Publikasjoner
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Dhariwal, Achal; Rajar, Polona; Silva, Gabriela Salvadori Da; Åmdal, Heidi Aarø; Berild, Dag & Saugstad, Ola Didrik
[Vis alle 11 forfattere av denne artikkelen]
(2024).
Prolonged hospitalization signature and early antibiotic effects on the nasopharyngeal resistome in preterm infants.
Nature Communications.
15(1).
doi:
10.1038/s41467-024-50433-7.
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Respiratory pathogens, commonly colonizing nasopharynx, are among the leading causes of death due to antimicrobial resistance. Yet, antibiotic resistance determinants within nasopharyngeal microbial communities remain poorly understood. In this prospective cohort study, we investigate the nasopharynx resistome development in preterm infants, assess early antibiotic impact on its trajectory, and explore its association with clinical covariates using shotgun metagenomics. Our findings reveal widespread nasopharyngeal carriage of antibiotic resistance genes (ARGs) with resistomes undergoing transient changes, including increased ARG diversity, abundance, and composition alterations due to early antibiotic exposure. ARGs associated with the critical nosocomial pathogen Serratia marcescens persist up to 8–10 months of age, representing a long-lasting hospitalization signature. The nasopharyngeal resistome strongly correlates with microbiome composition, with inter-individual differences and postnatal age explaining most of the variation. Our report on the collateral effects of antibiotics and prolonged hospitalization underscores the urgency of further studies focused on this relatively unexplored reservoir of pathogens and ARGs.
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Skaare, Dagfinn; Hannisdal, Anja; Kalager, Mette & Berild, Dag
(2023).
Måling av bruk av bredspektrede antibiotika i sykehus med etablerte og nye indikatorer.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
143(6).
doi:
10.4045/tidsskr.22.0427.
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Målet om 30 % reduksjon i bruk av bredspektrede antibiotika i sykehus fra 2012 til 2020 ble ikke nådd målt med standardindikatoren definerte døgndoser (DDD) per 100 liggedøgn. Vi ønsket å undersøke påliteligheten av standardindikatoren og utvalgte alternative indikatorer for antibiotikabruk, og hva som var reell reduksjon i bruk.
MATERIALE OG METODE
Vi inkluderte ti DDD-baserte indikatorer med justering for kombinasjoner av aktivitetsmarkør, innleggelseskategori (døgnopphold vs. alle innleggelser) og pasientsammensetning, og evaluerte disse etter hvordan hver indikator korrelerte med antibiotikaresistens i en egenutviklet modell. Deretter beregnet vi bruk av bredspektrede antibiotika i sykehus for perioden 2012–20 med indikatorer vurdert som valide, og sammenlignet indikatorene mht. endring i bruk og rangering av sykehus etter bruk. Som aktivitetsnøytral referanseindikator (nasjonalt og regionalt) benyttet vi forbruksrate (DDD per 1 000 innbyggere per døgn).
RESULTATER
Alle indikatorene for antibiotikabruk viste sterk korrelasjon med resistens. For fem indikatorer var korrelasjonen statistisk signifikant, hvorav indikatoren som kombinerte justering for totalt antall innlagte pasienter og pasientsammensetning, ga best samsvar med forbruksrate (35,6 %). Samme indikator viste også størst reduksjon i bruk (29,3 %) og ga flest sykehus som oppnådde minst 30 % reduksjon (13 av 22).
FORTOLKNING
Kombinert justering for antall innlagte pasienter og pasientsammensetning er en ny, robust indikator for antibiotikabruk som er egnet for sykehus på alle nivåer. Indikatoren kan benyttes parallelt med forbruksrate, som bør vurderes som ny standardindikator på nasjonalt og regionalt nivå.
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Fløystad, Hans Kristian; Holter, Jan Cato; Husebye, Einar; Siljan, William Ward; Berild, Dag & Holm, Are Martin
[Vis alle 7 forfattere av denne artikkelen]
(2023).
Nausea Predicts Bacteremia in Immunocompetent Patients with Pneumococcal Community-Acquired Pneumonia: Secondary Data Analysis from a Prospective Cohort.
Journal of Clinical Medicine.
12(12).
doi:
10.3390/jcm12123924.
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Background: In pneumococcal community-acquired pneumonia (CAP), bacteremia is associated with increased mortality, but initial clinical severity scores frequently fail to identify bacteremic patients at risk. We have previously shown that gastrointestinal symptoms are common among patients admitted to the hospital with pneumococcal bacteremia. The aim of this study was to examine gastrointestinal symptoms and inflammatory responses in bacteremic and non-bacteremic pneumococcal CAP in a prospective cohort of immunocompromised and immunocompetent patients hospitalized with CAP. Methods: Logistic regression analysis was used to estimate the predictive value of gastrointestinal symptoms for pneumococcal bacteremia in patients with CAP. The Mann–Whitney test was used to compare inflammatory responses in patients with bacteremic vs. non-bacteremic pneumococcal CAP. Results: Eighty-one patients with pneumococcal CAP were included, of whom 21 (26%) had bacteremia. Immunocompetent patients with pneumococcal CAP had an odds ratio of 16.5 (95% CI 3.0–90.9, p = 0.001) for bacteremia if nausea was present, whereas no such association was found in the immunocompromised patients (OR 0.22, 95% CI 0.02–2.05, p = 0.18). The serum levels of C-reactive protein, procalcitonin and interleukin 6 were significantly higher in the patients with bacteremic pneumococcal CAP compared to non-bacteremic pneumococcal CAP patients (p < 0.001, p = 0.005, and p = 0.019, respectively). Conclusions: In immunocompetent patients hospitalized with pneumococcal CAP, nausea may be a predictor of bacteremia. Bacteremic pneumococcal CAP patients display an increased inflammatory response compared to non-bacteremic pneumococcal CAP patients.
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Dhariwal, Achal; Bråten, Lars Christian Haugli; Sturød, Kjersti; Silva, Gabriela Salvadori Da; Bargheet, Ahmed & Åmdal, Heidi Aarø
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(2023).
Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistome.
Gut microbes.
ISSN 1949-0976.
15(1).
doi:
10.1080/19490976.2022.2157200.
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The collateral impact of antibiotics on the microbiome has attained increasing attention. However, the ecological consequences of long-term antibiotic exposure on the gut microbiome, including anti- biotic resistance, are still limited. Here, we investigated long-term exposure effects to amoxicillin on the human gut microbiome and resistome. Fecal samples were collected from 20 patients receiving 3-months of amoxicillin or placebo treatment as part of a Norwegian multicenter clinical trial on chronic low back pain (AIM study). Samples were collected at baseline, last day of treatment, and 9 months after antibiotic cessation. The abundance and diversity of microbial and resistome composi- tion were characterized using whole shotgun and functional metagenomic sequencing data. While the microbiome profiles of placebo subjects were stable over time, discernible changes in diversity and overall microbiome composition were observed after amoxicillin treatment. In particular, health- associated short-chain fatty acid producing species significantly decreased in proportion. However, these changes were short-lived as the microbiome showed overall recovery 9 months post-treatment. On the other hand, exposure to long-term amoxicillin was associated with an increase in total antimicrobial resistance gene load and diversity of antimicrobial resistance genes, with persistent changes even at 9 months post-treatment. Additionally, beta-lactam resistance was the most affected antibiotic class, suggesting a targeted response to amoxicillin, although changes at the gene level varied across individuals. Overall, our results suggest that the impact of prolonged amoxicillin exposure was more explicit and long-lasting in the fecal resistome than in microbiome composition. Such information is relevant for designing rational administration guidelines for antibiotic therapies.
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Christensen, Ingrid; Berild, Dag; Bjørnholt, Jørgen; Jelsness-Jørgensen, Lars-Petter; Debes, Sara Molvig & Haug, Jon Birger
(2023).
The Role of Procalcitonin as an Antimicrobial Stewardship Tool in Patients Hospitalized with Seasonal Influenza.
Antibiotics.
12(3).
doi:
10.3390/antibiotics12030573.
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Background: Up to 60% of the antibiotics prescribed to patients hospitalized with seasonal influenza are unnecessary. Procalcitonin (PCT) has the potential as an antimicrobial stewardship program (ASP) tool because it can differentiate between viral and bacterial etiology. We aimed to explore the role of PCT as an ASP tool in hospitalized seasonal influenza patients. Methods: We prospectively included 116 adults with seasonal influenza from two influenza seasons, 2018–2020. All data was obtained from a single clinical setting and analyzed by descriptive statistics and regression models. Results: In regression analyses, we found a positive association of PCT with 30 days mortality and the amount of antibiotics used. Influenza diagnosis was associated with less antibiotic use if the PCT value was low. Patients with a low initial PCT (<0.25 µg/L) had fewer hospital and intensive care unit (ICU) days and fewer positive chest X-rays. PCT had a negative predictive value of 94% for ICU care stay, 98% for 30 days mortality, and 88% for bacterial coinfection. Conclusion: PCT can be a safe rule-out test for bacterial coinfection. Routine PCT use in seasonal influenza patients with an uncertain clinical picture, and rapid influenza PCR testing, may be efficient as ASP tools.
