Nosocomial SARS-CoV-2 Infections and Mortality During Unique COVID-19 Epidemic Waves.

Importance: Quantifying the burden of nosocomial SARS-CoV-2 infections and associated mortality is necessary to assess the need for infection prevention and control measures. Objective: To investigate the occurrence of nosocomial SARS-CoV-2 infections and associated 30-day mortality among patients admitted to hospitals in Region Stockholm, Sweden. Design, Setting, and Participants: A retrospective, matched cohort study divided the period from March 1, 2020, until September 15, 2022, into a prevaccination period, early vaccination and pre-Omicron (period 1), and late vaccination and Omicron (period 2). From among 303 898 patients 18 years or older living in Region Stockholm, 538 951 hospital admissions across all hospitals were included. Hospitalized admissions with nosocomial SARS-CoV-2 infections were matched to as many as 5 hospitalized admissions without nosocomial SARS-CoV-2 by age, sex, length of stay, admission time, and hospital unit. Exposure: Nosocomial SARS-CoV-2 infection defined as the first positive polymerase chain reaction test result at least 8 days after hospital admission or within 2 days after discharge. Main Outcomes and Measures: Primary outcome of 30-day mortality was analyzed using time-to-event analyses with a Cox proportional hazards regression model adjusted for age, sex, educational level, and comorbidities. Results: Among 2193 patients with SARS-CoV-2 infections or reinfections (1107 women [50.5%]; median age, 80 [IQR, 71-87] years), 2203 nosocomial SARS-CoV-2 infections were identified. The incidence rate of nosocomial SARS-CoV-2 infections was 1.57 (95% CI, 1.51-1.64) per 1000 patient-days. In the matched cohort, 1487 hospital admissions with nosocomial SARS-CoV-2 infections were matched to 5044 hospital admissions without nosocomial SARS-CoV-2 infections. Thirty-day mortality was higher in the prevaccination period (adjusted hazard ratio [AHR], 2.97 [95% CI, 2.50-3.53]) compared with period 1 (AHR, 2.08 [95% CI, 1.50-2.88]) or period 2 (AHR, 1.22 [95% CI, 0.92-1.60]). Among patients with nosocomial SARS-CoV-2 infections, 30-day AHR comparing those with 2 or more doses of SARS-CoV-2 vaccination and those with less than 2 doses was 0.64 (95% CI, 0.46-0.88). Conclusions and Relevance: In this matched cohort study, nosocomial SARS-CoV-2 infections were associated with higher 30-day mortality during the early phases of the pandemic and lower mortality during the Omicron variant wave and after the introduction of vaccinations. Mitigation of excess mortality risk from nosocomial transmission should be a strong focus when population immunity is low through implementation of adequate infection prevention and control measures.

Oral streptococcal infective endocarditis among individuals at high risk following dental treatment: a nested case-crossover and case-control study.

Background: It is not clear whether Viridans Group Streptococcal Infective Endocarditis (VGS-IE) among individuals at high risk is more frequent following bacteraemia caused by invasive dental procedures (IDPs) than after daily bacteraemia caused by chewing and tooth brushing. The aim of this nested study was to assess if VGS-IE was temporally associated with IDPs in a national cohort of individuals at high risk. Methods: This nested case-control and case-crossover study was based on a Swedish national cohort study of 76,762 individuals at high risk of IE due to complex congenital heart disease, prosthetic heart valve or previous IE. Participants were living in Sweden between July 1st, 2008 and January 1st, 2018. The frequency of IDPs during the 3 months before VGS-IE was calculated and compared to controls (sampled 1:10). A case-crossover study was conducted to account for residual confounders. Participants were identified using the national patient register, and IDPs were identified using the national dental health register. Findings: 98,247 IDPs were carried out in the cohort during the study period: 624 occasions of oral surgery, 44,190 extractions and 53,433 sessions of subgingival scaling. The study could not confirm that IDPs were more common among cases (4.6%) than controls (4.1%), OR = 1.22 [95% Confidence Interval (CI) 0.64-2.3], or during case- (3.3%) than reference periods (3.8%), OR = 0.89 [95% CI: 0.68-1.17]. Restricting the analysis to the period when cessation of antibiotic prophylaxis for the prevention of IE in Swedish dentistry was recommended, from the 1st of October 2012 to the 1st of January 2018, did not alter the results of the case-control study: OR 0.64, 95% CI: 0.20-2.09, or the case-crossover study: OR 0.58, 95% CI: 0.15-2.19. Interpretation: The study could not confirm that VGS-IE is associated with IDPs among individuals at high risk. A study with larger sample size could clarify whether there is a lack of association. The finding of a small (<5%) proportion of cases temporally associated with IDPs is similar to that of the previous large-scale study on IDPs and VGS-IE. Funding: Funding was provided by the Board of doctoral education at Karolinska Institutet, the Public Health Agency of Sweden, Folktandvården Stockholm AB, Steering Group for Collaborative Odontological Research at Karolinska Institutet and Stockholm City County, and the Swedish Dental Association.

