To Örebro University

Denna fallrapport beskriver en behandlings­refraktär pneumokocksepsis med konstaterat omätbar hög methemoglobinnivå i blodet.

Methemoglobinemi är oftast läkemedelsutlöst, men medfödda orsaker som glukos-6-fosfatdehydrogenasbrist förekommer. Methemoglobinemi finns beskriven vid sepsis, men det är mycket ovanligt med höga halter av methemoglobin vid infektionstillstånd.

Kliniska symtom på methemoglobinemi är dyspné, illamående, cyanos, takykardi och sjunkande medvetandegrad.

Methemoglobinemi diagnostiseras med CO-oximetri. Indirekta tecken är chokladfärgat blod och acidos, diskrepans mellan SpO2 och SaO2 som inte svarar på syrgasbehandling och SpO2 runt 85 procent.

Methemoglobinemia is a condition characterized by tissue hypoxia and normal oxygen partial pressure in the blood. The methemoglobin is created through the oxidation of the hemoglobin molecule in erythrocytes, changing Fe2+ to its ferric state Fe3+, causing it to lose its oxygen-carrying capacity. The condition can be drug-induced, caused by congenital enzyme deficiency or triggered through disease processes such as sepsis. In this case report, we describe an 80-year-old woman who developed severe methemoglobinemia in connection with a fatal pneumococcal sepsis. 

OBJECTIVES: COVID-19 impacts physical and respiratory health, and the clinical presentation ranges from asymptomatic cases to severe infections requiring hospitalisation. While the long-term effects on lung function and physical capacity are well-documented in moderate to severe cases, the long-term outcome for individuals with mild COVID-19 remains poorly understood. This study investigates the long-term recovery of physical capacity and breathlessness among both hospitalised and non-hospitalised individuals.

METHODS: This prospective cohort study enrolled individuals with confirmed SARS-CoV-2 infection between April 2020 and May 2021 through the CoVUm-study. Participants underwent assessments of lung function at 3-6 months after infection and attended follow-ups up to three years post-infection. Physical capacity was evaluated at follow-ups, using the one-minute sit-to-stand test and the modified Medical Research Council scale to assess breathlessness.

RESULTS: The cohort included 291 participants, 35% of whom were hospitalised during SARS-CoV-2 infection. At the 3-year follow-up, 191 participants completed the physical capacity test and 179 had an assessment of breathlessness. Physical capacity improved significantly in the total cohort up to two years post-infection where improvement plateaued. Hospitalisation and impaired diffusing capacity were significantly associated with reduced physical capacity (beta -6.4, p < 0.001; beta -8.9, p < 0.001, respectively) and breathlessness (beta 3.9, p < 0.001; beta 1.6, p = 0.012, respectively). While non-hospitalised participants demonstrated improvements in physical capacity for up to two years, improvement for hospitalised individuals plateaued by six months.

CONCLUSION: Hospitalisation and impaired diffusing capacity are strong independent predictors of reduced physical capacity and persistent breathlessness up to three years post-infection. Non-hospitalised individuals also experience long-term reductions in physical capacity, underscoring the need for targeted rehabilitation strategies.

BACKGROUND: Current evidence indicates that Post COVID-19 Condition (PCC) is multifaceted with distinct phenotypes. While previous studies have identified symptom clusters-commonly featuring fatigue, respiratory symptoms, and cognitive impairment-findings have been inconsistent, and no clear consensus exists. Moreover, how these symptom clusters evolve over time, particularly beyond the first year post-infection, remains poorly understood.

METHODS: This multicentre prospective cohort study included 470 hospitalised and non-hospitalised adult individuals from the CoVUm study across four sites in Sweden between 2020 and 2021. Follow-ups were conducted up to 3 years after infection to assess persistent symptoms, health-related quality of life (HRQoL), and work capacity. Symptom clusters at 6 months were identified via hierarchical cluster analysis, and participants were tracked using a k-nearest neighbour algorithm.

