Risk factors of community-onset extended-spectrum ß-lactamase Escherichia coli and Klebsiella pneumoniae bacteraemia: an 11-year population-based case-control-control study in Denmark.

OBJECTIVES: To investigate and explore temporal changes in risk factors of community-onset extended-spectrum ß-lactamase (ESBL) Escherichia coli and Klebsiella pneumoniae bacteraemia in a region with low antibiotic resistance. METHODS: Population-based case-control study including 223 cases hospitalized with a first-time community-onset ESBL-producing E. coli and K. pneumoniae bacteraemia, 2214 non-ESBL E. coli and K. pneumoniae bacteraemia controls, and 2228 population controls in the North Denmark Region between 2007 and 2017. We used a conditional logistic regression to compute crude and adjusted (age, gender and co-morbidity) odds ratios (aORs) and 95% CIs of risk factors and compared selected risk factors between 2007-2011 and 2016-2017. RESULTS: Several conventional risk factors of ESBL E. coli or K. pneumoniae were identified compared with the population controls. Compared with the non-ESBL controls, use of fluoroquinolones (aOR 3.56, 95% CI 2.52-5.05), three or more admissions within the recent year (aOR 2.18, 95% CI 1.45-3.28), three or more antibiotic prescriptions within 15-365 days before the admission (aOR 2.18, 95% CI 1.53-3.10), male sex (aOR 2.01, 95% CI 1.50-2.69), admission within 1-91 days (aOR 1.84, 95% CI 1.37-2.48) and antibiotic within 15-91 days (aOR 1.82, 95% CI 1.37-2.42) inferred the highest risk. Assessment of temporal dynamics between 2007-2011 and 2016-2017 revealed a slight reduction in risk factors associated with direct health-care contact (e.g. hospital admission). CONCLUSIONS: Recent and frequent hospitalization, and exposure to antibiotics, especially use of fluoroquinolones, appeared to be associated specifically with ESBL production, and focus and interventions should be directed towards these areas. Our results indicated a dissemination of ESBLs into the community.

Outcome of community-onset ESBL-producing Escherichia coli and Klebsiella pneumoniae bacteraemia and urinary tract infection: a population-based cohort study in Denmark.

OBJECTIVES: To assess the impact of ESBL production on mortality and length of hospital stay (LOS) of community-onset infections due to Escherichia coli or Klebsiella pneumoniae. METHODS: A population-based cohort study including all adult patients hospitalized with a first-time community-onset E. coli or K. pneumoniae bacteraemia or urinary tract infection in the North Denmark Region between 2007 and 2017. For each bacterial agent, we computed 1 year Kaplan-Meier survival curves and cumulative incidence functions of LOS, and by use of Cox proportional hazard regression we computed HRs as estimates of 30 day and 1 year mortality rate ratios (MRRs) and LOS among patients with and without ESBL-producing infections. RESULTS: We included 24 518 cases (among 22350 unique patients), of whom 1018 (4.2%) were infected by an ESBL-producing bacterium. The 30 day cumulative mortality and adjusted MRR (aMRR) in patients with and without ESBL-producing isolates was as follows: E. coli bacteraemia (n = 3831), 15.8% versus 14.0%, aMRR = 1.01 (95% CI = 0.70-1.45); E. coli urinary tract infection (n = 17151), 9.5% versus 8.7%, aMRR = 0.97 (95% CI = 0.75-1.26); K. pneumoniae bacteraemia (n = 734), 0% versus 17.2%, aMRR = not applicable; and K. pneumoniae urinary tract infection (n = 2802), 13.8% versus 10.7%, aMRR = 1.13 (95% CI = 0.73-1.75). The 1 year aMRR remained roughly unchanged. ESBL-producing E. coli bacteraemia was associated with an increased LOS compared with non-ESBL production. CONCLUSIONS: ESBL production was not associated with an increased short- or long-term mortality in community-onset infections due to E. coli or K. pneumoniae, yet ESBL-producing E. coli bacteraemia was associated with an increased LOS.

Incidence of community-onset extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae infections: an 11-year population-based study in Denmark.

