Incidence of invasive infections with Group B streptococcus in adults in Norway 1996-2019: a nationwide registry-based case-control study.

PURPOSE: Group B streptococcus (GBS) colonizes the gastrointestinal and vaginal mucosa in healthy adults, but has also become an increasing cause of invasive infection. The aims of this study were to describe the incidence and factors associated with the occurrence of invasive GBS disease in adults in Norway. METHODS: We performed a nationwide retrospective case-control study of invasive GBS infections during 1996-2019, with two control groups; invasive Group A streptococcal disease (GAS) to control for changes in surveillance and diagnostics, and a second representing the general population. RESULTS: A total of 3710 GBS episodes were identified. The age-standardized incidence rate increased steadily from 1.10 (95% CI 0.80-1.50) in 1996 to 6.70 (95% CI 5.90-7.50) per 100,000 person-years in 2019. The incidence rate had an average annual increase of 6.44% (95% CI 5.12-7.78). Incidence rates of GAS varied considerably, and there was no evidence of a consistent change over the study period. GBS incidence was highest among adults > 60 years of age. Cardiovascular disease, cancer, and diabetes were the most common comorbid conditions. There was a shift in the distribution of capsular serotypes from three dominant types to more equal distribution among the six most common serotypes. CONCLUSIONS: The incidence of invasive GBS disease in adults increased significantly from 1996 to 2019. The increasing age of the population with accompanying underlying comorbid conditions might contribute to the increasing burden of invasive GBS disease. Interestingly, type 1 diabetes was also associated with the occurrence of invasive GBS disease.

Coding practice for sepsis 2008-21. / Kodepraksis ved sepsis 2008­21.

Background: Sepsis has a high incidence and mortality rate. Accurate data are needed for health service planning and for research, and there is a need to identify coding practices in Norway. Material and method: All patients over 17 years of age who had been admitted to Norwegian hospitals with sepsis in the period 2008-21 were identified using diagnostic codes for infection plus organ failure, and specific codes for sepsis, from the Norwegian Patient Registry. Results: There were 317 705 admissions with diagnostic codes for sepsis, of which 210 391 (66.2 %) were sepsis with a known focus, 77 627 (24.4 %) were of unknown focus and 29 687 (9.3 %) were codes for both a known and unknown focus. The percentage of sepsis episodes coded with a known focus varied between the health regions. The highest percentage was in the Western Norway Regional Health Authority (72.1 %, 95 % confidence interval (CI): 71.8 to 72.5), and the lowest was in the Central Norway Regional Health Authority (59.2 %, 95 %, CI 58.7 to 59.7). The use of codes with a known focus increased each year on average by 3.2 % (95 % CI 2.7 to 3.6, from 47.5 % in 2008 to 82.3 % in 2021), while the use of codes with an unknown focus decreased by 2.3 % (95 % CI -2.7 to -1.9) from 37.8 % in 2008 to 13.0 % in 2021. Known and unknown focus combined also decreased by 0.9 % per year on average (95 % CI -1.0 to -0.8) from 14.3 % in 2008 to 4.1 % in 2021. Interpretation: The coding of sepsis in Norwegian hospitals has become more uniform.

Epidemiological and clinical characteristics of immunocompromised patients infected with Pneumocystis jirovecii in a twelve-year retrospective study from Norway.

BACKGROUND: Pneumocystis pneumonia (PCP) severely menaces modern chemotherapy and immunosuppression. Detailed description of the epidemiology of Pneumocystis jirovecii today is needed to identify candidates for PCP-prophylaxis. METHODS: We performed a 12-year retrospective study of patients with P. jirovecii detected by polymerase chain reaction in Central Norway. In total, 297 patients were included. Comprehensive biological, clinical and epidemiological data were abstracted from patients' medical records. Regional incidence rates and testing trends were also assessed. RESULTS: From 2007 to 2017 we found a 3.3-fold increase in testing for P. jirovecii accompanied by a 1.8-fold increase in positive results. Simultaneously, regional incidence rates doubled from 5.0 cases per 100,000 person years to 10.8. A majority of the study population had predisposing conditions other than human immunodeficiency virus (HIV). Hematological (36.0%) and solid cancers (25.3%) dominated. Preceding corticosteroids were a common denominator for 72.1%. Most patients (74.4%) presented with at least two cardinal symptoms; cough, dyspnea or fever. Main clinical findings were hypoxia, cytopenias and radiological features consistent with PCP. A total of 88 (29.6%) patients required intensive care and 121 (40.7%) suffered at least one complication. In-hospital mortality was 21.5%. Three patients (1.0%) had received prophylaxis. CONCLUSIONS: P. jirovecii is re-emerging; likely due to increasing immunosuppressants use. This opportunistic pathogen threatens the life of heterogenous non-HIV immunosuppressed populations currently at growth. Corticosteroids seem to be a major risk factor. A strategy to increase prophylaxis is called for.