RESULTS: The most common symptoms at 6 months were fatigue (33 %), dyspnoea (32 %), mental fatigue (30 %), and concentration difficulties (28 %), with a median EQ-5D-5L index of 0.98 (IQR 0.93-1). Four distinct symptom clusters were identified: (i) "Few Symptoms" (n = 265, 57 %), (ii) "Respiratory Symptoms" (n = 66, 14 %), (iii) "Neurocognitive Symptoms" (n = 75, 16 %), and (iv) "Multisystem Symptoms" (n = 52, 11 %). Participants in the latter three clusters were older, had more comorbidities, and were more often hospitalised during primary COVID-19 infection. These clusters also had significantly lower HRQoL compared to the "Few Symptoms" cluster. Over time, more than half of participants transitioned to a cluster with fewer or no symptoms, with significant perceived HRQoL improvement in the "Multisystem Symptoms" cluster.

CONCLUSION: While many patients with PCC improved over time, a subset had persistent symptoms at 3 years, especially if primary infection required hospitalisation. The identification of symptom clusters and their trajectories over time contributes to a better understanding of PCC heterogeneity, ultimately bringing the field closer to consensus on the classification and long-term impact of PCC.

Background: International guidelines for Staphylococcus aureus vertebral osteomyelitis recommend 6 weeks of treatment, including oral follow-up using antibiotics with high bioavailability such as a fluoroquinolone/rifampicin combination. Oral flucloxacillin is not recommended due to low bioavailability and scarce evidence. However, flucloxacillin as oral follow-up treatment is common practice in Sweden based on favourable clinical experience, good tolerability, few interactions, and low ecological impact. Our aim was to review a single-centre experience of S. aureus vertebral osteomyelitis, with focus on flucloxacillin treatment.

Methods: A single-centre retrospective cohort of patients with Staphylococcus aureus vertebral osteomyelitis (n = 40) was identified between 2010 and 2016. Patients were further stratified by antibiotic treatment strategy with focus on oral flucloxacillin therapy (n = 24). Primary outcomes were relapse or death within 12 months of treatment initiation, and antibiotic-related adverse effects during treatment.

Results: Methicillin-susceptible S. aureus (MSSA) caused 38 of the infections (95%), and five patients (13%) died, all in-hospital. Flucloxacillin was used for at least 75% of the oral treatment duration in 24 patients (60%). Median antibiotic treatment duration among these patients was 125.5 days (IQR 95-182), 109 days (IQR 76-149) of which comprised oral antibiotics. There were two relapses and two deaths among the patients treated predominantly with flucloxacillin, resulting in a composite clinical cure rate of 83% (20 of 24).

Conclusions: Prolonged oral flucloxacillin administration could be a potential treatment option for MSSA vertebral osteomyelitis. A prospective study of optimal treatment duration and dosing strategies for flucloxacillin in vertebral osteomyelitis is warranted.

Aims: The objective was to compare anxiety, depression, and quality of life (QoL) in individuals living with type 1 (T1D) and type 2 (T2D) diabetes with matched controls during the second wave of the COVID-19 pandemic.

Methods: Via randomization, individuals living with diabetes T1D (n = 203) and T2D (n = 413), were identified during February-July 2021 through health-care registers. Population controls (n = 282) were matched for age, gender, and residential area. Questionnaires included self-assessment of anxiety, depression, QoL, and demographics in relation to SARS-CoV-2 exposure. Blood was collected through home-capillary sampling, and SARS-CoV-2 Nucleocapsid (NCP) and Spike antibodies (SC2_S1) were determined by multiplex Antibody Detection by Agglutination-PCR (ADAP) assays.

Results: Younger age and health issues were related to anxiety, depression, and QoL, with no differences between the study groups. Female gender was associated with anxiety, while obesity was associated with lower QoL. The SARS-CoV-2 NCP seroprevalence was higher in T1D (8.9 %) compared to T2D (3.9 %) and controls (4.0 %), while the SARS-CoV-2 SC2_S1 seroprevalence was higher for controls (25.5 %) compared to T1D (16.8 %) and T2D (14.0 %).

Conclusions: A higher SARS-CoV-2 infection rate in T1D may be explained by younger age and higher employment rate, and the associated increased risk for viral exposure.

BACKGROUND AND PURPOSE: Fracture-related infections (FRIs) after osteosynthesis for hip fractures have not been thoroughly investigated. Our primary aim was to assess the association between FRIs and mortality after osteosynthesis for hip fracture. Secondary aims were to investigate the incidence, microbiology, and general epidemiological aspects of these FRIs.

