Ventriculostomy-associated infection (VAI) in patients with acute brain injury-a retrospective study.

BACKGROUND: Ventriculostomy-associated infection (VAI) is common after external ventricular drains (EVD) insertion but is difficult to diagnose in patients with acute brain injury. Previously, we proposed a set of criteria for ruling out VAI in traumatic brain injury. This study aimed to validate these criteria. For exploratory purposes, we sought to develop and validate a score for VAI risk assessment in patients with different types of severe acute brain injury. METHODS: This retrospective cohort study included adults with acute brain injury who received an EVD and in whom CSF samples were taken over a period of 57 months. As standard non-coated bolt-connected EVDs were used. The predictive performance of biomarkers was analyzed as defined previously. A multivariable regression model was performed with five variables. RESULTS: A total of 683 patients with acute brain injury underwent EVD placement and had 1272 CSF samples; 92 (13.5%) patients were categorized as culture-positive VAI, 130 (19%) as culture-negative VAI, and 461 (67.5%) as no VAI. A low CSF WBC/RBC ratio (< 0.037), high CSF/plasma glucose ratio (> 0.6), and low CSF protein (< 0.5g/L) showed a positive predictive value of 0.09 (95%CI, 0.05-0.13). In the multivariable logistic regression model, days to sample (OR 1.09; 95%CI, 1.03-1.16) and CSF WBC/RBC ratio (OR 34.86; 95%CI, 3.94-683.15) were found to predict VAI. CONCLUSION: In patients with acute brain injury and an EVD, our proposed combined cut-off for ruling out VAI performed satisfactorily. Days to sample and CSF WBC/RBC ratio were found independent predictors for VAI in the multivariable logistic regression model.

Incidence and severity of SARS-CoV-2 infections in liver and kidney transplant recipients in the post-vaccination era: Real-life data from Denmark.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been associated with a high risk of adverse outcomes in solid organ transplant (SOT) recipients in the pre-vaccination era. In this retrospective cohort study, we examined the incidence and severity of COVID-19 in kidney and liver transplant recipients in Denmark in the post-vaccination era, from December 27, 2020, to December 27, 2021. We included 1428 SOT recipients with 143 cases of first-positive SARS-CoV-2 PCR test. The cumulative incidence of first-positive SARS-CoV-2 PCR test 1 year after initiation of vaccination was 10.4% (95% CI: 8.8-12.0), and the incidence was higher in kidney than in liver transplant recipients (11.6% [95% CI: 9.4-13.8] vs. 7.4% [95% CI: 5.1-9.8], p = .009). After the first-positive SARS-CoV-2 PCR test, the hospitalization rate was 31.5% (95% CI: 23.9-39.1), and 30-day all-cause mortality was 3.7% (95% CI: 0.5-6.8). Hospitalization was lower in vaccinated than in unvaccinated SOT recipients (26.4% [95% CI: 18.1-34.6] vs. 48.5% [95% CI: 31.4-65.5], p = .011), as was mortality (1.8% [95% CI: 0.0-4.3] vs. 9.1% [95% CI: 0.0-18.9], p = .047). In conclusion, SOT recipients remain at high risk of adverse outcomes after SARS-CoV-2 infections, with a lower risk observed in vaccinated than in unvaccinated SOT recipients.

All-cause Mortality Due to Bacteremia during a 60-Day Non-Physician Healthcare Worker Strike.

This study explored all-cause mortality of bacteremia diagnosed during a 60-day non-physician healthcare worker strike in 2008. A significant change, with 5.0% (95% confidence interval [CI] 1.2-8.7%, P < .01) absolute risk increase, was seen in 90-day mortality during the strike (n = 598) compared with the rest of the study period 2000-2015 (n = 75 647).

Intravenous mecillinam compared with other ß-lactams as targeted treatment for Escherichia coli or Klebsiella spp. bacteraemia with urinary tract focus.

