Assessment of a novel BLOOMY score for predicting mortality in hospitalised adults with bloodstream infection.

PURPOSE: A German multicentre study BLOOMY was the first to use machine learning approach to develop mortality prediction scores for bloodstream infection (BSI) patients, but the scores have not been assessed in other cohorts. Our aim was to assess how the BLOOMY 14-day and 6-month scores estimate mortality in our cohort of 497 cases with BSI. METHODS: Clinical data, laboratory data, and patient outcome were gathered retrospectively from patient records. The scores were calculated as presented in the BLOOMY study with the exception in the day of the evaluation. RESULTS: In our cohort, BLOOMY 14-day score estimated death by day 14 with an area under curve (AUC) of 0.87 (95% Confidence Interval 0.80-0.94). Using ≥ 6 points as a cutoff, sensitivity was 68.8%, specificity 88.1%, positive predictive value (PPV) 39.3%, and negative predictive value (NPV) 96.2%. These results were similar in the original BLOOMY cohort and outweighed both quick Sepsis-Related Organ Failure Assessment (AUC 0.76) and Pitt Bacteraemia Score (AUC 0.79) in our cohort. BLOOMY 6-month score to estimate 6-month mortality had an AUC of 0.79 (0.73-0.85). Using ≥ 6 points as a cutoff, sensitivity was 98.3%, specificity 10.7%, PPV 25.7%, and NPV 95.2%. AUCs of 6-month score to estimate 1-year and 5-year mortality were 0.80 (0.74-0.85) and 0.77 (0.73-0.82), respectively. CONCLUSION: The BLOOMY 14-day and 6-month scores performed well in the estimations of mortality in our cohort and exceeded some established scores, but their adoption in clinical work remains to be seen.

Long-term follow up of families with pathogenic NFKB1 variants reveals incomplete penetrance and frequent inflammatory sequelae.

Nuclear factor κ light-chain enhancer of activated B cells (NF-κB) family of evolutionarily conserved transcription factors are involved in key cellular signaling pathways. Previously, hypogammaglobulinemia and common variable immunodeficiency (CVID)-like phenotypes have been associated with NFKB1 variants and loss-of-function NFKB1 variants have been reported as the most common monogenic cause for CVID among Europeans. Here, we describe a Finnish cohort of NFKB1 carriers consisting of 31 living subjects in six different families carrying five distinct heterozygous variants. In contrast to previous reports, the clinical penetrance was not complete even with advancing age and the prevalence of CVID/hypogammaglobulinemia was significantly lower, whereas (auto)inflammatory manifestations were more common (42% of the total cohort). At current stage of knowledge, routine genetic screening of asymptomatic individuals is not recommended, but counseling of potential adult carriers seems necessary.

Risk of venous thromboembolism in COVID-19 infection.

The incidence of venous thromboembolism (VTE) for non-hospitalised patients with coronavirus disease-2019 infection has not been very widely studied. 13 019 persons with a positive SARS-CoV-2 nucleic acid amplification test were identified. In total, 447 (0.2%) VTEs were identified in the study population, 293 (66%) of these were pulmonary embolisms. A positive SARS-CoV-2 test did not increase the risk for VTE in the univariate analysis (odds ratio (OR): 1.0, 95% confidence interval (CI): 0.69-1.4) or multivariable analysis (OR: 1.36, 95% CI: 0.93-1.97).

Healthcare-associated blood stream infections in hematological patients in Finland during the years 2006-2016.

OBJECTIVES: The aim was to identify the clinical characteristics, outcome, and antimicrobial susceptibility of healthcare-associated bloodstream infections (BSIs) in hematological patients. METHODS: This retrospectively collected laboratory-based surveillance data include 3404 healthcare-associated BSIs in 2296 patients with a hematological malignancy in hospitals participating in the Finnish Hospital Infection Program from January 1, 2006, to December 31, 2016. RESULTS: The most common underlying diseases were acute myelogenous leukemia (35%) and non-Hodgkin lymphoma (22%). Gram-positive organisms accounted for 60%-46% and gram-negative organisms for 24%-36% of BSIs in 2006-2016. The most common causative organism was coagulase-negative staphylococci (CoNS) (n = 731). The 7- and 28-day case fatality rates were 5.2% and 11.4%, respectively, and was highest in BSIs caused by Candida species (10.8% and 30.8%). The median age of patients increased from 59 years in 2006-2008 to 62 years in 2015-2016 (P < .01). Five percent of S aureus isolates were resistant to methicillin and five percent of Pseudomonas aeruginosa isolates were multidrug-resistant. Four percent of Klebsiella and seven percent of E coli isolates were resistant to ceftazidime. CONCLUSIONS: The proportion of gram-positive bacteria decreased and gram-negative bacteria increased over time. The case fatality rate was low and the median age of patients increased during the study.

Spa type distribution in MRSA and MSSA bacteremias and association of spa clonal complexes with the clinical characteristics of bacteremia.

