Risk factors for SARS-CoV-2 infection: a test-negative case-control study with additional population controls in Norway.

OBJECTIVES: This study aims to assess risk factors for SARS-CoV-2 infection by combined design; first comparing positive cases to negative controls as determined by PCR testing and then comparing these two groups to an additional prepandemic population control group. DESIGN AND SETTING: Test-negative design (TND), multicentre case-control study with additional population controls in South-Eastern Norway. PARTICIPANTS: Adults who underwent SARS-CoV-2 PCR testing between February and December 2020. PCR-positive cases, PCR-negative controls and additional age-matched population controls. PRIMARY OUTCOME MEASURES: The associations between various risk factors based on self- reported questionnaire and SARS-CoV-2 infection comparing PCR-positive cases and PCR-negative controls. Using subgroup analysis, the risk factors for both PCR-positive and PCR-negative participants were compared with a population control group. RESULTS: In total, 400 PCR-positive cases, 719 PCR-negative controls and 14 509 population controls were included. Male sex was associated with the risk of SARS-CoV-2 infection only in the TND study (OR 1.9, 95% CI 1.4 to 2.6), but not when PCR-positive cases were compared with population controls (OR 1.2, 95% CI 0.9. to 1.5). Some factors were positively (asthma, wood heating) or negatively (hypertension) associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but lacked convincing association in the TND study. Smoking was negatively associated with the risk of SARS-CoV-2 infection in both analyses (OR 0.5, 95% CI 0.3 to 0.8 and OR 0.6, 95% CI 0.4 to 0.8). CONCLUSIONS: Male sex was a possible risk factor for SARS-CoV-2 infection only in the TND study, whereas smoking was negatively associated with SARS-CoV-2 infection in both the TND study and when using population controls. Several factors were associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but not in the TND study, highlighting the strength of combining case-control study designs during the pandemic.

SARS-CoV-2 antibody persistence after five and twelve months: A cohort study from South-Eastern Norway.

OBJECTIVES: To assess total antibody levels against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2) spike protein up to 12 months after Coronavirus Disease (COVID-19) infection in non-vaccinated individuals and the possible predictors of antibody persistence. METHODS: This is the first part of a prospective multi-centre cohort study. PARTICIPANTS: The study included SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) positive and negative participants in South-Eastern Norway from February to December 2020. Possible predictors of SARS-CoV-2 total antibody persistence was assessed. The SARS-CoV-2 total antibody levels against spike protein were measured three to five months after PCR in 391 PCR-positive and 703 PCR-negative participants; 212 PCR-positive participants were included in follow-up measurements at 10 to 12 months. The participants completed a questionnaire including information about symptoms, comorbidities, allergies, body mass index (BMI), and hospitalisation. PRIMARY OUTCOME: The SARS-CoV-2 total antibody levels against spike protein three to five and 10 to 12 months after PCR positive tests. RESULTS: SARS-CoV-2 total antibodies against spike protein were present in 366 (94%) non-vaccinated PCR-positive participants after three to five months, compared with nine (1%) PCR-negative participants. After 10 to 12 months, antibodies were present in 204 (96%) non-vaccinated PCR-positive participants. Of the PCR-positive participants, 369 (94%) were not hospitalised. The mean age of the PCR-positive participants was 48 years (SD 15, range 20-85) and 50% of them were male. BMI ≥ 25 kg/m2 was positively associated with decreased antibody levels (OR 2.34, 95% CI 1.06 to 5.42). Participants with higher age and self-reported initial fever with chills or sweating were less likely to have decreased antibody levels (age: OR 0.97, 95% CI 0.94 to 0.99; fever: OR 0.33, 95% CI 0.13 to 0.75). CONCLUSION: Our results indicate that the level of SARS-CoV-2 total antibodies against spike protein persists for the vast majority of non-vaccinated PCR-positive persons at least 10 to 12 months after mild COVID-19.

Low prevalence of tick-borne encephalitis virus antibodies in Norwegian blood donors.