BACKGROUND: Mecillinam (amdinocillin) is active against Gram-negative bacteria. Clinical data on the efficacy of IV mecillinam for severe urinary tract infections is sparse. OBJECTIVES: To assess the effectiveness of targeted IV mecillinam compared with other ß-lactams for bacteraemia with Escherichia coli and Klebsiella spp. and a urinary tract focus. PATIENTS AND METHODS: We performed a retrospective cohort study at five university hospitals in the Capital Region of Denmark from 1 January 2012 to 31 December 2017. We used Cox proportional hazard regression to compare the primary composite endpoint (all-cause mortality or bacteraemia recurrence within 30 days) between patients treated with mecillinam versus ampicillin, cefuroxime, piperacillin/tazobactam and meropenem. RESULTS: We included 1129 patients in the primary analysis, of which 146 were given IV mecillinam as targeted treatment. We found no significant difference in the primary endpoint between patients treated with mecillinam versus ampicillin and cefuroxime, but found a higher risk for the primary endpoint in the piperacillin/tazobactam and meropenem groups, with adjusted HRs of 2.22 (95% CI 1.24-3.97, P < 0.01) and 2.48 (95% CI 1.04-5.93, P = 0.04), respectively, compared with mecillinam. CONCLUSIONS: The results of this study suggest that IV mecillinam may be a suitable targeted treatment for bacteraemia with a urinary tract focus. However, these results need confirmation by randomized controlled studies.

Bacterial and fungal bloodstream infections in pediatric liver and kidney transplant recipients.

BACKGROUND: Bacterial and fungal bloodstream infections (BSI) are common after pediatric liver and kidney transplantations and associated with morbidity and mortality. However, knowledge about incidence rates, pathogen composition, and resistance patterns is limited. We aimed to describe the pattern of bacterial and fungal BSI in a cohort of pediatric liver and kidney transplant recipients. METHODS: A prospective study of 85 pediatric liver and kidney transplant recipients transplanted from 2010 to 2017 with a total of 390 person-years of follow-up. Clinical characteristics and BSI were retrieved from national registries assuring nationwide follow-up for at least 1 year. BSI incidence rates and pathogen composition were investigated and stratified by the time post-transplantation and type of transplanted organ. RESULTS: A total of 29 BSI were observed within the first 5 years post-transplantation with 16 different pathogens. The overall incidence rate of first BSI was 1.91 per 100 recipients per month (95% CI, 1.1-3.1) in the first year post-transplantation. The most common pathogens were Enterococcus faecium, Candida albicans, Escherichia coli, and Klebsiella pneumoniae. The pathogen composition depended on the transplanted organ with a higher proportion of BSI with Enterobacterales in kidney transplant recipients than in liver transplant recipients (67% vs. 20%, p = 0.03), while multiple pathogens were detected in the liver transplant recipients. CONCLUSIONS: BSI were common in pediatric liver and kidney transplant recipients and the pathogen composition differed between liver and kidney transplant recipients. Guidelines for empiric antibiotic therapy should consider the type of transplanted organ as well as the local resistance patterns.

The impact and prevalence of SARS-CoV-2 in patients with head and neck cancer and acute upper airway infection in a tertiary otorhinolaryngology referral center in Denmark.

