Quality, availability and suitability of antimicrobial stewardship guidance: a multinational qualitative study.

Background: Antimicrobial stewardship (AMS) programmes are established across the world to treat infections efficiently, prioritize patient safety, and reduce the emergence of antimicrobial resistance. One of the core elements of AMS programmes is guidance to support and direct physicians in making efficient, safe and optimal decisions when prescribing antibiotics. To optimize and tailor AMS, we need a better understanding of prescribing physicians' experience with AMS guidance. Objectives: To explore the prescribing physicians' user experience, needs and targeted improvements of AMS guidance in hospital settings. Methods: Semi-structured interviews were conducted with 36 prescribing physicians/AMS guidance users from hospital settings in Canada, Germany, Israel, Latvia, Norway and Sweden as a part of the international PILGRIM trial. A socioecological model was applied as an overarching conceptual framework for the study. Results: Research participants were seeking more AMS guidance than is currently available to them. The most important aspects and targets for improvement of AMS guidance were: (i) quality of guidelines; (ii) availability of infectious diseases specialists; and (iii) suitability of AMS guidance to department context. Conclusions: Achieving prudent antibiotic use not only depends on individual and collective levels of commitment to follow AMS guidance but also on the quality, availability and suitability of the guidance itself. More substantial commitment from stakeholders is needed to allocate the required resources for delivering high-quality, available and relevant AMS guidance to make sure that the prescribers' AMS needs are met.

Escherichia coli multilocus sequence type 38 from humans and broiler production represent distinct monophyletic groups.

Escherichia coli belonging to multilocus sequence type 38 (ST38) is a well-known cause of extra-intestinal infections in humans, and are frequently associated with resistance to extended-spectrum cephalosporins (ESCs). Resistance to carbapenems, mediated by blaOXA-genes has also been reported in this ST. Recently, the European Centre for Disease Prevention and Control (ECDC) released a rapid risk assessment on the increased detection of OXA-244 producing E. coli ST38 in humans, requesting further knowledge to determine the source. ST38 is also one of the most common STs among ESC-resistant E. coli from broiler production. Our aim was to investigate the genetic characteristics and relationship between E. coli ST38 from broiler production and humans, and to investigate if there has been a potential spillover between these sources. A total of 288 E. coli ST38 genomes isolated from humans in Europe (collected 2009-2019) and from Nordic broiler production (collected 2011-2014) were analyzed. The results showed distinct monophyletic clades associated to humans and broiler production. Furthermore, there were differences in the ESC resistance genes present in E. coli ST38 from the two sources. The blaOXA-244 gene was not present in E. coli from broiler production. Our results show that ST38 from humans and broiler production belong to well-separated clades, and suggest that the increased detection of OXA-244-producing E. coli ST38 in humans is not associated with spillover from broiler production.

A new method for near real-time, nationwide surveillance of nosocomial COVID-19 in Norway: providing data at all levels of the healthcare system, March 2020 to March 2022.

BackgroundGreat efforts have been made to minimise spread and prevent outbreaks of COVID-19 in hospitals. However, there is uncertainty in identifying nosocomial vs community-acquired infections. To minimise risks and evaluate measures, timely data on infection risk in healthcare institutions are required.AimsTo design an automated nationwide surveillance system for nosocomial COVID-19 using existing data to analyse the impact of community infection rates on nosocomial infections, to explore how changes in case definitions influence incidence and to identify patients and wards at highest risk and effects of SARS-CoV-2 variants.MethodsWe used data from the Norwegian real-time emergency preparedness register (Beredt C19), which includes all patients nationwide admitted to Norwegian hospitals between March 2020 and March 2022 with a positive SARS-CoV-2 PCR test during their hospital stay or within 7 days post-discharge. COVID-19 cases were assigned to categories depending on the time between admission and testing.ResultsInfection rates for definite/probable nosocomial COVID-19 increased from 0.081% in year 1 to 0.50% in year 2 in hospital admissions 7 days or longer. Varying the definitions resulted in large changes in registered nosocomial infections. Infection rates were similar across different ward types. By 2022, 58% of patients with a definite/probable nosocomial infection had received three vaccine doses.ConclusionAutomated national surveillance for nosocomial COVID-19 is possible based on existing data sources. Beredt C19 provided detailed information with only 5% missing data on hospitals/wards. Epidemiological definitions are possible to standardise, enabling easier comparison between regions and countries.