BACKGROUND: Tick-borne encephalitis (TBE) constitutes a public health concern in Europe. Certain coastal municipalities in southern Norway are considered TBE risk areas and in the last two years, there have been increasing numbers of TBE cases. Since the majority of infections are claimed to be asymptomatic, the aim of the current study was to assess the seroprevalence of antibodies to tick-borne encephalitis virus (TBEV) among unvaccinated adults living in a TBE endemic area in Norway. METHODS: One thousand one hundred and twenty-three blood donors living in Vestfold and Telemark county were included and associated sera were analysed for TBEV IgG antibodies. Information regarding tick bites, previous flavivirus exposure and knowledge regarding TBE and TBE prevention were obtained through a questionnaire. RESULTS: Fifty-eight samples were reactive by ELISA, of which 21 (36.2%) were confirmed by a TBEV-specific serum neutralization test. Of the 21 blood donors with neutralizing TBEV antibodies detected, 17 reported previous TBE vaccination. Thus, only four blood donors (0.4%) had TBEV neutralizing antibodies consistent with previously undergone TBEV infection. Regarding TBE awareness, half of the blood donors were familiar with TBE, but only 35% were aware of a preventive TBE vaccine. CONCLUSIONS: Our study indicates low prevalence of subclinical TBEV infections among blood donors living in Vestfold and Telemark county and there is a lack of awareness among general public.

Clinical and bacteriological efficacy of pivmecillinam treatment for uncomplicated urinary tract infections caused by ESBL-producing Escherichia coli: a prospective, multicentre, observational cohort study.

Objectives: To compare the clinical and bacteriological outcomes of pivmecillinam treatment for community-acquired urinary tract infections (UTIs) caused by ESBL-producing Escherichia coli versus non-ESBL-producing E. coli in an outpatient setting. Methods: A prospective, multicentre, observational cohort study of women aged ≥16 years, with pivmecillinam-treated community-acquired UTIs caused by E. coli with or without ESBL production, recruited from primary care, was conducted in the period from April 2013 to August 2016. Eighty-eight women (mean age 49.4 years) with community-acquired UTIs caused by ESBL-producing E. coli were compared with a control group of 74 women (mean age 50.1 years). Trial registration: Regional Committees for Medical and Health Research Ethics (REC) in Norway, ID 2011/2214, and ClinicalTrials.gov, ID NCT01531023. Results: The median time until symptom resolution after treatment initiation was 5 days for the ESBL cases and 3 days for the non-ESBL controls (P < 0.01). The proportion of women warranting a second antibiotic prescription in the follow-up period was higher for the ESBL cases [30/88 (34.1%) versus 10/72 (13.9%), P < 0.01]. Persistent bacteriuria was non-significantly more common among ESBL cases than in the control group [15/81 (18.5%) versus 6/67 (9.0%), P = 0.10]. A pivmecillinam dosage of 200 mg given three times daily for ≤5 days was associated with treatment failure (OR 4.77, 95% CI 1.40-19.44, P = 0.03) for the ESBL E. coli group. For the subgroup treated with 400 mg of pivmecillinam given three times daily there was no significantly increased OR for treatment failure between ESBL cases and the control group irrespective of treatment duration. Conclusions: Pivmecillinam given at 400 mg three times daily gave comparable clinical and bacteriological cure rates in women with community-acquired E. coli UTIs irrespective of ESBL production.

MRSA prevalence among healthcare personnel in contact tracings in hospitals. / MRSA-forekomst blant helsepersonell ved smitteoppsporing i sykehus.

BAKGRUNN: I norsk helsevesen gjennomføres omfattende tiltak for å hindre spredning av meticillinresistente Staphylococcus aureus (MRSA). Vi ønsket å undersøke hvor mange smitteoppsporinger som gjøres rundt nyoppdagede MRSA-tilfeller hos pasienter og ansatte i sykehus, og hvor ofte smitteoppsporingene fører til ytterligere funn hos helsepersonell. MATERIALE OG METODE: I denne retrospektive observasjonsstudien bidro smittevernenhetene ved åtte helseforetak i landets fire helseregioner med opplysninger om MRSA-funn hos helsepersonell etter gjennomførte MRSA-smitteoppsporinger. Data ble innhentet fra 14 ulike somatiske sykehus i årene 2012-15. RESULTATER: 10 142 ansatte i helsevesenet ble testet for MRSA, med positivt funn hos 31 ansatte (0,31 %). Hos 19 ansatte (0,19 %) ble det påvist samme MRSA-stamme som hos indekskasus. I kun to av 351 smitteoppsporinger (0,57 %) ble samme MRSA-stamme funnet hos mer enn én ansatt. FORTOLKNING: MRSA-smitteoppsporing i norske sykehus har et betydelig omfang, men det er sjelden det påvises MRSA hos helsepersonell i forbindelse med smitteoppsporing.