Prelabor rupture of membranes and the association with cerebral palsy in term born children: a national registry-based cohort study.

BACKGROUND: Guidelines regarding management of prelabor rupture of membranes (PROM) at term vary between immediate induction and expectant management. A long interval between PROM and delivery increases the risk for perinatal infections. Severe perinatal infections are associated with excess risk for cerebral palsy (CP) and perinatal death. We investigated if increasing intervals between PROM and delivery were associated with perinatal death or CP. METHODS: Eligible to participate in this population-based cohort-study were term born singletons without congenital malformations born in Norway during 1999-2009. Data was retrieved from the Medical Birth Registry of Norway (MBRN) and the Cerebral Palsy Register of Norway. In line with the registration in the MBRN, intervals between PROM and delivery of more than 24 h was defined as 'prolonged' and intervals between 12 and 24 h as 'intermediate'. Outcomes were stillbirth, death during delivery, neonatal mortality and CP. Logistic regression was used to calculate odds ratio (OR) with 95% confidence intervals (CI) for adverse outcomes in children born after prolonged and intermediate intervals, compared with a reference group comprising all children born less than 12 h after PROM or without PROM. RESULTS: Among 559,972 births, 34,759 children were born after intermediate and 30,332 were born after prolonged intervals. There was no association between increasing intervals and death during delivery or in the neonatal period, while the prevalence of stillbirths decreased with increasing intervals. Among children born after intermediate intervals 38 (0.11%) had CP, while among those born after prolonged intervals 46 (0.15%) had CP. Compared with the reference group, the OR for CP was 1.16 (CI; 0.83 to 1.61) after intermediate and 1.61 (CI; 1.19 to 2.18) after prolonged intervals. Adjusting for antenatal factors did not affect these associations. Among children with CP the proportion with diffuse cortical injury and basal ganglia pathology on cerebral MRI, consistent with hypoxic-ischemic injuries, increased with increasing intervals. CONCLUSION: Intervals between PROM and delivery of more than 24 h were associated with CP, but not with neonatal mortality or death during delivery. The inverse association with stillbirth is probably due to reverse causality.

Investigation of an outbreak caused by antibiotic-susceptible Klebsiella oxytoca in a neonatal intensive care unit in Norway.

AIM: Klebsiella spp. have been stated to be the most frequent cause of neonatal intensive care unit (NICU) outbreaks. We report an outbreak of Klebsiella oxytoca in a NICU at a tertiary care hospital in Norway between April 2016 and April 2017. This study describes the outbreak, infection control measures undertaken and the molecular methods developed. METHODS: The outbreak prompted detailed epidemiological and microbial investigations, where whole-genome sequencing (WGS) was particularly useful for both genotyping and development of two new K. oxytoca-specific real-time PCR assays. Routine screening of patients, as well as sampling from numerous environmental sites, was performed during the outbreak. A bundle of infection control measures was instigated to control the outbreak, among them strict cohort isolation. RESULTS: Five neonates had symptomatic infection, and 17 were found to be asymptomatically colonised. Infections varied in severity from conjunctivitis to a fatal case of pneumonia. A source of the outbreak could not be determined. CONCLUSION: This report describes K. oxytoca as a significant pathogen in a NICU outbreak setting and highlights the importance of developing appropriate microbiological screening methods and implementing strict infection control measures to control the outbreak in a setting where the source could not be identified.

