Antibiotikaresistens – kunnskapshull, utfordringer og aktuelle tiltak

publishedVersio

Novel Developmental Analyses Identify Longitudinal Patterns of Early Gut Microbiota that Affect Infant Growth

It is acknowledged that some obesity trajectories are set early in life, and that rapid weight gain in infancy is a risk factor for later development of obesity. Identifying modifiable factors associated with early rapid weight gain is a prerequisite for curtailing the growing worldwide obesity epidemic. Recently, much attention has been given to findings indicating that gut microbiota may play a role in obesity development. We aim at identifying how the development of early gut microbiota is associated with expected infant growth. We developed a novel procedure that allows for the identification of longitudinal gut microbiota patterns (corresponding to the gut ecosystem developing), which are associated with an outcome of interest, while appropriately controlling for the false discovery rate. Our method identified developmental pathways of Staphylococcus species and Escherichia coli that were associated with expected growth, and traditional methods indicated that the detection of Bacteroides species at day 30 was associated with growth. Our method should have wide future applicability for studying gut microbiota, and is particularly important for translational considerations, as it is critical to understand the timing of microbiome transitions prior to attempting to manipulate gut microbiota in early life

Experiences from multiplex PCR diagnostics of faeces in hospitalised patients: clinical significance of Enteropathogenic Escherichia coli (EPEC) and culture negative campylobacter

Background In hospitalised patients with diarrhoea a positive campylobacter stool Polymerase Chain Reaction (PCR) test with negative culture results as well as Enteropathogenic Escherichia coli (EPEC) positive stool PCRs, challenges the clinician and may lead the unexperienced clinician astray. The aim of the study was to elucidate the clinical significance of positive Campylobacter and/or EPEC test results in hospitalised patients with diarrhoea. Methods We conducted a retrospective case-case study. Case groups with 1) EPEC only and 2) EPEC in combination with any other pathogen in the PCR multiplex array, 3) PCR positive/culture negative Campylobacter, and 4) PCR positive/culture positive Campylobacter were compared. Medical records were reviewed and cases classified according to pre-specified clinical criteria as infectious gastroenteritis or non-infectious causes for diarrhoea. We analyzed the association between laboratory findings (the 4 subgroups) and the pre-specified clinical classification. We further sequenced culture negative campylobacter samples and tested EPEC for bundle forming pilus A (bfpA) gene, distinguishing typical from atypical EPEC. Results A total of 291 patients were included, 169 were PCR positive for Campylobacter and 122 for EPEC. For both pathogens, co-infections were more common in culture negative/PCR positive samples than in culture positive samples. Clinical characteristics differed significantly in and between groups. Campylobacter culture positive patients had very high prevalence of characteristics of acute infectious gastroenteritis, whereas patients with PCR positive test results only often had an alternative explanation for their diarrhoea. Culture positives were almost exclusively C. jejuni/coli, whereas in culture negatives, constituting a third of the total PCR positives, C. concisus was the most frequent species. The vast majority of EPEC only positives had documented non-infectious factors that could explain diarrhoea. The EPEC co-infected group mimicked the culture positive campylobacter group, with most patients fulfilling the infectious gastroenteritis criteria. Conclusions In hospitalised patients, positive PCR results for campylobacter and EPEC should be interpreted in a clinical context after evaluation of non-infectious diarrhoea associated conditions, and cannot be used as a stand-alone diagnostic tool

Nosocomial candidemia; risk factors and prognosis revisited; 11 years experience from a Norwegian secondary hospital.

The aim of the study was to review the epidemiology and prognosis of candidemia in a secondary hospital, and to examine the intra-hospital distribution of candidemia patients. Study design is a retrospective cohort study. Trough 2002-2012, 110 cases of candidemia were diagnosed, giving an incidence of 2, 6/100,000 citizens/year. Overall prognosis of candidemia was dismal, with a 30 days case fatality rate of 49% and one year case fatality rate of 64%. Candidemia was a terminal event in 55% of 30 days non-survivors, defined as Candida blood cultures reported positive on the day of death or thereafter (39%), or treatment refrained due to hopeless short-term prognosis (16%). In terminal event candidemias, advanced or incurable cancer was present in 29%. Non-survivors at 30 days were 9 years (median) older than survivors. In 30 days survivors, candidemia was not recognised before discharge in 13% of cases. No treatment were given and no deaths or complications were observed in this group. Candidemia patients were grouped into 8 patient categories: Abdominal surgery (35%), urology (13%), other surgery (11%), pneumonia (13%), haematological malignancy (7%), intravenous drug abuse (4%), other medical (15%), and new-borns (3%). Candidemia was diagnosed while admitted in the ICU in 46% of patients. Urology related cases were all diagnosed in the general ward. Multiple surgical procedures were done in 60% of abdominal surgery patients. Antibiotics were administered prior to candidemia in 87% of patients, with median duration 17 (1-108) days. Neutropenia was less common than expected in patients with candidemia (8/105) and closely associated to haematological malignancy (6/8). Compared with previous national figures the epidemiology of invasive candidiasis seems not to have changed over the last decade

