Use of inhaled corticosteroids and risk of acquiring Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease.

BACKGROUND: Inhaled corticosteroids (ICS) are commonly used to treat COPD and are associated with increased risk of pneumonia. The aim of this study was to assess if accumulated use of ICS is associated with a dose-dependent risk of a positive airway culture with Pseudomonas aeruginosa in patients with COPD. METHODS: We conducted a multiregional epidemiological cohort study including Danish COPD patients followed in outpatient clinics during 2010-2017. ICS use was categorised based on accumulated prescriptions redeemed 365 days prior to cohort entry. Cox proportional hazard regression model was used to estimate the risk of acquiring P. aeruginosa. Propensity score matched models were used as sensitivity analyses. RESULTS: A total of 21 408 patients were included in the study, of which 763 (3.6%) acquired P. aeruginosa during follow-up. ICS use was associated with a dose-dependent risk of P. aeruginosa (low ICS dose: HR 1.38, 95% CI 1.03 to 1.84, p=0.03; moderate ICS dose: HR 2.16, 95% CI 1.63 to 2.85, p<0.0001; high ICS dose: HR 3.58, 95% CI 2.75 to 4.65, p<0.0001; reference: no ICS use). A propensity matched model confirmed the results (high ICS dose compared with no/low/moderate ICS dose: HR 2.05, 95% CI 1.76 to 2.39, p p<0.0001). CONCLUSION: Use of ICS in patients with COPD followed in Danish outpatient clinics was associated with a substantially increased and dose-dependent risk of acquiring P. aeruginosa. Caution should be taken when administering high doses of ICS in severely ill patients with COPD. These results should be confirmed in comparable cohorts and other settings.

Randomised clinical trial: a 12-strain bacterial mixture versus faecal microbiota transplantation versus vancomycin for recurrent Clostridioides difficile infections.

BACKGROUND: A defined bacterial mixture could be a safer alternative to faecal microbiota transplantation (FMT). AIMS: To compare the efficacy of a 12-strain mixture termed rectal bacteriotherapy with either FMT or vancomycin for recurrent Clostridioides difficile infection (CDI) in an open-label 3-arm randomised controlled trial. METHODS: We screened all individuals positive for C difficile from May 2017 to March 2019. Persons with laboratory-confirmed recurrent CDI were included. Before FMT and rectal bacteriotherapy, we pre-treated with vancomycin for 7-14 days. Rectal bacteriotherapy was applied by enema on three consecutive days and FMT by enema once with possible repetition for two to three infusions within 14 days. The vancomycin group was treated for 14 days with additional five weeks of tapering for multiple recurrences. The primary outcome was clinical cure within 90 days. A secondary outcome was 180-day all-cause mortality. RESULTS: Participants in the FMT group (n = 34) were cured more often than participants receiving vancomycin (n = 31), 76% vs 45% (OR 3.9 (1.4-11.4), P < 0.01) or rectal bacteriotherapy (n = 31), 76% vs 52% (OR 3.0 (1.1-8.8), P = 0.04). Rectal bacteriotherapy and vancomycin performed similarly (P = 0.61). The mortality rate was 6% in the FMT group, 13% in the bacteriotherapy group and 23% in the vancomycin group. FMT tended to reduce mortality compared with vancomycin, OR 0.2 (0.04-1.12), P = 0.07. CONCLUSIONS: Rectal bacteriotherapy appears as effective as vancomycin but less effective than 1-3 FMTs. FMT by enema with 1-3 infusions is superior to vancomycin for treating recurrent C difficile infections and might reduce mortality.

Antibacterial use in the Faroe Islands, Iceland, and Denmark 1999-2011.

BACKGROUND: The Faroe Islands, Iceland, and Denmark are neighbouring Nordic countries with great ethnic, cultural, and political similarities and are relatively homogeneous. Important information about prescribing practices can be obtained by comparing the antibacterial use in these countries. The objective was to describe, compare, and analyse the use of systemic antibacterial agents in these countries during the y 1999-2011. METHODS: Data were obtained from the Faroe Islands, Iceland, and Denmark on systemic antibacterial use and expressed in defined daily dosages (DDD). Prescription data were also obtained for specific age groups. RESULTS: The total antibacterial use for the y 1999-2011 varied markedly between the 3 countries, with a mean use of 21.8 DDD/1000 inhabitants/day (DID) in Iceland, 17.7 in the Faroe Islands, and 16.3 in Denmark. The total use remained fairly constant over the years in the Faroe Islands and Iceland, whereas in Denmark it increased gradually from 13.5 DID in 1999 to 19.5 DID in 2011. The higher use in Iceland can be explained by much higher consumption of tetracyclines. There was also considerable variation in the use of individual penicillins and macrolides between the countries. CONCLUSIONS: Despite the great ethnic and cultural similarities of these 3 countries, we found marked differences in total antibacterial use and important differences in the use of individual antibacterials.