Aetiology and risk factors of community-acquired pneumonia in hospitalized patients in Norway.

BACKGROUND AND AIMS: In Norway, data on the aetiology of community-acquired pneumonia (CAP) in hospitalized patients are limited. The aims of this study were to investigate the bacterial aetiology of CAP in hospitalized patients in Norway, risk factors for CAP and possible differences in risk factors between patients with Legionnaire's disease and pneumonia because of other causes. METHODS: Adult patients with radiologically confirmed CAP admitted to hospital were eligible for the study. Routine aerobic and Legionella culture of sputum, blood culture, urinary antigen test for Legionella pneumophila and Streptococcus pneumoniae, polymerase chain reaction detection of Chlamydophila pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis from throat specimens, and serology for L. pneumophila serogroup 1-6 were performed. A questionnaire, which included demographic and clinical data, risk factors and treatment, was completed. RESULTS: We included 374 patients through a 20-month study period in 2007-2008. The aetiological agent was detected in 37% of cases. S. pneumoniae (20%) was the most prevalent agent, followed by Haemophilus influenzae (6%) and Legionella spp. (6%). Eight Legionella cases were diagnosed by urinary antigen test, of which four also had positive serology. In addition, 13 Legionella cases were diagnosed by serology. The degree of comorbidity was high. An increased risk of hospital-diagnosed Legionella pneumonia was found among patients with a diagnosis of chronic congestive heart failure. CONCLUSION: Our results indicate that S. pneumoniae is the most common bacterial cause of pneumonia in hospitalized patients, and the prevalence of Legionella pneumonia is probably higher in Norway than recognized previously.

Haemophilus influenzae with Non-Beta-Lactamase-Mediated Beta-Lactam Resistance: Easy To Find but Hard To Categorize.

Haemophilus influenzae is a major pathogen, and beta-lactams are first-line drugs. Resistance due to altered penicillin-binding protein 3 (rPBP3) is frequent, and susceptibility testing of such strains is challenging. A collection of 154 beta-lactamase-negative isolates with a large proportion of rPBP3 (67.5%) was used to evaluate and compare Etest (Haemophilus test medium [HTM]) and disk diffusion (EUCAST method) for categorization of susceptibility to aminopenicillins and cefuroxime, using MICs generated with broth (HTM) microdilution and clinical breakpoints from CLSI and EUCAST as the gold standards. In addition, the proficiency of nine disks in screening for the rPBP3 genotype (N526K positive) was evaluated. By Etest, both essential and categorical agreement were generally poor (<70%), with high very major errors (VME) (CLSI, 13.0%; EUCAST, 34.3%) and falsely susceptible rates (FSR) (CLSI, 87.0%; EUCAST, 88.3%) for ampicillin. Ampicillin (2 µg) with adjusted (+2 mm) zone breakpoints was superior to Etest for categorization of susceptibility to ampicillin (agreement, 74.0%; VME, 11.0%; FSR, 28.3%). Conversely, Etest was superior to 30 µg cefuroxime for categorization of susceptibility to cefuroxime (agreement, 57.1% versus 60.4%; VME, 2.6% versus 9.7%; FSR, 7.1% versus 26.8%). Benzylpenicillin (1 unit) (EUCAST screening disk) and cefuroxime (5 µg) identified rPBP3 isolates with highest accuracies (95.5% and 92.2%, respectively). In conclusion, disk screening reliably detects rPBP3 H. influenzae, but false ampicillin susceptibility is frequent with routine methods. We suggest adding a comment recommending high-dose aminopenicillin therapy or the use of other agents for severe infections with screening-positive isolates that are susceptible to aminopenicillins by gradient or disk diffusion.

Multilocus sequence typing and ftsI sequencing: a powerful tool for surveillance of penicillin-binding protein 3-mediated beta-lactam resistance in nontypeable Haemophilus influenzae.