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Berild, Dag; Jelsness-Jørgensen, Lars-Petter; Bjørnholt, Jørgen & Haug, Jon Birger
(2022).
Skreddersydde tiltak gir bedre antibiotikastyring i norske sykehus.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
142(5),
s. 1–3.
doi:
10.4045/tidsskr.22.0094.
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Christensen, Ingrid; Haug, Jon Birger; Berild, Dag; Bjørnholt, Jørgen; Skodvin, Brita & Jelsness-Jørgensen, Lars-Petter
(2022).
Factors Affecting Antibiotic Prescription among Hospital Physicians in a Low-Antimicrobial-Resistance Country: A Qualitative Study.
Antibiotics.
11(1).
doi:
10.3390/antibiotics11010098.
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Antimicrobial resistance (AMR) is a threat to hospital patients. Antimicrobial stewardship programs (ASPs) can counteract AMR. To optimize ASPs, we need to understand what affects physicians’ antibiotic prescription from several contexts. In this study, we aimed to explore the factors affecting hospital physicians’ antibiotic choices in a low-resistance country to identify potential targets for future ASPs. We interviewed 14 physicians involved in antibiotic prescription in a Norwegian hospital. The interviews were audiotaped, transcribed verbatim, and analyzed using thematic analysis. The main factors affecting antibiotic prescription were a high work pressure, insufficient staff resources, and uncertainties regarding clinical decisions. Treatment expectations from patients and next of kin, benevolence towards the patients, suboptimal microbiological testing, and limited time for infectious disease specialists to offer advisory services also affected the antibiotic choices. Future ASP efforts should evaluate the system organization and prioritizations to address and manage potential time-pressure issues. To limit the use of broad-spectrum antibiotics, improving microbiology testing and the routines for consultations with infectious disease specialists seems beneficial. We also identified a need among the prescribing physicians for a debate on ethical antibiotic questions.
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Rajar, Polona; Dhariwal, Achal; Silva, Gabriela Salvadori Da; Junges, Roger; Åmdal, Heidi Aarø & Berild, Dag
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(2022).
Microbial DNA extraction of high-host content and low biomass samples: Optimized protocol for nasopharynx metagenomic studies.
Frontiers in Microbiology.
13,
s. 1–15.
doi:
10.3389/fmicb.2022.1038120.
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Introduction Low microbial biomass and high human DNA content in nasopharyngeal aspirate samples hinder comprehensive characterization of microbiota and resistome. We obtained samples from premature infants, a group with increased risk of developing respiratory disorders and infections, and consequently frequent exposure to antibiotics. Our aim was to devise an optimal protocol for handling nasopharyngeal aspirate samples from premature infants, focusing on host DNA depletion and microbiome and resistome characterization. Methods Three depletion and three DNA extraction protocols were compared, using RT-PCR and whole metagenome sequencing to determine the efficiency of human DNA removal, taxonomic profiling and assignment of antibiotic resistance genes. Protocols were tested using mock communities, as well as pooled and individual patient samples. Results The only extraction protocol to retrieve the expected DNA yield from mock community samples was based on a lytic method to improve Gram positive recovery (MasterPure™). Host DNA content in non-depleted aliquots from pooled patient samples was 99%. Only samples depleted with MolYsis™ showed satisfactory, but varied reduction in host DNA content, in both pooled and individual patient samples, allowing for microbiome and resistome characterisation (host DNA content from 15% to 98%). Other depletion protocols either retrieved too low total DNA yields, preventing further analysis, or failed to reduce host DNA content. By using Mol_MasterPure protocol on aliquots from pooled patient samples, we increased the number of bacterial reads by 7.6 to 1,725.8-fold compared to non-depleted reference samples. PCR results were indicative of achieved microbial enrichment. Individual patient samples processed with Mol_MasterPure protocol varied greatly in total DNA yield, host DNA content (from 40% to 98%), species and antibiotic resistance gene richness. Discussion Despite high human DNA and low microbial biomass content in nasopharynx aspirates of preterm infants, we were able to reduce host DNA content to levels compatible with downstream shotgun metagenomic analysis, including bacterial species identification and coverage of antibiotic resistance genes. Whole metagenomic sequencing of microbes colonizing the nasopharynx may contribute to explaining the possible role of airway microbiota in respiratory conditions and reveal carriage of antibiotic resistance genes.
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Thaulow, Christian Magnus; Harthug, Stig; Nilsen, Roy Miodini; Eriksen, Beate Horsberg; Wathne, Jannicke Slettli & Berild, Dag
[Vis alle 7 forfattere av denne artikkelen]
(2022).
Are infants exposed to antimicrobials during the first 3 months of life at increased risk of recurrent use? An explorative data-linkage study.
Journal of Antimicrobial Chemotherapy.
ISSN 0305-7453.
77(5),
s. 1468–1475.
doi:
10.1093/jac/dkac024.
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Objectives
To investigate whether infants exposed to antimicrobials in hospital during the first 3 months of life had an increased risk of ambulatory antimicrobial use during the following year compared with infants not exposed to antimicrobials during the first 3 months of life.
Methods
Norwegian cohort study of infants less than 3 months consisting of one group exposed to antimicrobials recruited during hospitalization and one group not exposed to antimicrobials. Ten unexposed infants were matched with one exposed infant according to county of residence, birth year and month, and sex. The Norwegian Prescription Database was applied to register antimicrobial use from the month after discharge and 1 year onward. We defined comorbidity based on antimicrobials prescribed as reimbursable prescriptions due to underlying diseases.
Results
Of 95 infants exposed to antimicrobials during the first 3 months of life, 23% had recurrent use compared with 14% use in 950 unexposed infants [relative risk (RR) = 1.7 (95% CI = 1.1–2.5) and comorbidity-adjusted RR = 1.4 (95% CI = 0.9–2.2)]. The recurrence use rate in exposed term infants (≥37 weeks, n = 70) was 27% compared with 12% in their unexposed matches [RR 2.3 = (95% CI = 1.4–3.7) and comorbidity-adjusted RR = 1.9 (95% CI = 1.2–3.2). Of 25 exposed preterm infants, 3 (12%) had recurrent use. The total antimicrobial prescription rate was 674/1000 in the exposed group and 244/1000 in the unexposed group [incidence rate ratio = 2.8 (95% CI = 1.6–4.9)].
Conclusions
Infants exposed to antimicrobials during the first 3 months of life had an increased risk of recurrent use during the following year. This increased risk also appeared in term infants without infection-related comorbidity.
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Lekang, Katrine; Shekhar, Sudhanshu; Berild, Dag; Petersen, Fernanda Cristina & Winther-Larsen, Hanne Cecilie
(2022).
Effects of different amoxicillin treatment durations on microbiome diversity and composition in the gut.
PLOS ONE.
17(10),
s. e0275737–e0275737.
doi:
10.1371/journal.pone.0275737.
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Antibiotics seize an effect on bacterial composition and diversity and have been demonstrated to induce disruptions on gut microbiomes. This may have implications for human health and wellbeing, and an increasing number of studies suggest a link between the gut microbiome and several diseases. Hence, reducing antibiotic treatments may be beneficial for human health status. Further, antimicrobial resistance (AMR) is an increasing global problem that can be counteracted by limiting the usage of antibiotics. Longer antibiotic treatments have been demonstrated to increase the development of AMR. Therefore, shortening of antibiotic treatment durations, provided it is safe for patients, may be one measure to reduce AMR. In this study, the objective was to investigate effects of standard and reduced antibiotic treatment lengths on gut microbiomes using a murine model. Changes in the murine gut microbiome was assessed after using three different treatment durations of amoxicillin (3, 7 or 14 days) as well as a control group not receiving amoxicillin. Fecal samples were collected before and during the whole experiment, until three weeks past end of treatment. These were further subject for 16S rRNA Illumina MiSeq sequencing. Our results demonstrated significant changes in bacterial diversity, richness and evenness during amoxicillin treatment, followed by a reversion in terms of alpha-diversity and abundance of major phyla, after end of treatment. However, a longer restitution time was indicated for mice receiving amoxicillin for 14 days, and phylum Patescibacteria did not fully recover. In addition, an effect on the composition of Firmicutes was indicated to last for at least three weeks in mice treated with amoxicillin for 14 days. Despite an apparently reversion to a close to original state in overall bacterial diversity and richness, the results suggested more durable changes in lower taxonomical levels. We detected several families, genera and ASVs with significantly altered abundance three weeks after exposure to amoxicillin, as well as bacterial taxa that appeared significantly affected by amoxicillin treatment length. This may strengthen the argument for shorter antibiotic treatment regimens to both limit the emergence of antibiotic resistance and risk of gut microbiome disturbance.
