Evolution of Acinetobacter baumannii plasmids carrying the oxa58 carbapenemase resistance gene via plasmid fusion, IS26-mediated events and dif module shuffling.

Acinetobacter baumannii RepAci1-RepAci10 plasmids pA388 from a global clone 1 (GC1) isolate from Greece, and pACICU1 and variant pACICU1b from an Italian GC2 isolate were found to share a common ancestor. The ancestor formed via recombination between pdif sites in the widely-distributed RepAci1 plasmid pA1-1 and in a RepAci10 plasmid carrying the oxa58 carbapenem-resistance gene in a dif module. Each plasmid includes copies of IS26 and multiple dif modules surrounded by 28 bp pdif sites resembling the chromosomal dif site, including one carrying the oxa58 gene. Plasmid sequences were compared to identify factors driving their evolution and divergence. IS26-mediated events, recombination between pdif sites and homologous recombination have all contributed. A translocatable unit that includes oxa58, generated by an IS26-mediated adjacent deletion, had been re-inserted by IS26 adjacent to an IS26 in pACICU1b to create the oxa58 gene duplication previously found in pACICU1. The oxa58 duplication has been lost from pACICU1b and the Tn6020 variant carrying the aphA1 (kanamycin, neomycin resistance) gene in pA388 has been lost from pACICU1/1b via recombination between directly-oriented IS26 copies. Two dif modules located between directly-oriented pdif sites in pA388 have been lost from pACICU1/1b and the product of this and other deletion events as well as inversion of dif modules located between inversely-oriented pdif sites were detected experimentally in pA388 DNA by PCR. Also, the new junctions were detected in a minority of reads in pA388 long-read sequence data. Inversion and deletion were only detected when the spacers in the pdif sites were identical and equivalent events involving mismatched spacers were not detected.

Community use of oral antibiotics transiently reprofiles the intestinal microbiome in young Bangladeshi children.

Antibiotics may alter the gut microbiome, and this is one of the mechanisms by which antimicrobial resistance may be promoted. Suboptimal antimicrobial stewardship in Asia has been linked to antimicrobial resistance. We aim to examine the relationship between oral antibiotic use and composition and antimicrobial resistance in the gut microbiome in 1093 Bangladeshi infants. We leverage a trial of 8-month-old infants in rural Bangladesh: 61% of children were cumulatively exposed to antibiotics (most commonly cephalosporins and macrolides) over the 12-month study period, including 47% in the first 3 months of the study, usually for fever or respiratory infection. 16S rRNA amplicon sequencing in 11-month-old infants reveals that alpha diversity of the intestinal microbiome is reduced in children who received antibiotics within the previous 7 days; these samples also exhibit enrichment for Enterococcus and Escherichia/Shigella genera. No effect is seen in children who received antibiotics earlier. Using shotgun metagenomics, overall abundance of antimicrobial resistance genes declines over time. Enrichment for an Enterococcus-related antimicrobial resistance gene is observed in children receiving antibiotics within the previous 7 days, but not earlier. Presence of antimicrobial resistance genes is correlated to microbiome composition. In Bangladeshi children, community use of antibiotics transiently reprofiles the gut microbiome.

A case of successful pregnancy managed in a patient living with Motor Neurone Disease for more than 3 years.

A woman in her 20s presented with progressive weakness of her left arm and leg, slurred speech and swallowing difficulties. The clinical presentation and neurophysiological tests were consistent with motor neuron disease. She was referred to the regional ventilation unit for respiratory muscle function testing. This confirmed restrictive spirometry and borderline sniff nasal inspiratory pressure and cough peak expiratory flow. Three years later, she presented with an unplanned pregnancy and expressed the wish to continue the pregnancy to term. She was monitored throughout pregnancy with interval respiratory muscle testing and was reviewed in the high-risk pregnancy anaesthetic clinic. She was also closely monitored by the obstetrics and gynaecology team. A multidisciplinary team meeting between all stakeholders agreed on caesarean section delivery at 34 weeks. The pregnancy and the delivery were without complications; the baby was healthy and both mother and baby remain well to date.

Exploring cancer support needs for older African-American men with prostate cancer.

PURPOSE: The purpose of this study was to explore cancer support and financial issues related to cancer care experienced by African-American men with prostate cancer and to understand whom they relied on for resource issues during diagnosis and treatment. METHODS: This is a descriptive qualitative study of 23 rural and urban 65 years old and older African-American prostate cancer survivors. Five focus groups were conducted containing African-American prostate cancer survivors who were recruited from community-based centers (e.g., churches, barbershops, diners, and primary care clinics) in central Virginia and Maryland. Focus group discussions were audiotaped, transcribed, and coded. Data were organized and managed using a qualitative analysis software program. Emerging themes uncovered specific problems for older rural African-American men with cancer, and focus group data were examined for potential solutions to these problems. RESULTS: Two common themes emerged: (1) family and physician support are important, and (2) insurance is a necessity for appropriate health care. A difference between rural and urban African-American prostate cancer survivors emerged as well: difference in spirituality during diagnosis and treatment. CONCLUSIONS: Rural and urban African-American prostate cancer survivors' major support resource was their wives. Health insurance played a critical role as a support source by decreasing anxiety and financial hardships. Understanding rural and urban African-American prostate cancer survivors' support needs and challenges in relation to cancer diagnosis and treatment will allow nurses and other health-care providers to tailor cancer health plans more effectively for this population.