Effects of patient-level risk factors, departmental allocation and seasonality on intrahospital patient transfer patterns: network analysis applied on a Norwegian single-centre data set.

OBJECTIVES: Describe patient transfer patterns within a large Norwegian hospital. Identify risk factors associated with a high number of transfers. Develop methods to monitor intrahospital patient flows to support capacity management and infection control. DESIGN: Retrospective observational study of linked clinical data from electronic health records. SETTING: Tertiary care university hospital in the Greater Oslo Region, Norway. PARTICIPANTS: All adult (≥18 years old) admissions to the gastroenterology, gastrointestinal surgery, neurology and orthopaedics departments at Akershus University Hospital, June 2018 to May 2019. METHODS: Network analysis and graph theory. Poisson regression analysis. OUTCOME MEASURES: Primary outcome was network characteristics at the departmental level. We describe location-to-location transfers using unweighted, undirected networks for a full-year study period. Weekly networks reveal changes in network size, density and key categories of transfers over time. Secondary outcome was transfer trajectories at the individual patient level. We describe the distribution of transfer trajectories in the cohort and associate number of transfers with patient clinical characteristics. RESULTS: The cohort comprised 17 198 hospital stays. Network analysis demonstrated marked heterogeneity across departments and throughout the year. The orthopaedics department had the largest transfer network size and density and greatest temporal variation. More transfers occurred during weekdays than weekends. Summer holiday affected transfers of different types (Emergency department-Any location/Bed ward-Bed ward/To-From Technical wards) differently. Over 75% of transferred patients followed one of 20 common intrahospital trajectories, involving one to three transfers. Higher number of intrahospital transfers was associated with emergency admission (transfer rate ratio (RR)=1.827), non-prophylactic antibiotics (RR=1.108), surgical procedure (RR=2.939) and stay in intensive care unit or high-dependency unit (RR=2.098). Additionally, gastrosurgical (RR=1.211), orthopaedic (RR=1.295) and neurological (RR=1.114) patients had higher risk of many transfers than gastroenterology patients (all effects: p<0.001). CONCLUSIONS: Network and transfer chain analysis applied on patient location data revealed logistic and clinical associations highly relevant for hospital capacity management and infection control.

Transmission of SARS-CoV-2 into and within immigrant households: nationwide registry study from Norway.

BACKGROUND: Minority groups and immigrants have been hit disproportionally hard by COVID-19 in many developed countries, including Norway. METHODS: Using individual-level registry data of all Norwegian residents, we compared infections across all multiperson households. A household with at least one member born abroad was defined as an immigrant household. In households where at least one person tested positive for SARS-CoV-2 from 1 August 2020 to 1 May 2021, we calculated secondary attack rates (SARs) as the per cent of other household members testing positive within 14 days. Logistic regression was used to adjust for sex, age, household composition and geography. RESULTS: Among all multiperson households in Norway (n=1 422 411), at least one member had been infected in 3.7% of the 343 017 immigrant households and 1.4% in the 1 079 394 households with only Norwegian-born members. SARs were higher in immigrant (32%) than Norwegian-born households (20%). SARs differed considerably by region, and were particularly high in households from West Asia, Eastern Europe, Africa and East Asia, also after adjustment for sex and age of the secondary case, household composition and geography. CONCLUSION: SARS-CoV-2 is more frequently introduced into multiperson immigrant households than into households with only Norwegian-born members, and transmission within the household occurs more frequently in immigrant households. The results are likely related to living conditions, family composition or differences in social interaction, emphasising the need to prevent introduction of SARS-CoV-2 into these vulnerable households.

Persisting symptoms three to eight months after non-hospitalized COVID-19, a prospective cohort study.

