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AbstractObjective:To study whether replacement of nosocomial ampicillin-resistant Enterococcus faecium(ARE) clones by vancomycin-resistant E. faecium(VRE), belonging to the same genetic lineages, increases mortality in patients with E. faeciumbacteremia, and to evaluate whether any such increase is mediated by a delay in appropriate antibiotic therapy.Design:Retrospective, matched-cohort study.Setting:The study included 20 Dutch and Danish hospitals from 2009 to 2014.Patients:Within the study period, 63 patients with VRE bacteremia (36 Dutch and 27 Danish) were identified and subsequently matched to 234 patients with ARE bacteremia (130 Dutch and 104 Danish) for hospital, ward, length of hospital stay prior to bacteremia, and age. For all patients, 30-day mortality after bacteremia onset was assessed.Methods:The risk ratio (RR) reflecting the impact of vancomycin resistance on 30-day mortality was estimated using Cox regression with further analytic control for confounding factors.Results:The 30-day mortality rates were 27% and 38% for ARE in the Netherlands and Denmark, respectively, and the 30-day mortality rates were 33% and 48% for VRE in these respective countries. The adjusted RR for 30-day mortality for VRE was 1.54 (95% confidence interval, 1.06–2.25). Although appropriate antibiotic therapy was initiated later for VRE than for ARE bacteremia, further analysis did not reveal mediation of the increased mortality risk.Conclusions:Compared to ARE bacteremia, VRE bacteremia was associated with higher 30-day mortality. One explanation for this association would be increased virulence of VRE, although both phenotypes belong to the same well-characterized core genomic lineage. Alternatively, it may be the result of unmeasured confounding.

Pregnant women who have group B streptococcal bacteria in their vagina during the later part of their pregnancy are more likely to have a premature birth. This was the conclusion of a study of 2,846 births in Denmark.

The presence of particular microorganisms and the absence of Lactobacillus bacteria in the vagina are strongly associated with bacterial vaginosis. Researchers identified vaginal microorganisms in 3,174 pregnant women. Vaginosis in pregnancy increases the risk of amniotic infection and premature delivery. The presence of Gardnerella vaginalis, Mycoplasma hominis, and anaerobic bacteria, plus the absence of Lactobacillus species of bacteria, was associated with bacterial vaginosis in 75% of cases.

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OBJECTIVESeasonal variation is a characteristic of many infectious diseases, but relatively little is known about determinants thereof. We studied the impact of place of acquisition and patient characteristics on seasonal variation of bacteremia caused by the 3 most common pathogens.DESIGNSeasonal variation analysis.METHODSIn 3 Danish health regions (2.3 million total inhabitants), patients with bacteremia were identified from 2000 through 2011 using information from laboratory information systems. Analyses were confined to Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. Additional data were obtained from the Danish National Hospital Registry for the construction of admission histories and calculation of the Charlson comorbidity index (CCI). Bacteremias were categorized as community acquired, healthcare associated (HCA), and hospital acquired. We defined multiple subgroups by combining the following characteristics: species, acquisition, age group, gender, CCI level, and location of infection. Assuming a sinusoidal model, seasonal variation was assessed by the peak-to-trough (PTT) ratio with a 95% confidence interval (CI).RESULTSIn total, we included 16,006 E. coli, 6,924 S. aureus, and 4,884 S. pneumoniaebacteremia cases. For E. coli, the seasonal variation was highest for community-acquired cases (PTT ratio, 1.24; 95% CI, 1.17–1.32), was diminished for HCA (PTT ratio, 1.14; 95% CI, 1.04–1.25), and was missing for hospital-acquired cases. No seasonal variation was observed for S. aureus. S. pneumoniaeshowed high seasonal variation, which did not differ according to acquisition (overall PTT ratio, 3.42; 95% CI, 3.10–3.83).CONCLUSIONSSeasonal variation was mainly related to the species although the place of acquisition was important for E. coli.Infect Control Hosp Epidemiol2016;37:946–953