PURPOSE: To determine the prevalence of SARS-CoV-2 at a Danish tertiary referral otorhinolaryngology clinic during the first wave of the COVID-19 pandemic among patients with suspected acute upper airway infection (UAI) and patients operated for head and neck cancer (HNC), respectively. To monitor changes in the number of patient encounters for acute UAI and the number of referrals for the workup of HNC. TRIAL REGISTRATION: NCT-04356560 (Clinicaltrials.gov). METHODS: Prospective enrolled case series of all patients with suspected acute UAI (n = 88) and of patients undergoing surgery for HNC (n = 96), respectively, from March 23rd to May 5th, 2020, at a public tertiary referral otorhinolaryngology clinic in Denmark. SARS-CoV-2 was diagnosed with nasopharyngeal and oropharyngeal swabbing. Patients with suspected acute UAI had symptoms and definitive diagnoses registered in a database. Trends in the number of referrals and patient encounters were retrieved from an electronic patient journal system and analyzed retrospectively. RESULTS: Eighty-eight patients with acute UAI were enrolled including 55 men and 34 women, median age of 31 years (range: 10 months to 82 years). One patient (1.1%) tested positive. Among 96 patients operated for HNC, zero tested positive. The number of referrals for HNC workup, and patient encounters for peritonsillar abscesses, decreased markedly in the first 3 weeks. CONCLUSION: The prevalence of SARS-CoV-2 during the first 6 weeks of the first wave was minimal among patients with acute UAI and zero among patients operated for HNC. The decrease in referrals for the workup of HNC may increase time to treatment initiation and patient morbidity.

COVID-19 infection rate among tertiary referral center otorhinolaryngology healthcare workers.

IMPORTANCE: Otorhinolaryngology is considered one of the medical specialties with a high risk for exposure to corona disease 2019 (COVID-19). Uncontrolled transmission in a hospital department poses a risk to both healthcare workers (HCWs) and patients. OBJECTIVE: To monitor SARS-CoV-2 incidence, transmission, and antibody development among HCWs to identify high risk procedures, pathways, and work areas within the department. METHODS: Prospective cohort study of HCWs using repetitive oro- and nasopharygeal swab samples, antibody tests, and self-reported symptoms questionnaires at a tertiary referral center in Copenhagen, Denmark. RESULTS: 347/361 (96%) HCWs participated. Seven (1.9%) were positive on swab tests and none had symptoms. Fifteen (4.2%) developed antibodies. Only one case of potential transmission between HCWs was identified. Infection rates were low and no procedures or areas within the department were identified as exposing HCWs to a higher risk. CONCLUSIONS AND RELEVANCE: Adherence to the surveillance program was high. The low incidence among HCW during the first wave of the COVID-19 pandemic may reflect local transmission and infection control precautions, as well as a low infectious burden in the Danish society.

Prevalence and recurrence of bacteraemia in hospitalised people who inject drugs - a single Centre retrospective cohort study in Denmark.

BACKGROUND: People who inject drugs (PWID) have increased risk of acquiring blood-transmitted chronic viral infections such as Hepatitis B (HBV), Hepatitis C (HCV) and Human Immunodeficiency Virus (HIV) as well as increased risk of acquiring bacterial infections. We aimed to identify and describe bacteraemic episodes, their recurrence rates, predictive and prognostic factors amongst hospitalised PWID. METHODS: In this retrospective cohort study, we included 257 hospitalised PWID during 2000-2006 with follow up at the Department of Infectious Diseases, Hvidovre Hospital, Denmark. Data collection included comorbidity (HBV-, HCV-, HIV-, and psychiatric comorbidities), social information (contact to an addiction treatment centre, homelessness), opioid substitution treatment (OST), treatment completion and microbiology findings. There was a 10-years follow-up regarding mortality. RESULTS: The study identified 257 patients classified as PWID. Of these, 58 (22.6%) had at least one episode of bacteraemia during their first hospital admission. Recurrence was found in 29 (50.0%) of the bacteraemia cases. Staphylococcus aureus was the dominant microorganism of both first and recurrent episodes with 24 (41.4%) and nine (31.4%) of cases, respectively. A psychiatric diagnose was significantly associated with a lower risk of bacteraemia in the multivariate analysis (OR: 0.29, [95%CI: 0.11-0.77], P = 0.01). Mortality was significantly higher in patients with bacteraemia (17.2% vs. 3.0%, P < 0.01, OR: 6.67 [95%CI: 2.33-20], P < 0.01). CONCLUSIONS: In hospitalised PWID, bacteraemia was found in 22.6% and was associated with at higher mortality. The most common microorganism of bacteraemia was S. aureus. Psychiatric comorbidity was significantly associated with a lower risk of bacteraemia.