Predicting security incidents in high secure male psychiatric care.

PURPOSE: The contribution of environmental and organisational factors in predicting security incidents within a high secure male psychiatric setting is considered using a series of connected studies; a systematic literature review comprising 41 studies and five inquiries (Study 1) to identify core themes of likely importance; application of these themes to incident data through assessment of the ward culture, as perceived by 73 male psychiatric patients and 157 staff (Study 2); and detailed examination of noted relevant factors in the form of interpersonal style, meaningful activity and physical environmental characteristics in a study comprising 62 patients and 151 staff (Study 3). It was predicted that security incidents would be identified through inclusion of environmental and organisational factors. RESULTS: The systematic review demonstrated the importance of accounting for staff characteristics, patient interactions, physical environment and meaningful activity. The subsequent study noted the importance of only specific aspects of the social environment, with the final study demonstrating that incidents were associated with controlling interpersonal styles of staff, lower perceived fairness, and less involvement in off-ward activities. Perception of fair treatment and off-ward activities mediated the staff interpersonal style and security incident relationship. CONCLUSIONS: The research proposes a preliminary framework - the McKenna Framework for understanding Incidents in Secure Settings (M-FISS) - to explain the occurrence of security incidents in secure psychiatric care.

Pharmaconutrition: a new emerging paradigm.

PURPOSE OF REVIEW: This paper highlights recent studies of interest and provides rationale for why deficiencies with the current scientific paradigm of immunonutrition has produced studies with conflicting results, and why it should be replaced with a new paradigm termed 'pharmaconutrition'. RECENT FINDINGS: Considering the overall treatment effect of immune-modulating nutrients, parenteral glutamine is recommended in patients receiving parenteral nutrition, while enteral glutamine should be considered in burn and trauma patients. Antioxidants, particularly selenium, should be considered for critically ill patients, and enteral formulas enriched with fish oils are recommended in patients with acute respiratory distress syndrome. Arginine-supplemented diets are not recommended. There are currently insufficient data to enable useful recommendations on the optimal route, timing, duration and dosage of each nutrient. The pending results of a large, rigorously designed, randomized trial, however, in which nutrients are viewed and tested as pharmacological agents, promise to clarify some of the current ambiguities and inform future practice. SUMMARY: This review provides insights into why the current paradigm of immunonutrition has failed to consistently demonstrate a beneficial effect of key immunomodulating nutrients, and offers a timely solution through the new paradigm of pharmaconutrition.

Zinc supplementation in critically ill patients: a key pharmaconutrient?

The purpose of the present paper is to provide a rationale for zinc supplementation as a potential therapeutic agent in critically ill patients by describing its role in health and disease, conducting a systematic review of current randomized trials in critical care, considering optimum route and dose of administration, and making recommendations for future research. Normal zinc homeostasis is required for a functional immune system, adequate antioxidant capacity, glucose homeostasis, and wound healing. In addition, zinc is a required cofactor for many enzymes, transcription factors, and replication factors. In non-critically ill patients, zinc supplementation has been associated with an improvement in markers of immune function. In critically ill patients, only 4 randomized trials have examined the effect of zinc supplementation on clinical outcomes. When all 4 studies were aggregated, zinc supplementation was associated with a nonsignificant reduction in mortality (relative risk = 0.63, 95% confidence intervals 0.25-1.59, P = .33) and length of stay in intensive care (-0.35 days, -0.85 to 0.15; P = .17). Thus, because of the paucity of clinical data, there is inadequate evidence to recommend the routine use of high-dose zinc supplementation in the critically ill. A first step would be to determine the optimal dose that has a maximal positive effect on underlying inflammatory, immunologic, and metabolic processes yet is safe and tolerated by critically ill patients. Subsequently, large, rigorously designed, randomized trials are required to elucidate the efficacy of such doses of zinc supplementation in this patient population.

Implementation of the Canadian Clinical Practice Guidelines for Nutrition Support: a multiple case study of barriers and enablers.

BACKGROUND: The Canadian Nutrition Support Clinical Practice Guidelines (CPGs), published in 2003, were designed to improve nutrition support practices in intensive care units (ICUs). However, their impact to date has been modest. This study aimed to identify important barriers and enablers to implementation of these guidelines. METHODS: Case studies were completed at 4 Canadian ICUs. Semistructured interviews were conducted with 7 key informants at each site. During the interviews, the key informants were asked about their perceptions of the barriers and enablers to implementation of the Canadian Nutrition Support CPGs. Interview transcripts were analyzed qualitatively, using a framework approach. RESULTS: Resistance to change, lack of awareness, lack of critical care experience, clinical condition of the patient, resource constraints, a slow administrative process, workload, numerous guidelines, complex recommendations, paucity of evidence, and outdated guidelines were cited as the main barriers to guideline implementation. Agreement of the ICU team, easy access to the guidelines, ease of application, incorporation into daily routine, education and training, the dietitian as an opinion leader, and open discussion were identified as the primary enabling factors. Although consistent across all sites, the influence of these factors seemed to differ by site and profession. CONCLUSIONS: Our findings suggest that implementation of the Canadian Nutrition Support CPGs is profoundly complex and is determined by practitioner, patient, institutional, and guideline factors. Further research is required to quantify the impact of each barrier and enabler and the mechanism by which they influence guideline adherence.