Long-COVID-19 is a proposed syndrome negatively affecting the health of COVID-19 patients. We present data on self-rated health three to eight months after laboratory confirmed COVID-19 disease compared to a control group of SARS-CoV-2 negative patients. We followed a cohort of 8786 non-hospitalized patients who were invited after SARS-CoV-2 testing between February 1 and April 15, 2020 (794 positive, 7229 negative). Participants answered online surveys at baseline and follow-up including questions on demographics, symptoms, risk factors for SARS-CoV-2, and self-rated health compared to one year ago. Determinants for a worsening of self-rated health as compared to one year ago among the SARS-CoV-2 positive group were analyzed using multivariate logistic regression and also compared to the population norm. The follow-up questionnaire was completed by 85% of the SARS-CoV-2 positive and 75% of the SARS-CoV-2 negative participants on average 132 days after the SARS-CoV-2 test. At follow-up, 36% of the SARS-CoV-2 positive participants rated their health "somewhat" or "much" worse than one year ago. In contrast, 18% of the SARS-CoV-2 negative participants reported a similar deterioration of health while the population norm is 12%. Sore throat and cough were more frequently reported by the control group at follow-up. Neither gender nor follow-up time was associated with the multivariate odds of worsening of self-reported health compared to one year ago. Age had an inverted-U formed association with a worsening of health while being fit and being a health professional were associated with lower multivariate odds. A significant proportion of non-hospitalized COVID-19 patients, regardless of age, have not returned to their usual health three to eight months after infection.

Rapid nanopore-based DNA sequencing protocol of antibiotic-resistant bacteria for use in surveillance and outbreak investigation.

Outbreak investigations are essential to control and prevent the dissemination of pathogens. This study developed and validated a complete analysis protocol for faster and more accurate surveillance and outbreak investigations of antibiotic-resistant microbes based on Oxford Nanopore Technologies (ONT) DNA whole-genome sequencing. The protocol was developed using 42 methicillin-resistant Staphylococcus aureus (MRSA) isolates identified from former well-characterized outbreaks. The validation of the protocol was performed using Illumina technology (MiSeq, Illumina). Additionally, a real-time outbreak investigation of six clinical S. aureus isolates was conducted to test the ONT-based protocol. The suggested protocol includes: (1) a 20 h sequencing run; (2) identification of the sequence type (ST); (3) de novo genome assembly; (4) polishing of the draft genomes; and (5) phylogenetic analysis based on SNPs. After the sequencing run, it was possible to identify the ST in 2 h (20 min per isolate). Assemblies were achieved after 4 h (40 min per isolate) while the polishing was carried out in 7 min per isolate (42 min in total). The phylogenetic analysis took 0.6 h to confirm an outbreak. Overall, the developed protocol was able to at least discard an outbreak in 27 h (mean) after the bacterial identification and less than 33 h to confirm it. All these estimated times were calculated considering the average time for six MRSA isolates per sequencing run. During the real-time S. aureus outbreak investigation, the protocol was able to identify two outbreaks in less than 31 h. The suggested protocol enables identification of outbreaks in early stages using a portable and low-cost device along with a streamlined downstream analysis, therefore having the potential to be incorporated in routine surveillance analysis workflows. In addition, further analysis may include identification of virulence and antibiotic resistance genes for improved pathogen characterization.

Is increased Staphylococcus aureus colonization during military service caused by specific genotypes? Molecular examination of long-term carriage in a prospective cohort study.

A 22% increase in Staphylococcus aureus colonization was observed in Norwegian recruits during first year of military service. The aim was to determine whether specific genotypes caused the increase and to examine carriage status based on genotyping. Characterization of S. aureus from nose, throat and perineum sampled at enrolment and discharge included spa typing, MLVA, detection of PVL genes and antimicrobial susceptibility testing. spa typing demonstrated high and stable genetic diversity. The three most frequent spa types were found in 15% of recruits at enrolment and in 29% at discharge. Only t084 increased significantly (p = 0.02). Subtyping revealed that t084, t065 and t002 consisted of 13, 6 and 11 different MLVA types, respectively, at discharge. The military cohort (n = 265) consisted of S. aureus carriers of identical genotype (n = 99, 38%), carriers of non-identical genotype (n = 52, 20%), intermittent carriers (n = 86, 33%) and non-carriers (n = 27, 10%). Carrier status was indefinable for one recruit due to unavailable isolates for genotyping. Antibiotic resistance towards erythromycin, fusidic acid and clindamycin increased significantly and above national surveillance levels. The observed increase in S. aureus colonization during military service was caused by many different genotypes implying many transmission routes. Genotype did not correlate with colonization niche or carriage status.