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Thaulow, Christian Magnus; Blix, Hege Salvesen; Nilsen, Roy Miodini; Eriksen, Beate Horsberg; Wathne, Jannicke Slettli & Berild, Dag
[Vis alle 7 forfattere av denne artikkelen]
(2022).
Antibiotic use in children before, during and after hospitalisation.
Pharmacoepidemiology and Drug Safety.
ISSN 1053-8569.
31(7),
s. 749–757.
doi:
10.1002/pds.5438.
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Purpose
To investigate ambulatory antibiotic use in children during 1 year before and 1 year after in-hospital antibiotic exposure compared to children from the general population that had not received antibiotics in-hospital.
Methods
Explorative data-linkage cohort study from Norway of children aged 3 months to 17 years. One group had received antibiotics in-Hospital (H+), and one group had not received antibiotics in-hospital (H-). The H+ group was recruited during admission in 2017. Using the Norwegian Population Registry, 10 children from the H- group were matched with one child from the H+ group according to county of residence, age and sex. We used the Norwegian Prescription Database to register antibiotic use 1 year before and 1 year after the month of hospitalisation.
Results
Of 187 children in the H+ group, 83 (44%) received antibiotics before hospitalisation compared to 288/1870 (15%) in the H- group, relative risk (RR) 2.88 (95% confidence interval 2.38–3.49). After hospitalisation, 86 (46%) received antibiotics in the H+ group compared to 311 (17%) in the H- group, RR 2.77 (2.30–3.33). Comorbidity-adjusted RR was 2.30 (1.84–2.86) before and 2.25 (1.81–2.79) after hospitalisation. RR after hospitalisation was 2.55 (1.99–3.26) in children 3 months-2 years, 4.03 (2.84–5.71) in children 3–12 years and 2.07 (1.33–3.20) in children 13–17 years.
Conclusions
Children exposed to antibiotics in-hospital had two to three times higher risk of receiving antibiotics in ambulatory care both before and after hospitalisation. The link between in-hospital and ambulatory antibiotic exposure should be emphasised in future antibiotic stewardship programs.
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Möller, Vidar; Östholm-Balkhed, Åse; Berild, Dag; Fredriksson, Mats; Gottfredsson, Magnus & Holmbom, Martin
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(2021).
Antibiotic resistance among major pathogens compared to hospital treatment guidelines and antibiotic use in Nordic hospitals 2010–2018.
Infectious Diseases.
ISSN 2374-4235.
53(8),
s. 607–618.
doi:
10.1080/23744235.2021.1910338.
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Background The Nordic countries have comparable nationwide antibiotic resistance surveillance systems and individual antibiotic stewardship programmes. The aim of this study was to assess antibiotic resistance among major pathogens in relation to practice guidelines for hospital antibiotic treatment and antibiotic use in Nordic countries 2010–2018. Methods Antibiotic resistance among invasive isolates from 2010–2018 and aggregated antibiotic use were obtained from the European Centre for Disease Prevention and Control. Hospital practice guidelines were obtained from national or regional guidelines. Results Antibiotic resistance levels among Escherichia coli and Klebsiella pneumoniae were similar in all Nordic countries in 2018 and low compared to the European mean. Guidelines for acute pyelonephritis varied; 2nd generation cephalosporin (Finland), 3rd generation cephalosporins (Sweden, Norway), ampicillin with an aminoglycoside or aminoglycoside monotherapy (Denmark, Iceland and Norway). Corresponding guidelines for sepsis of unknown origin were 2nd (Finland) or 3rd (Sweden, Norway, Iceland) generation cephalosporins, carbapenems, (Sweden) combinations of penicillin with an aminoglycoside (Norway, Denmark), or piperacillin-tazobactam (all Nordic countries). Methicillin-resistant Staphylococcus aureus rates were 0–2% and empirical treatment with anti-MRSA antibiotics was not recommended in any country. Rates of penicillin non-susceptibility among Streptococcus pneumoniae were low (<10%) except in Finland and Iceland (<15%), but benzylpenicillin was recommended for community-acquired pneumonia in all countries. Conclusion Despite similar resistance rates among Enterobacteriaceae there were differences in practice guidelines for pyelonephritis and sepsis. National surveillance of antibiotic resistance can be used for comparison and optimization of guidelines and stewardship interventions to preserve the low levels of antibiotic resistance in Nordic countries.
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Berild, Dag
(2020).
Poor antimicrobial therapy, commendable candour.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
140(14).
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Thaulow, Christian Magnus; Lindemann, Paul Christoffer; Klingenberg, Claus; Berild, Dag; Blix, Hege Salvesen & Myklebust, Tor Åge
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(2020).
Epidemiology and Antimicrobial Susceptibility of Invasive Bacterial Infections in Children—A Population-Based Study From Norway.
The Pediatric Infectious Disease Journal.
ISSN 0891-3668.
40(5),
s. 403–410.
doi:
10.1097/INF.0000000000003013.
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Objective: To describe epidemiology and antimicrobial susceptibility testing (AST) data of bacteria causing invasive infections in Norwegian children (0–18 years).<p> <p>Methods: Population-based observational study using prospectively collected AST data from the Norwegian Surveillance System of Antimicrobial Resistance from 2013 to 2017. We included all clinically relevant bacterial isolates (blood and cerebrospinal fluid), and compared incidence of invasive infections and AST data in isolates from children and adults.<p> <p>Results: We included 1173 isolates from children and 44,561 isolates from adults. Staphylococcus aureus accounted for 220/477 (46.2%, 95% CI: 41.6–50.7) of all isolates in schoolchildren (6–18 years). Compared with Streptococcus pneumonia isolates from adults (N = 2674), we observed higher nonsusceptibility rates to penicillin in isolates from children (N = 151), 11.9% versus 5.8%, P < 0.01; also higher resistance rates to erythromycin (11.3% vs. 4.9%, P < 0.01), clindamycin (9.3% vs. 3.6%, P < 0.001), and trimethoprim/sulfamethoxazole (17.9% vs. 6.4%, P < 0.001). Compared with Escherichia coli isolates in adults (N = 9073), we found lower rates of ESBL in isolates from children (N = 212), 2.4% versus 6.4%, P < 0.05.<p> <p>Conclusion: The study indicates the importance of microbiologic surveillance strategies in children and highlights the need for pediatric AST data. The high rates of nonsusceptibility to commonly used antibiotics among S. pneumoniae in children and the high burden of invasive S. aureus infections in schoolchildren calls for modifications of Norwegian guidelines.
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Rajar, Polona; Saugstad, Ola Didrik; Berild, Dag; Dutta, Anirban; Greisen, Gorm & Lausten-Thomsen, Ulrik
[Vis alle 11 forfattere av denne artikkelen]
(2020).
Antibiotic stewardship in premature infants: a systematic review.
Neonatology.
ISSN 1661-7800.
117(6),
s. 673–686.
doi:
10.1159/000511710.
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<b><i>Introduction:</i></b> Antibiotic treatment in premature infants is often empirically prescribed, and practice varies widely among otherwise comparable neonatal intensive care units. Unnecessary and prolonged antibiotic treatment is documented in numerous studies. Recent research shows serious side effects and suggests long-term adverse health effects in prematurely born infants exposed to antibiotics in early life. One preventive measure to reduce unnecessary antibiotic exposure is implementation of antibiotic stewardship programs. Our objective was to review the literature on implemented antibiotic stewardship programs including premature infants with gestational age ≤34 weeks. <b><i>Methods:</i></b> Six academic databases (PubMed [Medline], McMaster PLUS, Cochrane Database of Systematic Reviews, UpToDate, Cochrane Central Register of Controlled Trials, and National Institute for Health and Care Excellence) were systematically searched. PRISMA guidelines were applied. <b><i>Results:</i></b> The search retrieved 1,212 titles of which 12 fitted inclusion criteria (11 observational studies and 1 randomized clinical trial). Included articles were critically appraised. We grouped the articles according to common area of implemented stewardship actions: (1) focus on reducing initiation of antibiotic therapy, (2) focus on shortening duration of antibiotic therapy, (3) various organizational stewardship implementations. The heterogeneity of cohort composition, of implemented actions and of outcome measures made meta-analysis inappropriate. We provide an overview of the reduction in antibiotic use achieved. <b><i>Conclusion:</i></b> Antibiotic stewardship programs can be effective for premature newborns especially when multifactorial and tailored to this population, focusing on reducing initiation or on shortening the duration of antibiotic therapy. Programs without specific measures were less effective.