Stratification by interferon-γ release assay level predicts risk of incident TB.

INTRODUCTION: Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting. METHODS: In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009-30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model. RESULTS: The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL). CONCLUSIONS: Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI.

Prevalence of Sexually Transmitted Infections among Married Women in Rural Nepal.

Introduction: We have previously determined the prevalence of human papillomavirus (HPV) infection among women in rural Nepal. In the current study, we also wanted to examine the prevalence of and risk factors for other sexually transmitted infections (STIs) in the same population. Methods: Population-based study of nonpregnant women ≥ 15 years who were married or had a history of marriage in the past, residing in five rural villages in Nepal. Data on sociodemographic characteristics, reproductive history, and genitourinary symptoms were collected, and a gynecological examination was conducted. Cervical samples were analyzed by real-time PCR for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis and HPV, and a serum sample was analyzed for syphilis, hepatitis B virus (HBV) and HIV infection by serology. Results: Of 2416 eligible women, 62% participated. Trichomoniasis, Chlamydia trachomatis infection, HPV and HBV infection, and syphilis were detected in 5.4%, 0.8%, 14.3%, 0.3%, and 0.2% of the women. None had gonorrhea or HIV infection. Of those with genitourinary symptoms, 6.3% had a curable STI. Vaginal discharge classified as abnormal by gynecological examination, but not self-reported discharge, was significantly associated with laboratory diagnosis of a curable STI. Risk factors for trichomoniasis were reproductive age and high cast/ethnicity. Due to low prevalence, risk factors for other STIs could not be disclosed. Conclusion: We observed high prevalence of HPV infection followed by trichomoniasis, while other STIs were rare among women in rural Nepal. There was no association between genitourinary symptoms and laboratory-confirmed STIs.

Community-Based Health Education has Positive Influence on the Attitude to Cervical Cancer Screening among Women in Rural Nepal.

The main purpose of this study was to assess the knowledge of cervical cancer among women in rural Nepal and explore the feasibility and impact of a community-based awareness program on cervical cancer. Community-based educational meetings on cervical cancer and its prevention were conducted among women's groups in rural Nepal. Through a questionnaire, the women's baseline knowledge of risk factors, symptoms, and perceived risk of cervical cancer were identified. The willingness to participate in cervical cancer screening was compared before and after the educational meeting. The meetings were followed by a cervical cancer screening program. Among the 122 participants at the educational meeting, only 6 % had heard of cervical cancer. Their baseline knowledge of risk factors and symptoms was poor. The proportion of women willing to participate in cervical screening increased from 15.6 to 100 % after attending the educational meeting. All the study subjects participated in the screening program. Additionally, the study participants recruited a further 222 of their peers for screening. Poor knowledge of cervical cancer among women in rural Nepal highlights the urgency of public awareness programs for cervical cancer at a national level. A community-based awareness program can change women's attitude to cervical screening, and women's groups can play a major role in promoting participation in cervical cancer screening programs.

Insights from a decade of surveillance: Molecular epidemiology of methicillin-resistant Staphylococcus aureus in Norway from 2008 to 2017.

AIM: Norway has a low prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and reporting of all MRSA cases has been mandatory, including infections and carriage, since 1995 and 2005 accordingly. This provides a unique window to study the spread of MRSA in Norway over time. The aim of this study was to analyze the nationwide trends in the molecular epidemiology of MRSA in Norway over a period of 10 years. METHODS: Clinical and epidemiological data as well as bacterial genotype (spa-type and PVL) were analyzed for all reported MRSA cases in Norway in the period 2008-2017. RESULTS: During the study period, there were 15,200 MRSA cases reported in Norway, from 14,386 patients. The notification rate per 100,000 population increased by 15% annually, rising from 14.2 in 2007 to 48.6 in 2017. This increase was primarily driven by MRSA carriage and community-associated MRSA cases. The incidence of invasive infections remained stable and low, at less than 0.5. The incidence of healthcare-associated MRSA showed an increasing trend, while the number of outbreak-related cases, particularly those associated with nursing homes, decreased. Overall, there were significantly more MRSA infections in males than females. Interestingly, there was a significantly higher prevalence of MRSA infections in female young adolescents compared to males. spa-typing revealed a very heterogeneous MRSA population (D = 0.97), predominantly impacted by international travel and migration patterns, and less by domestic spread in the community. CONCLUSIONS: This study highlights that Norway, while still classified as a low-prevalence country, has experienced a significant increase in the incidence of MRSA between 2008 and 2017, which can predominantly be attributed to CA-MRSA and MRSA carriage.