Treatment duration of pivmecillinam in men, non-pregnant and pregnant women for community-acquired urinary tract infections caused by Escherichia coli: a retrospective Danish cohort study.

OBJECTIVES: To evaluate the importance of treatment duration for therapeutic efficacy of pivmecillinam for community-acquired urinary tract infections (UTIs) caused by Escherichia coli. METHODS: A retrospective cohort study was conducted between 1 January 2010 and 30 September 2016 in adults with community-acquired E. coli bacteriuria, treated empirically with pivmecillinam. Regimens of 3, 5 and 7 days were compared using clinical treatment failure (i.e. redemption of a new antibiotic or hospitalization due to UTI) within 14 and 30 days as outcome. HR and risk difference with 95% CI were estimated for treatment failure. Results were stratified by age (18-50, 51-70, >70 years) and sex. RESULTS: Of the 21864 cases of E. coli UTI that were analysed, 2524 (11.5%) were in men. In 954 cases (4.4%) E. coli produced ESBL and 125 (13.1%) of the cases were in men. The 3 day regimen increased the risk of treatment failure for all groups. The risk differences between the 3 and 5 day regimens were <10% for women, but >10% for men. Comparing the 7 day and 5 day regimens, only women aged >50 years demonstrated an increased risk of treatment failure within 14 days with the 5 day regimen, but not within 30 days. CONCLUSIONS: With the current data, where data on clinical classification of the E. coli UTI were missing, a 5 day treatment with pivmecillinam at 400 mg three times daily seems to be the rational recommendation for lower UTI in men, pregnant women and women >50 years old. A 3 day regimen seems sufficient for non-pregnant women <50 years old.

LRE-Finder, a Web tool for detection of the 23S rRNA mutations and the optrA, cfr, cfr(B) and poxtA genes encoding linezolid resistance in enterococci from whole-genome sequences.

OBJECTIVES: In enterococci, resistance to linezolid is often mediated by mutations in the V domain of the 23S rRNA gene (G2576T or G2505A). Furthermore, four genes [optrA, cfr, cfr(B) and poxtA] encode linezolid resistance in enterococci. We aimed to develop a Web tool for detection of the two mutations and the four genes encoding linezolid resistance in enterococci from whole-genome sequence data. METHODS: LRE-Finder (where LRE stands for linezolid-resistant enterococci) detected the fraction of Ts in position 2576 and the fraction of As in position 2505 of the 23S rRNA and the cfr, cfr(B), optrA and poxtA genes by aligning raw sequencing reads (fastq format) with k-mer alignment. For evaluation, fastq files from 21 LRE isolates were submitted to LRE-Finder. As negative controls, fastq files from 1473 non-LRE isolates were submitted to LRE-Finder. The MICs of linezolid were determined for the 21 LRE isolates. As LRE-negative controls, 26 VRE isolates were additionally selected for linezolid MIC determination. RESULTS: LRE-Finder was validated and showed 100% concordance with phenotypic susceptibility testing. A cut-off of 10% mutations in position 2576 and/or position 2505 was set in LRE-Finder for predicting a linezolid resistance phenotype. This cut-off allows for detection of a single mutated 23S allele in both Enterococcus faecalis and Enterococcus faecium, while ignoring low-level sequencing noise. CONCLUSIONS: A Web tool for detection of the 23S rRNA mutations (G2576T and G2505A) and the optrA, cfr, cfr(B) and poxtA genes from whole-genome sequences from enterococci is now available online.

Asymptomatic Carriers Contribute to Nosocomial Clostridium difficile Infection: A Cohort Study of 4508 Patients.

