Antibiotic resistant Klebsiella pneumoniae is a leading public health threat and gastrointestinal carriage is an established risk factor for subsequent infections during hospitalization. Our study contributes new knowledge of risk factors for gastrointestinal carriage and the genomic population structure of K. pneumoniae colonizing humans in a representative sample of a general population in a community setting. Altogether, 2,975 participants (54% women) >40 y in the population-based Tromsø Study: Tromsø7, Norway (2015-2016) were included. Fecal samples were screened for K. pneumoniae, which were characterized using whole-genome sequencing. Risk factors for carriage were analyzed using multivariable logistic regression on data from questionnaires and the Norwegian Prescription Database. Prevalence of K. pneumoniae gastrointestinal carriage was 16.3% (95% CI 15.0-17.7, no gender difference). Risk factors associated with carriage included age ≥60 y, travel to Greece or Asia past 12 months (adjusted odds ratio 1.49, 95% CI 1.11-2.00), Crohn's disease/ulcerative colitis (2.26, 1.20-4.27), use of proton pump inhibitors (1.62, 1.18-2.22) and non-steroidal anti-inflammatory drugs past 6 months (1.38, 1.04-1.84), and antibiotic use the last month (1.73, 1.05-2.86). Prevalence was higher among those having used combinations of drug classes and decreased over time with respect to preceding antibiotic use. The K. pneumoniae population was diverse with 300 sequence types among 484 isolates distributed across four phylogroups. Only 5.2% of isolates harbored acquired resistance and 11.6% had virulence factors. Identification of risk factors for gastrointestinal carriage allows for identification of individuals that may have higher risk of extraintestinal infection during hospitalization. The findings that specific diseases and drugs used were associated with carriage show an impact of these possibly through modulating the human gut microbiota promoting colonization. The diverse population structure of carriage isolates reflects the ecologically adaptive capacity of the bacterium and challenges for vaccine prospects and the identification of reservoirs as a potential source for human colonization.

We determined the species distribution and prevalence of ampicillin resistance, high-level gentamicin resistance (HLGR) and vancomycin resistance among clinical enterococcal isolates from five Nordic laboratories (Bergen, Tromsø, Uppsala, Aarhus and Reykjavik). Isolates represented three different groups: (i) all blood culture isolates from 1999; (ii) consecutive in-patient isolates (maximum 40); and (iii) consecutive outpatient isolates (maximum 40) collected during March to May 2000. Antimicrobial use data were collected at the national and hospital level. A high proportion (31.4%) of Enterococcus faecium was detected among blood culture isolates, in contrast to only 4.2% among isolates from outpatients. Ampicillin resistance was not found in Enterococcus faecalis, in contrast to 48.8% in E. faecium isolates. HLGR rates varied considerably between laboratories (1.1-27.6%). Acquired vancomycin resistance was not detected. There were no significant differences in the prevalences of HLGR between in-patient and outpatient isolates at individual hospitals. A cluster of clonally related ampicillin-resistant and HLGR E. faecium isolates was demonstrated in one of the hospitals. The lowest level of hospital antimicrobial use, the lowest proportion of E. faecium and the lowest prevalence of resistance were observed in Reykjavik. The study showed a relatively low level of resistance in enterococci, as compared with most European countries and the USA. However, there were large differences between hospitals with regard to the relative proportion of E. faecium isolates, their susceptibility to ampicillin and gentamicin, as well as the prevalence of HLGR in E. faecalis isolates. This indicates a potential for further improvement of antibiotic policies, and possibly hospital infection control, to maintain the low resistance levels observed in these countries.

Infants can be exposed to clinically relevant doses of lamotrigine through breast-feeding. Individual risk/benefit assessment is important, and close monitoring of both mother and child is advisable, especially during the first 3 weeks postpartum.

Disclosure of potential conflict of interest: M. Ohlin receives grant support from the Swedish Research Council. P. A. W€ urtzen and L. H. Christensen are employees of ALK. The rest of the authors declare that they have no relevant conflicts of interest.