Travel to Asia is a strong predictor for carriage of cephalosporin resistant E. coli and Klebsiella spp. but does not explain everything; prevalence study at a Norwegian hospital 2014-2016.

Background: We aimed to estimate the prevalence of faecal carriage of extended-spectrum cephalosporin (ESC) resistant E. coli and K. pneumoniae (ESCr-EK) and vancomycin resistant enterococci (VRE) in patients upon hospital admission and identify factors associated with carriage to better target interventions and to guide empirical antibiotic treatment. Methods: Between October 2014 and December 2016, we recruited patients admitted to a Norwegian university hospital. A rectal swab and questionnaire covering possible risk factors for colonisation were collected upon admission. Isolates were characterized by phenotypic methods. ESCr-EK isolates were subject to whole genome sequencing. We calculated prevalence and adjusted prevalence ratios (aPR) using binomial regression. Results: Of 747 patients, 45 (6.0%) were colonised with ESCr-EK, none with VRE. The ESCr-EK isolates in 41 patients were multidrug resistant; no isolates were non-suceptible to meropenem. Prevalence of ESCr-EK was higher among travellers to Asia (aPR = 6.6; 95%CI 3.6-12; p < 0.001). No statistical significant difference in carriage was observed between departments, age or any other factors in the univariable analyses. Conclusions: The observed prevalence of ESCr-EK colonisation upon admission was in the same range but lower than that reported in similar studies from Europe. Travel to Asia was a strong predictor for colonisation of ESCr-EK to be considered when administering empirical antimicrobial treatment. As less than one third of colonised patients had travelled to Asia, and no other factors investigated were found to be strongly associated with carriage, these findings underscore that healthcare personnel must apply standard infection control precautions for all patients.

Implications of stx loss for clinical diagnostics of Shiga toxin-producing Escherichia coli.

The dynamics related to the loss of stx genes from Shiga toxin-producing Escherichia coli remain unclear. Current diagnostic procedures have shortcomings in the detection and identification of STEC. This is partly owing to the fact that stx genes may be lost during an infection or in the laboratory. The aim of the present study was to provide new insight into in vivo and in vitro stx loss in order to improve diagnostic procedures. Results from the study support the theory that loss of stx is a strain-related phenomenon and not induced by patient factors. It was observed that one strain could lose stx both in vivo and in vitro. Whole genome comparison of stx-positive and stx-negative isolates from the same patient revealed that different genomic rearrangements, such as complete or partial loss of the parent prophage, may be factors in the loss of stx. Of diagnostic interest, it was shown that patients can be co-infected with different E. coli pathotypes. Therefore, identification of eae-positive, but stx-negative isolates should not be interpreted as "Shiga toxin-lost" E. coli without further testing. Growth and recovery of STEC were supported by different selective agar media for different strains, arguing for inclusion of several media in STEC diagnostics.

Genotypic characterization of gentamicin and cephalosporin resistant Escherichia coli isolates from blood cultures in a Norwegian university hospital 2011-2015.