In-hospital mortality, readmission, and prolonged length of stay risk prediction leveraging historical electronic patient records.

Objective: This study aimed to investigate the predictive capabilities of historical patient records to predict patient adverse outcomes such as mortality, readmission, and prolonged length of stay (PLOS). Methods: Leveraging a de-identified dataset from a tertiary care university hospital, we developed an eXplainable Artificial Intelligence (XAI) framework combining tree-based and traditional machine learning (ML) models with interpretations and statistical analysis of predictors of mortality, readmission, and PLOS. Results: Our framework demonstrated exceptional predictive performance with a notable area under the receiver operating characteristic (AUROC) of 0.9625 and an area under the precision-recall curve (AUPRC) of 0.8575 for 30-day mortality at discharge and an AUROC of 0.9545 and AUPRC of 0.8419 at admission. For the readmission and PLOS risk, the highest AUROC achieved were 0.8198 and 0.9797, respectively. The tree-based models consistently outperformed the traditional ML models in all 4 prediction tasks. The key predictors were age, derived temporal features, routine laboratory tests, and diagnostic and procedural codes. Conclusion: The study underscores the potential of leveraging medical history for enhanced hospital predictive analytics. We present an accurate and intuitive framework for early warning models that can be easily implemented in the current and developing digital health platforms to predict adverse outcomes accurately.

Identification and characterisation of carbapenem-resistant Streptococcus nidrosiense sp. nov. isolated from blood culture.

Background: This study aimed to investigate a highly resistant strain of Streptococcus sp. isolated from a patient with bloodstream infection and determine its taxonomic classification. Methods: The strain was isolated from blood culture from a 65-year-old male patient admitted to St. Olavs University hospital, Trondheim, Norway, in 2023. Antimicrobial susceptibility testing as well as phenotypic and biochemical characterization were performed. Whole genome sequencing was conducted and genomic comparison to Streptococcus type strains was carried out. Results: The strain was initially identified as Streptococcus mitis/oralis but showed significant genetic differences, suggesting that it belonged to an undescribed species within the Streptococcus genus. Phenotypic and biochemical characterization identified the strain as a non-motile, facultative anaerobic bacterium with α-hemolysis. Antimicrobial susceptibility testing showed resistance to all beta-lactams tested. Genomic analyses confirmed the classification of the strain as a novel species, which was designated Streptococcus nidrosiense. Conclusion: This study combines conventional phenotypic tests with whole genome sequencing for accurate taxonomic classification of a bacterial strain isolated from blood culture. The identification of a novel species within the Streptococcus genus contributes to the understanding of microbial diversity and antibiotic resistance of the Streptococcus genus in clinical settings.

Predicting In-Hospital Death from Derived EHR Trajectory Features.

Medical histories of patients can predict a patient's immediate future. While most studies propose to predict survival from vital signs and hospital tests within one episode of care, we carried out selective feature engineering from longitudinal medical records in this study to develop a dataset with derived features. We thereafter trained multiple machine learning models for the binary prediction of whether an episode of care will culminate in death among patients suspected of bloodstream infections. The machine learning classifier performance is evaluated and compared and the feature importance impacting the model output is explored. The extreme gradient boosting model achieved the best performance for predicting death in the next hospital episode with an accuracy of 92%. Age at the time of the first visit, length of history, and information related to recent episodes were the most critical features.

Enteroaggregative Escherichia coli in mid-Norway: A prospective, case control study.