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Fløystad, Hans Kristian; Berild, Jacob Dag; Brandsæter, Bjørn Jardar; Vestrheim, Didrik Frimann; Berild, Dag & Holm, Are Martin
(2020).
Gastrointestinal symptoms in invasive pneumococcal disease: A cohort study.
BMC Infectious Diseases.
20(1).
doi:
10.1186/s12879-020-05211-3.
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Background The study aimed to assess whether gastrointestinal (GI) symptoms at admission are associated with increased short-term mortality in patients with invasive pneumococcal disease (IPD). Methods We included all patients with IPD at Aker University Hospital in Oslo, Norway, from 1993 to 2008. Clinical data were registered. Survival data were retrieved from official registries. We used Cox regression and Kaplan-Meier curve to compare mortality within 28 days of admission in patients with and without GI symptoms. Results Four hundred sixteen patients were included. Of these, 108 patients (26%) presented with GI symptoms, and 47 patients (11%) with GI symptoms only. Patients with GI symptoms were younger (p < 0.001) and had less cardiovascular disease (p < 0.001), pulmonary disease (p = 0.048), and cancer (p = 0.035) and received appropriate antibiotic treatment later. After adjusting for risk factors, we found an increased hazard ratio of 2.28 (95% CI 1.31–3.97) in patients presenting with GI symptoms. In patients with GI symptoms only there was an increased hazard ratio of 2.24 (95% CI 1.20–4.19) in univariate analysis, which increased to 4.20 (95% CI 2.11–8.39) after multivariate adjustment. Fewer patients with GI symptoms only received antibiotics upon admission. Conclusions A large proportion of IPD patients present with GI symptoms only or in combination with other symptoms. GI symptoms in IPD are associated with increased short-term mortality.
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Christensen, Ingrid; Haug, Jon Birger; Berild, Dag; Bjørnholt, Jørgen Vildershøj & Jelsness-Jørgensen, Lars-Petter
(2020).
Hospital physicians' experiences with procalcitonin - implications for antimicrobial stewardship; a qualitative study.
BMC Infectious Diseases.
20(1).
doi:
10.1186/s12879-020-05246-6.
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Background. Procalcitonin is an inflammatory biomarker that is sensitive for bacterial infections and a promising clinical decision aid in antimicrobial stewardship programs. However, there are few studies of physicians’ experiences concerning the use of PCT. The objective of this study was to investigate whether hospital physicians’ experience with procalcitonin after 18 months of use can inform the PCT implementation in antimicrobial stewardship programs. Materials/methods. We deployed a qualitative approach using semi-structured interviews with 14 hospital physicians who had experience with procalcitonin in clinical practice. Interviews were audio-taped, transcribed verbatim and analysed using thematic analysis. Results. Physicians reported a knowledge gap, which made them uncertain about the appropriate procalcitonin use, interpretation, and trustworthiness. Simultaneously, the physicians experienced procalcitonin as a useful clinical decision aid but emphasised that their clinical evaluation of the patient was the most important factor when deciding on antibiotic treatment. Conclusions. Procalcitonin was regarded a helpful clinical tool, but the physicians called for more knowledge about its appropriate uses. Active implementation of unambiguous procalcitonin algorithms and physician education may enhance the utility of the test as an antimicrobial stewardship adjunct.
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Thaulow, Christian Magnus; Berild, Dag; Eriksen, Beate Horsberg; Myklebust, Tor Åge & Blix, Hege Salvesen
(2019).
Potential for More Rational Use of Antibiotics in Hospitalized Children in a Country With Low Resistance: Data From eight Point Prevalence Surveys.
The Pediatric Infectious Disease Journal.
ISSN 0891-3668.
38(4),
s. 384–389.
doi:
10.1097/INF.0000000000002106.
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Abstract
BACKGROUND:
Antimicrobial resistance (AMR) is low in Norway, but to prevent an increase the Norwegian Government has launched a National Strategy including a 30% reduction of broad-spectrum antibiotics (BSA) in hospitals within 2020. BSA are defined as second- and third-generation cephalosporins, carbapenems, piperacillin/tazobactam and quinolones. There are no recent studies of antibiotic use in Norwegian hospitalized children.
AIM OF THE STUDY:
To describe the use of antibiotics with emphasis on BSA in Norwegian hospitalized children and neonates in order to detect possibilities for optimization.
METHODS:
Data were extracted from eight national point prevalence surveys of systemic antibiotic prescriptions in Norwegian hospitals between 2015 and 2017. The choices of antibiotics were compared with the empirical recommendations given in available Norwegian guidelines. In total, 1323 prescriptions were issued for 937 patients.
RESULTS:
Twenty-four percent of pediatric inpatients were given antibiotics. Adherence to guidelines was 48%, and 30% (95% CI 27%-33%) of all patients on antibiotics received BSA. We identified only small variations in use of BSA between hospitals. One third of the patients on antibiotic therapy received prophylaxis whereof 13% where given BSA. In 30% of prescriptions with BSA, no microbiological sample was obtained prior to treatment.
CONCLUSION:
This study reveals an excess of prescriptions with BSA in relation to the low resistance rate in Norway. Our findings reveal areas for improvement that can be useful in the forthcoming antibiotic stewardship programs in Norwegian pediatric departments
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Aasbrenn, Marit Nymoen; Skeie, Ivar & Berild, Dag
(2019).
Compliance to antibiotic guidelines leads to more appropriate use of antibiotics in skin and soft tissue infections in injecting drug users.
Infectious Diseases.
ISSN 2374-4235.
51(8),
s. 570–577.
doi:
10.1080/23744235.2019.1617435.
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<i>Background</i>: Knowledge about the treatment of skin and soft tissue infections in injecting drug users in countries with a low prevalence of antibiotic resistance is limited. We investigated bacterial antibiotic resistance and treatment of skin and soft tissue infections in Norwegian drug users.<p> <p><i>Methods</i>: We performed a two year clinical cross-sectional observational study in a Norwegian hospital. Data were collected retrospectively from hospital records. We examined bacteriological findings and antibiotic resistance, and evaluated compliance to treatment guidelines and appropriateness of empirical antibiotic therapy relative to results of cultures and susceptibility testing. Descriptive and univariate analyses were performed.<p> <i>Results</i>: Hundred and thirty-five injecting drug users were admitted with skin and soft tissue infection in the study period. Cultures were obtained from 103 (77%) abscesses and eight (24%) erysipelas and cellulitis, with bacterial growth in 80 (78%) and five (63%), respectively. Streptococci and staphylococci were the most prevalent bacteria, but methicillin-resistant <i>Staphylococcus aureus</i> was found in only one patient. Compliance to hospital antibiotic guidelines was 70%. Ninety-one per cent of patients in the compliant and 79% in the non-compliant group were given effective empirical antibiotics (<i>p</i> = .334). In the non-compliant group, significantly more patients received broad-spectrum empirical antibiotics (p < .001). In 30 cases where adjustment of antibiotic therapy was possible according to susceptibility testing, this was performed in only 14 cases.<p> <p><i>Conclusions</i>: Bacteria and resistance patterns did not differ significantly from the skin and soft tissue infections in the general population in Norway. Compliance to antibiotic guidelines led to significantly less use of broad-spectrum antibiotics and to good bacterial coverage. General guidelines for treatment should be applied to injecting drug users with skin and soft tissue infections.
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Thaulow, Christian Magnus; Berild, Dag; Blix, Hege Salvesen; Brigtsen, Anne Karin; Myklebust, Tor Åge & Eriksen, Beate Horsberg
(2019).
Can We Optimize Antibiotic Use in Norwegian Neonates? A Prospective Comparison Between a University Hospital and a District Hospital.
Frontiers in Pediatrics.
7:440,
s. 1–11.
doi:
10.3389/fped.2019.00440.
