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Background: Use of third-generation cephalosporins, such as cefotaxime, is associated with an increased risk of selection for antimicrobial resistance, so alternative antibiotics need to be considered. The aim of the present study was to evaluate intestinal colonisation with third-generation cephalosporin-resistant pathogens following use of temocillin-an alternative antibiotic to cefotaxime that is potentially less prone to disturbing the intestinal microbiota-in empirical treatment of febrile urinary tract infection (UTI)., Methods: We did a randomised, multicentre, superiority, open-label phase 4 trial in patients who had been admitted to inpatient care in 12 Swedish hospitals with suspected or diagnosed febrile UTI (complicated or uncomplicated). To meet inclusion criteria, a patient was required to have at least one sign or symptom of pyelonephritis (ie, flank pain; costovertebral angle tenderness; and changes to urinary frequency or urgency or dysuria), a fever of 38·0°C or higher, and a positive urine dipstick (for nitrites, white blood cells, or both). Participants were also required to have an indication for intravenous antibiotic treatment. Participants were randomly assigned (1:1) to receive either 2 g temocillin or 1-2 g cefotaxime, by local investigators opening consecutive sealed randomisation envelopes that were generated centrally in advance. Both drugs were administered intravenously every 8 h. The trial was open label for investigators and patients, but those doing the microbiological analyses were masked to the groups. Participants were treated with antibiotics for 7-10 days (or up to 14 days if they had bacteraemia), at least 3 days of which were on the study drug; at day 4 and later, participants who were showing improvement could be given an oral antibiotic (ciprofloxacin, ceftibuten, cefixime, or co-trimoxazole). Patients not showing improvement were regarded as having treatment failures. Rectal swabs were collected at three timepoints: at baseline (before the first dose), after the last dose of study drug, and 7-10 days after treatment stopped. The composite primary outcome was colonisation with Enterobacterales with reduced susceptibility to third-generation cephalosporins, or colonisation with toxin-producing Clostridioides difficile, or both, to evaluate disturbance of the intestinal microbiota. The study is registered in the EU Clinical Trials Register (EudraCT 2015-003898-15)., Findings: Between May 20, 2016, and July 31, 2019, 207 patients were screened for eligibility, of whom 55 patients were excluded. 152 participants were randomly assigned to groups: 77 (51%) patients received temocillin, 75 (49%) patients received cefotaxime. The composite primary endpoint was met by 18 (26%) of 68 participants receiving temocillin versus 30 (48%) of 62 patients receiving cefotaxime (risk difference -22% [95% CI -42% to -3%]), showing superiority of temocillin versus cefotaxime (ie, less disturbance of the intestinal microbiota). 43 adverse events were reported in 40 (52%) of 77 patients in the temocillin group, versus 46 adverse events in 34 (45%) of 75 patients in the cefotaxime group. Most events were of mild to moderate severity. 21 (27%) patients in the temocillin and 17 (23%) patients in the cefotaxime group had an adverse event that was considered to be associated with the study drug., Interpretation: Temocillin was found to be less selective than cefotaxime of Enterobacterales with reduced susceptibility to third-generation cephalosporins, and it could therefore be a favourable alternative in the empirical treatment of febrile UTI. Use of this antibiotic could reduce hospital transmission and health-care-associated infections by these pathogens., Funding: Public Health Agency of Sweden., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In early June 2018, an increase in non-travel-related cases of Legionella non- pneumophila Legionnaires' disease (LD) was observed in Sweden and a national outbreak investigation was started. Outbreak cases were defined as notified confirmed or probable cases of L. non- pneumophila LD, with symptom onset after 1 April 2018. From April to August 2018, 41 cases were reported, 30 of whom were identified as L. longbeachae. We conducted a case-control study with 27 cases and 182 matched controls. Results from the case-control study indicated that gardening and handling commercial bagged soil, especially dusty dry soil, were associated with disease. L. longbeachae was isolated in soils from cases' homes or gardens, but joint analysis of soil and human specimens did not identify any genetic clonality. Substantial polyclonality was noted between and within soil samples, which made finding a genetic match between soil and human specimens unlikely. Therefore, whole genome sequencing may be of limited use to confirm a specific soil as a vehicle of transmission for L. longbeachae. Handling soil for residential gardening was associated with disease and the isolation of L. longbeachae in different soils provided further evidence for Legionella non -pneumophila infection from soil.