The effect of absent or deferred antibiotic treatment on complications of common infections in primary care.

OBJECTIVES: The objective of this study was to compare the incidence rate for complications to upper respiratory tract infections (URTIs), including acute bronchitis and lower urinary tract infections (UTIs), for those treated with antibiotics compared to those who were not. METHODS: This was a population-based retrospective cohort study in Sweden. Patients diagnosed with otitis, pharyngotonsillitis, sinusitis, acute bronchitis, and lower UTI in primary care between 2014 and 2020 were included. Data on prescribed and dispensed antibiotics and comorbidities for each subject were collected. The outcome we investigated was the number of infectious complications within 30 days and if antibiotic treatment had any effect on risk reduction. RESULTS: There were 202,995 episodes of otitis, 388,158 pharyngotonsillitis, 125,792 sinusitis, 220,960 bronchitis, and 377,954 lower UTIs in our cohort. No increased risk for complications was seen for untreated compared with treated cases with URTI. For lower UTI, the adjusted odds ratio for febrile UTI or bloodstream infection was 1.53 (95% confidence interval 1.39-1.68). CONCLUSION: The risk for infectious complications from common URTIs is low and not modified by antibiotic treatment. On the contrary, patients diagnosed with UTI in whom antibiotics were withheld had an increased 30 days risk for severe infections.

The accuracy of fully automated algorithms for surveillance of healthcare-onset Clostridioides difficile infections in hospitalized patients.

We developed and validated a set of fully automated surveillance algorithms for healthcare-onset CDI using electronic health records. In a validation data set of 750 manually annotated admissions, the algorithm based on International Classification of Disease, Tenth Revision (ICD-10) code A04.7 had insufficient sensitivity. Algorithms based on microbiological test results with or without addition of symptoms performed well.

Cost-Effectiveness Analysis of Temocillin Treatment in Patients with Febrile UTI Accounting for the Emergence of Antibiotic Resistance.

BACKGROUND: Antibiotic resistance has been listed as one of the biggest threats to global health today. A recent study has shown that treating febrile urinary tract infections with temocillin instead of cefotaxime leads to a reduced selection of antibiotic-resistant bacteria. However, a potential challenge with prioritizing temocillin over cefotaxime is the cost consequences. OBJECTIVE: This study aimed to assess the cost effectiveness of using temocillin compared to cefotaxime in treating febrile urinary tract infections in a model that takes the emergence of antibiotic resistance into account. METHODS: We used a Markov cohort model to estimate the costs and health effects of temocillin and cefotaxime treatment in febrile urinary tract infections in a Swedish setting. Health effects were assessed in terms of quality-adjusted life-years, and the primary outcome was the cost per quality-adjusted life-year gained with temocillin compared to cefotaxime. We used a 5-year time horizon. RESULTS: The model results showed that temocillin treatment led to better health outcomes at a higher total cost. The cost per quality-adjusted life-year gained was approximately 38,400 EUR. Results from the sensitivity analysis suggested a 63% probability of temocillin being cost effective at a threshold of 50,000 EUR. Furthermore, results showed that the cost effectiveness of temocillin in febrile urinary tract infections is highly dependent on the drug cost. CONCLUSIONS: As antibiotic consumption is a driving force of resistance, it is essential to consider the development of resistance when studying the health economic consequences of antibiotic treatments. In doing so, this study found temocillin to be cost effective for febrile urinary tract infections.

Evaluation of a pneumonia multiplex PCR panel for detection of bacterial respiratory tract pathogens from serial specimens collected from hospitalized COVID-19 patients.