BACKGROUND: The use of molecular methods has led to increased detection of Enteroaggregative Escherichia coli (EAEC) in faecal samples. Studies have yielded conflicting results regarding the clinical relevance of this finding. The objective of this study was to investigate the prevalence of EAEC in faecal samples from patients with diarrhoea and healthy controls and describe characteristics of EAEC positive persons. METHODS: From March 1st, 2017 to February 28th, 2019, we investigated all consecutive faecal samples from patients with diarrhoea received at the laboratory and collected faecal samples from randomly invited healthy controls from mid-Norway. Real-time multiplex PCR was used for detection of bacterial, viral, and parasitic pathogens. We registered sex, age, urban versus non-urban residency, and travel history for all participants. Statistical analyses were performed with Pearson chi-squared test, Kruskal-Wallis test, and Mann-Whitney U test. RESULTS: We identified EAEC in 440 of 9487 (4.6%) patients with diarrhoea and 8 of 375 (2.2%) healthy controls. The EAEC prevalence was 19.1% among those with diarrhoea and recent foreign travel and 2.2% in those without travel history independent of diarrhoea. Concomitant pathogens were detected in 64.3% of EAEC-positive patients with diarrhoea. The median age was 28.5 in those with EAEC-positive diarrhoea and 38 in those with EAEC-negative diarrhoea (p <0.01). In patients with diarrhoea, travel was reported in 72% of those with EAEC and concomitant pathogens, and 54% and 12% in those with only EAEC and no EAEC, respectively (p <0.01). CONCLUSIONS: EAEC was a common detection, particularly in patients with diarrhoea and recent international travel, and was found together with other intestinal pathogens in the majority of cases. Our results suggest that domestically acquired EAEC is not associated with diarrhoea. Patients with EAEC-positive diarrhoea and concomitant pathogens were young and often reported recent travel history compared to other patients with diarrhoea.

Cryptosporidium species and subtypes in Norway: predominance of C. parvum and emergence of C. mortiferum.

PCR-based diagnostics has revealed the previously largely unknown Cryptosporidium transmission and infections in high-income countries. This study aimed to determine domestic and imported subtypes of Cryptosporidium species in Norway, evaluate their demographic distribution, and identify potential small outbreaks. Cryptosporidium-positive human faecal samples were obtained from six medical microbiology laboratories between February 2022 and January 2024, together with 22 Cryptosporidium-positive animal samples. Species and subtypes were identified by sequencing PCR products from gp60 and SSU rRNA genes. Most cryptosporidiosis cases occurred during late summer/early autumn, primarily in children and young adults. Of 550 human samples, 359 were successfully characterized molecularly (65%), revealing infection with 10 different Cryptosporidium species. C. parvum occurred in 245 (68%) human isolates with IIa and IId being major allele families, with distinct regional distribution patterns of common subtypes. A kindergarten outbreak with 5 cases was due to C. parvum IIaA14G1R1. C. mortiferum was identified in 33 (9.2%) human cases of which 24 were known to be of domestic origin, making it the second most common species in human autochthonous cases in Norway. All C. mortiferum isolates were of the same genotype; XIVaA20G2T1, including 13 cases from a suspected small outbreak in Trøndelag. C. hominis occurred in 68 typed cases (19%), but mostly in infections acquired abroad, with allele families Ib and If occurring most often. In conclusion, this study of recent Cryptosporidium spp. and subtypes in Norway, highlights the predominance of C. parvum and the emergence of C. mortiferum among autochthonous cases.

The combination of pleconaril, rupintrivir, and remdesivir efficiently inhibits enterovirus infections in vitro, delaying the development of drug-resistant virus variants.

Enteroviruses are a significant global health concern, causing a spectrum of diseases from the common cold to more severe conditions like hand-foot-and-mouth disease, meningitis, myocarditis, pancreatitis, and poliomyelitis. Current treatment options for these infections are limited, underscoring the urgent need for effective therapeutic strategies. To find better treatment option we analyzed toxicity and efficacy of 12 known broad-spectrum anti-enterovirals both individually and in combinations against different enteroviruses in vitro. We identified several novel, synergistic two-drug and three-drug combinations that demonstrated significant inhibition of enterovirus infections in vitro. Specifically, the triple-drug combination of pleconaril, rupintrivir, and remdesivir exhibited remarkable efficacy against echovirus (EV) 1, EV6, EV11, and coxsackievirus (CV) B5, in human lung epithelial A549 cells. This combination surpassed the effectiveness of single-agent or dual-drug treatments, as evidenced by its ability to protect A549 cells from EV1-induced cytotoxicity across seven passages. Additionally, this triple-drug cocktail showed potent antiviral activity against EV-A71 in human intestinal organoids. Thus, our findings highlight the therapeutic potential of the pleconaril-rupintrivir-remdesivir combination as a broad-spectrum treatment option against a range of enterovirus infections. The study also paves the way towards development of strategic antiviral drug combinations with virus family coverage and high-resistance barriers.

