Escherichia coli is the most common cause of urinary tract infection (UTI). The pathogenic isolates are becoming increasingly resistant to antibiotics; with a worldwide dissemination of resistant sequence types (ST). We characterized three different uropathogenic E. coli populations, from non-hospitalized patients to describe the genetic kinship between resistant and susceptible isolates. We studied the populations by use of multi-locus sequence typing (MLST) and abbreviated-multi locus variable number of tandem repeat analysis (a-MLVA). Urine samples submitted for testing, by general practitioners, were identified at Dept. of Clinical Microbiology at Hvidovre Hospital, Denmark, from Oct. 2011 to July 2012. We included 94 fully susceptible, 94 resistant (non-ESBL) and 98 Extended Spectrum Beta-lactamases- (ESBL)-producing E. coli isolates. The ESBL population was dominated vastly by ST131 (51 %), ST38 (9 %) and ST69 (6 %). In the resistant group ST69 (18 %), ST73 (11 %) and ST131 (15 %) were the largest clusters. In the susceptible population more STs and a-MLVA codes were identified compared to the other groups and ST73 and ST95 were found as the only clusters with 16 % and 6 %, respectively. Ninety-eight per cent of the ESBL-producing E. coli isolates were CTX-M-producers. ST131 dominated the population of community-associated uropathogenic ESBL-producing E. coli, but was less frequent among non-ESBL-producing E. coli. The fully susceptible E. coli population was a much more diverse group than the resistant and ESBL-producing E. coli populations. Overall, these findings suggest that dominant ESBL-producing lineages are derived from UPEC lineages already established in the general UPEC population.

In response to a considerable increase in the infections caused by ESBL/AmpC-producing Klebsiella pneumonia in 2008, a multidisciplinary intervention, with a main focus on antimicrobial stewardship, was carried out at one university hospital. Four other hospitals were used as controls. Stringent guidelines for antimicrobial treatment and prophylaxis were disseminated throughout the intervention hospital; cephalosporins were restricted for prophylaxis use only, fluoroquinolones for empiric use in septic shock only, and carbapenems were selected for penicillin-allergic patients, infections due to ESBL/AmpC-producing and other resistant bacteria, in addition to their use in severe sepsis/septic shock. Piperacillin-tazobactam ± gentamicin was recommended for empiric treatments of most febrile conditions. The intervention also included education and guidance on infection control, as well as various other surveillances. Two year follow-up data on the incidence rates of patients with selected bacterial infections, outcomes, and antibiotic consumption were assessed, employing before-and-after analysis and segmented regression analysis of interrupted time series, using the other hospitals as controls. The intervention led to a sustained change in antimicrobial consumption, and the incidence of patients infected with ESBL-producing K. pneumoniae decreased significantly (p<0.001). The incidences of other hospital-associated infections also declined (p’s<0.02), but piperacillin-tazobactam-resistant Pseudomonas aeruginosa and Enterococcus faecium infections increased (p’s<0.033). In wards with high antimicrobial consumption, the patient gut carrier rate of ESBL-producing bacteria significantly decreased (p = 0.023). The unadjusted, all-cause 30-day mortality rates of K. pneumoniae and E. coli were unchanged over the four-year period, with similar results in all five hospitals. Although not statistically significant, the 30-day mortality rate of patients with ESBL-producing K. pneumoniae decreased, from 35% in 2008–2009, to 17% in 2010–2011. The two-year follow-up data indicated that this multidisciplinary intervention led to a statistically significant decrease in the incidence of ESBL/AmpC-resistant K. pneumoniae infections, as well as in the incidences of other typical hospital-associated bacterial infections.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been associated with a high risk of adverse outcomes in solid organ transplant (SOT) recipients in the pre-vaccination era. In this retrospective cohort study, we examined the incidence and severity of COVID-19 in kidney and liver transplant recipients in Denmark in the post-vaccination era, from December 27, 2020, to December 27, 2021. We included 1428 SOT recipients with 143 cases of first-positive SARS-CoV-2 PCR test. The cumulative incidence of first-positive SARS-CoV-2 PCR test 1 year after initiation of vaccination was 10.4% (95% CI: 8.8–12.0), and the incidence was higher in kidney than in liver transplant recipients (11.6% [95% CI: 9.4–13.8] vs. 7.4% [95% CI: 5.1–9.8], p = .009). After the first-positive SARS-CoV-2 PCR test, the hospitalization rate was 31.5% (95% CI: 23.9–39.1), and 30-day all-cause mortality was 3.7% (95% CI: 0.5–6.8). Hospitalization was lower in vaccinated than in unvaccinated SOT recipients (26.4% [95% CI: 18.1–34.6] vs. 48.5% [95% CI: 31.4–65.5], p = .011), as was mortality (1.8% [95% CI: 0.0–4.3] vs. 9.1% [95% CI: 0.0–18.9], p = .047). In conclusion, SOT recipients remain at high risk of adverse outcomes after SARS-CoV-2 infections, with a lower risk observed in vaccinated than in unvaccinated SOT recipients.