The genetic distribution of invasive methicillin-susceptible (MSSA) and resistant S. aureus (MRSA) strains has to be addressed in order to target infection control strategies. A large MRSA epidemic caused by a certain MRSA strain (spa type 067) broke out in 2001 in our health district. We wanted to investigate the current spa type distribution in MRSA and MSSA bacteremias and assess the potential association of spa clonal complexes (spaCC) with the clinical characteristics of S. aureus bacteremia. One hundred nine invasive MRSA isolates and 353 invasive MSSA isolates were spa typed and grouped into clonal complexes (spaCC). Spa type distribution was compared to that of colonizing MRSA strains. Spa type and spaCC data linked to clinical information on the course of bacteremic cases was used to search for differences in virulence between strains. Spa type distribution in MRSA is less heterogenic than in MSSA. t067 dominates both in MRSA colonisations and in invasive findings. Among MSSA, no such dominating strains were found. Of spaCCs, mortality was the highest in spaCC 067 (25.6%). SpaCC 008 was more often associated with endocarditis than other CCs (22.7 vs 5.8%, p = 0.013), spaCC 2133 with skin infections (68.4 vs 36.4%, p = 0.007), and spaCC 012 with foreign body infections (25.0 vs 9.3%, p = 0.029) than other clonal complexes. A single successful strain can explain the major proportion of MRSA among S. aureus bacteremias. Certain spaCCs showed association with certain clinical characteristics. These findings suggest that S. aureus strains differ in their virulence and invasiveness.

A Serratia marcescens outbreak in a neonatal intensive care unit was successfully managed by rapid hospital hygiene interventions and screening.

AIM: Serratia marcescens is a rare, but important, pathogen in hospital-acquired infections, especially in neonatal units. Outbreaks may cause significant mortality among neonates. This study describes how an outbreak of S. marcescens was handled in a neonatal intensive care unit in Finland in June 2015. METHODS: Tampere University Hospital is the only hospital that offers intensive care for preterm neonates in the Pirkanmaa health district area in Finland. Between June 9, 2015 and June 29, 2015, seven neonates were screened positive for S. marcescens in the hospital. We examined the management and outcomes, including environmental sampling. RESULTS: Two of the seven neonates developed a bloodstream infection, and one with S. marcescens sepsis died after six days of antibiotic treatment. The outbreak was rapidly managed with active hospital hygiene interventions, including strict hand hygiene, cleaning, patient screening, contact precautions and education. Environmental sampling was limited to one water tap and a ventilator, and the results were negative. The outbreak was contained within three weeks, and no further cases appeared. The screening of healthcare workers was not necessary. CONCLUSION: A S. marcescens outbreak caused significant morbidity in neonates and one death. Rapid hospital hygiene interventions and patient screening effectively contained the outbreak.

Damaging heterozygous mutations in NFKB1 lead to diverse immunologic phenotypes.

BACKGROUND: The nuclear factor κ light-chain enhancer of activated B cells (NF-κB) signaling pathway is a key regulator of immune responses. Accordingly, mutations in several NF-κB pathway genes cause immunodeficiency. OBJECTIVE: We sought to identify the cause of disease in 3 unrelated Finnish kindreds with variable symptoms of immunodeficiency and autoinflammation. METHODS: We applied genetic linkage analysis and next-generation sequencing and functional analyses of NFKB1 and its mutated alleles. RESULTS: In all affected subjects we detected novel heterozygous variants in NFKB1, encoding for p50/p105. Symptoms in variant carriers differed depending on the mutation. Patients harboring a p.I553M variant presented with antibody deficiency, infection susceptibility, and multiorgan autoimmunity. Patients with a p.H67R substitution had antibody deficiency and experienced autoinflammatory episodes, including aphthae, gastrointestinal disease, febrile attacks, and small-vessel vasculitis characteristic of Behçet disease. Patients with a p.R157X stop-gain experienced hyperinflammatory responses to surgery and showed enhanced inflammasome activation. In functional analyses the p.R157X variant caused proteasome-dependent degradation of both the truncated and wild-type proteins, leading to a dramatic loss of p50/p105. The p.H67R variant reduced nuclear entry of p50 and showed decreased transcriptional activity in luciferase reporter assays. The p.I553M mutation in turn showed no change in p50 function but exhibited reduced p105 phosphorylation and stability. Affinity purification mass spectrometry also demonstrated that both missense variants led to altered protein-protein interactions. CONCLUSION: Our findings broaden the scope of phenotypes caused by mutations in NFKB1 and suggest that a subset of autoinflammatory diseases, such as Behçet disease, can be caused by rare monogenic variants in genes of the NF-κB pathway.

Concordance between the old and new diagnostic criteria for periprosthetic joint infection.