Carbapenemase-producing Enterobacteriaceae (CPE) are increasing worldwide, and are a major threat to healthcare systems. Recent European data support that many countries have interregional spread of CPE or an endemic situation. In Sweden mandatory laboratory reporting of CPE of both colonisation and infection has been practiced since 2007 and since 2012 also by treating physicians. Between 2007 and 2013, 94 cases of CPE were detected in Sweden, out of which 24 were considered to cause clinical infections (bloodstream infection (n=4), urinary tract infection (n=12), wound infection (n=4), respiratory tract infection (n=2) and catheter related (n=2). The majority were detected in the hospital setting through faecal screening or as probable colonisers in clinical cultures. Travel abroad was observed in the majority of the patients (81%), and among them 84% had been hospitalised. During the study period only two chains of transmissions in Swedish hospitals were reported, involving four patients. Klebsiella pneumoniae was the primarily isolated species (n=57) followed by Escherichia coli (n=29). blaNDM was the predominant carbapenemase gene (n=36), followed by blaOXA-48-group, blaKPC and blaVIM. In 26/94 cases (28%) isolates were categorised as possible XDR (extensively drug-resistant). CPE are increasing in Sweden, but are still at a comparably low level., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Extended-spectrum β-lactamase (ESBL) -producing Enterobacteriaceae have been notifiable according to the Swedish Communicable Disease Act since 2007. A major increase in the number of cases has been observed, with 2099 cases in 2007 and 7225 cases in 2012. The majority of the isolates are Escherichia coli. Additionally, Swedish data on the prevalence of ESBL-producing invasive isolates of E. coli are available through EARS-Net, and through biannual point prevalence studies, where molecular characterization of isolates from the entire country is carried out. This paper describes major trends in the Swedish epidemiology of ESBL-producing E. coli in the period 2007-2012. Isolates from the point prevalence studies were subjected to antimicrobial susceptibility testing, ESBL genotyping, pulsed-field gel electrophoresis, multi-locus sequence typing and phylogenetic grouping with PCR. The distribution of sequence types, resistance genes and susceptibility levels were all stable over the three study periods. The dominating resistance gene conferring ESBL was blaCTX -M-15 , found in 54-58% of the isolates. ST131 represented 34-38% of the isolates. Other major sequence types were ST38, ST69, ST405, ST617 and ST648, each representing 2-6% of the isolates. Phylogenetic group B2 was the most common, and was observed in 41-47% of the isolates. However, among ST131 isolates the B2 phylogenetic group represented 90-98% of the isolates. The most important epidemiological difference seen over time was that the median age of infected women decreased from 62 to 52 years (p <0.0001) and infected men from 67 to 64 years. A potential explanation might be the shift towards a higher proportion of community-acquired infections in individuals lacking comorbidities., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Acquired resistance to cephalosporins in Enterobacteriaceae is a global problem. After an outbreak at Uppsala University Hospital of extended-spectrum β-lactamase (ESBL)-positive Klebsiella pneumoniae producing CTX-M-15, there was a shift from AmpC to ESBL production among Escherichia coli isolates. To explore the basis for this epidemiological shift, 46 E. coli isolates (ESBLs, n = 23; AmpC, n = 23) were characterized with regard to genetic relatedness, β-lactamase, replicon and integron types, antibiotic resistance profiles, and genes encoding virulence factors. In addition, the survival in the environment and on hospital-associated materials was analysed. CTX-M-15 was the most frequent ESBL (78%). Only three (13%) of the AmpC enzymes were harboured on plasmids (CMY-2, DHA-1). Independent of plasmid-mediated beta-lactamase, IncF plasmids predominated and only class I integrons were detected. The ESBL producers carried more virulence genes (p = 0.04), exhibited a broader resistance phenotype (p = 0.01) and survived significantly longer (p = 0.03) on different materials than the AmpC-producing isolates. In conclusion, ESBL-producing isolates had properties which are likely to augment their competitiveness. Apart from antibiotic resistance and virulence factors, extended survival in the environment could be a selective trait for successful ESBL-producing E. coli strains., (© 2013 APMIS. Published by John Wiley & Sons Ltd.)

A selection of plasmid-mediated AmpC-producing Escherichia coli isolates carrying blaCMY-2 from Swedish broilers were characterized to establish their relatedness to and a possible overlap with human clinical E. coli isolates. The results showed diversity among the E. coli isolated from broilers, indicating that the spread in the population was not due to one strain. However, only one type of plasmid belonging to replicon type incK was identified. Furthermore, there were no indications of spread of blaCMY-2 E. coli isolates from broilers to human clinical settings, although Swedish broilers may be a source of blaCMY-2 and/or the plasmid carrying blaCMY-2 ., (©2013 The Authors Clinical Microbiology and Infection ©2013 European Society of Clinical Microbiology and Infectious Diseases.)

The aim of this study was to investigate the prevalence of extended-spectrum beta-lactamase (ESBL)-producing bacteria in patients at various hospital wards and in a group of relatively healthy volunteers, in order to obtain greater knowledge on how common these bacterial strains are in hospital settings and in the general community. Participants (n = 427) were enrolled at a University Hospital and at Primary Health Care Units (PHCUs) in Sweden in 2008 and 2010. The participants provided rectal swabs, which were tested for the occurrence of ESBL-producing bacteria. Positive samples were analysed with polymerase chain reaction (PCR) methods for bacterial strain typing and ESBL phylogroups. In 2008, the prevalence was 2.1% (2/96) in PHCU subjects and 1.8% (2/113) in hospital patients. In 2010, the prevalence was 3.0% (3/100) in PHCU subjects and 6.8% (8/118) in hospital patients. The dominating phylogroups were CTX-M-1 and CTX-M-9. All ESBL-positive isolates were Escherichia coli. We found a higher prevalence of ESBL faecal carriage than expected, both in the hospital setting and in the PHCU group.