Mecillinam for the treatment of acute pyelonephritis and bacteremia caused by Enterobacteriaceae: a literature review Filip Jansåker,1,2 Niels Frimodt-Møller,3 Thomas L Benfield,2,4 Jenny Dahl Knudsen1,3 1Department of Clinical Microbiology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; 2Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 3Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 4Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark Purpose: The pharmacokinetic properties of mecillinam (MEC) for urinary tract infections are excellent, and the resistance rate in Enterobacteriaceae is low compared to other recommended antibiotics. The oral prodrug pivmecillinam (P-MEC) has been used successfully as first choice for cystitis in the Nordic countries for many years. Norwegian and Danish guidelines also recommend P-MEC for acute uncomplicated pyelonephritis (AUP) and intravenous (IV) MEC for suspected urosepsis (only in Denmark). Here, we wish to present an updated investigation on the clinical data behind these recommendations together with sparse but more current clinical data.Methods: Prospective clinical trials evaluating MEC as monotherapy or in polytherapy with one other beta-lactam (mostly ampicillin [AMP]) for pyelonephritis or bacteremia were reviewed. Outcomes of primary interest were clinical and bacteriological success and relapse, respectively. Search databases used were PubMed, Cochrane Library, and Embase.Results: Twelve clinical studies (1979–2015) were included in this integrated literature review. Clinical success was seen in 38/51 (75%) patients treated with MEC as monotherapy and in 152/164 (93%) patients treated with MEC and one other beta-lactam. Bacteriological success was seen in 35/47 (74%) and 117/167 (70%) patients treated with MEC alone and with one other beta-lactam, respectively. In complicated infections, bacteriological success was much lower. Clinical relapse rate was not well described. Several uropathogenic bacteremia cases were treated successfully with MEC alone (ie, 10/15 [67%] and 13/15 [87%] for clinical and bacteriological success, respectively) or with one other beta-lactam (ie, 57/65 [88%] and 53/63 [84%] for clinical and bacteriological success, respectively). However, data on bacteremia are very sparse. Adverse reactions were few and mild (73/406 [18%]) and primarily seen when AMP was co-administered (69/73 [95%]). No serious adverse reactions were reported.Conclusion: IV MEC or oral P-MEC for 14 days may be suitable for the treatment of AUP and pediatric pyelonephritis. Randomized controlled trials using a single standardized dose of P-MEC compared to other current recommendations are warranted. Similarly, more evidence is required before MEC should be recommended for bacteremia or sepsis due to Enterobacteriaceae. Keywords: pyelonephritis, mecillinam, review, pivmecillinam, amdinocillin

The Danish Collaborative Bacteraemia Network (DACOBAN) research database includes microbiological data obtained from positive blood cultures from a geographically and demographically well-defined population serviced by three clinical microbiology departments (1.7 million residents, 32% of the Danish population). The database also includes data on comorbidity from the Danish National Patient Registry, vital status from the Danish Civil Registration System, and clinical data on 31% of nonselected records in the database. Use of the unique civil registration number given to all Danish residents enables linkage to additional registries for specific research projects. The DACOBAN database is continuously updated, and it currently comprises 39,292 patients with 49,951 bacteremic episodes from 2000 through 2011. The database is part of an international network of population-based bacteremia registries from five developed countries on three continents. The main purpose of the DACOBAN database is to study surveillance, risk, and prognosis. Sex- and age-specific data on background populations enables the computation of incidence rates. In addition, the high number of patients facilitates studies of rare microorganisms. Thus far, studies on Staphylococcus aureus, enterococci, computer algorithms for the classification of bacteremic episodes, and prognosis and risk in relation to socioeconomic factors have been published.

Staphylococcus aureus bacteremia (SAB) is frequently encountered in the hospital setting, and current guidelines recommend at least 14 days of antibiotic treatment for SAB in order to minimize risks of secondary deep infections and relapse. However, evidence to support these treatment recommendations remains scarce. Patients with uncomplicated SAB are known to have a low of risk of recurrence and death. Reducing treatment length in uncomplicated SAB would reduce the total consumption of antibiotics, duration of hospital admission, and potentially the risk of adverse events. With SAB7 we seek to determine if 7 days of antibiotic treatment in patients with uncomplicated SAB is non-inferior to 14 days of treatment. The study is designed as a randomized, non-blinded, non-inferiority, multicenter interventional study. Primary measure of outcome will be 90-day survival without clinical or microbiological failure to treatment or relapse. Secondary outcomes include the prevalence of severe adverse effects, in particular secondary infection with Clostridium difficile, all-cause mortality, as well as public health related costs. Patients identified with uncomplicated SAB who have received 7 days of protocol-approved antibiotics will be eligible for inclusion and randomized 1:1 in two parallel arms to either (i) discontinue antibiotic treatment at day 7 or (ii) to continue antibiotic treatment for a total of 14 days. Main exclusion criteria include signs of complicated SAB, such as the presence of secondary deep infections, persistent bacteremia, and implantable devices. Patients are followed for 6 months with clinical examinations, consecutive blood tests, and registration of adverse events. A total of 284 patients are to be included at ten centers across Denmark. The primary endpoint will be tested with a statistical non-inferiority margin of 10 percentage points. SAB 7 will determine if 7 days of antibiotic treatment in patients with uncomplicated SAB is sufficient and safe. Results of the study will provide important knowledge on optimized SAB management and could potentially modify the current treatment recommendations. ClinicalTrails.gov, H-17027414 . Registered on May 2, 2018. The Danish Medicines Agency (EudraCT), 2017–003529-13. Registered on October 30, 2017.