Carrier prevalence and risk factors for colonisation of multiresistant bacteria in Danish emergency departments: a cross-sectional survey.

OBJECTIVES: The aim of this study was to describe the carrier prevalence and demographic variation of four different multiresistant bacteria (MRB) among acute patients in Danish emergency departments (EDs): methicillin-resistant Staphylococcus aureus (MRSA), carbapenemase-producing enterobacteria (CPE), extended-spectrum beta-lactamase-producing enterobacteria (ESBL) and vancomycin-resistant enterococci (VRE), and to analyse the association of MRB carriage to a range of potential risk factors. DESIGN: Multicentre descriptive and analytic cross-sectional survey. SETTING: Eight EDs and four clinical microbiology departments in Denmark. PARTICIPANTS: Adults visiting the ED. MAIN OUTCOME MEASURES: Swabs from nose, throat and rectum were collected and analysed for MRSA, ESBL, VRE and CPE. The primary outcome was the prevalence of MRB carriage, and secondary outcomes relation to risk factors among ED patients. RESULTS: We included 5117 patients in the study. Median age was 68 years (54-77) and gender was equally distributed. In total, 266 (5.2%, 95% CI 4.6 to 5.8) were colonised with at least one MRB. No significant difference was observed between male and female patients, between age groups and between university and regional hospitals. Only 5 of the 266 patients with MRB were colonised with two of the included bacteria and none with more than two. CPE prevalence was 0.1% (95% CI 0.0 to 0.2), MRSA prevalence was 0.3% (95% CI 0.2 to 0.5), VRE prevalence was 0.4% (95% CI 0.3 to 0.6) and ESBL prevalence was 4.5% (95% CI 3.9 to 5.1). Risk factors for MRB carriage were previous antibiotic treatment, previous hospital stay, having chronic respiratory infections, use of urinary catheter and travel to Asia, Oceania or Africa. CONCLUSION: Every 20th patient arriving to a Danish ED brings MRB to the hospital. ESBL is the most common MRB in the ED. The main risk factors for MRB carriage are recent antibiotic use and travel abroad. TRIAL REGISTRATION NUMBER: NCT03352167;Post-results.

Cross sectional study of multiresistant bacteria in Danish emergency departments: prevalence, patterns and risk factors for colonization (AB-RED project).

BACKGROUND: Multiresistant bacteria (MRB) is an increasing problem. Early identification of patients with MRB is mandatory to avoid transmission and to target the antibiotic treatment. The emergency department (ED) is a key player in the early identification of patients who are colonized with MRB. There is currently sparse knowledge of both prevalence and risk factors for colonization with MRSA, ESBL, VRE, CPE and CD in acutely admitted patients in Western European countries including Denmark. To develop evidence-based screening tools for identifying carriers of resistant bacteria among acutely admitted patients, systematic collection of information on risk factors and exposures is required. Since a geographical variation is suspected, it is desirable to include emergency departments across the country. The aim of this project is to provide a comprehensive overview of prevalence and risk factors for MRSA, ESBL, VRE, CPE and CD colonization in patients admitted to Danish ED's. The objectives are to describe the prevalence and demography of resistance, co-infections, to identify risk factors for carrier state and to develop and validate a screening tool for identification of carriers. METHODS: Multicenter descriptive and analytic cross-sectional survey from January-May 2018 of around 10.000 acutely admitted patients > 18 years in 8 EDs for carrier state and risk factors for antibiotic resistant bacteria. Information about the background and possible risk factors for carrier status together with swabs from the nose, throat and rectum is collected and analyzed for MRSA, ESBL, VRE, CPE and CD. The prevalence of the resistant bacteria are calculated at hospital level, regional level and national level and described with relation to residency, sex, age and risk factors. A screening model for identification of carrier stage of resistant bacteria is developed and validated. DISCUSSION: The study will provide the prevalence of colonized patients with resistant bacteria on arrival to the ED and variation in demographic patterns, and will develop a clinical tool to identify certain risk groups. This will enable the clinician to target antibiotic treatments and to reduce the in-hospital spreading of resistant bacteria. This knowledge is important for implementing and evaluating antimicrobial stewardships, screening and infection control strategies. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03352167 (registration date: 20. November 2017).

Impact of appropriate empirical antibiotic treatment on recurrence and mortality in patients with bacteraemia: a population-based cohort study.

BACKGROUND: Data on the impact of empirical antibiotic treatment (EAT) on patient outcome in a population-based setting are sparse. We assessed the association between EAT and the risk of recurrence within one year, short-term- (2-30 days) and long-term (31-365 days) mortality in a Danish cohort of bacteraemia patients. METHODS: A cohort study including all patients hospitalized with incident bacteraemia during 2007-2008 in the Copenhagen City and County areas and the North Denmark Region. EAT was defined as the antibiotic treatment given at the 1st notification of a positive blood culture. The definition of recurrence took account of pathogen species, site of infection, and time frame and was not restricted to homologous pathogens. The vital status was determined through the civil registration system. Association estimates between EAT and the outcomes were estimated by Cox and logistic regression models. RESULTS: In 6483 eligible patients, 712 (11%) had a recurrent episode. A total of 3778 (58%) patients received appropriate EAT, 1290 (20%) received inappropriate EAT, while EAT status was unrecorded for 1415 (22%) patients. The 2-30 day mortality was 15.1%, 17.4% and 19.2% in patients receiving appropriate EAT, inappropriate EAT, and unknown EAT, respectively. Among patients alive on day 30, the 31-365 day mortality was 22.3% in patients given appropriate EAT compared to 30.7% in those given inappropriate EAT. Inappropriate EAT was independently associated with recurrence (HR 1.25; 95% CI = 1.03-1.52) and long-term mortality (OR 1.35; 95% CI = 1.10-1.60), but not with short-term mortality (OR 0.85; 95% CI = 0.70-1.02) after bacteraemia. CONCLUSIONS: Our data indicate that appropriate EAT is associated with reduced incidence of recurrence and lower long-term mortality following bacteraemia.

Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism.

OBJECTIVE: The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. METHODS: Meal tests with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition. RESULTS: Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postprandial gut hormone release. CONCLUSION: As evaluated by selective cultivation of gut bacteria, a broad-spectrum 4-day antibiotics course with vancomycin, gentamycin and meropenem induced shifts in gut microbiota composition that had no clinically relevant short or long-term effects on metabolic variables in healthy glucose-tolerant males. TRIAL REGISTRATION: clinicaltrials.gov NCT01633762.

The association between demographic factors and increased antibiotic consumption in Denmark 2001 to 2010.

From 2001 to 2010, the consumption of antibiotics in Denmark increased by 32%. The objective of this study was to investigate the potential demographic factors associated with this increase. Defined daily doses (DDD) per 1000 inhabitant-days for the leading antibiotic groups and substances in primary health care in 2001 and 2010 were adjusted for population size and compared between and within age groups and genders. An increased antibiotic consumption was observed for all age groups between 2001 and 2010. Particular age-specific increases in the consumption of tetracyclines, extended-spectrum penicillins, and amoxicillin/clavulanic acid were observed. The generally increased consumption of antibacterial agents in the Danish population during the past decade was driven by people older than 65 y and, to a lesser extent, those aged 20-39 y. Evidence suggests that this increase may reflect general practitioners prescribing more antibiotics per visit and in larger doses.

Effect of generics on price and consumption of ciprofloxacin in primary healthcare: the relationship to increasing resistance.

BACKGROUND: The introduction of generic versions of drugs has often resulted in an increase in the consumption of the agents involved. In December 2001, generic ciprofloxacin was marketed in Denmark. Our objective was to evaluate, in a community setting, the effect of price on consumption of ciprofloxacin and on ciprofloxacin resistance in Escherichia coli urine isolates. METHODS: We conducted a retrospective ecological study collecting monthly national data on the number of marketed versions and primary healthcare (PHC) sales of ciprofloxacin during January 1995-December 2005. Data were compared with a median price per defined daily dose (DDD) of ciprofloxacin during September 1999-December 2005. Yearly PHC consumption data from seven Danish counties were compared with the antimicrobial resistance profiles of PHC E. coli urine isolates. RESULTS: During 2002, the number of marketed versions increased from 3 to 10, and the median price per DDD decreased by 53%. From 2002 to 2005, the total consumption of oral ciprofloxacin in PHC increased significantly from 0.13 DDD/1000 inhabitant-days to 0.33 DDD/1000 inhabitant-days. During the same period, the frequency of ciprofloxacin resistance increased by 200%. A statistically significant correlation was found between the consumption of ciprofloxacin and the ciprofloxacin resistance rate in E. coli urine isolates, independent of the introduction of generic ciprofloxacin. CONCLUSIONS: After the introduction of generic ciprofloxacin, a significant increase in the total consumption of oral ciprofloxacin in PHC was observed in Denmark. The increase in consumption was significantly correlated with ciprofloxacin resistance in E. coli obtained from urine isolates.

Consequences of increased antibacterial consumption and change in pattern of antibacterial use in Danish hospitals.

OBJECTIVES: Antibacterial consumption is increasing in many countries around the world, and it is increasingly recognized as the main reason for the emergence of resistance. This study was implemented to analyse antibacterial consumption in public hospitals in Denmark during 2001-07 as a follow-up on a prior analysis and furthermore, to investigate the consequences of the occurrence of resistance. METHODS: National data on the consumption of antibacterials for systemic use in Danish public hospitals were obtained from 2001 through 2007. Consumption data were compared with antimicrobial resistance in all isolates recorded from either blood samples (Escherichia coli and Klebsiella pneumoniae) or urine samples (E. coli) submitted for susceptibility testing to the participating Departments of Clinical Microbiology during 2001-07. RESULTS: The consumption of combinations of penicillins including beta-lactamase inhibitors, cephalosporins, carbapenems and fluoroquinolones continued to increase from 19.2% of the total consumption in hospitals in Denmark in 2001 to 38.2% in 2007. Quinolone resistance in E. coli isolates from blood and urine samples increased significantly from 2001 through 2007. Furthermore, multiresistant K. pneumoniae emerged. CONCLUSIONS: The consumption of 'broad-spectrum' antibacterial agents has continued to increase in Danish hospitals. At the same time, an increasing resistance in clinical isolates towards the same antibacterial agents has been observed. However, more detailed information on the specific consumption of the antibacterial agents might help to restrict or reverse the increasing use of 'broad-spectrum' antibacterial agents and perhaps also the increasing antimicrobial resistance.