We investigated the concordance between the Unyvero Hospitalized Pneumonia (HPN) application and quantitative culture for detection of bacterial pathogens from serial lower respiratory tract (LRT) specimens collected from the same subject. Comparison of results from HPN application and culture was evaluated using 69 LRT samples from 27 subjects, using two evaluation approaches. False positive detections by the HPN application was 29% (20/69) in Evaluation I vs 10% (7/68) in Evaluation II. Additional pathogens detected by the HPN application could be confirmed in many instances by culture positivity for the same organism from previous or subsequent samples from the same subject.

Production loss and sick leave caused by antibiotic resistance: a register-based cohort study.

BACKGROUND: Adverse economic consequences of antibiotic resistance, both in health care systems and in society at large, have been estimated to emerge and significantly affect the global economy. To date, most studies of the societal costs of antibiotic resistance have had a macroeconomic perspective, using the number of attributable deaths as a quantifier for production loss. In contrast, there have been few studies of the consequences of antibiotic resistance in terms of the length of sick leave and hence the impact of morbidity on production loss. The aim of our study was to estimate the production loss from ill health caused by antibiotic resistance. METHOD: To estimate additional production loss due to antibiotic resistance, we used Swedish register-based cohort data to determine days of long-term sick leave (LTSL) for episodes of infection caused by resistant and susceptible bacteria respectively. We collected patient data for four common infection types (bloodstream infection, urinary tract infection, skin and soft tissue infection, and pneumonia), as well as, antibiotic susceptibility test data, and total days of LTSL. We used a two-part model to estimate the number of LTSL days attributable to resistance, and controlled for comorbidities and demographic variables such as age and gender. RESULTS: The results show that antibiotic resistance adds an additional 8.19 days of LTSL compared with a similar infection caused by susceptible bacteria, independent of infection type and resistance type. Furthermore, the results suggest that production loss due to temporary sick leave caused by antibiotic resistance in a working-age population amounts to about 7% of total health care costs attributable to antibiotic resistance in Sweden. CONCLUSION: Estimating the effect of antibiotic resistance in terms of temporary production loss is important to gain a better understanding of the economic consequences of antibiotic resistance in society and, by extension, enable more effective resource allocation to combat further emergence of resistance. Society's economic costs of antibiotic resistance are, however, probably much greater than those of sick leave due to disease alone.

Bacterial co-infections in community-acquired pneumonia caused by SARS-CoV-2, influenza virus and respiratory syncytial virus.

BACKGROUND: A mismatch between a widespread use of broad-spectrum antibiotic agents and a low prevalence of reported bacterial co-infections in patients with SARS-CoV-2 infections has been observed. Herein, we sought to characterize and compare bacterial co-infections at admission in hospitalized patients with SARS-CoV-2, influenza or respiratory syncytial virus (RSV) positive community-acquired pneumonia (CAP). METHODS: A retrospective cohort study of bacterial co-infections at admission in SARS-CoV-2, influenza or RSV-positive adult patients with CAP admitted to Karolinska University Hospital in Stockholm, Sweden, from year 2011 to 2020. The prevalence of bacterial co-infections was investigated and compared between the three virus groups. In each virus group, length of stay, ICU-admission and 30-day mortality was compared in patients with and without bacterial co-infection, adjusting for age, sex and co-morbidities. In the SARS-CoV-2 group, risk factors for bacterial co-infection, were assessed using logistic regression models and creation of two scoring systems based on disease severity, age, co-morbidities and inflammatory markers with assessment of concordance statistics. RESULTS: Compared to influenza and RSV, the bacterial co-infection testing frequency in SARS-CoV-2 was lower for all included test modalities. Four percent [46/1243 (95% CI 3-5)] of all SARS-CoV-2 patients had a bacterial co-infection at admission, whereas the proportion was 27% [209/775 (95% CI 24-30)] and 29% [69/242 (95% CI 23-35)] in influenza and RSV, respectively. S. pneumoniae and S. aureus constituted the most common bacterial findings for all three virus groups. Comparing SARS-CoV-2 positive patients with and without bacterial co-infection at admission, a relevant association could not be demonstrated nor excluded with regards to risk of ICU-admission (aHR 1.53, 95% CI 0.87-2.69) or 30-day mortality (aHR 1.28, 95% CI 0.66-2.46) in adjusted analyses. Bacterial co-infection was associated with increased inflammatory markers, but the diagnostic accuracy was not substantially different in a scoring system based on disease severity, age, co-morbidities and inflammatory parameters [C statistic 0.66 (95% CI 0.59-0.74)], compared to using disease severity, age and co-morbidities only [C statistic 0.63 (95% CI 0.56-0.70)]. CONCLUSIONS: The prevalence of bacterial co-infections was significantly lower in patients with community-acquired SARS-CoV-2 positive pneumonia as compared to influenza and RSV positive pneumonia.

