Antibiotic Resistance Policy and the Stewardship Role of the Nurse.

Government policy, at all levels, should reflect current scientific evidence to curb the spread of multidrug-resistant organisms (MDROs) and to promote healthier lives for citizens and the global community. The World Health Organization estimates that approximately 63,000 Americans die annually of infections from MDROs. Annual spending in the United States used to combat MDRO infections surpassed $35 billion in 2015. This article is a review of U.S. policy regarding MDROs and focuses on several means with which nurses can implement antibiotic stewardship within their practices to stall the creation and global spread of antibiotic-resistant organisms. Nurses are vital to successfully implementing methods of antibiotic stewardship as they are at the center of multidisciplinary health care teams and have the greatest direct patient contact of all members within the team. Methods of antibiotic stewardship include limiting the use of antibiotics within animal husbandry industries, promotion of health care policy in line with antibiotic stewardship standards, and adopting more stringent clinical prescribing practices of antibiotics used in human therapies. Application of these improvements to U.S. federal, state, and local facility policies is in line with current scientific evidence and will provide a framework for cohesive partnerships with nations and institutions abroad that also struggle with the spread of MDROs in their own communities.

Upregulation of interleukin-12 and -17 in active inflammatory bowel disease.

BACKGROUND: Cytokines are essential mediators of the intestinal inflammation during active episodes of inflammatory bowel disease (IBD). Interleukin (IL)-12 and IL-17 are potent immunoregulatory cytokines whose roles in the pathogenesis of IBD are unknown. The aim of this study was to evaluate the colonic expression of IL-12 and IL-17 genes in IBD. METHODS: Fifty-one patients (22 with ulcerative colitis (UC), 17 with Crohn disease (CD), and 12 controls) who underwent colonoscopy were included. IBD disease activity was determined using a clinical grading scale. The degree of inflammation, as well as the content of CD4+ T cells (synthesizing IL-17) and CD68+ macrophages (synthesizing IL-12) in colonic biopsies, was determined. The amounts of IL-12 and IL-17 mRNA were assessed by RT-PCR, using GAPDH as an internal standard. RESULTS: In colonic specimens, IL-17 mRNA expression was increased in moderately and severely active UC (P = 0.03) and in all degrees of activity in CD (P < 0.04). Levels of IL-12 mRNA were upregulated in both active UC and active CD compared to controls (P < 0.02). In cases of remission, IL-12 mRNA expression was similar to that found in control samples. Compared to controls, histological examination showed significant differences in signs of chronic and acute inflammation in UC (P < 0.01) and CD (P < 0.02), revealing a high correlation between clinical disease activity and histological scoring (r2 = 0.92, P < 0.005). Whereas CD4+ T cells were observed in lymphocyte aggregates located profound in the lamina propria, CD68+ macrophages were primarily found just underneath the surface epithelium. The density of CD4+ and CD68+ cells correlated significantly with the amounts of IL-17 and IL-12 mRNA, respectively (P < 0.05). CONCLUSION: The expression of both IL-12 and IL-17 mRNA is induced in active UC and CD and may thus be involved in sustaining the intestinal inflammation in IBD. Inhibition of IL-12 or IL-17 might be future therapeutic targets in IBD.

Expression of 5-lipoxygenase mRNA is unchanged in the colon of patients with active inflammatory bowel disease.

BACKGROUND: In inflammatory bowel disease (IBD) the disease activity correlates with colonic concentrations of leukotrienes (LTs). The enzyme 5-lipoxygenase (5-LO) is responsible for the enzymatic production of LTs. It has previously been demonstrated in experimental models of inflammation, that 5-LO is activated through intracellular translocation of the pre-formed enzyme, and increased constitutive activation of 5-LO has been demonstrated in idiopathic pulmonary fibrosis. The objective of the present study was to investigate whether de novo synthesis of 5-LO is increased in patients with quiescent IBD, or is induced during acute exacerbations of IBD. METHODS: Sixty-one individuals were included in the study. Twenty-eight had ulcerative colitis (UC), 21 had Crohn's disease (CD), and 12 were healthy controls. A standard rigid rectoscopy was performed in all individuals. The degree of inflammation was assessed using a semi-quantitative scale. A mucosal biopsy was taken from the most inflamed area as judged macroscopically. mRNA for 5-LO was detected using a RT-PCR technique, and the assay applied was evaluated by control experiments. RESULTS: The expression of mRNA for 5-LO in colonic biopsies was similar in IBD patients with quiescent disease and healthy controls. When grouped according to endoscopically assessed disease activity the fraction of patients demonstrating 5-LO mRNA in colonic biopsies showed no significant change (p > 0,6; chi2 -test for trend). CONCLUSIONS: This study demonstrates no significant relationship between endoscopically assessed disease activity and relative presence of mRNA for 5-LO in colonic biopsies. Thus, there is no evidence of increased expression of 5-LO mRNA in either quiescent or active stages of IBD.