The relationship between nutritional intake and clinical outcomes in critically ill patients: results of an international multicenter observational study.

PURPOSE: The objective of this study was to examine the relationship between the amount of energy and protein administered and clinical outcomes, and the extent to which pre-morbid nutritional status influenced this relationship. METHODS: We conducted an observational cohort study of nutrition practices in 167 intensive care units (ICUs) across 21 [corrected] countries. Patient demographics were collected, and the type and amount of nutrition received were recorded daily for a maximum of 12 days. Patients were followed prospectively to determine 60-day mortality and ventilator-free days (VFDs). We used body mass index (BMI, kg/m2) as a marker of nutritional status prior to ICU admission. Regression models were developed to evaluate the relationship between nutrition received and 60-day mortality and VFDs, and to examine how BMI modifies this relationship. RESULTS: Data were collected on 2,772 mechanically ventilated patients who received an average of 1,034 kcal/day and 47 g protein/day. An increase of 1,000 cal per day was associated with reduced mortality [odds ratio for 60-day mortality 0.76; 95% confidence intervals (CI) 0.61-0.95, p = 0.014] and an increased number of VFDs (3.5 VFD, 95% CI 1.2-5.9, p = 0.003). The effect of increased calories associated with lower mortality was observed in patients with a BMI <25 and > or =35 with no benefit for patients with a BMI 25 to <35. Similar results were observed when comparing increasing protein intake and its effect on mortality. CONCLUSIONS: Increased intakes of energy and protein appear to be associated with improved clinical outcomes in critically ill patients, particularly when BMI is <25 or > or =35.

Factors predicting adherence to the Canadian Clinical Practice Guidelines for nutrition support in mechanically ventilated, critically ill adult patients.

PURPOSE: The aim of this study was to determine factors that are associated with adherence to the Canadian nutrition support clinical practice guidelines (CPGs). MATERIALS AND METHODS: We conducted a secondary analysis of data from a prospective observational cohort study of nutrition support practices in 58 intensive care units (ICUs) across Canada, grouped into 50 clusters. Adequacy of enteral nutrition (EN) (energy received from EN / energy prescribed by the dietitian x 100), was used as a marker of adherence to the guidelines. We applied hierarchical modeling techniques to examine the impact of various hospital, ICU, and patient factors on EN adequacy. RESULTS: The overall average EN adequacy was 51.3% (SE, 1.8%). In a multiple regression analysis, after adjusting for varying days of observation, hospital type (academic 54.3% vs community 45.2%, P < .001), admission category of the patient (medical 60.2% vs surgical 39.2%, P < .001), and sex of the patient (male 46.5% vs female 52.8%, P < .001) were found to be significant predictors of EN adequacy and adherence to the Canadian nutrition support CPGs. CONCLUSIONS: Specific hospital, ICU, and patient characteristics influence adherence to the Canadian nutrition support CPGs. Further research is required to illuminate the mechanisms by which female and surgical patients and community hospitals lead to lower guideline adherence.

Feeding critically ill patients: what is the optimal amount of energy?

Hypermetabolism and malnourishment are common in the intensive care unit. Malnutrition is associated with increased morbidity and mortality, and most intensive care unit patients receive specialized nutrition therapy to attenuate the effects of malnourishment. However, the optimal amount of energy to deliver is unknown, with some studies suggesting that full calorie feeding improves clinical outcomes but other studies concluding that caloric intake may not be important in determining outcome. In this narrative review, we discuss the studies of critically ill patients that examine the relationship between dose of nutrition and clinically important outcomes. Observational studies suggest that achieving targeted caloric intake might not be necessary since provision of approximately 25% to 66% of goal calories may be sufficient. Randomized controlled trials comparing early aggressive use of enteral nutrition compared with delayed, less aggressive use of enteral nutrition suggest that providing increased calories with early, aggressive enteral nutrition is associated with improved clinical outcomes. However, energy provision with parenteral nutrition, either instead of or supplemental to enteral nutrition, does not offer additional benefits. In summary, the optimal amount of calories to provide critically ill patients is unclear given the limitations of the existing data. However, evidence suggests that improving adequacy of enteral nutrition by moving intake closer to goal calories might be associated with a clinical benefit. There is no role for supplemental parenteral nutrition to increase caloric delivery in the early phase of critical illness. Further high-quality evidence from randomized trials investigating the optimal amount of energy intake in intensive care unit patients is needed.