Infective Endocarditis Among High-risk Individuals Before and After the Cessation of Antibiotic Prophylaxis in Dentistry: A National Cohort Study.

BACKGROUND: A few years after the publication of the British guidelines, national recommendations were published by the Swedish Medical Products Agency in October 2012, promoting the cessation of antibiotic prophylaxis in dentistry for the prevention of infective endocarditis (IE). The aim of this study was to evaluate whether the incidence of oral streptococcal IE increased among high-risk individuals after October 2012. METHODS: This nationwide cohort study included all adult individuals (>17 years) living in Sweden from January 2008 to January 2018, with a diagnose code or surgical procedure code indicating high risk of IE. Cox proportional hazard models were performed to calculate adjusted ratios of oral streptococcal IE before and after October 2012 between high-risk individuals and references. RESULTS: This study found no increased incidence of oral streptococcal IE among high-risk individuals during the 5 years after the cessation, compared with before. Hazard rate ratios were 15.4 (95% confidence interval [CI]: 8.3-28.5) before and 20.7 (95% CI: 10.0-42.7) after October 2012 for prevalent high-risk individuals. Corresponding ratios for incident high-risk individuals were 66.8 (95% CI: 28.7-155.6) and 44.6 (95% CI: 22.9-86.9). Point estimates for interaction with time period were 1.4 (95% CI: .6-3.5) and 0.8 (95% CI: .5-1.3) for prevalent and incident high-risk individuals, respectively. CONCLUSION: The results suggest that the current Swedish recommendation not to administer antibiotic prophylaxis for the prevention of IE in dentistry has not led to an increased incidence of oral streptococcal IE among high-risk individuals.

Reduced dispensing of prescribed antibiotics during the Covid-19 pandemic has not increased severe complications from common infections.

BACKGROUND: Sweden has seen an accelerated decline in the number of dispensed antibiotic prescriptions from an already low level during the Covid-19 pandemic. This prompted us to explore whether the decrease in antibiotic prescriptions has reached a critically low level and resulted in an increase in treatment of severe complications from common infections. The aim was to study if the accelerated decrease in antibiotic sales has led to an increase in complications in outpatients with common infections. METHOD: A population-based nationwide registry study based on the Swedish Prescribed Drug Register and the National Patient Register. RESULTS: The total number of dispensed antibiotic prescriptions decreased by 17% during 2020 compared to 2019. The decrease was most pronounced in younger age groups and for antibiotics targeting respiratory tract infections. The number of hospital admissions and visits to open specialist care due to pneumonia or complications related to otitis, tonsillitis, or sinusitis decreased by 4-44%. Prescriptions and numbers of visits or admissions due to urinary tract infections and skin infections remained largely unchanged compared to previous years. CONCLUSION: No increase in complications due to common bacterial infections could be detected despite an unprecedented decline in dispensed antibiotic prescriptions in outpatient care in 2020. The decrease in dispensed antibiotic prescriptions from pharmacies was probably primarily related to a general decrease in the incidence of respiratory infections due to the recommendations and restrictions implemented to mitigate the Covid-19 pandemic in Sweden. This in return led to fewer doctors' visits and consequently to fewer occasions to prescribe antibiotics, be they warranted or not.

Ventilator-Associated Lower Respiratory Tract Bacterial Infections in COVID-19 Compared With Non-COVID-19 Patients.