Comparisons of infant Escherichia coli isolates link genomic profiles with adaptation to the ecological niche.

BACKGROUND: Despite being one of the most intensely studied model organisms, many questions still remain about the evolutionary biology and ecology of Escherichia coli. An important step toward achieving a more complete understanding of E.coli biology entails elucidating relationships between gene content and adaptation to the ecological niche. RESULTS: Here, we present genome comparisons of 16 E.coli strains that represent commensals and pathogens isolated from infants during a specific time period in Trondheim, Norway. Using differential gene content, we characterized enrichment profiles of the collection of strains relating to phylogeny, early vs. late colonization, pathogenicity and growth rate. We found clear gene content distinctions relating to the various grouping criteria. We also found that different categories of strains use different genetic elements for similar biological processes. The sequenced genomes included two pairs of strains where each pair was isolated from the same infant at different time points. One pair, in which the strains were isolated four months apart, showed maintenance of an early colonizer genome profile but also gene content and codon usage changes toward the late colonizer profile. Lastly, we placed our sequenced isolates into a broader genomic context by comparing them with 25 published E.coli genomes that represent a variety of pathotypes and commensal strains. This analysis demonstrated the importance of geography in shaping strain level gene content profiles. CONCLUSIONS: Our results indicate a general pattern where alternative genetic pathways lead toward a consistent ecological role for E.coli as a species. Within this framework however, we saw selection shaping the coding repertoire of E.coli strains toward distinct ecotypes with different phenotypic properties.

Role of fungal burden in risk stratification of HIV-negative patients with Pneumocystis pneumonia: A 12-year, retrospective, observational, multicenter cohort.

OBJECTIVES: This study aimed to explore the role of fungal burden in risk stratification of patients without HIV-negative patients with Pneumocystis pneumonia (PCP). METHODS: This was a retrospective analysis of the characteristics associated with 30-day mortality in patients who were positive for P. jirovecii using polymerase chain reaction in bronchoalveolar lavage fluid between 2006 and 2017 in a multicenter cohort from Central Norway. The fungal burden was indicated by the cycle threshold (CT) values from semiquantitative real-time polymerase chain reaction targeting the ß-tubulin gene. RESULTS: We included 170 patients with proven or probable PCP. The all-cause 30-day mortality was 18.2%. After adjusting for host characteristics and premorbid corticosteroid use, a higher fungal burden was associated with a higher risk of dying: adjusted odds ratio 1.42 (95% confidence interval 0.48-4.25) for a CT value 31-36, increasing to odds ratio 5.43 (95% confidence interval 1.48-19.9) for a CT value ≤30 compared with patients with a CT value ≥37. The Charlson comorbidity index (CCI) improved the risk stratification: patients with a CT value ≥37 and CCI ≤2 had a 9% mortality risk compared with 70% among those with a CT value ≤30 and CCI ≥6. Comorbid cardiovascular disease, solid tumors, immunological disorders, premorbid corticosteroids, hypoxemia, abnormal leukocyte counts, low serum albumin, and C-reactive protein ≥100 were also independently associated with 30-day mortality. The sensitivity analyses did not suggest selection bias. CONCLUSION: Fungal burden may improve the risk stratification of patients without HIV-negative patients with PCP.

High levels of discordant antimicrobial therapy in hospital-acquired bloodstream infections is associated with increased mortality in an intensive care, low antimicrobial resistance setting.