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Background: Worldwide, a large proportion of neonates are prescribed antibiotics without having infections leading to increased antimicrobial resistance, disturbance of the evolving microbiota, and increasing the risk of various chronical diseases. Comparing practice between different hospitals/settings is important in order to optimize antibiotic stewardship. Aim: To investigate and compare the potential for improved antibiotic stewardship in neonates in two Norwegian hospitals with different academic culture, with emphasis on antibiotic exposure in unconfirmed infections, treatment length/doses, CRP values and the use of broad-spectrum antibiotics (BSA). All types of infections were investigated, but the main focus was on early-onset sepsis (EOS). Methods: We conducted a prospective observational cohort study of antibiotic use in a Norwegian university hospital (UH) and a district hospital (DH), 2017. Unconfirmed infections were defined as culture negative infections that neither fulfilled the criteria for clinical infection (clinical symptoms, maximum CRP >30 mg/L, and treatment for at least 5 days). Results: Ninety-five neonates at the DH and 89 neonates at the UH treated with systemic antibiotics were included in the study. In total, 685 prescriptions (daily doses) of antibiotics were given at the DH and 903 at the UH. Among term and premature infants (≥ 28 weeks), 82% (75% at the UH and 86% at the DH, p = 0.172) of the treatments for suspected EOS were for unconfirmed infections, and average treatment length in unconfirmed infections was 3.1 days (both hospitals). Median dose for aminoglycoside was higher for term infants at the UH (5.96, 95% CI 5.02–6.89) compared to the DH (4.98, 95% CI 4.82–5.14; p < 0.001). At the UH, all prescriptions with aminoglycosides were gentamicin, while tobramycin accounted for 93% of all prescriptions with aminoglycosides at the DH. Conclusion: There is a potential for reduction in both antibiotic exposure and treatment length in these two neonatal units, and a systematic risk/observational algorithm of sepsis should be considered in both hospitals. We revealed no major differences between the UH and DH, but doses and choice of aminoglycosides varied significantly.
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Thaulow, Christian Magnus; Blix, Hege Salvesen; Eriksen, Beate Horsberg; Ask, Ingvild; Myklebust, Tor Åge & Berild, Dag
(2019).
Using a period incidence survey to compare antibiotic use in children between a university hospital and a district hospital in a country with low antimicrobial resistance: a prospective observational study.
BMJ Open.
9(5),
s. 1–10.
doi:
10.1136/bmjopen-2018-027836.
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Objectives To describe and compare antibiotic use in relation to indications, doses, adherence rate to guidelines and rates of broad-spectrum antibiotics (BSA) in two different paediatric departments with different academic cultures, and identify areas with room for improvement.
Design Prospective observational survey of antibiotic use.
Setting Paediatric departments in a university hospital (UH) and a district hospital (DH) in Norway, 2017. The registration period was 1 year at the DH and 4 months at the UH.
Participants 201 children at the DH (mean age 3.8: SD 5.1) and 137 children at the UH (mean age 2.0: SD 5.9) were treated with systemic antibiotics by a paediatrician in the study period and included in the study.
Outcome measures Main outcome variables were prescriptions of antibiotics, treatments with antibiotics, rates of BSA, median doses and adherence rate to national guidelines.
Results In total, 744 prescriptions of antibiotics were given at the UH and 638 at the DH. Total adherence rate to guidelines was 75% at the UH and 69% at the DH (p=0.244). The rate of treatments involving BSA did not differ significantly between the hospitals (p=0.263). Use of BSA was related to treatment of central nervous system (CNS) infections, patients with underlying medical conditions or targeted microbiological treatment in 92% and 86% of the treatments, at the UH and DH, respectively (p=0.217). A larger proportion of the children at the DH were treated for respiratory tract infections (p<0.01) compared with the UH. Children at the UH were treated with higher doses of ampicillin and cefotaxime (p<0.05) compared with the DH.
Conclusion Our results indicate that Norwegian paediatricians have a common understanding of main aspects in rational antibiotic use independently of working in a UH or DH. Variations in treatment of respiratory tract infections and in doses of antibiotics should be further studied.
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Beovic, B; Pulcini, C; Dumartin, C; Nerat, B; Maurel, C & Berild, Dag
(2018).
Legal framework of amtimicrobial stewardship in hospitals (LEASH): a European Society of Clinical Microbiology and Infectious Diseases (ESCMID) cross-sectional survey.
International Journal of Antimicrobial Agents.
ISSN 0924-8579.
doi:
10.1016/j.ijantimicag.2018.07.019.
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Eliassen, Knut Eirik Ringheim; Reiso, Harald; Berild, Dag & Lindbæk, Morten
(2018).
Comparison of phenoxymethylpenicillin, amoxicillin, and doxycycline for erythema migrans in general practice. A randomized controlled trial with a 1-year follow-up.
Clinical Microbiology and Infection (CMI).
ISSN 1198-743X.
24(12),
s. 1290–1296.
doi:
10.1016/j.cmi.2018.02.028.
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Berild, Andrea Gran; Erichsen, Stian Didrik & Berild, Dag
(2018).
Behandling av pneumoni oppstått utenfor sykehus.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
138(19),
s. 1818–1822.
doi:
10.4045/tidsskr.17.1115.
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Shekhar, Sudhanshu; Khan, Rabia; Ferreira, Daniela M.; Mitsi, Elena; German, Esther & Rørvik, Gro Herredsvela
[Vis alle 10 forfattere av denne artikkelen]
(2018).
Antibodies reactive to commensal Streptococcus mitis show cross-reactivity with virulent Streptococcus pneumoniae serotypes.
Frontiers in Immunology.
9:747,
s. 1–10.
doi:
10.3389/fimmu.2018.00747.
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Current vaccines against Streptococcus pneumoniae, a bacterial species that afflicts people by causing a wide spectrum of diseases, do not protect against all pneumococcal serotypes. Thus, alternative vaccines to fight pneumococcal infections that target common proteins are under investigation. One promising strategy is to take advantage of immune cross-reactivity between commensal and pathogenic microbes for cross-protection. In this study, we examined the antibody-mediated cross-reactivity between S. pneumoniae and Streptococcus mitis, a commensal species closely related to S. pneumoniae. Western blot analysis showed that rabbit antisera raised against S. mitis reacted with multiple proteins of virulent S. pneumoniae strains (6B, TIGR4, and D39). Rabbit anti-S. pneumoniae IgG antibodies also showed binding to S. mitis antigens. Incubation of rabbit antisera raised against S. mitis with heterologous or homologous bacterial lysates resulted in marked inhibition of the developments of bands in the Western blots. Furthermore, plasma IgG antibodies from adult human volunteers intranasally inoculated with S. pneumoniae 6B revealed enhanced S. mitis-specific IgG titers compared with the pre-inoculation samples. Using an on-chip protein microarray representing a number of selected membrane and extracellular S. pneumoniae proteins, we identified choline-binding protein D (CbpD), cell division protein (FtsH), and manganese ABC transporter or manganese-binding adhesion lipoprotein (PsaA) as common targets of the rabbit IgG antibodies raised against S. mitis or S. pneumoniae. Cumulatively, these findings provide evidence on the antibody-mediated cross-reactivity of proteins from S. mitis and S. pneumoniae, which may have implications for development of effective and wide-range pneumococcal vaccines.
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Bjerva, Marianne; Berild, Dag & Jacobsen, Dag
(2017).
En veltrent mann med mekanisk aortaklaffog leggsmerter.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
137(2),
s. 113–116.
doi:
10.4045/tidsskr.15.1337.
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Roaldsnes, Erlend; Eikeland, Randi & Berild, Dag
(2017).
Lyme-nevroborreliose ved uspesifikke nevrologiske symptomer.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
137(2),
s. 101–104.
doi:
10.4045/tidsskr.15.1115.
Fulltekst i vitenarkiv
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Fløystad, Hans Kristian; Holm, Are Martin; Sandvik, Leiv; VESTRHEIM, DIDRIK FRIMANN; Brandsæter, Bjørn Jardar & Berild, Dag
(2017).
Increased long-term mortality after survival of invasive pneumococcal disease: a population-based study.
Infectious Diseases.
ISSN 2374-4235.
49(5),
s. 365–372.
doi:
10.1080/23744235.2016.1271997.
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Objectives: We studied if patients surviving hospitalization for invasive pneumococcal disease (IPD) have an increased long-term mortality.
Methods: In this population-based case-control study, we assessed adults discharged from Aker University Hospital in Oslo, Norway, from 1993 to 2008 after surviving IPD. Mortality among the study population was compared to the general Norwegian population using standardized mortality ratios (SMR). Median follow-up time was 7.2 years (range 5 days to 21.1 years). Associated factors were also investigated.