OBJECTIVES: Ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with prolonged length of stay and increased mortality. We aimed to investigate the occurrence of bacterial VA-LRTI among mechanically ventilated COVID-19 patients and compare these findings to non-COVID-19 cohorts throughout the first and second wave of the pandemic. DESIGN: Retrospective cohort study. SETTING: Karolinska University Hospital, Stockholm, Sweden. PATIENTS: All patients greater than or equal to 18 years treated with mechanical ventilation between January 1, 2011, and December 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort consisted of 20,223 ICU episodes (479 COVID-19), with a VA-LRTI incidence proportion of 30% (129/426) in COVID-19 and 18% (1,081/5,907) in non-COVID-19 among patients ventilated greater than or equal to 48 hours. The median length of ventilator treatment for COVID-19 patients was 10 days (interquartile range, 5-18 d), which was significantly longer than for all other investigated specific diagnoses. The VA-LRTI incidence rate per 1,000 ventilator days at risk was 31 (95% CI, 26-37) for COVID-19 and 34 (95% CI, 32-36) for non-COVID-19. With COVID-19 as reference, adjusted subdistribution hazard ratios for VA-LRTI was 0.29-0.50 (95% CI, < 1) for influenza, bacterial pneumonia, acute respiratory distress syndrome, and severe sepsis, but 1.38 (95% CI, 1.15-1.65) for specific noninfectious diagnoses. Compared with COVID-19 in the first wave of the pandemic, COVID-19 in the second wave had adjusted subdistribution hazard ratio of 1.85 (95% CI, 1.14-2.99). In early VA-LRTI Staphylococcus aureus was more common and Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli less common in COVID-19 patients, while Serratia species was more often identified in late VA-LRTI. CONCLUSIONS: COVID-19 is associated with exceptionally long durations of mechanical ventilation treatment and high VA-LRTI occurrence proportions. The incidence rate of VA-LRTI was compared with the pooled non-COVID-19 cohort, however, not increased in COVID-19. Significant differences in the incidence of VA-LRTI occurred between the first and second wave of the COVID-19 pandemic.

Clinical phenotypes and outcomes of SARS-CoV-2, influenza, RSV and seven other respiratory viruses: a retrospective study using complete hospital data.

BACKGROUND: An understanding of differences in clinical phenotypes and outcomes COVID-19 compared with other respiratory viral infections is important to optimise the management of patients and plan healthcare. Herein we sought to investigate such differences in patients positive for SARS-CoV-2 compared with influenza, respiratory syncytial virus (RSV) and other respiratory viruses. METHODS: We performed a retrospective cohort study of hospitalised adults and children (≤15 years) who tested positive for SARS-CoV-2, influenza virus A/B, RSV, rhinovirus, enterovirus, parainfluenza viruses, metapneumovirus, seasonal coronaviruses, adenovirus or bocavirus in a respiratory sample at admission between 2011 and 2020. RESULTS: A total of 6321 adult (1721 SARS-CoV-2) and 6379 paediatric (101 SARS-CoV-2) healthcare episodes were included in the study. In adults, SARS-CoV-2 positivity was independently associated with younger age, male sex, overweight/obesity, diabetes and hypertension, tachypnoea as well as better haemodynamic measurements, white cell count, platelet count and creatinine values. Furthermore, SARS-CoV-2 was associated with higher 30-day mortality as compared with influenza (adjusted HR (aHR) 4.43, 95% CI 3.51 to 5.59), RSV (aHR 3.81, 95% CI 2.72 to 5.34) and other respiratory viruses (aHR 3.46, 95% CI 2.61 to 4.60), as well as higher 90-day mortality, ICU admission, ICU mortality and pulmonary embolism in adults. In children, patients with SARS-CoV-2 were older and had lower prevalence of chronic cardiac and respiratory diseases compared with other viruses. CONCLUSIONS: SARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.

The clinical and microbiological efficacy of temocillin versus cefotaxime in adults with febrile urinary tract infection, and its effects on the intestinal microbiota: a randomised multicentre clinical trial in Sweden.