Background: Data elucidating trends of community-onset extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae infections remain sparse in low prevalence areas. We conducted a population-based study to determine the incidence, temporal trends and co-resistance of community-onset ESBL infections.Methods: We identified all recorded episodes of E. coli and K. pneumoniae bacteraemia and urinary tract infections in adult patients (>15 years) in the North Denmark Region between 2007-2017. Using population-based registries, we obtained information on demographics and place of acquisition, and investigated the standardized incidence rates and temporal trends of community-onset ESBL infections and the associated patterns of co-resistance.Results: A total of 3741 episodes of community-onset ESBL E. coli or K. pneumoniae infections were observed during the study period, with the annual standardized incidence rate increasing from 7.5 to 105 per 100,000 person-years between 2007-2017. The increase was conveyed primarily by a rise in E. coli urinary tract infections shifting from being mainly healthcare-associated to community-acquired. ESBL-producing isolates increased from 0.5 to 4.0% with considerable co-resistance.Conclusion: The proportion of E. coli and K. pneumoniae isolates producing ESBL have increased considerably in the North Denmark Region. The increasing incidence and frequent co-resistance should raise awareness among physicians responsible for empirical antibiotic treatment.

Incidence and predictors of intravenous acyclovir-induced nephrotoxicity.

To assess the incidence, predictive factors, and prognosis of acyclovir-induced nephrotoxicity. We conducted a historical prospective cohort study of patients treated with intravenous acyclovir in North Denmark Region from 2009 to 2016. Information on baseline demographics, co-morbidities, plasma creatinine, and treatment was obtained from the medical records. The primary outcome was an increase of ≥ 40 µmol/L in plasma creatinine level from baseline. We included 276 patients treated with intravenous acyclovir of which 29 (10.5%) met the primary outcome. In 14 cases, the treating physician considered acyclovir the main reason for nephrotoxicity, whereas a potential competing cause of renal impairment was present among the 15 remaining patients. Hypertension was the only predictive factor associated with nephrotoxicity (risk ratio (RR), 2.77; 95% confidence interval (CI), 1.41-5.46), while having no co-morbidities was protective (RR, 0.32; CI, 0.16-0.63). In all cases, the nephrotoxicity was reversible following rehydration and dose reduction or discontinuation of the drug. However, the normalized plasma creatinine upon treatment was significantly higher between cases with acyclovir-induced nephrotoxicity than cases with a potential competing cause (median [interquartile range (IQR)], 93.5 µmol/L [85-108] vs 75 µmol/L [66.5-88]; p = 0.019). Acyclovir-induced, reversible nephrotoxicity was observed in 5.1-10.5% of patients. It is difficult to predict who will develop acyclovir-induced nephrotoxicity; it may occur late in treatment and hypertension was the only independent predictive factor, while the absence of co-morbidities was protective. Ensuring hydration, frequent evaluations of renal function, and corresponding dose adjustment of intravenous acyclovir treatment seem prudent.

Drug-Eluting Balloons in the Treatment of Coronary De Novo Lesions: A Comprehensive Review.

Drug-eluting balloons (DEBs) have emerged as a new application in percutaneous coronary intervention. DEBs have proven successful in the treatment of in-stent restenosis, but their role in de novo lesions is less clear. This paper provides a review of the current studies where DEBs have been used in coronary de novo lesions, either as part of a DEB-only strategy or in combination with another device, mainly a bare metal stent (BMS). By searching Pubmed and Embase we were able to identify 52 relevant studies, differing in design, intervention, and clinical setting, including patients with small vessel disease, bifurcation lesions, complex long lesions, acute myocardial infarction, diabetes mellitus, and elderly. In 23 studies, a DEB was combined with a BMS, 25 studies used a DEB-only strategy with only provisional BMS implantation, and four studies combined a DEB with a drug-eluting stent (DES). In the vast majority of studies, DEB in combination with BMS does not seem to improve clinical or angiographic outcome compared with DES, whereas a DEB-only strategy seems promising, especially when predilatation and geographical mismatch are taken into account. A lower risk of recurrent thrombosis with DEB compared with DES is not evident from the current studies. In conclusion, the main indication for DEB seems to be small vessel disease, especially in clinical scenarios in which a contraindication to dual antiplatelet therapy exists. The main approach should be a DEB-only strategy with only provisional bailout stenting, which has shown interesting results in different clinical scenarios. In general, larger randomized controlled studies with prolonged follow-up comparing DEB with best in class DES are warranted. Technical developments of DEBs including the use of different drugs might potentially improve the efficacy of such treatment.