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Background There is a well-described association between bacteremia with bovis group streptococci or Clostridium septicum and an increased probability of a colorectal cancer (CRC) diagnosis. We wanted to investigate the existence of a similar association between CRC and bacteremia with other bacteria belonging to the gut microbiota.. Methods A population based cohort study in a population about 2 million people including 45 774 bacteremia episodes and 231 387 blood culture negative cases was performed in the Region of Southern Denmark and Region Zealand from 2007–2016. Episodes of bacteremia were combined with the Danish central register for CRC. We performed Cox’s regression analysis with hazard ratios (HRs) and 95% confidence intervals (CIs). Results The study results confirmed previous findings of an increased risk of a CRC diagnosis after bacteremia with the bovis group streptococci (risk within a year: 4.3%; HR [95% CI]: 8.46 [3.51–20.4]) or C. septicum (20.8%; 76.2 [42.0–138]). Furthermore, Bacteroides ovatus (6.7%; 20.3 [5.04–81.8]), Bacteroides uniformis (5.4%; 16.2 [4.02–65.7]), Clostridium tertium (3.6 %; 13.9 [1.96–99.4]), Fusobacterium spp. (excluding F. necrophorum) (3.0 %; 8.51 [2.73–26.5]), and Gram-positive anaerobic cocci (3.6 %; 10.9 [4.50–26.3]) were also associated with an increased risk of a CRC diagnosis compared to patients with negative blood cultures (0.4%). Conclusions Bacteremia with specific gut microbiota anaerobic bacteria is associated with a high risk of a diagnosis of CRC, indicating the need for colorectal workup. Importantly, this strategy also holds the possible additional benefit of detecting adenomas or other premalignant conditions, which were not included in the present study.

Here, we present the first MLST scheme for Bacteroides fragilis , one of the most abundant pathogenic bacteria in the human gut microbiota. The scheme enables standard classification and monitoring of B. fragilis on a worldwide scale and groups the majority of current isolate data in one place.

Objectives It is unknown whether invasive procedures are associated with brain abscess.Methods Nationwide, population-based, matched case?control study of patients with culture verified brain abscess in Denmark from 1989 to 2016. Exposure was invasive procedures 0?6?months before study inclusion.Results We identified 435 patients and 3909 controls. The level of comorbidity was higher among patients with brain abscess than among controls. A total of 48 cases (11%) had one or more invasive procedures 0?6?months before study inclusion (adjusted odds ratios (aOR) of 3.6 (95% confidence interval (CI): 2.5?5.1), a population attributable fractions of 8% (95% CI: 7?9)). In primary care, ear, nose and throat (ENT) procedures were associated with brain abscess (aOR of 4.0 (95% CI: 2.0?8.0)), but gastrointestinal endoscopies were not (aOR of 1.0 (95% CI: 0.3?3.2)). No bronchoscopies were performed in primary care. In the hospital-based setting, ENT procedures, bronchoscopies and gastrointestinal endoscopies were associated with an increased risk of brain abscess (aOR of 14.5 (95% CI: 4.8?43.8), 20.3 (95% CI: 3.8?110.1) and 3.4 (95% CI: 2.0?5.6), respectively).Conclusions The association between invasive procedures and brain abscess was more pronounced in the hospital-based setting than in primary care. Objectives: It is unknown whether invasive procedures are associated with brain abscess. Methods: Nationwide, population-based, matched case–control study of patients with culture verified brain abscess in Denmark from 1989 to 2016. Exposure was invasive procedures 0–6 months before study inclusion. Results: We identified 435 patients and 3909 controls. The level of comorbidity was higher among patients with brain abscess than among controls. A total of 48 cases (11%) had one or more invasive procedures 0–6 months before study inclusion (adjusted odds ratios (aOR) of 3.6 (95% confidence interval (CI): 2.5–5.1), a population attributable fractions of 8% (95% CI: 7–9)). In primary care, ear, nose and throat (ENT) procedures were associated with brain abscess (aOR of 4.0 (95% CI: 2.0–8.0)), but gastrointestinal endoscopies were not (aOR of 1.0 (95% CI: 0.3–3.2)). No bronchoscopies were performed in primary care. In the hospital-based setting, ENT procedures, bronchoscopies and gastrointestinal endoscopies were associated with an increased risk of brain abscess (aOR of 14.5 (95% CI: 4.8–43.8), 20.3 (95% CI: 3.8–110.1) and 3.4 (95% CI: 2.0–5.6), respectively). Conclusions: The association between invasive procedures and brain abscess was more pronounced in the hospital-based setting than in primary care.