BACKGROUND: Use of third-generation cephalosporins, such as cefotaxime, is associated with an increased risk of selection for antimicrobial resistance, so alternative antibiotics need to be considered. The aim of the present study was to evaluate intestinal colonisation with third-generation cephalosporin-resistant pathogens following use of temocillin-an alternative antibiotic to cefotaxime that is potentially less prone to disturbing the intestinal microbiota-in empirical treatment of febrile urinary tract infection (UTI). METHODS: We did a randomised, multicentre, superiority, open-label phase 4 trial in patients who had been admitted to inpatient care in 12 Swedish hospitals with suspected or diagnosed febrile UTI (complicated or uncomplicated). To meet inclusion criteria, a patient was required to have at least one sign or symptom of pyelonephritis (ie, flank pain; costovertebral angle tenderness; and changes to urinary frequency or urgency or dysuria), a fever of 38·0°C or higher, and a positive urine dipstick (for nitrites, white blood cells, or both). Participants were also required to have an indication for intravenous antibiotic treatment. Participants were randomly assigned (1:1) to receive either 2 g temocillin or 1-2 g cefotaxime, by local investigators opening consecutive sealed randomisation envelopes that were generated centrally in advance. Both drugs were administered intravenously every 8 h. The trial was open label for investigators and patients, but those doing the microbiological analyses were masked to the groups. Participants were treated with antibiotics for 7-10 days (or up to 14 days if they had bacteraemia), at least 3 days of which were on the study drug; at day 4 and later, participants who were showing improvement could be given an oral antibiotic (ciprofloxacin, ceftibuten, cefixime, or co-trimoxazole). Patients not showing improvement were regarded as having treatment failures. Rectal swabs were collected at three timepoints: at baseline (before the first dose), after the last dose of study drug, and 7-10 days after treatment stopped. The composite primary outcome was colonisation with Enterobacterales with reduced susceptibility to third-generation cephalosporins, or colonisation with toxin-producing Clostridioides difficile, or both, to evaluate disturbance of the intestinal microbiota. The study is registered in the EU Clinical Trials Register (EudraCT 2015-003898-15). FINDINGS: Between May 20, 2016, and July 31, 2019, 207 patients were screened for eligibility, of whom 55 patients were excluded. 152 participants were randomly assigned to groups: 77 (51%) patients received temocillin, 75 (49%) patients received cefotaxime. The composite primary endpoint was met by 18 (26%) of 68 participants receiving temocillin versus 30 (48%) of 62 patients receiving cefotaxime (risk difference -22% [95% CI -42% to -3%]), showing superiority of temocillin versus cefotaxime (ie, less disturbance of the intestinal microbiota). 43 adverse events were reported in 40 (52%) of 77 patients in the temocillin group, versus 46 adverse events in 34 (45%) of 75 patients in the cefotaxime group. Most events were of mild to moderate severity. 21 (27%) patients in the temocillin and 17 (23%) patients in the cefotaxime group had an adverse event that was considered to be associated with the study drug. INTERPRETATION: Temocillin was found to be less selective than cefotaxime of Enterobacterales with reduced susceptibility to third-generation cephalosporins, and it could therefore be a favourable alternative in the empirical treatment of febrile UTI. Use of this antibiotic could reduce hospital transmission and health-care-associated infections by these pathogens. FUNDING: Public Health Agency of Sweden.

Cerebrospinal fluid cell count variability is a major confounding factor in external ventricular drain-associated infection surveillance diagnostics: a prospective observational study.

BACKGROUND: External ventricular drain (EVD)-related infections (EVDIs) are feared complications that are difficult to rapidly and correctly diagnose, which can lead to unnecessary treatment with broad-spectrum antibiotics. No readily available diagnostic parameters have been identified to reliably predict or identify EVDIs. Moreover, intraventricular hemorrhage is common and affect cerebrospinal fluid (CSF) cellularity. The relationship between leukocytes and erythrocytes is often used to identify suspected infection and triggers the use of antibiotics pending results of cultures, which may take days. Cell count based surveillance diagnostics assumes a homogeneous distribution of cells in the CSF. Given the intraventricular sedimentation of erythrocytes on computed tomography scans this assumption may be erroneous and could affect diagnostics. AIMS: To evaluate the consistency of cell counts in serially sampled CSF from EVDs, with and without patient repositioning, to assess the effect on infection diagnostics. METHODS: We performed a prospective single-center study where routine CSF sampling was followed by a second sample after 10 min, allocated around a standard patient repositioning, or not. Changes in absolute and pairwise cell counts and ratios were analyzed, including mixed regression models. RESULTS: Data from 51 patients and 162 paired samples were analyzed. We observed substantial changes in CSF cellularity as the result of both resampling and repositioning, with repositioning found to be an independent predictor of bidirectional cellular change. Glucose and lactate levels were affected, however clinically non-significant. No positive CSF cultures were seen during the study. Thirty percent (30%) of patients changed suspected EVDI status, as defined by the cell component of local and national guidelines, when resampling after repositioning. CONCLUSIONS: CSF cell counts are not consistent and are affected by patient movement suggesting a heterogeneity in the intraventricular space. The relationship between leukocytes and erythrocytes was less affected than absolute changes. Importantly, cell changes are found to increase with increased cellularity, often leading to changes in suspected EVDI status. Faster and more precise diagnostics are needed, and methods such as emerging next generation sequencing techniques my provide tools to more timely and accurately guide antibiotic treatment. Trial Registration NCT04736407, Clinicaltrials.gov, retrospectively registered 2nd February 2021.