BACKGROUND: Beta-lactam resistance in Haemophilus influenzae due to ftsI mutations causing altered penicillin-binding protein 3 (PBP3) is increasing worldwide. Low-level resistant isolates with the N526K substitution (group II low-rPBP3) predominate in most geographical regions, while high-level resistant isolates with the additional S385T substitution (group III high-rPBP3) are common in Japan and South Korea.Knowledge about the molecular epidemiology of rPBP3 strains is limited. We combined multilocus sequence typing (MLST) and ftsI/PBP3 typing to study the emergence and spread of rPBP3 in nontypeable H. influenzae (NTHi) in Norway. RESULTS: The prevalence of rPBP3 in a population of 795 eye, ear and respiratory isolates (99% NTHi) from 2007 was 15%. The prevalence of clinical PBP3-mediated resistance to ampicillin was 9%, compared to 2.5% three years earlier. Group II low-rPBP3 predominated (96%), with significant proportions of isolates non-susceptible to cefotaxime (6%) and meropenem (20%). Group III high-rPBP3 was identified for the first time in Northern Europe.Four MLST sequence types (ST) with characteristic, highly diverging ftsI alleles accounted for 61% of the rPBP3 isolates. The most prevalent substitution pattern (PBP3 type A) was present in 41% of rPBP3 isolates, mainly carried by ST367 and ST14. Several unrelated STs possessed identical copies of the ftsI allele encoding PBP3 type A.Infection sites, age groups, hospitalization rates and rPBP3 frequencies differed between STs and phylogenetic groups. CONCLUSIONS: This study is the first to link ftsI alleles to STs in H. influenzae. The results indicate that horizontal gene transfer contributes to the emergence of rPBP3 by phylogeny restricted transformation.Clonally related virulent rPBP3 strains are widely disseminated and high-level resistant isolates emerge in new geographical regions, threatening current empiric antibiotic treatment. The need of continuous monitoring of beta-lactam susceptibility and a global system for molecular surveillance of rPBP3 strains is underlined. Combining MLST and ftsI/PBP3 typing is a powerful tool for this purpose.

Emergence of OXA-carbapenemase- and 16S rRNA methylase-producing international clones of Acinetobacter baumannii in Norway.

This study was designed to investigate the molecular epidemiology and antibiotic-resistance characteristics of 11 carbapenem-resistant clinical isolates of Acinetobacter baumannii obtained in Norway between 2004 and 2009. Interestingly, all the isolates were linked with recent hospitalization outside Norway. The epidemiological status was investigated by multilocus sequence typing (MLST), multiplex PCR assays for major international clones, typing of blaOXA-51-like variants and PFGE. The genotypic-resistance characteristics, including the occurrence of OXA-carbapenemase-encoding and 16S rRNA methylase-encoding genes and class 1 integrons, were investigated by PCR assays and sequencing. Seven isolates were found to harbour blaOXA-66 and belong to MLST clonal complexes (CCs) CC2P (Pasteur Institute scheme) and CC92B (Bartual scheme), and international clone II. One isolate harboured blaOXA-69, and belonged to CC1P, CC109B and international clone I. Two isolates belonged to sequence group 9, probably a subgroup of international clone I, and one isolate belonged to sequence group 4, a proposed novel international clone. All isolates contained an acquired OXA-carbapenemase-encoding gene: blaOXA-23-like (n=9), blaOXA-24-like (n=1) and blaOXA-58-like (n=1). Four isolates with high-level aminoglycoside-resistance contained the 16S rRNA methylase-encoding armA gene. Class 1 integrons with six different variable regions were detected. Sequence analysis of gene cassettes identified four aminoglycoside (aacA4, aac(6')-Im, aadA1 and aacC1), two chloramphenicol (catB8 and cm1A5), one ß-lactamase (blaOXA-20) and one rifampicin (arr-2) resistance gene in various combinations. In conclusion, the occurrence of A. baumannii isolates producing OXA carbapenemase and 16S rRNA methylase in Norway was related to the worldwide distribution of international clones I and II, and the emergence of novel international clones.

Proposal for common Nordic epidemiological terms and definitions for methicillin-resistant Staphylococcus aureus (MRSA).