Background: Salmonella enterica is among the major burdens for public health at global level. Typing of salmonellae below the species level is fundamental for different purposes, but traditional methods are expensive, technically demanding, and time-consuming, and therefore limited to reference centers. Fourier transform infrared (FTIR) spectroscopy is an alternative method for bacterial typing, successfully applied for classification at different infra-species levels.Aim: This study aimed to address the challenge of subtyping Salmonella enterica at O-serogroup level by using FTIR spectroscopy. We applied machine learning to develop a novel approach for S. enterica typing, using the FTIR-based IR Biotyper® system (IRBT; Bruker Daltonics GmbH & Co. KG, Germany). We investigated a multicentric collection of isolates, and we compared the novel approach with classical serotyping-based and molecular methods.Methods: A total of 958 well characterized Salmonella isolates (25 serogroups, 138 serovars), collected in 11 different centers (in Europe and Japan), from clinical, environmental and food samples were included in this study and analyzed by IRBT. Infrared absorption spectra were acquired from water-ethanol bacterial suspensions, from culture isolates grown on seven different agar media. In the first part of the study, the discriminatory potential of the IRBT system was evaluated by comparison with reference typing method/s. In the second part of the study, the artificial intelligence capabilities of the IRBT software were applied to develop a classifier for Salmonella isolates at serogroup level. Different machine learning algorithms were investigated (artificial neural networks and support vector machine). A subset of 88 pre-characterized isolates (corresponding to 25 serogroups and 53 serovars) were included in the training set. The remaining 870 samples were used as validation set. The classifiers were evaluated in terms of accuracy, error rate and failed classification rate.Results: The classifier that provided the highest accuracy in the cross-validation was selected to be tested with four external testing sets. Considering all the testing sites, accuracy ranged from 97.0% to 99.2% for non-selective media, and from 94.7% to 96.4% for selective media.Conclusions: The IRBT system proved to be a very promising, user-friendly, and cost-effective tool for Salmonella typing at serogroup level. The application of machine learning algorithms proved to enable a novel approach for typing, which relies on automated analysis and result interpretation, and it is therefore free of potential human biases. The system demonstrated a high robustness and adaptability to routine workflows, without the need of highly trained personnel, and proving to be suitable to be applied with isolates grown on different agar media, both selective and unselective. Further tests with currently circulating clinical, food and environmental isolates would be necessary before implementing it as a potentially stand-alone standard method for routine use.

Background Brain abscesses are frequently caused by oral cavity bacteria, but whether dental status and invasive dental procedures are important risk factors is unknown. Methods A nationwide, population-based, case-control study examined the association between dentist’s visits and invasive dental procedures and risk of brain abscess caused by oral cavity bacteria from 1989 through 2016. Date of brain abscess diagnosis was considered the index date. Using risk-set sampling, 10 population controls per case were individually matched by age, sex, and residential area. Conditional logistic regression was used to compute odds ratios with 95% confidence intervals (CIs), adjusted for comorbidity. Results We identified 362 patients with culture-proven brain abscess caused by oral cavity bacteria. The median age was 53 years (interquartile range, 39–65 years) and 220 (61%) were male. Invasive dental procedures within 6 months before the index date was observed in 21 of 362 (6%) patients with brain abscess and 179 of 3257 (5%) population controls (adjusted odds ratio [aOR], 1.07 [95% CI, .67–1.70]). Two hundred thirteen of 362 (59%) patients with brain abscess had visited their dentist within 1 year before the index date compared with 1944 of 3257 (60%) of population controls (aOR, 0.99 [95% CI, .77–1.26]). Using no dentist’s visits as reference, we observed aORs of 0.95 (95% CI, .64–1.40) for 1–2 visits within 3 years of the index date and 1.01 (95% CI, .76–1.35) for 3 or more visits. Conclusions Recent invasive dental procedures and number of dentist’s visits were not associated with culture-verified brain abscess caused by oral cavity bacteria.