BackgroundAppropriate antibiotic prescribing is associated with favourable levels of antimicrobial resistance (AMR) and clinical outcomes. Most intervention studies on antibiotic prescribing originate from settings with high level of AMR. In a Norwegian hospital setting with low level of AMR, the literature on interventions for promoting guideline-recommended antibiotic prescribing in hospital is scarce and requested. Preliminary studies have shown improvement potentials regarding antibiotic prescribing according to guidelines. We aimed to promote appropriate antibiotic prescribing in patients with community-acquired pneumonia (CAP) and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) at a respiratory medicine department in a Norwegian University hospital. Our specific objectives were to increase prescribing of appropriate empirical antibiotics, reduce high-dose benzylpenicillin and reduce total treatment duration.MethodsWe performed an audit and feedback intervention study, combined with distribution of a recently published pocket version of the national clinical practice guideline. We included patients discharged with CAP or AECOPD and prescribed antibiotics during hospital stay, and excluded those presenting with aspiration, nosocomial infection and co-infections. The pre- and post-intervention period was 9 and 6 months, respectively. Feedback was provided orally to the department physicians at an internal-educational meeting. To explore the effect of the intervention on appropriate empirical antibiotics and mean total treatment duration we applied before-after analysis (Student’s t-test) and interrupted time series (ITS). We used Pearson’s χ2 to compare dose changes.ResultsIn the pre-and post-intervention period we included 253 and 155 patients, respectively. Following the intervention, overall mean prescribing of appropriate empirical antibiotics increased from 61.7 to 83.8 % (P < 0.001), overall mean total treatment duration decreased from 11.2 to 10.4 days (P = 0.015), and prescribing of high-dose benzylpenicillin decreased from 48.8 to 38.6 % (P = 0.125). With ITS we found that six months post-intervention, the effect on appropriate empirical antibiotic prescribing had increased and sustained, while the effect on treatment duration was at pre-intervention level.ConclusionThe combination of audit and feedback plus distribution of a pocket version of guideline recommendations led to a substantial increase in prescribing of appropriate empirical antibiotics, which is important due to favourable effect on AMR and clinical outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1426-1) contains supplementary material, which is available to authorized users.

BackgroundThe use of antimicrobials is associated with the emergence of antimicrobial resistance (AMR), and self-medication increases the risk of the inappropriate use of antimicrobials. This study aims to describe the knowledge, attitudes, and practices (KAP) regarding self-medication with antimicrobials among residents in Lilongwe, Malawi.MethodologyThis study has a cross-sectional, mixed-methods design. We conducted two focus group discussions (n=15) to describe community attitudes towards self-medication with antimicrobials and used a structured questionnaire to collect data on individual KAP regarding self-medication from 105 respondents.ResultsSelf-medication was common, and the sources of these medicines were market vendors, pharmacies, drugs shared with friends and family and those leftover from previous treatments. The lack of medical supplies, long distances to health facilities, poor attitudes of medical professionals towards patients, and past experience with the disease and treatment are the main factors that influence self-medication. KAP respondents had little knowledge of antimicrobials, their use, or any awareness of AMR. Seventy-four per cent (n=78) were unable to differentiate antimicrobials from other categories of medicines, and 92.4% wrongly responded that antimicrobials could be used to stop a fever. Concerning attitudes towards self-medication, over 54% wrongly believe that antimicrobials are effective in treating common colds. In regard to practice, 53% reported that they would use antimicrobials to treat upper respiratory infections, and 41% agreed that they must complete antibiotic therapy even if they are improving. Logistic regression analysis found that stocking antimicrobials at home for future use significantly promotes self-medication whereas an awareness of AMR would reduce self-medication.ConclusionSelf-medication is a public health risk that needs to be addressed urgently. Findings from this study point to the need for multifaceted interventions.

We used a controlled before-and-after design with the aims of reducing both the total consumption of antibiotics and the use of broad-spectrum antibiotics against acute otitis media (AOM), and to study to what extent prescriptions for antibiotics against AOM were dispensed. Information on evidence-based treatment of uncomplicated AOM was provided to doctors and nurses, and written guidelines were implemented. Pamphlets and oral information concerning symptomatic treatment and the limited effect of antibiotic use in AOM were given to parents. Eligible patients were 819 children aged 1-15 y. The proportion of patients receiving a prescription for antibiotics was reduced from 90% at baseline to 74% during the study period. The proportion of prescriptions for penicillin V increased from 72% at baseline to 85% during the study period. There were no significant changes at the control site. The proportion of dispensed prescriptions was 70% both at baseline and during the study period. Educational efforts reduced the total consumption of antibiotics and the use of broad-spectrum antibiotics for AOM in children aged 1-15 y at an emergency call service. Data on antibiotic use in AOM based only on prescribing overestimates the use of antibiotics.

PurposeFollowing a TV documentary in 2013, there was a tremendous increase in low dose naltrexone (LDN) use in a wide range of unapproved indications in Norway. We aim to describe the extent of this sudden and unprecedented increase in LDN prescribing, to characterize patients and LDN prescribers, and to estimate LDN dose sizes.MethodsLDN prescriptions recorded in the Norwegian Prescription Database (NorPD) in 2013 and 2014, and sales data not recorded in NorPD from the only Norwegian LDN manufacturer were included in the study.ResultsAccording to NorPD, 15 297 patients (0.3% of population) collected at least one LDN prescription. The actual number of users was higher as at least 23% of total sales were not recorded in NorPD. After an initial wave, there was a steady stream of new and persistent users throughout the study period. Median patient age was 52 years, and 74% of patients were female. Median daily dose was 3.7 mg. Twenty percent of all doctors and 71% of general medicine practitioners registered in Norway in 2014 prescribed LDN at least once.ConclusionsThe TV documentary on LDN in Norway was followed by a large increase in LDN prescribing, and the proportion of LDN users went from an insignificant number to 0.3% of the population. There was a high willingness to use and prescribe off label despite limited evidence. Observed median LDN dose, and age and gender distribution were as expected in typical LDN using patients. © 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.