Results: We assessed 372 patients of whom 184 patients died during the observation period. Mortality was increased for 10 years after surviving hospitalization for IPD. Patients aged 18-64 years had a one-year SMR of 18.8 (95% CI: 10.0-32.1) and a 10-year SMR of 6.0 (95% CI: 4.4-8.0). SMR for the first five years among patients with and without underlying conditions were 10.7 (95% CI: 7.0-15.5) and 2.8 (95% CI: 0.9-6.4), respectively. Patients older than 65 years had a one-year SMR of 1.8 (95% CI: 1.2-2.7) and a 10-year SMR of 1.6 (95% CI: 1.4-1.9).
Conclusions: Patients surviving IPD had an increased long-term mortality compared to the general population. This was particularly pronounced in patients with known underlying conditions. These findings suggest that IPD is a negative prognostic marker, and that a closer follow-up of patients who have suffered IPD is warranted.
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Raastad, Ragnhild; Tvete, Ingunn Fride; Abrahamsen, Tore G; Berild, Dag; Leegaard, Truls Michael & Walberg, Mette
[Vis alle 7 forfattere av denne artikkelen]
(2015).
A worrying trend in weight-adjusted paediatric antibiotic use in a Norwegian tertiary care hospital.
Acta Paediatrica.
ISSN 0803-5253.
104(7),
s. 687–692.
doi:
10.1111/apa.12994.
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Aim
The World Health Organization recommends the defined daily dose (DDD) as the standard unit of measurement for antibiotic use, but this is not applicable in children. We aimed to assess paediatric antibiotic use in a Norwegian tertiary care hospital using a novel weight-adjusted method.
Methods
We obtained antibiotic purchase data from the hospital pharmacy and administrative data for all admissions from 2002 to 2009 to the paediatric wards at Oslo University Hospital, Rikshospitalet. Recommended daily doses per 100 kg days (RDDs/kg days) were calculated based on national guidelines for paediatric antibiotic use, length of stay and estimated weight for sex and age using national growth references.
Results
Total antibiotic use increased significantly from 51.8 to 65.5 RDDs/100 kg days. We found statistically significant annual increases in the consumption of carbapenems (18.0%), third-generation cephalosporins (6.0%) and imidazole derivatives (6.6%) and a considerable difference between total antibiotic use measured in RDDs/100 kg days and DDDs/100 bed days for neonates.
Conclusion
Weight-adjusted antibiotic use provided a more meaningful description of the quantities of antibiotics consumed than DDDs/100 bed days, particularly for neonates. Total antibiotic use, use of meropenem, third-generation cephalosporins and imidazole derivatives increased significantly despite low prevalence of antibiotic-resistant pathogens.
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Fagan, Mark Stephan; Lindbæk, Morten; Grude, Nils; Reiso, Harald; Romøren, Maria & Skaare, Dagfinn
[Vis alle 7 forfattere av denne artikkelen]
(2015).
Antibiotic resistance patterns of bacteria causing urinary tract infections in the elderly living in nursing homes versus the elderly living at home: an observational study.
BMC Geriatrics.
15.
doi:
10.1186/s12877-015-0097-x.
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Background Antibiotic resistance is a problem in nursing homes. Presumed urinary tract infections (UTI) are the most common infection. This study examines urine culture results from elderly patients to see if specific guidelines based on gender or whether the patient resides in a nursing home (NH) are warranted. Methods This is a cross sectional observation study comparing urine cultures from NH patients with urine cultures from patients in the same age group living in the community. Results There were 232 positive urine cultures in the NH group and 3554 in the community group. Escherichia coli was isolated in 145 urines in the NH group (64 %) and 2275 (64 %) in the community group. There were no clinically significant differences in resistance. Combined, there were 3016 positive urine cultures from females and 770 from males. Escherichia coli was significantly more common in females 2120 (70 %) than in males 303 (39 %)(p < 0.05). Enterococcus faecalis was significantly less common in females 223(7 %) than males 137 (18 %) (p < 0.05). For females, there were lower resistance rates to ciprofloxacin among Escherichia coli (7 % vs 12 %; p < 0.05) and to mecillinam among Proteus mirabilis (3 % vs 12 %; p < 0.05). Conclusions Differences in resistance rates for patients in the nursing home do not warrant separate recommendations for empiric antibiotic therapy, but recommendations based on gender seem warranted.
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Haug, Jon Birger; Berild, Dag; Walberg, Mette & Reikvam, Åsmund
(2014).
Hospital- and patient-related factors associated
with differences in hospital antibiotic use: analysis
of national surveillance results.
Antimicrobial Resistance & Infection Control.
3(40).
doi:
10.1186/s13756-014-0040-5.
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Background Surveillance data of antibiotic use are increasingly being used for benchmarking purposes, but there is a lack of studies dealing with how hospital- and patient-related factors affect antibiotic utilization in hospitals. Our objective was to identify factors that may contribute to differences in antibiotic use. Methods Based on pharmacy sales data (2006–2011), use of all antibiotics, all penicillins, and broad-spectrum antibiotics was analysed in 22 Health Enterprises (HEs). Antibiotic utilization was measured in World Health Organisation defined daily doses (DDDs) and hospital-adjusted (ha)DDDs, each related to the number of bed days (BDs) and the number of discharges. For each HE, all clinical specialties were included and the aggregated data at the HE level constituted the basis for the analyses. Fourteen variables potentially associated with the observed antibiotic use – extracted from validated national databases – were examined in 12 multiple linear regression models, with four different measurement units: DDD/100 BDs, DDD/100 discharges, haDDD/100 BDs and haDDD/100 discharges. Results Six variables were independently associated with antibiotic use, but with a variable pattern depending on the regression model. High levels of nurse staffing, high proportions of short (<2 days) and long (>10 days) hospital stays, infectious diseases being the main ICD-10 diagnostic codes, and surgical diagnosis-related groups were correlated with a high use of all antibiotics. University affiliated HEs had a lower level of antibiotic utilization than other institutions in eight of the 12 models, and carried a high explanatory strength. The use of broad-spectrum antibiotics correlated strongly with short and long hospital stays. There was a residual variance (30%–50% for all antibiotics; 60%–70% for broad-spectrum antibiotics) that our analysis did not explain. Conclusions The factors associated with hospital antibiotic use were mostly non-modifiable. By adjusting for these factors, it will be easier to evaluate and understand observed differences in antibiotic use between hospitals. Consequently, the inter-hospital differences can be more confidently acted upon. The residual variation is presumed to largely reflect prescriber-related factors.
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Fagan, Mark Stephan; Lindbæk, Morten; Reiso, Harald & Berild, Dag
(2014).
A simple intervention to reduce inappropriate ciprofloxacin prescribing in the emergency department.
Scandinavian Journal of Infectious Diseases.
ISSN 0036-5548.
46(7),
s. 481–485.
doi:
10.3109/00365548.2014.880187.
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Aldrin, Magne; Raastad, Ragnhild; Tvete, Ingunn Fride; Berild, Dag; Frigessi, Arnoldo & Leegaard, Truls Michael
[Vis alle 9 forfattere av denne artikkelen]
(2013).
Antibiotic resistance in hospitals: a ward-specific random effect model in a low antibiotic consumption environment.
Statistics in Medicine.
ISSN 0277-6715.
32(8),
s. 1407–1418.
doi:
10.1002/sim.5636.
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Association between previous antibiotic use and emergence of antibiotic resistance has been reported for several microorganisms. The relationship has been extensively studied, and although the causes of antibiotic resistance are multi-factorial, clear evidence of antibiotic use as a major risk factor exists. Most studies are carried out in countries with high consumption of antibiotics and corresponding high levels of antibiotic resistance, and currently, little is known whether and at what level the associations are detectable in a low antibiotic consumption environment. We conduct an ecological, retrospective study aimed at determining the impact of antibiotic consumption on antibiotic-resistant Pseudomonas aeruginosa in three hospitals in Norway, a country with low levels of antibiotic use. We construct a sophisticated statistical model to capture such low signals. To reduce noise, we conduct our study at hospital ward level. We propose a random effect Poisson or binomial regression model, with a reparametrisation that allows us to reduce the number of parameters. Inference is likelihood based. Through scenario simulation, we study the potential effects of reduced or increased antibiotic use. Results clearly indicate that the effects of consumption on resistance are present under conditions with relatively low use of antibiotic agents. This strengthens the recommendation on prudent use of antibiotics, even when consumption is relatively low.
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Fagan, Mark Stephan; Mæhlen, Marthe Thoresen; Lindbæk, Morten & Berild, Dag
(2012).
Antibiotic prescribing in nursing homes in an area with low prevalence of antibiotic resistance: Compliance with national guidelines.