The recent increase in the incidence of methicillin-resistant Staphylococcus aureus in all the Nordic countries prompted the Scandinavian Society for Antimicrobial Chemotherapy (SSAC) to create the 'SSAC Working Party on MRSA' with the objective to identify methods to keep the invasive MRSA infections in the Nordic countries below 1%. The lack of common definitions was recognized as a major obstacle for a joint Nordic effort to combat MRSA. The aim of this publication is to present proposals for epidemiological definitions of individual cases, for how to report MRSA frequency per country, and for communication of MRSA strain characteristics between the countries.

Uncomplicated urinary tract infections. Bacterial findings and efficacy of empirical antibacterial treatment.

OBJECTIVE: To assess bacterial aetiology, antimicrobial susceptibility and efficacy of empirical treatment in uncomplicated urinary tract infections and to evaluate the dipstick as a diagnostic tool. DESIGN: Prospective study. SETTING: Clinical microbiology laboratory and 17 general practice clinics in Telemark County, Norway. SUBJECTS: A total of 184 female patients between 15 and 65 years of age with symptoms of uncomplicated urinary tract infection. MAIN OUTCOME MEASURES: Results from dipstick testing (leucocyte esterase and nitrite), bacterial culture, susceptibility patterns and efficacy of empirical antibacterial therapy on symptoms. RESULTS: Significant bacteruria was detected in 140 (76%) of the 184 urines. The leukocyte esterase test was of little help in predicting culture-positive UTI. A positive nitrite test accurately predicted culture-positivity, while a negative result was ambiguous. The most common bacterium, E. coli, was found in 112 (80%) of the 140 positive urines and was predominantly sensitive to ciprofloxacin (100%), mecillinam (94%), nitrofurantoin (97%), trimethoprim (88%), and sulphonamide (81%), and to a lesser extent to ampicillin (72%). In 18 patients the causative bacterium was resistant to the therapeutic agent used; 7 of these returned to their GP with persisting symptoms while in 11 symptoms resolved without further treatment. CONCLUSION: The study confirms E. coli as the predominant cause of uncomplicated UTI. Since in the majority of cases the bacterium found was susceptible to the locally preferred antimicrobials and the patients' symptoms were cured, empiric therapy is found to be an effective practice in the study area and, by inference, in others with similar antimicrobial susceptibility patterns.

A fusidic acid-resistant clone of Staphylococcus aureus associated with impetigo bullosa is spreading in Norway.

OBJECTIVE: To investigate the possibility that the increased prevalence of fusidic acid-resistant Staphylococcus aureus in Norway is caused by clonal spread. METHODS: Fusidic acid-resistant and -susceptible clinical isolates of S. aureus from patients with skin infections in the Norwegian county of Telemark and fusidic acid-resistant isolates from other parts of Scandinavia were compared. MICs of fusidic acid for bacterial isolates and pulsed-field gel electrophoresis (PFGE) patterns were investigated. Prevalence data for fusidic acid-resistant S. aureus for the period 1992-2001 were obtained. RESULTS: The prevalence of fusidic acid resistance in S. aureus increased from 1992 to 2001. Eighty per cent of the resistant isolates investigated shared an identical PFGE pattern. The same pattern was found in fusidic acid-resistant isolates from other parts of Scandinavia. Fusidic acid-resistant S. aureus was typically found in impetigo bullosa-like skin disease in children mostly in the summer months. CONCLUSIONS: Fusidic acid resistance among S. aureus is increasing in Norway and is predominantly caused by one clone of S. aureus. The clone may spread further to other countries, and dissemination may be facilitated by extensive use of topical fusidic acid.

[Aerococcus urinae and urinary tract infection]. / Aerococcus urinae og urinveisinfeksjon.

BACKGROUND: Bacteriological investigation of urine often shows the presence of alpha-haemolytic streptococci, but the clinical significance of this finding may be unclear. Among the alpha-haemolytic streptococci found in urine is Aerococcus urinae, which is pathogenic. MATERIAL AND METHODS: We present a prospective study of the prevalence and antibiotic susceptibility of A urinae in urine samples sent to a microbiology laboratory in Norway. RESULTS: Seven out of 27 alpha-haemolytic streptococcal isolates were A urinae. This represents 0.3% of all urine isolates from our laboratory. Appropriate methods for identification and resistance determination are described. INTERPRETATION: Microbiological laboratories should include identification of A urinae in their diagnostic repertoire. Recommended treatment against A urinae is ampicillin or nitrofurantoin.