Colonic expression and synthesis of interleukin 13 and interleukin 15 in inflammatory bowel disease.

UNLABELLED: A dysregulated local immune reaction with unbalanced cytokine expression seems essential in inflammatory bowel disease (IBD), i.e. ulcerative colitis (UC) and Crohn's disease (CD). Since the roles of interleukin (IL-)13 and IL-15 remain unclear, this study aimed at studying intestinal expression of IL-13 and IL-15 in IBD. METHODS: In colonic biopsies from 24 UC, 18 CD, and 12 controls IL-13 and IL-15 were measured using ELISA, and their gene expressions were assessed by RT-PCR. Leukocytes were visualised histochemically. RESULTS: Concentrations of IL-13 were decreased in UC (median 56 pg/mg tissue; interquartile range 30-99 pg/mg) compared to CD (82 pg/mg tissue; 41-122;P=0.004) and controls (83 pg/mg tissue; 18-134;P>0.05), and lower in active UC (53 pg/mg tissue; 33-96) than in inactive UC (80 pg/mg tissue; 65-99;P=0.02). IL-15 concentrations were higher in CD patients (34 pg/mg tissue; 24-53) as compared to controls (20 pg/mg tissue; 15-21;P=0.001) whilst being 22 pg/mg tissue (15-32) in UC. IL-13 mRNA and IL-15 mRNA were detected in 20% and 15%, respectively. Infiltration of leukocytes correlated inversely with IL-13 levels (P=0.02). CONCLUSION: Active UC is associated with decreased colonic IL-13 suggesting that IL-13 levels are diminished as a part of UC exacerbations, or that exacerbations follow active downregulation of IL-13.

Expression of cyclooxygenase-2 mRNA in active inflammatory bowel disease.

OBJECTIVES: In inflammatory bowel disease (IBD), increased amounts of prostaglandins correlate to disease activity. Prostaglandins are produced via the cyclooxygenase (COX) pathway and exhibit both pro- and anti-inflammatory effects. Whereas COX-1 is a constitutive enzyme present at all times and is thought to produce the cytoprotective prostaglandins, COX-2 represents the inducible form of cyclooxygenase leading to production of proinflammatory prostaglandins. In inflammatory bowel disease it is yet unclear whether COX-2 plays a role in the inflammatory response. The purpose of this study was to evaluate the role of COX-2 in inflammatory bowel disease. METHODS: Of the 44 individuals included in the study, 22 had ulcerative colitis, 11 had Crohn's disease, and 11 were healthy controls. Standard rigid rectoscopy was performed. The degree of inflammation was assessed using a semiquantitative scale. A biopsy was taken from the most affected area. mRNAs for COX-1 and COX-2 were detected using reverse transcription-polymerase chain reaction. RESULTS: The fraction of patients demonstrating COX-2 mRNA significantly increased with increasing disease activity (p < 0.005), whereas the fraction of patients demonstrating COX-1 mRNA remained unchanged (p > 0.05). CONCLUSIONS: This study demonstrates a clear relationship between endoscopic activity and relative presence of mRNA for COX-2. In contrast mRNA for COX-1 is detected equally often. This indicates that COX-2 is involved in the acute inflammatory response of chronic inflammatory bowel disease.

A simple filter-paper technique allows detection of mucosal cytokine levels in vivo in ulcerative colitis. Interleukin-1 and interleukin-1-receptor antagonist.

A simple filter-paper method for in vivo assessment of cytokines in intestinal mucosa of patients with ulcerative colitis (UC) was developed and evaluated. Twenty-eight patients were included. Twenty-three patients had ulcerative colitis (UC) and five irritable bowel syndrome (IBS). Inflammation was assessed endoscopically. Through a rectoscope, filter paper was applied to the macroscopically most inflamed area of the rectal mucosa until soaked. The filter paper was transferred to a buffer solution, and IL-1 beta and IL-1ra were assessed using ELISA. Positive correlations between endoscopic grading and In(IL-1 beta) (P < 0.0001) and In(IL-1ra) (P < 0.001) and a negative correlation between endoscopic grading and In(IL-1ra /IL-1 beta) (P < 0.02) were found. In measurements during and after a flare-up no significant change in IL-1ra but a significant decrease in IL-1 beta was detected, which is in agreement with investigations on biopsies. In conclusion, the filter-paper technique is an easily applicable, low-risk method that provides a means of monitoring cytokines in vivo in UC.