Tonsillar Microbiota: a Cross-Sectional Study of Patients with Chronic Tonsillitis or Tonsillar Hypertrophy.

Chronic tonsillitis (CT) and tonsillar hypertrophy (TH) are common tonsillar diseases that are related to infection and inflammation. Little is known about tonsillar microbiota and its role in CT and TH. This study aims to identify palatine tonsillar microbiota both on the surface and in the core tissues of CT and TH patients. In total, 22 palatine tonsils were removed and collected from CT and TH patients who underwent surgery. The surface and core microbiota in the tonsils of CT and TH patients were compared using 16S rRNA gene sequencing of V3-V4 regions. Differential tonsillar microbiotas were found in the CT versus TH patients and surface versus core tissues. Further, a higher relative abundance of bacterial genera, including Haemophilus, Streptococcus, Neisseria, Capnocytophaga, Kingella, Moraxella, and Lachnospiraceae [G-2] in patients with TH and Dialister, Parvimonas, Bacteroidales [G-2], Aggregatibacter, and Atopobium in patients with CT, was observed. Of these, the differential genera of Dialister, Parvimonas, and Neisseria served as key factors in the tonsillar microbiota network. Notably, four representable tonsillar microbial types were identified, with one, consisting of a higher abundance of Haemophilus and Neisseria, exclusively detected in the TH patients. This study analyzed the different tonsillar microbiota from the surface and core tissues of CT and TH patients. Several bacteria and various microbial types related to CT and TH were identified, along with potential bacterial networks and related immune pathways.IMPORTANCE The human microbiota has been shown to be functionally connected to infectious and inflammation-related diseases. So far, only limited studies had been performed on tonsillar microbiota, although tonsils play an essential role in the human immune defense system and encountered numerous microorganisms. Our work presented different tonsillar microbiota from surface and core tissues of chronic tonsillitis (CT) and tonsillar hypertrophy (TH) patients. Notably, one tonsillar microbiota type, which contains a higher abundance of Haemophilus and Neisseria, was only detected in the TH patients. Furthermore, certain bacteria, such as Haemophilus, Neisseria, Dialister, and Parvimonas, may serve as microbial biomarkers to discriminate CT patients from TH patients. These data provide important microbiota data in the tonsillar research area and are highly useful for researchers both in the oral microbiome field and clinical field.

Incidence of infective endocarditis caused by viridans group streptococci in Sweden - effect of cessation of antibiotic prophylaxis in dentistry for risk individuals.

INTRODUCTION: In October 2012, the Swedish Medical Products Agency published new recommendations for the cessation of prophylactic antibiotics in dentistry for the prevention of infective endocarditis (IE). Previously, 2 g of amoxicillin per os would be administered 1 h before invasive dental procedures to patients with valve prosthesis, complicated heart valve disease, and to those with previous endocarditis. OBJECTIVES: The aim of this study was to evaluate whether the total incidence of IE caused by oral viridans group streptococci (VGS) or IE caused by staphylococci, increased in Sweden after the introduction of the new recommendations. METHODS: The incidence of IE in Sweden before and after October 2012 was calculated and compared using an interrupted time series analysis. Separate analyses were conducted for the total incidence of IE, and IE caused by VGS or Staphylococcus aureus. Cases of IE were identified using the Swedish national registry of IE, which has existed since 1995 and contains data from all Swedish hospital clinics specialising in infectious disease. All cases with hospital admission date from the 1st of Jan 2008, to the 31st of Dec 2017 were included. The incidence calculations were corrected for annual changes in population size using data from the Swedish government agency Statistics Sweden. RESULTS: The results show no statistically significant increase in the slope of the trend line of the total incidence of IE, IE caused by VGS or S. aureus in the Swedish general population after October 2012, compared to before. CONCLUSION: The results suggest that the recommended cessation of prophylactic antibiotics for the prevention of IE in dentistry has not led to an increased incidence of IE caused by oral streptococci among the Swedish population.

Fatal encephalitis associated with coronavirus OC43 in an immunocompromised child.