BACKGROUND & AIMS: Nosocomial infections with Clostridium difficile present a considerable problem despite numerous attempts by health care workers to reduce risk of transmission. Asymptomatic carriers of C difficile can spread their infection to other patients. We investigated the effects of asymptomatic carriers on nosocomial C difficile infections. METHODS: We performed a population-based prospective cohort study at 2 university hospitals in Denmark, screening all patients for toxigenic C difficile in the intestine upon admittance, from October 1, 2012, to January 31, 2013. Screening results were blinded to patients, staff, and researchers. Patients were followed during their hospital stay by daily registration of wards and patient rooms. The primary outcomes were rate of C difficile infection in exposed and unexposed patients and factors associated with transmission. RESULTS: C difficile infection was detected in 2.6% of patients not exposed to carriers and in 4.6% of patients exposed to asymptomatic carriers at the ward level (odds ratio for infection if exposed to carrier, 1.79; 95% confidence interval, 1.16-2.76). Amount of exposure correlated with risk of C difficile infection, from 2.2% in the lowest quartile to 4.2% in the highest quartile of exposed patients (P = .026). Combining the load of exposure to carriers and length of stay seemed to have an additive effect on the risk of contracting C difficile. CONCLUSIONS: In a population-based prospective cohort study in Denmark, we found that asymptomatic carriers of toxigenic C difficile in hospitals increase risk of infection in other patients.

Evaluation of local instillation of antibiotics in infected walled-off pancreatic necrosis.

BACKGROUND: Infected walled-off pancreatic necrosis (WON) is associated with increased morbidity and mortality. Systemic antibiotics are the main treatment, but are associated with adverse reactions and risk of superinfections. This study evaluates the efficacy of local instillation of antibiotics into WON. METHODS: We performed a retrospective cohort study of all consecutive patients with infected WON, who were treated with endoscopic transmural drainage and necrosectomy (ETDN) at a tertiary referral hospital between 2012 and 2016. A total of 91 patients were included. Patients often received concomitant intravenous and local antibiotics. Local antibiotics were added to the irrigation fluid depending on microbiological findings. A beneficial response was defined as the eradication of a microbe on subsequent culturing. Univariable and multivariable logistic regression analyses were used to evaluate antimicrobial efficacy. RESULTS: At the first drainage 81 (86%) patients had infected and 10 sterile WON. Among patients with bacterial infections, neither local nor systemic antibiotics were associated with the eradication of microbes between first and second culture. Between the second and third culture, the use of local antibiotics was associated with the eradication of microbes (OR, 2.54; 95% CI, 1.25-5.18; p = 0.01), but not systemic antibiotics (OR, 0.75; 95% CI, 0.38-1.38; p = 0.33). Twelve patients had fungal infections treated with local amphotericin B between first and second culture. The fungus was eradicated in all 12 patients. CONCLUSION: Local instillation of antibiotics may be a promising supplement to systemic administration.

WGS-based surveillance of third-generation cephalosporin-resistant Escherichia coli from bloodstream infections in Denmark.

Objectives: To evaluate a genome-based surveillance of all Danish third-generation cephalosporin-resistant Escherichia coli (3GC-R Ec ) from bloodstream infections between 2014 and 2015, focusing on horizontally transferable resistance mechanisms. Methods: A collection of 552 3GC-R Ec isolates were whole-genome sequenced and characterized by using the batch uploader from the Center for Genomic Epidemiology (CGE) and automatically analysed using the CGE tools according to resistance profile, MLST, serotype and fimH subtype. Additionally, the phylogenetic relationship of the isolates was analysed by SNP analysis. Results: The majority of the 552 isolates were ESBL producers (89%), with bla CTX-M-15 being the most prevalent (50%) gene, followed by bla CTX-M-14 (14%), bla CTX-M-27 (11%) and bla CTX-M-101 (5%). ST131 was detected in 50% of the E. coli isolates, with the remaining isolates belonging to 73 other STs, including globally disseminated STs (e.g. ST10, ST38, ST58, ST69 and ST410). Five of the bloodstream isolates were carbapenemase producers, carrying bla OXA-181 (3) and bla OXA-48 (2). Phylogenetic analysis revealed 15 possible national outbreaks during the 2 year period, one caused by a novel ST131/ bla CTX-M-101 clone, here observed for the first time in Denmark. Additionally, the analysis revealed three individual cases with possible persistence of closely related clones collected more than 13 months apart. Conclusions: Continuous WGS-based national surveillance of 3GC-R Ec , in combination with more detailed epidemiological information, can improve the ability to follow the population dynamics of 3GC-R Ec , thus allowing for the detection of potential outbreaks and the effects of changing treatment regimens in the future.