BACKGROUND: Bloodstream infections (BSI) occur frequently and are associated with severe outcomes. In this study we aimed to investigate proportions of patients that received discordant empirical antimicrobial therapy and its association to mortality. METHODS: A retrospective cohort study model was undertaken to outline BSI in an intensive care, single centre, and low antimicrobial resistance prevalence setting. We used descriptive statistics to delineate proportions of patients that received discordant empirical antimicrobial therapy, and a correlation model and a logistic regression model to calculate the association with mortality and predictors of receiving discordant therapy, respectively. RESULTS: From 2014 to 2018 we included 270 BSI episodes, of which one third were hospital-acquired. Gram negative, Gram positive, and anaerobic pathogens were detected in 49.0%, 45.3% and 5.7% respectively. The proportion of isolates that conferred extended-spectrum beta-lactamase (ESBL) properties were 5.9% among enterobactereales, and no methicillin-resistant Staphylococcus aureus isolates were detected. Empirical antimicrobial therapy for community-acquired (CA) and hospital-acquired (HA) BSI were discordant at day 0 in 6.5% and 24.4%, respectively (p<.001). Discordant therapy was significantly associated with mortality at day 28 (p=.041). HA-onset BSI, enterococcal BSI and BSI of intraabdominal origin were statistically significant predictors of receiving discordant therapy. CONCLUSION: A significant proportion of HA-BSI did not receive effective antimicrobial therapy and this was significantly associated with mortality. The results underscore the need for more accurate diagnostic tools, improved communication between the microbiological laboratory and the clinicians, and antimicrobial stewardship measures.

Empirical antimicrobial therapy for bloodstream infections not compliant with guideline was associated with discordant therapy, which predicted poorer outcome even in a low resistance environment.

OBJECTIVES: To characterise all bloodstream infections (BSIs) in a low antimicrobial resistance (AMR) prevalence setting with regard to the appropriateness of empirical antimicrobial therapy, compliance with the national clinical practice guideline, de-escalation practice and outcome. METHODS: A retrospective observational study including patients aged ≥ 18 years admitted to a university hospital in central Norway with positive blood culture in 2019. RESULTS: We included 756 BSI episodes in our analysis. Empirical antimicrobial therapy was in accordance with the national guideline in 534 (70.6%), and not in accordance in 190 (25.1%) of the BSI episodes. There was a statistically significant association between compliance with the national guideline and concordant empirical antimicrobial therapy (p = .001). De-escalation of antimicrobial therapy was possible but not done in 217 (31.1%) of the BSI episodes. Variables identified as independent predictors of discordant empirical antimicrobial therapy included hospital department, type of empirical antimicrobial regimen, bacterial species, and AMR. Independent predictors of intra-hospital case fatality rate were coverage of empirical antimicrobial therapy, CCI-score, SAPS-II score, site of infection, and type of empirical antimicrobial regimen. Furthermore, the intra-hospital and long-term unadjusted all-cause case fatality rates were increased (p < .001, log-rank test for overall difference in survival) for the patients who received discordant empirical antimicrobial therapy. CONCLUSION: Our study shows that empirical antimicrobial therapy initiated in accordance with national guideline recommendations increases the likelihood of receiving concordant therapy. Discordant empirical antimicrobial therapy was associated with poorer outcomes, even in a setting with low AMR prevalence.

The Streptococcus agalactiae R3 surface protein is encoded by sar5.

Streptococcus agalactiae (group B streptococcus; GBS) is an important human pathogen causing pneumonia, sepsis and meningitis in neonates, as well as infections in pregnant women, immunocompromised individuals, and the elderly. For the future control of GBS-inflicted disease, GBS surface exposed proteins are particularly relevant as they may act as antigens for vaccine development and/or as serosubtype markers in epidemiological settings. Even so, the genes encoding some of the surface proteins established as serosubtype markers by antibody-based methods, like the R3 surface protein, are still unknown. Here, by examining a Norwegian GBS collection consisting of 140 strains, we find that R3 protein expression correlates with the presence of the gene sar5. By inducible expression of sar5 in an R3-negative bacterial strain we show that the sar5 gene product is specifically recognized by an R3 monoclonal antibody. With this we identify sar5 as the gene encoding the R3 surface protein, a serosubtype marker of hitherto unknown genetic origin.