Background: Cephalosporin resistance in clinical E. coli isolates is increasing internationally. The increase has been caused by virulent and often multidrug-resistant clones, especially the extended spectrum ß-lactamase (ESBL) producing E. coli clone O25b-ST131. Methods: In Norway, recommended empirical treatment of sepsis consists of gentamicin and penicillin combined, or a broad-spectrum cephalosporin. To investigate if increased gentamicin and cephalosporins resistance rates in our hospital could be caused by specific clones, we conducted a retrospective study on E. coli blood culture isolates from 2011 through 2015. All E. coli isolates non-susceptible to gentamicin and/or third-generation cephalosporins were genotyped using multiple-locus variable-number of tandem repeat analysis (MLVA) and compared with antibiotic susceptible isolates. The frequency of the most common genes causing ESBL production (blaCTX-M, blaampC) was examined by Real-Time PCR. Results: A total of 158 cephalosporin and/or gentamicin resistant and 97 control isolates were differentiated into 126 unique MLVA types. Of these, 31% of the isolates belonged to a major MLVA cluster consisting of 41% of the gentamicin resistant and 35% of the cephalosporin resistant isolates. The majority (65/80 isolates) of this MLVA cluster contained MLVA types associated with the E. coli O25b-ST131 clone. Genes encoding CTX-M enzyme phylogroups 1 and 9 occurred in 65% and 19% of cephalosporin resistant isolates, respectively, whereas blaampC-CIT was identified in 3%. Conclusion: No local E. coli bacteraemia clone was identified. Antibiotic resistance was dispersed over a variety of genotypes. However, association with the international E. coli O25b-ST131 clone was frequent and may be an important driver behind increased resistance rates. Monitoring and preventing dissemination of these resistant clones are important for continued optimal treatment.

First environmental sample containing plasmid-mediated colistin-resistant ESBL-producing Escherichia coli detected in Norway.

We hereby report the detection of the plasmid borne mcr-1 gene conferring colistin resistance in an extended-spectrum ß-lactamase (ESBL) producing Escherichia coli ST10 strain retrieved from seawater at a public beach in Norway. The sample was collected in September 2010 and was investigated by whole-genome sequencing in 2016. This report illustrates that E. coli strains carrying plasmid-mediated colistin resistance genes have also reached areas where this drug is hardly used at all. Surveillance of colistin resistance in environmental, veterinary, and human strains is warranted also in countries where colistin resistance is rare in clinical settings.

Anti-pertussis antibody kinetics following DTaP-IPV booster vaccination in Norwegian children 7-8 years of age.

At the age of 7-8 years a booster of diphtheria, tetanus, acellular pertussis and polio vaccine is recommended for children in Norway. In this cross-sectional study we have analysed the antibody levels against pertussis vaccine antigens in sera from 498 children aged 6-12 years. The purposes of this study were to investigate the duration of the booster response against the pertussis vaccine antigens pertussis toxin (PT) and filamentous haemagglutinin (FHA); to determine the presence of high levels of pertussis antibodies in absence of recent vaccination; and to analyse how booster immunisation may interfere with the serological pertussis diagnostics. Prior to the booster the IgG antibody levels against PT revealed a geometric mean of 7.3IU/ml. After the booster the geometric mean peak anti-PT IgG response reached to 45.6IU/ml, followed by a steady decline in antibody levels over the next few years. The IgG anti-FHA levels followed the anti-PT IgG profiles. Three years after the booster the geometric mean IgG levels were only slightly above pre-booster levels. Prior to the booster 44% of the sera contained ≤5IU/ml of anti-PT IgG compared to18% 3 years after and 30% 4 years after the booster. When recently vaccinated children were excluded, 6.2% of the children had anti-PT IgG levels above 50IU/ml which may indicate pertussis infection within the last 2 years. This study indicates that the currently used acellular pertussis vaccines induce moderate immune responses to the pertussis antigens and that the antibodies wane within few years after the booster. This lack of sustained immune response may partly be responsible for the increased number of pertussis cases observed in this age group during the last years.

High prevalence of faecal carriage of ESBL-producing Enterobacteriaceae in Norwegian patients with gastroenteritis.