Objective.We examined whether specific time windows after hospital admission reflected a sharp transition between community and hospital acquisition of bacteremia. We further examined whether different time windows to distinguish between community acquisition, healthcare association (HCA), and hospital acquisition influenced the results of prognostic models.Design.Population-based cohort study.Setting.Hospitals in 3 areas of Denmark (2.3 million inhabitants) during 2000–2011.Methods.We computed graphs depicting proportions of males, absence of comorbidity, microorganisms, and 30-day mortality pertaining to bacteremia 0, 1, 2, …, 30, and 31 days and later after admission. Next, we assessed whether different admission (0–1, 0–2, 0–3, 0–7 days) and HCA (30, 90 days) time windows were associated with changes in odds ratio (OR) and area under the receiver operating characteristic (ROC) curve for 30-day mortality, adjusting for sex, age, comorbidity, and microorganisms.Results.For 56,606 bacteremic episodes, no sharp transitions were detected on a specific day after admission. Among the 8 combined time windows, ORs for 30-day mortality varied from 1.30 (95% confidence interval [CI], 1.23–1.37) to 1.99 (95% CI, 1.48–2.67) for HCA and from 1.36 (95% CI, 1.24–1.50) to 2.53 (95% CI, 2.01–3.20) for hospital acquisition compared with community acquisition. Area under the ROC curve changed marginally from 0.684 (95% CI, 0.679–0.689) to 0.700 (95% CI, 0.695–0.705).Conclusions.No time transitions unanimously distinguished between community and hospital acquisition with regard to sex, comorbidity, or microorganisms, and no difference in 30-day mortality was seen for HCA patients in relation to a 30- or 90-day time window. ORs decreased consistently in the order of hospital acquisition, HCA, and community acquisition, regardless of time window combination, and differences in area under the ROC curve were immaterial.

ABSTRACTThe genus Oscillibacterhas been known since 2007, but no association to human infection has been reported. Here, we present four cases of Oscillibacter ruminantiumbacteremia from hospitals across Denmark from 2001 to 2010. Correct identification is now possible, as the 16S rRNA gene sequence was recently made publicly available.

One of the biggest concerns associated with transgastric surgery is contamination and risk of intra-abdominal infection with microbes introduced from the access route. The purpose of this study was to evaluate the effect of oral decontamination with chlorhexidine on microbial contamination of the endoscope.In a prospective, randomized, single-blinded, clinical trial the effect of chlorhexidine mouth rinse was evaluated. As a surrogate for the risk of intra-abdominal contamination during transgastric surgery, microbial contamination of the endoscope during upper endoscopy was examined. Patients referred to upper endoscopy were assessed for eligibility and randomized to either chlorhexidine or no mouth rinse. Culture samples were collected from gastric aspirates and endoscopes. The primary outcome measure was colony forming units (CFU) in the endoscope samples. Secondary outcome measures were species specific effect of chlorhexidine on micro-organisms with abscess forming capabilities and the effect of proton pump inhibitor (PPI) treatment on CFU.Chlorhexidine mouth rinse resulted in a significant reduction of CFU in the endoscope samples (p= 0.001). There was no species specific effect and micro-organisms with abscess forming capabilities were equally present. PPI treatment was associated with significantly higher CFU counts in both the gastric (p= 0.004) and endoscope samples (p= 0.049).Chlorhexidine mouth rinse was effective in reducing microbial contamination of the endoscope, but micro-organisms with abscess forming capabilities were still present. PPI treatment significantly increased CFU and should be discontinued before transgastric surgery.

To investigate the rate of occurrence, clinical presentation, predisposing factors and frequency of secondary bacteremia 132 patients with significant Staphylococcus aureus bacteriuria were reviewed retrospectively. Staphylococcus aureus accounted for 3.3 per cent of all positive urine cultures. Most patients were elderly men. The most important predisposing factors in the urinary tract were indwelling catheters (63 per cent), obstruction (56 per cent) and instrumentation or surgery (43 per cent). Bacteremia developed secondary to bacteriuria in all 11 patients (8.3 per cent). For that reason Staphylococcus aureus bacteriuria should be regarded as a hazardous condition, especially in patients with predisposing factors in the urinary tract.