Monitoring of omeprazole treatment in gastro-oesophageal reflux disease.

OBJECTIVE: To test our standard dosing regimen in omeprazole treatment of gastro-oesophageal reflux disease (GORD) and to determine whether 'non-responders' could be pinpointed. DESIGN: A reverse dose-response examination using increasing doses of omeprazole. The study was conducted as an open consecutive clinical study. Response was measured by 24-h pH-metry, symptoms, endoscopy and histopathology. SETTING: All patients had been referred to one of the partaking departments for evaluation of oesophageal reflux symptoms. PATIENTS: A total of 62 patients were included, 29 with systemic sclerosis and 33 consecutively included patients suffering from idiopathic oesophageal reflux. RESULTS: Approximately one-third of the patients required doses higher than 40 mg of omeprazole/day (up to 140 mg/day) to abolish GOR. No cases of tachyphylaxia or bile-induced oesophagitis were seen in this study. In all patients subjected to dose titration we were able to achieve healing of oesophagitis assessed by symptom scoring, endoscopy and histopathology. No prediction of final dose of omeprazole could be made. CONCLUSION: Four weeks after reaching a dose level of omeprazole that ensured the abolition of GOR, healing of oesophagitis according to endoscopic/histological evaluation was obtained in all patients. Persistent oesophagitis, i.e. bile induced, was not found.

Morning or evening dosage of omeprazole for gastro-oesophageal reflux disease?

BACKGROUND AND AIMS: When routinely checking patients receiving omeprazole treatment for gastro-oesophageal reflux, we have been finding patients with surprisingly low nocturnal gastric pH. The aim of this study was to evaluate the impact of timing of the 40 mg omeprazole once daily regimen. METHODS: We evaluated the difference in effect of 40 mg omeprazole, given as a morning or evening dose, in 17 patients with gastro-oesophageal reflux disease. Gastric and oesophageal pH was recorded by portable 24-h two-channel pH-metry in a cross-over design of 14 days of morning and 14 days of evening administration. RESULTS: In five patients pathological reflux was abolished by both regimens, four only during morning dosage, and three only during evening dosage. In the remaining five patients abolition of pathological reflux was not achieved. The therapeutic outcome and patient preference for morning or evening administration were closely related to the individual oesophageal pH curves. Patients with reflux induced by physical activity had a clear preference for morning dosage, patients with nocturnal reflux showed a clear preference for evening dosage. Gastric pH profiles showed a high inter-individual variation; paired statistics, however, revealed a significant impact of dosage timing on the gastric pH profile. After morning dosage the work-day part (the first 7 h) of the gastric pH profile is 0.72 +/- 0.91 (mean difference of pairs +/- s.d.) higher than after evening dosage (P < 0.01). After evening dosage the gastric pH during the supine period is 0.64 +/- 0.83 (mean difference of pairs +/- s.d.) higher than after morning dosage (P = 0.02). CONCLUSION: The timing of a 40 mg omeprazole dosage regimen has a clinically significant impact on the 24-h pH profile, and that--by relating to the patient 24-hour oesophageal pH-metry in combination with the patient symptomatology--the timing of this dosage is highly important for therapeutic efficacy.

Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in active inflammatory bowel disease.

Intercellular adhesion molecule (ICAM)-1 promotes the initial interaction between macrophages and T cells during immune activation. We have measured serum levels of soluble ICAM-1 (sICAM-1) by ELISA in 27 patients with ulcerative colitis (UC), 31 with Crohn's disease (CD), and 29 healthy subjects. The median sICAM-1 serum concentration was significantly increased in inflammatory bowel disease (IBD) patients (355 ng/ml, range 195-855) compared to controls (245 ng/ml, 155-580) (P = 0.001). Variance analysis for trend showed that sICAM-1 levels were significantly higher in patients with active CD and UC, compared to those with inactive disease and controls (P = 0.00002). The concentration of sICAM-1 was higher in CD patients (365 ng/ml 230-470) compared to UC (300 ng/ml 195-855) (P = 0.01). Furthermore, weak but significant correlations were found between serum levels of sICAM-1 and: soluble IL-2 receptors, orosomucoid, and C-reactive protein. It is suggested that increased circulating sICAM-1 levels may reflect increased adhesiveness and signal transmission across cells, probably as a result of shedding of the parent molecule during local cellular immunoresponses in vivo.