A child with pre-B acute lymphoblastic leukaemia (ALL) developed fatal encephalitis associated with human coronavirus OC43 (HCoV-OC43). During chemotherapy the child had a persistent HCoV-OC43 respiratory infection and later developed progressive encephalitis. Cerebrospinal fluid was negative for pathogens including HCoV-OC43, but a brain biopsy was HCoV-OC43-positive by metagenomic next-generation sequencing.

Validation of automated sepsis surveillance based on the Sepsis-3 clinical criteria against physician record review in a general hospital population: observational study using electronic health records data.

BACKGROUND: Surveillance of sepsis incidence is important for directing resources and evaluating quality-of-care interventions. The aim was to develop and validate a fully-automated Sepsis-3 based surveillance system in non-intensive care wards using electronic health record (EHR) data, and demonstrate utility by determining the burden of hospital-onset sepsis and variations between wards. METHODS: A rule-based algorithm was developed using EHR data from a cohort of all adult patients admitted at an academic centre between July 2012 and December 2013. Time in intensive care units was censored. To validate algorithm performance, a stratified random sample of 1000 hospital admissions (674 with and 326 without suspected infection) was classified according to the Sepsis-3 clinical criteria (suspected infection defined as having any culture taken and at least two doses of antimicrobials administered, and an increase in Sequential Organ Failure Assessment (SOFA) score by >2 points) and the likelihood of infection by physician medical record review. RESULTS: In total 82 653 hospital admissions were included. The Sepsis-3 clinical criteria determined by physician review were met in 343 of 1000 episodes. Among them, 313 (91%) had possible, probable or definite infection. Based on this reference, the algorithm achieved sensitivity 0.887 (95% CI: 0.799 to 0.964), specificity 0.985 (95% CI: 0.978 to 0.991), positive predictive value 0.881 (95% CI: 0.833 to 0.926) and negative predictive value 0.986 (95% CI: 0.973 to 0.996). When applied to the total cohort taking into account the sampling proportions of those with and without suspected infection, the algorithm identified 8599 (10.4%) sepsis episodes. The burden of hospital-onset sepsis (>48 hour after admission) and related in-hospital mortality varied between wards. CONCLUSIONS: A fully-automated Sepsis-3 based surveillance algorithm using EHR data performed well compared with physician medical record review in non-intensive care wards, and exposed variations in hospital-onset sepsis incidence between wards.

Temporal Dynamics and Risk Factors for Bloodstream Infection With Extended-spectrum ß-Lactamase-producing Bacteria in Previously-colonized Individuals: National Population-based Cohort Study.

Background: Little is known of the long-term risks of bloodstream infection (BSI) with extended spectrum ß-lactamase-producing Enterobacteriaceae (EPE) in previously-colonized individuals. We investigated EPE-BSI risks and associated risk factors during 6 years following EPE colonization. Methods: We performed a population-based cohort study in Sweden using national health registers. Subjects were followed from their first EPE finding in feces (n = 5513) or urine (n = 17189). The effects of co-morbidity, sociodemography, and outpatient antibiotic dispensation on EPE-BSI risks were assessed. The EPE-BSI risks were compared to those of 45161 matched population-based reference subjects. Results: The cumulative 6-year EPE-BSI incidences were 3.8%, 1.6%, and 0.02% in the urine, feces, and reference cohorts, respectively. The incidences decreased exponentially during the first 6-12 months. Among EPE-exposed subjects, urological disorders were associated with the highest adjusted cause-specific hazard ratio (aCSHR) for subsequent EPE-BSIs (3.40, 95% confidence interval 2.47-4.69). The aCSHRs were between 1.62-2.20 for male sex, immunosuppression, diabetes, malignancy, lung disease, baseline urine source, and Klebsiella pneumoniae, compared to the Escherichia coli baseline sample. Antibiotics with selective activity against gram-negative bacilli-but mostly not EPE (trimethoprim-sulfamethoxazole, fluoroquinolones, oral cephalosporins, and penicillins with extended spectrums)-and pivmecillinam were associated with doubled EPE BSI risk during the 3 months after antibiotic dispensation in EPE-colonized subjects. Conclusions: EPE in urine or feces is a substantial risk factor for subsequent EPE-BSIs, but the risk declines rapidly during the first year after detection. In EPE-colonized individuals, specific risk factors can be used to identify subgroups for targeted interventions, such as eradication therapy.