Scandinavian Journal of Primary Health Care.
ISSN 0281-3432.
30(1),
s. 10–15.
doi:
10.3109/02813432.2011.629156.
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Objective. To examine antibiotic prescribing in nursing homes and determine to what degree the prescribing was in accordance with the national guidelines for antibiotic prescribing. Design. Retrospective examination of patients’ records who were prescribed antibiotics in the period 1 March 2007 to 28 February 2008. Setting and patients. Patients residing in the nursing homes of Arendal, Norway. Main outcome measures. Choice of antibiotic in respect of the recommendations in the national guidelines for antibiotic prescribing. Results. A total of 714 antibiotic courses were prescribed to 327 patients yielding a prevalence of 6.6%. Compliant prescribing was 77% for urinary tract infections (UTI), 79% for respiratory tract infections (RTI), and 76% for skin and soft tissue infections (SSTI). Ciprofloxacin was responsible for 63% of non-compliant prescribing. On the respite wards there was a higher rate of total prescribing, non-compliant prescribing, and prescribing by physicians employed at the local hospital. Conclusion. Guidelines for antibiotic use must be implemented actively and efforts to improve antibiotic prescribing in nursing homes must be aimed at both nursing home and hospital physicians.
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Brandsæter, Bjørn Jardar; Pillgram, Magnus; Berild, Dag; Kjekshus, Harald; Kran, Anne-Marte Bakken & Bergersen, Bente Magny
(2011).
Hospitalised patients with suspected 2009 H1N1 Influenza A in a hospital in Norway, July - December 2009.
BMC Infectious Diseases.
11.
doi:
10.1186/1471-2334-11-75.
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Background The main objective of this study was to describe the patients who were hospitalised at Oslo University Hospital Aker during the first wave of pandemic Influenza A (H1N1) in Norway. Methods Clinical data on all patients hospitalised with influenza-like illness from July to the end of November 2009 were collected prospectively. Patients with confirmed H1N1 Influenza A were compared to patients with negative H1N1 tests. Results 182 patients were hospitalised with suspected H1N1 Influenza A and 64 (35%) tested positive. Seventeen patients with positive tests (27%) were admitted to an intensive care unit and four patients died (6%). The H1N1 positive patients were younger, consisted of a higher proportion of non-ethnic Norwegians, had a higher heart rate on admission, and fewer had pre-existing hypertension, compared to the H1N1 negative patients. However, hypertension was the only medical condition that was significantly associated with a more serious outcome defined as ICU admission or death, with a univariate odds ratio of the composite endpoint in H1N1 positive and negative patients of 6.1 (95% CI 1.3-29.3) and 3.2 (95% CI 1.2-8.7), respectively. Chest radiography revealed pneumonia in 24/59 H1N1 positive patients. 63 of 64 H1N1 positive patients received oseltamivir. Conclusions The extra burden of hospitalisations was relatively small and we managed to admit all the patients with suspected H1N1 influenza without opening new pandemic isolation wards. The morbidity and mortality were similar to reports from comparable countries. Established hypertension was associated with more severe morbidity and patients with hypertension should be considered candidates for vaccination programs in future pandemics.
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Haug, Jon Birger; Berild, Dag; Walberg, Mette & Reikvam, Åsmund
(2011).
Increased antibiotic use in Norwegian hospitals despite a low antibiotic resistance rate.
Journal of Antimicrobial Chemotherapy.
ISSN 0305-7453.
66(11),
s. 2643–2646.
doi:
10.1093/jac/dkr361.
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Abrahamsen, Tore G; Andresen, Stein Erik; Haug, Ola; Lelek, Michaela; Ringertz, Signe H & Berild, Dag
[Vis alle 12 forfattere av denne artikkelen]
(2008).
A controlled intervention study to improve antibiotic use in a Russian paediatric hospital.
International Journal of Antimicrobial Agents.
ISSN 0924-8579.
31(5),
s. 478–483.
doi:
10.1016/j.ijantimicag.2008.01.009.
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A controlled intervention study was performed in a paediatric hospital in Russia to improve antibiotic use and to see whether improvements persisted. During October–December 2002, clinical and microbiological data, antibiotic use, costs and outcome were recorded at two wards for gastrointestinal infections (GIIs) and two wards for respiratory tract infections (RTIs). Guidelines for diagnosis and treatment of infections were developed and implemented at one ward for GIIs and one ward for RTIs in 2003. The other two wards served as controls. The same data were recorded during the same 3-month periods in 2003 and 2004. At the intervention ward, the percentage of patients with GII who received antibiotics decreased from 94% in 2002 to 41% in 2003, but increased to 73% in 2004. In RTI patients these percentages were 90% in 2002, 53% in 2003 and 83% in 2004. The proportions of patients who received antibiotics in 2004 were still lower than in 2002: risk difference (RD) = 0.217 (P ≤ 0.001) in GIIs and RD = 0.073 (P = 0.013) in RTIs. From 2002 to 2004 there was a decrease in cephalosporin use (P = 0.021) and an increase in penicillin use (P = 0.032) in pneumonia. There was no difference in mortality, duration of fever or duration of hospital stay between the intervention and control wards. Antibiotic use could be halved without compromising the quality of patient care, but 1 year after the intervention the use of antibiotics approached pre-intervention levels. Strategies to sustain the effect of interventions are needed.
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Berild, Dag & Eliassen, Knut Eirik
(2008).
Meningitt N71 (del av kap 7.10).
I Lindbæk, Morten (Red.),
Nasjonale faglige retningslinjer for antibiotikabruk i primærhelsetjenesten (Helsedirektoratet bestillingsnummer IS-1593).
Helsedirektoratet og Antibiotikasenteret for primærmedisin (ASP).
ISSN 9788280811127.
s. 180–182.
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Berild, Dag & Eliassen, Knut Eirik
(2008).
Sepsis A78 (del av kap 7.10).
I Lindbæk, Morten (Red.),
Nasjonale faglige retningslinjer for antibiotikabruk i primærhelsetjenesten (Helsedirektoratet bestillingsnummer IS-1593).
Helsedirektoratet og Antibiotikasenteret for primærmedisin (ASP).
ISSN 9788280811127.
s. 183–185.
Fulltekst i vitenarkiv
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Berild, Dag & Eliassen, Knut Eirik
(2008).
Endokardittprofylakse K70 (del av kap 7.10).
I Lindbæk, Morten (Red.),
Nasjonale faglige retningslinjer for antibiotikabruk i primærhelsetjenesten (Helsedirektoratet bestillingsnummer IS-1593).
Helsedirektoratet og Antibiotikasenteret for primærmedisin (ASP).
ISSN 9788280811127.
s. 186–186.
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Eliassen, Knut Eirik & Berild, Dag
(2008).
Borreliose (Lymes sykdom) S73, A78 (del av kap 7.10).
I Lindbæk, Morten (Red.),
Nasjonale faglige retningslinjer for antibiotikabruk i primærhelsetjenesten (Helsedirektoratet bestillingsnummer IS-1593).
Helsedirektoratet og Antibiotikasenteret for primærmedisin (ASP).
ISSN 9788280811127.
s. 175–179.
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Berild, Dag; Småbrekke, L.; Halvorsen, Dag S.; Lelek, Michaela; Stahlsberg, EM. & Ringertz, Signe Holta
(2003).
Clostridium difficile infections related to antibiotic use and infection control facilities in two university hospitals.
Journal of Hospital Infection.
ISSN 0195-6701.
54(3),
s. 202–6.
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Berild, Dag
(2002).
Småfolk mot storfolk,
Frisk nok for livet.
Pantagruel forlag, Oslo.
ISSN 9788279001386.
s. 83–89.
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Berild, Dag; Ringertz, Signe Holta; Åbyholm, Gunnar; Lelek, Michaela & Fosse, Brita
(2002).
Impact of an antibiotic policy on antibiotic use in a paediatric department.
International Journal of Antimicrobial Agents.
ISSN 0924-8579.
20,
s. 333–338.
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Holm, Arne; Berild, Dag; Ringertz, Signe Holta; Høiby, Ernst Arne & Haaheim, Lars R.
(2002).
Occurrence and clinical presentation of systemic pneumococcal infections in an unselected population.
European Journal of Clinical Microbiology and Infectious Diseases.
ISSN 0934-9723.
21,
s. 465–67.
Fulltekst i vitenarkiv
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Berild, Dag; Ringertz, Signe Holta & Lelek, Michaela
(2002).
Appropriate antibiotic use according to diagnoses and bacteriological findings. Report of 12 point-prevalence studies on antibiotic use in a university hospital.