Penicillins, can be used in treatment of infections due to Prevotella species if they are susceptible to penicillin. Early and accurate preliminary detection of β-lactamase-producing isolates is crucial for treatment of infection. The aim of this study was to determine β-lactamase-producing Prevotella species by MALDI-TOF MS and screen them for the presence of cfxA gene, responsible for β-lactamase production. A total of 500 clinically relevant Prevotella isolates, collected from 13 countries for the previous European antibiotic resistance surveillance study, were tested. Susceptibility testing was performed against ampicillin and ampicillin/sulbactam by Etest methodology. EUCAST guidelines were used for susceptibility interpretations; the isolates with MIC value ≤ 0.5 for ampicillin were considered susceptible and >2 resistant. All Prevotella isolates, were tested for detection of β-lactamase activity by MALDI-TOF MS (Vitek® MS Research Use Only) system and the presence of the cfxA gene by PCR method. The susceptibility levels of the isolates to ampicillin/sulbactam and ampicillin were 99.6% and 43.4%, respectively. A total 59% of isolates presented β-lactamase activity and 60.8% were cfxA gene positive. Both these tests were positive for isolates in the resistant category. Additionally, >95% of the isolates (n = 65) which ampicillin MIC values ranged from >0.5 μg/mL to 2 μg/ml displayed β-lactamase activity. We also found that the MALDI-TOF MS-based β-lactamase assay delivers results in 2 h. We found a high concordance between the MALDI-TOF MS β-lactamase results in terms of cfxA β-lactamase gene presence. MALDI-TOF MS may serve as a simple and efficient alternative method of the existing phenotypic and PCR-based methods.

Background Carbapenemase-producing Escherichia coli are increasing worldwide. In recent years, an increase in OXA-244-producing E. coli isolates has been seen in the national surveillance of carbapenemase-producing organisms in Denmark. Aim Molecular characterisation and epidemiological investigation of OXA-244-producing E. coli isolates from January 2016 to August 2019. Methods For the epidemiological investigation, data from the Danish National Patient Registry and the Danish register of civil registration were used together with data from phone interviews with patients. Isolates were characterised by analysing whole genome sequences for resistance genes, MLST and core genome MLST (cgMLST). Results In total, 24 OXA-244-producing E. coli isolates were obtained from 23 patients. Among the 23 patients, 13 reported travelling before detection of the E. coli isolates, with seven having visited countries in Northern Africa. Fifteen isolates also carried an extended-spectrum beta-lactamase gene and one had a plasmid-encoded AmpC gene. The most common detected sequence type (ST) was ST38, followed by ST69, ST167, ST10, ST361 and ST3268. Three clonal clusters were detected by cgMLST, but none of these clusters seemed to reflect nosocomial transmission in Denmark. Conclusion Import of OXA-244 E. coli isolates from travelling abroad seems likely for the majority of cases. Community sources were also possible, as many of the patients had no history of hospitalisation and many of the E. coli isolates belonged to STs that are present in the community. It was not possible to point at a single country or a community source as risk factor for acquiring OXA-244-producing E. coli.

Using Nanopore sequencing, we describe here the circular genome of an Escherichia coli sequence type 410 (ST410) strain with five closed plasmids. A large 111-kb incompatibility group F (IncF) plasmid harbored blaNDM-5 and 16 other resistance genes. A 51-kb IncX3 plasmid carried QnrS1 and blaOXA-181. E. coli isolates with both blaNDM-5 and blaOXA-181 carbapenemases are rare.

A multidrug-resistant strain of Pseudomonas putida was isolated from the urine of a 65-year-old women hospitalized for serious clinical conditions. Using whole genome sequencing a novel blaIMP gene, blaIMP-58 was discovered and characterized.

To evaluate the safety and the pharmacokinetic interaction between amprenavir and delavirdine after multiple dose administration in healthy volunteers.This was a prospective, open-label, randomized, controlled, two-sequence, two-period multiple dose study with 18 healthy subjects. Volunteers were randomly assigned to amprenavir, 600 mg twice a day, or delavirdine, 600 mg twice a day, for 10 days, followed by both drugs for another 10 days with pharmacokinetic evaluation on day 10 and day 20. Adverse events were recorded throughout the study.Amprenavir decreased all the delavirdine pharmacokinetic parameters apart from tmax. Delavirdine C12h dropped from 7,916 to 933 ng ml-1 (median decrease 5,930 ng ml-1, 95% CI 3,013, 8,955 ng ml-1). A decrease in amprenavir t(1/2) was also seen leading to almost identical median amprenavir C24h values. No serious clinical adverse events were observed during the study. The most frequently reported effects were gastrointestinal symptoms, headache, fatigue and rash.Amprenavir is an effective inducer of delavirdine metabolism, probably through its effect on hepatic CYP3A4. This could have consequences in other drug-drug interaction situations. Delavirdine is an inhibitor of amprenavir metabolism. The regimen of amprenavir 600 mg and delavirdine 600 mg twice a day is not recommended when an antiretroviral effect from delavirdine is required.