, including age, critical illness, Charlson Comorbidity Index score, cerebrovascular disease, diabetes mellitus, serum creatinine, creatinine clearance, serum osmolarity, baseline hyperglycemia and macronutrient provision found that obesity was not an independent predictor of hyperglycemic episodes (odds ratio [OR] on day 1, 1.047; 95% CI, 0.639-1.717; P=0.8551 and OR on day 2, 0.964; 95% CI, 0.611-1.521; P=0.8758).

“Our experience shows that conservative dextrose infusion rates may minimize the risk of hyperglycemia in adult hospitalized patients with obesity receiving parenteral nutrition, and that obesity is not an independent predictor of hyperglycemic episodes during the first two days of parenteral nutrition initiation,” Dr. Bingham said.  She added that her institution’s guidelines of “vigilant” blood glucose concentration monitoring every four to six hours in PN recipients may have also contributed to the low rates of hyperglycemia.

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Introduction

Nosocomial infections are mainly caused by the gram-negative bacteria . The emergence of multidrug resistant (MDR) strains has led to increased mortality, morbidity and hospitalization costs. Carbapenems have been effective in treating various bacterial infections including MDR nosocomial infections. However, excessive and indiscriminate use of this drug has recently led to an epidemic rise in carbapenem resistance. Optimizing antibiotic utilization and exploring alternate drug therapies can be a potential way to curb carbapenem resistance.

Aim

The clinical efficacy of novel antibiotic adjuvant entity (ceftriaxone + sulbactam + ethylenediaminetetra acetic acid ) has been evaluated in the treatment of various nosocomial infections in this study.

Treatment Strategy

• A total of 59 patients were enrolled
• CSE-1034 therapy was initiated empirically in all the patients and continued based on the results of culture sensitivity and clinical outcome.
• Patients were eligible to switch over to other treatment regimens after 3 days of empirical therapy
• A dose of 3 g/12 h of CSE-1034, 1 g/8 h of meropenem and colistin with a loading dose of 9 MIU followed by BD doses of 4.5 MIU was used
• The patients were divided into 2 groups based on the antimicrobial sensitivity
• Group 1 – showing sensitivity to CSE-1034 (n=51) and
• Group 2 – resistant to CSE-1034 (n=8)
• Group 1 was further subdivided into
  • Group 1A – continued with CSE-1034 therapy (n=49)
  • Group 1B – switched to CSE-1034 and colistin combination therapy (n=2)

Results

• A total of 59 culture-positive patients with mean age of 57 ± 19 years were evaluated
• Escherichia coli was the most predominant pathogen isolated, followed by Acinetobacter baumannii, Klebsiella pneumonia, and Pseudomonas aeruginosa as seen in Figure 1.

Conclusion

• It can be concluded that the use of CSE‑1034 of ceftriaxone, sulbactam, and ethylenediaminetetraacetic acid is an effective option for the treatment of MDR nosocomial infections including pneumonia and cUTI.

• Antibiotic sensitivity analyses revealed that isolated pathogens from 78% were nearly sensitive to meropenem, 86% to CSE-1034, and nearly 100% to colistin
• The highest susceptibility to CSE-1034 was observed in E. coli (94%), followed by A. baumannii (87.5%) and K. pneumoniae (81.8%)
• Clinical cure rate with different antibiotics has been shown in Figure 2.

Conclusion

• It can be concluded that the use of CSE‑1034 of ceftriaxone, sulbactam, and ethylenediaminetetraacetic acid is an effective option for the treatment of MDR nosocomial infections including pneumonia and cUTI.

The post Novel Antibiotic Adjuvant Entity Might Be an Effective Empirical Therapy for Treating Nosocomial Infections first appeared on Serene.

Introduction

The significant prevalence, increasing antimicrobial resistance and suboptimal clinical outcomes of patients with nosocomial pneumonia warrants the need for optimization of the antimicrobial dose. Meropenem, a carbapenem, is known to be effective against many pathogens causing nosocomial pneumonia. However, there is insufficient data regarding the intrapulmonary pharmacokinetics (PK) of meropenem when administered by continuous infusion (CI).  

Aim

This study assessed the PK of two dosages of meropenem (3 g vs 6 g/day by CI) in the plasma and epithelial lining fluid (ELF) in critically ill patients with nosocomial pneumonia. 

Methods

Treatment Strategy

• Out of 31 patients, meropenem 1 g/8 h and  2 g/8 h by CI (8 h infusion) was administered to 16 and 15 patients respectively
• Blood and ELF samples were obtained on 3^rd or 4^th day of treatment once a steady state was achieved
• Blood samples were collected pre-infusion and at 1.5, 3, 6, and 8 h after the start of meropenem infusion.
• ELF samples were obtained simultaneously at 6 h post-infusion by bronchoalveolar lavage (BAL) during a standardized fiberoptic bronchoscopy
• Plasma and ELF meropenem concentrations were modeled using a population methodology, and Monte Carlo simulations were performed to estimate the probability of attaining (PTA) a free ELF concentration of 50% of time above MIC (50% fT>MIC), which results in logarithmic killing and the suppression of resistance in experimental models of pneumonia. 

Endpoints

• Median meropenem concentrations in plasma and ELF
• Probability of target attainment (PTA)

Results

• Median (IQR) meropenem plasma concentrations in the 2 g/8 h group were statistically higher at all times points compared to the 1 g/8 h group.
• The median (IQR) of meropenem AUC_0–24 h in the plasma and ELF has been compared in table 1.

Table 1. Comparison of median (IQR) of meropenem in plasma and ELF

• The penetration ratio was approximately 30% and was comparable between the dosage groups.
• An optimal PTA was achieved for MIC values < 2 mg/L with a dose of 1 g/8 h and for MIC values < 4 mg/L with a higher dose of 2 g/8 h as per the Monte Carlo simulations.

Conclusion

• Administration of meropenem by continuous infusion improves drug exposure in plasma and epithelial lining fluid (ELF) in critically ill patients with nosocomial pneumonia
• The highest licensed dose of 6 g/day (2 g/8 h) seemed to be necessary to achieve an optimal coverage in ELF for all susceptible isolates (MIC ≤ 2 mg/L) in patients with conserved renal function.
• An alternative therapy should be considered in the treatment of nosocomial pneumonia caused by gram-negative bacteria with a MIC greater than 2 mg/L.

The post Pharmacokinetics of Meropenem by Continuous Infusion in Critically Ill Patients with Nosocomial Pneumonia first appeared on Serene.