"Population structure of drug-susceptible,-resistant and ESBL-producing Escherichia coli from community-acquired urinary tract".

BACKGROUND: Escherichia coli is the most common cause of urinary tract infection (UTI). The pathogenic isolates are becoming increasingly resistant to antibiotics; with a worldwide dissemination of resistant sequence types (ST). We characterized three different uropathogenic E. coli populations, from non-hospitalized patients to describe the genetic kinship between resistant and susceptible isolates. We studied the populations by use of multi-locus sequence typing (MLST) and abbreviated-multi locus variable number of tandem repeat analysis (a-MLVA). Urine samples submitted for testing, by general practitioners, were identified at Dept. of Clinical Microbiology at Hvidovre Hospital, Denmark, from Oct. 2011 to July 2012. We included 94 fully susceptible, 94 resistant (non-ESBL) and 98 Extended Spectrum Beta-lactamases- (ESBL)-producing E. coli isolates. RESULTS: The ESBL population was dominated vastly by ST131 (51 %), ST38 (9 %) and ST69 (6 %). In the resistant group ST69 (18 %), ST73 (11 %) and ST131 (15 %) were the largest clusters. In the susceptible population more STs and a-MLVA codes were identified compared to the other groups and ST73 and ST95 were found as the only clusters with 16 % and 6 %, respectively. Ninety-eight per cent of the ESBL-producing E. coli isolates were CTX-M-producers. CONCLUSION: ST131 dominated the population of community-associated uropathogenic ESBL-producing E. coli, but was less frequent among non-ESBL-producing E. coli. The fully susceptible E. coli population was a much more diverse group than the resistant and ESBL-producing E. coli populations. Overall, these findings suggest that dominant ESBL-producing lineages are derived from UPEC lineages already established in the general UPEC population.

Relative efficacy of cefuroxime versus dicloxacillin as definitive antimicrobial therapy in methicillin-susceptible Staphylococcus aureus bacteraemia: a propensity-score adjusted retrospective cohort study.

OBJECTIVES: The objective of the present study was to compare the efficacy of cefuroxime with that of dicloxacillin as definitive antimicrobial therapy in methicillin-susceptible Staphylococcus aureus bacteraemia (MS-SAB) using a Danish bacteraemia database, information on the indication for antimicrobial therapy, multivariate adjustment and propensity score (PS) matching. METHODS: This was a retrospective cohort study. MS-SAB cases from 1 January 2006 to 31 December 2008 were included from a total of seven hospitals in the greater Copenhagen area and seven hospitals in the North Denmark Region. Information including demographics, antimicrobial therapy and clinical condition was obtained. The physician's note detailing the indication for starting empirical antimicrobial therapy was given special attention. Hazard ratios (HRs) and 95% CIs for 30 day and 90 day mortality were calculated using PS-adjusted Cox proportional hazards regression analyses. In addition, PS matching was performed. RESULTS: A total of 691 patients with MS-SAB received either dicloxacillin (n = 368) or cefuroxime (n = 323) as definitive antimicrobial therapy. Twenty-eight different indications for empirical antimicrobial therapy were identified and grouped into eight categories. There was no statistically significant difference in 30 day mortality between the two groups (HR 1.02, 95% CI 0.68-1.52). Definitive antimicrobial therapy with cefuroxime was associated with increased 90 day mortality in a PS-adjusted multivariate analysis (HR 1.43, 95% CI 1.03-1.98) and in the PS matching (OR 1.65, 95% CI 1.06-2.56). Antimicrobial therapy for an indication of 'severe infection' was independently associated with 90 day mortality (HR 1.97, 95% CI 1.19-3.28). CONCLUSIONS: Definitive antimicrobial therapy with cefuroxime was associated with significantly higher 90 day mortality than was dicloxacillin therapy in patients with MS-SAB.