Scandinavian Journal of Infectious Diseases.
ISSN 0036-5548.
34,
s. 56–60.
Fulltekst i vitenarkiv
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Tobiassen, T.; Berild, Dag & Hjortdahl, Per
(2002).
Antibiotikabruk i sykehjem.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
122,
s. 2376–78.
Fulltekst i vitenarkiv
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Berild, Dag; Ringertz, Signe Holta; Aabyholm, G.; Lelek, Michaela & Fosse, Brita
(2002).
Impact of an antibiotic policy on antibiotic use in a paediatric department. Individual based follow-up shows that antibiotics were used correctly according to diagnoses and bacteriological findings.
International Journal of Antimicrobial Agents.
ISSN 0924-8579.
20,
s. 333–38.
Fulltekst i vitenarkiv
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Berild, Dag; Ringertz, Signe Holta; Lelek, Michaela & Fosse, Brita
(2001).
Antibiotic Guidelines Lead to Reductions in the Use and Cost of Antibiotics in a University Hospital.
Scandinavian Journal of Infectious Diseases.
ISSN 0036-5548.
33,
s. 63–67.
Fulltekst i vitenarkiv
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Berild, Dag; Ringertz, Signe Holta; Lelek, Michaela & Fosse, Brita
(2000).
Antibiotic guidelines lead to reduction on the use and cost of antibiotics in a university hospital.
Scandinavian Journal of Infectious Diseases.
ISSN 0036-5548.
Fulltekst i vitenarkiv
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Løvstad, Renata Z.; Berild, Dag & Berntsen, Anne Gina
(2000).
Intraspinale infeksjoner hos pasienter behandlet med epiduralanalgesi.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
Fulltekst i vitenarkiv
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Jensenius, Mogens; Høiby, Ernst Arne; Berild, Dag; Stiris, Morten & Ringertz, Signe Holta
(2000).
Difficulties in diagnosing Brucella spondylitis.
Scandinavian Journal of Infectious Diseases.
ISSN 0036-5548.
32,
s. 425–426.
Fulltekst i vitenarkiv
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Lindbæk, Morten; Berild, Dag; Straand, Jørund & Hjortdahl, Per
(1999).
Influence of prescription patterns in general practice on anti-microbial resistance in Norway.
British Journal of General Practice.
ISSN 0960-1643.
s. 436–440.
Fulltekst i vitenarkiv
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Berild, Dag & Digranes, Asbjørn
(1999).
Engangsdosering av aminoglykosider.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
119,
s. 3152–6.
Fulltekst i vitenarkiv
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Steinsvoll, Svein E B; Myint, Maung Maung; Odden, Kåre; Berild, Dag & Schenck, Karl
(1997).
Reduced serum IgG responses to bacteria from dental plaque in patients with HIV infection.
Journal of Clinical Periodontology.
ISSN 0303-6979.
24,
s. 823–829.
Fulltekst i vitenarkiv
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Steinsvoll, Svein E B; Myint, Maung Maung; Odden, Kåre; Berild, Dag & Schenck, Karl
(1997).
Reduced serum IgG reactivities with bacteria from dental plaque in HIV-infected persons with periodontitis.
Journal of Clinical Periodontology.
ISSN 0303-6979.
24,
s. 823–829.
Fulltekst i vitenarkiv
Se alle arbeider i NVA
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Rajar, Polona; Dhariwal, Achal; Salvadori, Gabriela; Junges, Roger; Åmdal, Heidi Aarø & Berild, Dag
[Vis alle 12 forfattere av denne artikkelen]
(2022).
Microbial DNA extraction of high-host content and low biomass samples: optimized protocol for nasopharynx metagenomic studies.
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Low microbial biomass and high human DNA content in nasopharyngeal aspirate samples hinder comprehensive characterization of microbiota and resistome. We obtained samples from premature infants, a group with increased risk of developing respiratory disorders and infections, and consequently frequent exposure to antibiotics. Our aim was to devise an optimal protocol for handling nasopharyngeal aspirates from premature infants, focusing on host DNA depletion and microbiome and resistome characterization. Three depletion and three DNA extraction protocols were compared, using RT-PCR and whole metagenome sequencing to determine the efficiency of human DNA removal, taxonomic profiling and assignment of antibiotic resistance genes. Protocols were tested using mock communities, as well as pooled and individual patient samples. The only extraction protocol to retrieve the expected DNA yield from mock community samples was based on a lytic method to improve Gram positive recovery (MasterPure™). Only samples depleted with MolYsis™ showed satisfactory, but varied reduction in host DNA content, in both pooled and individual patient samples, allowing for microbiome and resistome characterisation (host DNA content from 15% to 98%). PCR results were indicative of achieved microbial enrichment. Despite high human DNA and low microbial biomass content in nasopharynx aspirates of preterm infants, we were able to reduce host DNA content to levels compatible with downstream shotgun metagenomic analysis, including bacterial species identification and coverage of antibiotic resistance genes. Whole metagenomic sequencing of microbes colonizing the nasopharynx may contribute to explaining the possible role of airway microbiota in respiratory conditions and reveal carriage of antibiotic resistance genes.
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Thaulow, Christian Magnus; Berild, Dag; Blix, Hege Salvesen; Brigtsen, Anne Karin; Myklebust, Tor Åge & Eriksen, Beate Horsberg
(2022).
Corrigendum: Can We Optimize Antibiotic Use in Norwegian Neonates? A Prospective Comparison Between a University Hospital and a District Hospital (Front. Pediatr., (2019), 7, (440), 10.3389/fped.2019.00440).
Frontiers in Pediatrics.
10.
doi:
10.3389/fped.2022.862484.
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Aavitsland, Preben; Berild, Dag; Emmert, Andreas; Horn, Morten Andreas & Rørtveit, Guri
(2014).
Vitenskapelighet og forsvarlighet.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
134(2),
s. 138–139.
doi:
10.4045/tidsskr.13.1682.
Fulltekst i vitenarkiv
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Berild, Dag & Lindbæk, Morten
(2010).
Antibiotikabruk til bekymring :.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
130(20),
s. 2010–2010.
Fulltekst i vitenarkiv
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Berild, Dag; Abrahamsen, Tore G; Andresen, S.; Bjørløw, E. & Ivanova, S.
(2004).
The effect of a controlled intervention to improve antibiotic use in a Russian Paediatric hospital.
Fulltekst i vitenarkiv
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Berild, Dag & Lindbæk, Morten
(2002).
Får norske barn for mye antibiotika?
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
122,
s. 2690–2690.
Fulltekst i vitenarkiv
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Berild, Dag & Lindbæk, Morten
(2002).
Får norske barn for mye antibiotika?
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
s. 122–122.
Fulltekst i vitenarkiv
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Berild, Dag
(2000).
Antibiotic guidelines lead to reduction in the use and cost of antibiotics in a university hospital.
Fulltekst i vitenarkiv
-
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Berild, Dag
(2000).
Presentation of the Norwegian guidelines for antibiotic use in general practice.
Fulltekst i vitenarkiv
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Steinsvoll, Svein E B; Myint, Maung Maung; Odden, Kåre; Berild, Dag & Schenck, Karl
(1995).
Serum IgG and IgA responses to bacteria from dental plauqe in patients with HIV infection.
Fulltekst i vitenarkiv
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Steinsvoll, Svein E B; Myint, Maung Maung; Odden, Kåre; Berild, Dag & Schenck, Karl
(1995).
Serum Immune Responses to Oral Bacteria in Patients with HIV Infection.
Fulltekst i vitenarkiv
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Sæterdal, Ingvil von Mehren; Akselsen, Per Espen; Berild, Dag; Harboe, Ingrid; Odgaard-Jensen, Jan & Reinertsen, Even
[Vis alle 8 forfattere av denne artikkelen]
(2010).
Antibiotikabehandling i sykehus, peroral versus intravenøs behandling.
Folkehelseinstituttet.
ISSN 9788281213241.
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Denne rapporten adresserer problemstillingen:
Er det forskjell i effekt mellom peroral og intravenøs antibiotikabehandling av infeksjonssykdommer hos store og viktige pasientgrupper. Rapporten besvarer ikke spørsmålet om når (hvor tidlig) det kan skiftes fra intravenøs til peroral behandling.
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Berild, Dag & Lindbæk, Morten
(1999).
Er vi på vei inn i den postantibiotiske æraen?
Munksgaard, København.
ISSN 9788716121097.
Fulltekst i vitenarkiv
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Publisert
16. nov. 2011 10:18
- Sist endret
2. nov. 2015 11:19