Nosocomial Candidemia; Risk Factors and Prognosis Revisited; 11 Years Experience from a Norwegian Secondary Hospital

The aim of the study was to review the epidemiology and prognosis of candidemia in a secondary hospital, and to examine the intra-hospital distribution of candidemia patients. Study design is a retrospective cohort study. Trough 2002–2012, 110 cases of candidemia were diagnosed, giving an incidence of 2, 6/100000 citizens/year. Overall prognosis of candidemia was dismal, with a 30 days case fatality rate of 49 % and one year case fatality rate of 64%. Candidemia was a terminal event in 55 % of 30 days non-survivors, defined as Candida blood cultures reported positive on the day of death or thereafter (39%), or treatment refrained due to hopeless short-term prognosis (16%). In terminal event candidemias, advanced or incurable cancer was present in 29%. Non-survivors at 30 days were 9 years (median) older than survivors. In 30 days survivors, candidemia was not recognised before discharge in 13 % of cases. No treatment were given and no deaths or complications were observed in this group. Candidemia patients were grouped into 8 patient categories: Abdominal surgery (35%), urology (13%), other surgery (11%), pneumonia (13%), haematological malignancy (7%), intravenous drug abuse (4%), other medical (15%), and new-borns (3%). Candidemia was diagnosed while admitted in the ICU in 46 % of patients. Urology related cases were all diagnosed in the general ward. Multiple surgical procedures were done in 60 % of abdominal surgery patients. Antibiotics were administered prior to candidemia in 87 % of patients, with median duration 17 (1–108) days. Neutropenia was less common than expected in patients with candidemia (8/105) and closely associated to haematologica

The first tigecycline resistant Enterococcus faecium in Norway was related to tigecycline exposure

ABSTRACT: Objectives: We describe the first tigecycline resistant enterococcal isolate in Norway and the mechanisms involved. Material and methods: The Norwegian National Advisory Unit on Detection of Antimicrobial Resistance (K-res). received in 2022 an Enterococcus faecium blood culture isolate with decreased susceptibility to tigecycline from a hospitalized patient in the South-Eastern Norway Health region for confirmatory testing. K-res verified a tigecycline-resistant E. faecium (TigR) with broth microdilution MIC of 0.5 mg/L. The patient had received treatment with tigecycline because of an infection with a linezolid- and vancomycin-resistant but tigecycline susceptible E. faecium (TigS) 47 days prior to the detection of the corresponding tigecycline-resistant isolate. Whole-genome comparisons, cgMLST and SNP analyses revealed that the two ST117 strains were closely related. Results: The TigR isolate showed a novel deletion of 2 amino acids (K57Y58) in a polymorphic region of ribosomal protein S10 previously associated with tigecycline resistance and a deletion of the tet(M) leader peptide previously related to increased expression of tet(M) and tigecycline resistance in enterococci. Conclusions: Genomic and epidemiological analyses confirm that the two E. faecium (TigR and TigS) are closely related isolates of the same strain and that the two deletions (in rpsJ and of tet(M) leader peptide) account for the tigecycline resistance in TigR

Risk factors/descriptives according to clinical categories.

<p>*N (%),</p>#<p>median (range).</p><p>Antiboitic days: total number of days with antibiotic treatment until days of candidemia.</p><p>IDU: Intravenous drug use. CVC: central venous catheter. TPN: Total parenteral nutrition. RRT: Renal replacement therapy.</p

Clinical characteristics according to 30 days outcome of candidemia.

<p>Values represent n (%) except * given as median (range).</p

Thirty days cummulative survival according to clinical recognisable categories.

<p>IDU and Urology compated to all other categories (Other surgery, Abdominal surgery, Other medical, Pneumonia, Hematology). * Log rank test p = 0,0425.</p

Candidemia incidence proportion (95% CI) per 1000 admitted per year, for patients above 18 years, in selected departments^* 2002–2012.

<p>*data for department of admittance are not available for all department throughout the entire observational period.</p><p>95% CI calculated according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103916#pone.0103916-Mermel1" target="_blank">[15]</a>.</p