[Notable increase in the consumption of antibiotics in general practice]. / Markant stigning i antibiotikaforbruget i almen praksis.

The antimicrobial consumption in primary health care has increased notably during the latest decade. The increase has predominantly been among broad-spectrum antimicrobial agents. Denmark is no longer among the European countries with the lowest consumption. The reasons for these changes are not fully explained, but increased dosage for each treated patient and more patients treated have played an important role. To some extent, the consumption meets with relevant quality indicators for antibiotic prescribing, but the use of resistance inducing antibiotics needs to be limited according to guidelines.

[Increasing antimicrobial consumption in hospitals]. / Stigende antibiotikaforbrug på sygehusene.

The antimicrobial consumption in hospital care has increased steadily during the latest decade. Now, broad-spectrum antimicrobial agents dominate the consumption at the expense of beta-lactamase sensitive penicillins. The reasons for these changes are not fully understood, but increased activity at the hospitals, higher resistance rates and the emergence of resistant nosocomial bacterial infections have played an important role. Denmark is no longer among the European countries with the lowest consumption. This indicates the need to implement restriction on antimicrobial usage in hospital care.

Implementation of e-Bug in Denmark.

Bacterial resistance to antimicrobial agents in primary healthcare is low in Denmark compared with most other European countries. Denmark has a vaccination programme for children that recommends immunization against 10 infectious diseases, including a heptavalent pneumococcal conjugate vaccine (PCV7) and a vaccine against human papillomavirus (HPV). Outbreaks in schools due to other infectious illnesses are well recognized and have seasonal variations. A quarter of young people have had a sexually transmitted disease before the age of 25 years. Denmark had a considerable interest in joining the e-Bug project to keep a focus on the low prevalence of bacterial resistance and the prevention of infectious diseases, and to maintain the acceptance of the immunization programme. Furthermore, the Danish Folkeskole, which is the Danish municipal primary and lower secondary school, uses the principle of differentiated teaching, integrating information technology, and there are no recommended textbooks in the curriculum. The teaching is organized so that it both strengthens and develops an individual student's ability to act and care for themselves and for society in general. e-Bug, in its design, was seen as a tool that could be implemented well in the Danish Folkeskole, as it fulfils the goals on teaching methods and output. Two thousand e-Bug packs were printed, 100 local education authorities and 1507 school principals were contacted, and e-Bug was presented to important stakeholders in relevant scientific magazines and at meetings. It has been well accepted.

Recurrent bacteraemia: A 10-year regional population-based study of clinical and microbiological risk factors.

BACKGROUND: A population-based nested case-control study was conducted in order to characterize patient factors and microbial species associated with recurrent bacteraemia. METHODS: All patients with bacteraemia in a Danish region during 1996-2006 were investigated. Recurrence was defined based on pathogen identity, site of infection and time frame, and not restricted to homologous pathogens. RESULTS: We identified 8672 patients with first-time bacteraemia, of whom 1003 (12%) had a recurrence within 1 year. The proportion of mono-microbial bacteraemia was similar for first (86%) and recurrent episodes (84%). An unknown focus was common in both episodes (22.7 and 29.1%, respectively). Independent predictors of a recurrence (incidence rate ratio, 95% confidence interval) included health care-associated (2.4; 1.9-3.0) and nosocomial bacteraemia (2.1; 1.8-2.6), poly-microbial Gram-positive bacteraemia (2.7; 1.6-4.6), and fungaemia (2.2; 1.4-3.5), a Charlson co-morbidity index score of 1-2 (1.7; 1.4-2.1), inappropriate empirical antimicrobial chemotherapy (1.3; 1.1-1.5), a gastro-intestinal tract focus (2.3; 1.7-3.0), a liver/biliary tract focus (2.7; 2.0-3.6), an iv-catheter focus (2.0; 1.4-2.8), endocarditis (2.7; 1.6-4.3), and an unknown focus (1.9; 1.5-2.3). CONCLUSIONS: This study showed recurrent bacteraemia to be common and the following risk factors were identified: a health care-associated or nosocomial origin, poly-microbial or fungal aetiology, a focus within the abdomen, endocardium, iv-catheter-related or unknown, a Charlson co-morbidity index score of >1 and inappropriate empirical antimicrobial chemotherapy.