In the 25-year period 1968-92, 3,317 out of 477,420 patients admitted to Frederiksberg Hospital experienced 3,491 episodes of bacteremia. Enterobacteriaceae dominated as causative agents (57%), following by Gram-positive cocci (31%) and anaerobes (7%). Polymicrobial bacteremia was found in 8% of the episodes. The incidence of Enterobacteriaceae bacteremia culminated in the middle (1978-82) of the period (4.7/1,000 admissions) and decreased during the last decade. Gram-positive bacteremia increased throughout the period (from 1.8 to 2.9; p < 0.001), due mainly to increasing incidences of bacteremia caused by non-hemolytic streptococci, Streptococcus pneumoniae and coagulase-negative staphylococci. Bacteroides fragilis accounted for a rising incidence of anaerobic bacteremia (from 0.3 to 0.7; p < 0.05). Clinical data were available for the 2,599 bacteremic episodes in the 20-year period 1968-87. 59% of these were hospital acquired. Of those, 38% were associated with indwelling catheters, mainly bladder catheters (28%) and i.v. lines (7%). The urinary tract dominated as source of bacteremia (46%), followed by the respiratory (11%) and the gastrointestinal tract (9%). Half of the patients had predisposing underlying diseases, most frequently malignancies (20%) and diabetes mellitus (7%). The mortality rate related to bacteremia decreased from 25% to 11% (p < 0.001). More than half (55%) of the fatal cases related to bacteremia occurred within the first 2 days after the first positive blood culture was obtained. Logistic regression analysis defined 7 variables that independently influenced the outcome related to bacteremia: age, source, culture verification of source, shock, body temperature, leukocyte count and empiric antibiotic treatment. A local knowledge of the most common causative microorganisms, the most common sources and the outcome of bacteremia, are of the utmost importance in the selection of the initial empirical antibiotic regimens.

To ascertain whether the microbiological etiology of bacteremia among patients with hematological malignancies has changed in Denmark, the species distribution of clinically relevant blood culture isolates from the Hematological Department at Rigshospitalet, Copenhagen in 1990 was compared with 2 previous studies (1970-72; 1981-85). In addition, time trends of the etiology of bacteremia among hematological patients in Copenhagen (eastern Denmark) and in Århus (western Denmark) were compared. In contrast to many other studies, a significant increase in the proportion of Gram-negative aerobes was observed in Copenhagen (from 43% in 1981-85 to 55% in 1990; p <0.05), whereas in Århus the proportion of Gram-positive aerobes increased steadily during the 1980s (from 34% to 51%; p <0.05). In Copenhagen, non-hemolytic streptococci and Xanthomonas maltophilia increased significantly and accounted for 10% (p <0.01) and 5% (p <0.05) respectively, of all isolates in 1990, whereas Staphylococcus aureus during the 2 decades studied decreased from 25% to 8% (p <0.001). In both regions, a decrease was observed in the proportion of Pseudomonas aeruginosa which accounted for only about 5% of all isolates in 1990. No changes were observed in the rates of anaerobes and yeasts. Several factors may contribute to the reported differences in the etiology of bacteremia among hematological patients, e.g. criteria used to assign the clinical significance of the isolate, blood culture system used, practice of using indwelling intravenous catheters, different policies with respect to antimicrobial treatment, and the degree of immunosuppression. A local surveillance of blood culture isolates is mandatory if changes in etiology and resistance development are to be detected.

Epidemiological, microbiological and clinical characteristics of 14 episodes of Xanthomonas maltophilia bacteremia in 12 seriously immunocompromised hematological patients, admitted to Rigshospitalet in Copenhagen over the 3-year period 1989-91, were evaluated. The results were compared with a randomly selected control group of 25 patients with Escherichia coli bacteremia. Hospital acquired bacteremia was more common among the patients with X. maltophilia bacteremia (p < 0.01). Treatment with broad-spectrum antibiotics before the bacteremic episode was markedly more common among the patients with X. maltophilia bacteremia (p < 0.001). The presence of a central venous catheter and previous treatment with corticosteroids were more frequent in patients with X. maltophilia bacteremia (p < 0.05). The X. maltophilia blood culture isolates were generally resistant to aminoglycosides and most β-lactams. The mortality rates related to bacteremia caused by X. maltophilia and E. coli were 14% and 20%, respectively.