Empiric treatment of healthcare-associated central nervous system infections in Denmark: do we need carbapenems?

BACKGROUND: Carbapenems are widely used for empiric treatment of healthcare-associated central nervous system (CNS) infections. We investigated the feasibility of a carbapenem-sparing strategy, utilising a third-generation cephalosporin (ceftriaxone or cefotaxime) (combined with vancomycin) for the empirical treatment of healthcare-associated CNS infections in Eastern Denmark. METHODS: The departments of neurosurgery and neuro-intensive care at Copenhagen University Hospital Rigshospitalet. First, we analysed local microbiological data (1st January 2020-31st August 2022) to identify microorganisms non-susceptible to third-generation cephalosporin. Subsequently, we assessed all carbapenem prescriptions over a three-month period for their indication and justification. RESULTS: In total, 25,247 bacterial cultures were identified, of which 2,563 CNS-related, were included in the analysis. The positivity rate was 10.5% (n = 257/2439) for cerebrospinal-fluid samples and 75.8% (n = 95/124) for brain parenchyma. CNS samples from five individual patients revealed bacteria non-susceptible to third generation cephalosporins (Enterobacter spp. (n = 3), Pseudomonas spp. (n = 2), Klebsiella spp. (n = 2), Citrobacter freundii (n = 1)). All five patients had been hospitalised for ≥10days at the time-point of antibiotic therapy. Out of 11,626 sets of blood cultures, a total of 10 individual patients had Gram-negative blood-stream infections with resistance to ceftriaxone and piperacillin/tazobactam. 140 days-of-therapy (32%) with carbapenem in 18 patients (36%) were definitively or possibly indicated according to guidelines, none were indicated for healthcare-associated CNS-infections. CONCLUSION: An empiric treatment strategy relying on a third-generation cephalosporin appears suitable for healthcare-associated CNS infections at our tertiary hospital, serving a population of 2.6 million. However, in patients with prolonged hospitalization (≥10 days), immunosuppression, prior broad-spectrum antibiotic use, or history of resistant Gram-negative bacteria, empirical prescription of carbapenem may be needed.

Effectiveness of penicillin, dicloxacillin and cefuroxime for penicillin-susceptible Staphylococcus aureus bacteraemia: a retrospective, propensity-score-adjusted case-control and cohort analysis.

OBJECTIVES: Penicillin-susceptible Staphylococcus aureus isolates account for a fifth of cases of S. aureus bacteraemia (SAB) in Denmark, but little is known about treatment outcomes with penicillins or other antimicrobials. Here we compare penicillin, dicloxacillin and cefuroxime as definitive treatments in relation to 30 day mortality. METHODS: A retrospective chart review of 588 penicillin-susceptible S. aureus cases at five centres from January 1995 to December 2010. Data on demographics, antimicrobial treatment, clinical signs and symptoms, and mortality at day 30 were collected. Hazard ratios (HRs) with 95% CIs associated with mortality were modelled using propensity-score-adjusted Cox proportional hazards regression analysis. Propensity-score-matched case-control studies were carried out. RESULTS: Definitive therapy with cefuroxime was associated with an increased risk of 30 day mortality compared with penicillin (adjusted HR 2.54, 95% CI 1.49-4.32). Other variables that were statistically significantly associated with 30 day mortality included increasing age, disease severity and a primary respiratory focus. Osteomyelitis/arthritis was associated with a lower risk of death than were other secondary manifestations. Propensity-score-matched case-control studies confirmed an increased risk of 30 day mortality: cefuroxime treatment (39%) versus penicillin treatment (20%), P = 0.037; and cefuroxime treatment (38%) versus dicloxacillin treatment (10%), P = 0.004. CONCLUSIONS: Definitive therapy for penicillin-susceptible SAB with cefuroxime was associated with a significantly higher mortality than was seen with therapy with penicillin or dicloxacillin.