We conducted a cross-sectional study to examine the prevalence of faecal carriage of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in patients with gastroenteritis. During April 2011, all faecal samples submitted to our hospital laboratory were examined for ESBL-producing Enterobacteriaceae. Isolates expressing an ESBL phenotype were investigated for the presence of genes encoding broad-spectrum beta-lactamases, ESBLs, carbapenemases, and plasmid-mediated AmpC. Information on age, gender, and travel history was extracted from the laboratory records. In total 273 faecal samples were included. The overall carrier rate in the study population was 15.8%. The ESBL carrier rate among patients with no history of recent travel, or where this information was missing, was 10.3%. In contrast, the carrier rate was 56.3% (odds ratio 16.3, p < 0.001) among patients with a record of travel to Asia. Two ESBL-producing isolates were identified as enteropathogenic Escherichia coli. Co-resistance between third-generation cephalosporins, trimethoprim-sulfamethoxazole, and fluoroquinolones was seen in 49% of isolates. No carbapenemase-producers were found.

High rate of per oral mecillinam treatment failure in community-acquired urinary tract infections caused by ESBL-producing Escherichia coli.

A population-based study was performed to investigate the efficacy of mecillinam treatment of community-acquired urinary tract infections (CA-UTI) caused by extended-spectrum ß-lactamase (ESBL) producing Escherichia coli. The study was conducted in South-Eastern Norway. Data from patients with CA-UTI caused by ESBL-producing and non-producing (random controls) E. coli were collected through interviews, questionnaires, medical records and the Norwegian Prescription Database. Treatment failure was defined as a new antibiotic prescription appropriate for UTI prescribed within two weeks after the initial antimicrobial therapy. Multivariable logistic regression analysis was performed to identify treatment agents and patient- or bacterial traits associated with treatment failure. A total of 343 patients (mean age 59) were included, of which 158 (46%) were treated with mecillinam. Eighty-one patients (24%, mean age 54) had infections caused by ESBL producing E. coli, and 41 of these patients (51%) received mecillinam as the primary treatment. Mecillinam treatment failure was observed in 18 (44%) of patients infected by ESBL-producing strains and in 16 (14%) of patients with a CA-UTI caused by ESBL non-producing strains. Multivariable analysis showed that ESBL status (odds ratio (OR) 3.2, 95% confidence interval (CI) 1.3-7.8, p = 0.009) and increased MIC of mecillinam (OR 2.0 for each doubling value of MIC, CI 1.4-3.0, p<0.001) were independently associated with mecillinam treatment failure. This study showed a high rate of mecillinam treatment failure in CA-UTIs caused by ESBL producing E. coli. The high failure rate could not be explained by the increased MIC of mecillinam alone. Further studies addressing the use of mecillinam against ESBL-producing E. coli, with emphasis on optimal dosing and combination therapy with ß-lactamase inhibitors, are warranted.

[Cases of MRSA in nursing homes in Oslo 2005-11]. / MRSA-funn i sykehjem i Oslo 2005-11.

BACKGROUND: The number of infections caused by MRSA has increased substantially in Norway in the past decade. It is an objective to prevent MRSA from becoming established in nursing homes and hospitals. The purpose of the article is to describe the features of the development of MRSA cases found in nursing homes in Oslo. MATERIALS AND METHOD: We carried out a retrospective study of registered cases of MRSA (both sufferers and carriers) in Oslo in 2005-11. Data were obtained from the City of Oslo municipal health services' MRSA database and from genotyping carried out at Akershus University Hospital. RESULTS: The annual number of cases of MRSA found in Oslo increased during the period 2005-11 from 92 in 2005 to 268 in 2011, a total of 1198 cases. Of these, 224 cases (19%) were registered in nursing homes, distributed among 22 institutions, 158 residents and 66 staff, with an average of 32 cases annually (14-58 spread). Twenty-eight of 50 nursing homes had no cases of MRSA, while 159 of the cases were related to outbreaks of MRSA. Three of 20 outbreaks affected residents only. The nursing home isolates consisted of 40 different spa types, of which 160 (71%) of the isolates were clustered in three clonal complexes. The most common spa type t304 was found in 116 (52%) of the cases. INTERPRETATION: Cases of MRSA in Oslo in total increased sharply from 2005 to 2011, while the number of cases in nursing homes was stable. It is, however, uncertain whether this reflects the actual incidence.