METHODS: This retrospective single-center study included 1,455 patients > 18 years old with non-pathological hip fractures treated with osteosynthesis between 2015 and 2019. Medical records were reviewed and FRIs were diagnosed based on current consensus criteria. The follow-up period was 2 years. Mortality was estimated using Kaplan-Meier survival analysis. Cox regression analyses were performed to investigate the potential association between FRIs, as a time-dependent variable, and increased mortality.

RESULTS: The median age for the entire cohort was 83 (interquartile range 75-89) years and 69% were females. At the 2-year follow-up mark, the crude mortality rate was 33% in the non-FRI group and 69% (11 of 16 patients) in the FRI group. Cox regression analysis assessing mortality risk revealed a hazard ratio of 3.5 (95% confidence interval [CI] 1.9-6.4) when adjusted for confounders. The incidence of FRI was 1.1% (16 of 1,455 patients). Staphylococcus aureus was the most common pathogen. Most FRI patients (94%) required at least 1 revision and 56% underwent ≥ 2 revision.

CONCLUSION: We found an association between FRIs after hip fracture osteosynthesis and increased mortality, underscoring the critical need for FRI prevention measures in this frail patient group. The incidence and microbiological findings were consistent with previous studies.

Fracture-related infections (FRI) pose a serious complication with an incidence of 1-2%. This study aimed to analyze compensation claims submitted to The Swedish National Patient Insurance Company (LÖF) because of FRI after closed/open reduction and internal fixation (C/ORIF) in the four most common fracture sites (proximal humerus, distal radius, hip, ankle). Patients registered in the LÖF database with a suspected FRI between 2011 and 2021 were identified by matching International Classification of Diseases and procedural codes indicative of a combination of fractures to the proximal humerus, distal radius, hip and ankle, C/ORIF and infection. Medical records were reviewed for fracture sites, pathogens and complications. Data from the Swedish Fracture Register (SFR) were extracted to estimate the proportion of reported claims to the presumed number of FRI. Of 122 FRI identified in the LÖF database, 34 were after C/ORIF in the proximal humerus, 12 in the distal radius, 28 in the hip and 48 in the ankle. LÖF compensated 111 patients (91%). Median time from C/ORIF to an FRI was 3 weeks (interquartile range 2-6), and 95% of all FRI occurred within 1 year after C/ORIF. Staphylococcus aureus was the most common pathogen in patients with a distal radius, hip and ankle FRI. In contrast, Cutibacterium spp. were the most common aetiology in FRI of the proximal humerus. The total number of fractures treated with C/ORIF in the four fracture sites registered in the SFR during 2021 was 18,711. Most of the FRI patients were diagnosed within the first year after C/ORIF, and 91% of the patients received compensation. Given an expected FRI incidence of 1-2%, our estimates with extrapolated data from the SFR indicate that < 10% of affected patients applied for compensation.

BACKGROUND: Dalbavancin, a semisynthetic lipoglycopeptide with exceptionally long half-life and Gram-positive spectrum, is an attractive option for infections requiring prolonged therapy, including prosthetic joint infections (PJIs).

OBJECTIVES: To investigate the prevalence of reduced susceptibility to dalbavancin in a strain collection of Staphylococcus epidermidis from PJIs, and to investigate genomic variation in isolates with reduced susceptibility selected during growth under dalbavancin exposure.

METHODS: MIC determination was performed on S. epidermidis isolates from a strain collection (n = 64) and from one patient with emerging resistance during treatment (n = 4). These isolates were subsequently cultured on dalbavancin-containing agar and evaluated at 48 h; MIC determination was repeated if phenotypical heterogeneity was detected during growth. Population analysis profile (PAP-AUC) was performed in isolates where a  ≥ 2-fold increase in MIC was detected, together with corresponding parental isolates (n = 21). Finally, WGS was performed.

RESULTS: All strains grew at 48 h on agar containing 0.125 mg/L dalbavancin. PAP-AUC demonstrated significant differences between parental and derived strains in four of the eight analysed groups. An amino acid change in the walK gene coinciding with emergence of phenotypic resistance was detected in the patient isolates, whereas no alterations were found in this region in the in vitro derived strains.

CONCLUSIONS: Exposure to dalbavancin may lead to reduced susceptibility to dalbavancin through either selection of pre-existing subpopulations, epigenetic changes or spontaneous mutations during antibiotic exposure. Source control combined with adequate antibiotic concentrations may be important to prevent emerging reduced susceptibility during dalbavancin treatment.