The effects of sociodemographic factors and comorbidities on sepsis: A nationwide Swedish cohort study.

Sepsis is a severe condition, representing a significant public health concern, especially in the elderly. There is, however, little insight into the potential effects of sociodemographic factors and comorbidities on sepsis incidence and how these factors interact. This was a nationwide open cohort study including individuals (N = 6 746 010) in Sweden ≥ 18 years of age spanning from 1997 to 2018, with 116 175 995 person years of follow-up. The outcome was time to first occurrence of sepsis. The following variables were included in the analysis: sociodemographic factors (age, sex, income, education, marital status, region of residency, and country of origin), severe mental disorders (schizophrenia and bipolar disorders), and Charlson Comorbidity Index. Interaction tests were conducted. A total of 161 558 individuals were diagnosed with sepsis during the study period, corresponding to an incidence rate of 13.9 per 10 000 person years (95% CI: 13.8 - 14.0). The main findings were that male sex, high age, low education, and comorbid conditions were positively associated with sepsis, after adjustments for the other covariates. Being aged 80 years and above yielded a HR of 18.19 (95% CI: 17.84 - 18.55) and the effect of high age was more than twice as high in men than in women. In conclusion, this large nationwide cohort found that several sociodemographic factors and comorbid conditions were independently associated with sepsis and men were more affected by higher age than women. These findings can help improve sepsis awareness and preventive work in risk groups.

Differences in the distribution of pathogens and antimicrobial resistance in bloodstream infections in migrants compared with non-migrants in Denmark.

BACKGROUND: We wish to study disparities in bloodstream infections in migrants and non-migrants by comparing the distribution of pathogens and their resistance patterns in long-term migrants with that in non-migrants in Denmark. METHODS: The study is based on a cohort of migrants, who received residency in Denmark between 1993 and 2015 and a control group of non-migrants. The cohort was linked to a database of bloodstream infections from 2000 to 2015 covering two regions in Denmark. First-time bloodstream infections in individuals ≥18 years of age at the time of sampling were included. We calculated odds ratios adjusted for age, sex, year of sampling, comorbidity, and place of acquisition (hospital- or community-acquired). RESULTS: We identified 4,703 bloodstream infection cases. Family-reunified migrants and refugees had higher odds of Escherichia coli than non-migrants (OR 1.89 95%CI: 1.46-2.44 and OR 1.55 95%CI: 1.25-1.92) and lower odds of Streptococcus pneumoniae (OR 0.38 95%CI: 0.21-0.67 and OR 0.52 95%CI: 0.34-0.81). Differences in pathogen distribution were only prevalent in community-acquired bloodstream infections. Refugees had higher odds of Escherichia coli resistant to piperacillin-tazobactam, ciprofloxacin, and gentamicin compared with non-migrants. Family-reunified migrants had higher odds of Escherichia coli and other Enterobacterales resistant to ciprofloxacin. CONCLUSIONS: Migrants had a higher proportion of community-acquired bloodstream infections with Escherichia coli as well as higher odds of bloodstream infections with resistant Escherichia coli compared with non-migrants. These novel results are relevant for improving migrant health by focussing on preventing and treating infections especially with Escherichia coli such as urinary tract and abdominal infections.