The bacteremic rate following transurethral instrumentation and the possibility of a serum bactericidal activity test to predict which patients that were at an increased risk of developing bacteremia was evaluated. Of 33 investigated patients, all elderly men, 14 underwent transurethral prostatic resection, 14 cystoscopy and 5 urethrotomy. None of the patients received prophylactic antibiotic treatment. The majority (97%) of the patients had bacteria isolated from the urinary tract before the instrumentation. Gram-positive cocci accounted for about two thirds (64%) and Gram-negative rods for about one third (31%) of all isolates. The most frequent species isolated were coagulase negative staphylococci (29%), Streptococcus faecalis (19%) and Klebsiella pneumoniae (12%). The bacteremic rate was 21%. None of the patients developed septicemia. Forty-four per cent of the patients with ≥105 colony forming unitdm1 (cfu/ml) in urine developed bacteremia compared with 8% in patients with a sterile urine or less than 105 cfu/ml in urine (p < 0.05). The urethral/prostatic flora was the source of bacteremia in at least one patient. Eighty-one per cent of the isolated strains were serum resistant. About half (54%) of the Gram-negative rods were more or less sensitive against actual, fresh patient serum. All Gram-positive cocci were resistant. There was no difference in the serum sensitivity between bacteria isolated from bacteremic patients and non-bacteremic patients. In conclusion, this study confirmed the relative high risk of developing bacteremia following transurethral instrumentation, especially if the urine is infected. The urethral and prostatic flora should not be ignored. Coagulase negative staphylococci should be thought of when antibiotic prophylaxis is given. The investigated serum bactericidal activity test could not predict the development of bacteremia. Other factors in the host defence system must be involved in the clearing of bacteria from blood

The purpose of the study was to develop a small animal model of intraperitoneal infection without mortality and with a catabolic response to the infection, viz. to mimic the clinical situation in man. Intraperitoneal infection was induced in female Wistar rats by deposition of a gelatin capsule containing a mixture of Escherichia coliand Bacteroides fragilisand adjuvant substances. Seven groups of animals were infected with different bacterial inocula (0.2–4.3times106CPU) to establish reproducible and dose‐dependent changes in mortality, body weight in relation to food intake, blood cultures, peripheral blood leukocyte counts, and abscess formation on autopsy. No mortality was observed in animals with an inoculum below 2.2times106CFU in spite of positive blood cultures. Initial weight loss was followed by weight gain in all animals except the group infected with the low inoculum (0.2times106CFU). This group had no mortality, was in a catabolic state for three days, indicated by weight loss in spite of nearly normal food intake, and the infectious state was supported by intraperitoneal dissemination of small abscesses. The low‐grade character of the infection was reflected by changes in peripheral blood lymphocyte and neutrophil ***granulocyte concentrations. In conclusion, this study presents a small animal model with a reproducible dose response to the bacterial challenge, allowing prolonged studies of metabolic changes following infection.

Objectives: Knowledge concerning the distribution of antibiotics in bone tissue is valuable for pharmacokinetic and clinical use. Unfortunately, appropriate techniques are difficult to apply. We introduced microdialysis catheters to cancellous bone tissue for the investigation of gentamicin levels and compared the pharmacokinetics measured with values obtained from bone samples. Methods: After two microdialysis catheters had been inserted into cancellous bone, eight pigs received an intravenous bolus of 240 mg of gentamicin. Microdialysates and bone samples were obtained over a period of 6 h and drug concentrations were measured. Results: The area under the curves of the two microdialysates and bone samples were 1569, 1721 and 1533 mg·min/L (ANOVA, P=0.81). Reproducibility of the measurements from the microdialysates was defined as the mean ratio of AUC6/catheter no. 1/AUC6/catheter no. 2. This ratio was 1.02. Conclusions: Microdialysis is a suitable, relatively non-invasive and reproducible technique for dynamic and quantitative measurement of gentamicin levels in experimental research.