PURPOSE: There is no uniform definition for periprosthetic joint infection (PJI). New diagnostic criteria were formulated in an international consensus meeting in 2013 and adopted by Centers for Disease Control (CDC) in 2016. The purpose of this study is to compare the new diagnostic criteria with the old CDC criteria from the year 1992. METHODS: Patients, who had been treated for PJI of hip or knee from 2002 to 2014, in a tertiary care hospital, were identified. Patient records were reviewed by a physician to identify PJI cases fulfilling the old or new CDC criteria and to record data concerning the diagnostic criteria. PJI frequencies were calculated for the two diagnostic criteria sets. Cross tables were formed to compare the concordance between the two sets of criteria in the whole material and in different clinical subgroups. RESULTS: Overall 405 cases fulfilling either or both sets of criteria for PJI were identified. 73 (18%) of the patients fulfilled only the old criteria, whereas only one (0.2%) fulfilled only the new criteria. Of the patients who did not fulfil the new criteria, in 39 (53%) the diagnosis was based solely on the clinician's opinion. CONCLUSIONS: The number of PJIs is notably lower when using the new, more objective, diagnostic criteria. A large portion of the cases diagnosed as infection by the treating clinician, did not fulfil the new diagnostic criteria.

Smoking is associated with aggravated kidney injury in Puumala hantavirus-induced haemorrhagic fever with renal syndrome.

BACKGROUND: Previous studies indicate that smoking affects the outcome of some infections and is a risk factor for Puumala virus (PUUV) infection. The aim of this study was to assess the effect of smoking on the clinical severity of PUUV infection and the prevalence of smoking in patients with PUUV infection. METHODS: A questionnaire on smoking habits was sent to 494 patients in 2012, who had been treated in Tampere University Hospital, Finland, for serologically confirmed PUUV infection during years 1982-2012. RESULTS: Of all patients, 357 (72%) participated. Maximum plasma creatinine level measured during acute illness was significantly higher in current smokers than in non-smokers (median: 273 versus 184 µmol/L, P < 0.001). Current smokers had a higher maximum blood leucocyte count than non-smokers (median: 10.8 versus 8.9 × 10(9)/L, P < 0.001) and they were younger than non-smokers (38 versus 45 years, P < 0.001). There were no differences between current smokers and non-smokers in the other variables reflecting the severity of PUUV infection. Altogether 51% were current smokers at the time of onset of the illness, 57% of males and 36% of females. During these years in Finland, smoking among males in the same aged population has decreased from 33 to 22% and among females, smoking has varied between 14 and 20%. CONCLUSIONS: Smoking is common in patients with PUUV infection. Current smokers suffer from more severe acute kidney injury (AKI) and they have higher leucocyte count than non-smokers in PUUV infection. Smoking cessation decreases the risk of severe AKI to the same level as observed in never-smokers.

Acquisition of complement factor H is important for pathogenesis of Streptococcus pyogenes infections: evidence from bacterial in vitro survival and human genetic association.

Streptococcus pyogenes (or group A streptococcus [GAS]) is a major human pathogen causing infections, such as tonsillitis, erysipelas, and sepsis. Several GAS strains bind host complement regulator factor H (CFH) via its domain 7 and, thereby, evade complement attack and C3b-mediated opsonophagocytosis. Importance of CFH binding for survival of GAS has been poorly studied because removal of CFH from plasma or blood causes vigorous complement activation, and specific inhibitors of the interaction have not been available. In this study, we found that activation of human complement by different GAS strains (n = 38) correlated negatively with binding of CFH via its domains 5-7. The importance of acquisition of host CFH for survival of GAS in vitro was studied next by blocking the binding with recombinant CFH5-7 lacking the regulatory domains 1-4. Using this fragment in full human blood resulted in death or radically reduced multiplication of all of the studied CFH-binding GAS strains. To study the importance of CFH binding in vivo (i.e., for pathogenesis of streptococcal infections), we used our recent finding that GAS binding to CFH is diminished in vitro by polymorphism 402H, which is also associated with age-related macular degeneration. We showed that allele 402H is suggested to be associated with protection from erysipelas (n = 278) and streptococcal tonsillitis (n = 209) compared with controls (n = 455) (p < 0.05). Taken together, the bacterial in vitro survival data and human genetic association revealed that binding of CFH is important for pathogenesis of GAS infections and suggested that inhibition of CFH binding can be a novel therapeutic approach in GAS infections.

Methicillin-resistant Staphylococcus aureus epidemic restricted to one health district in Finland: a population-based descriptive study in Pirkanmaa, Finland, years 2001-2011.

BACKGROUND: The incidence of methicillin-resistant Staphylococcus aureus (MRSA) has been low in the Scandinavian countries, including Finland. METHODS: We report a population-based, prospective survey of an exceptionally large ongoing MRSA epidemic in a Finnish health district (HD), Pirkanmaa HD, during 2001-2011 caused by 1 strain, spa t067 (FIN-16). RESULTS: The first FIN-16 case in the HD was identified in 2000. Ten years later, 2447 carriers had been found in 95 different institutions. MRSA in carriers was mostly health care-associated (98%). The epidemic emerged in long-term care facilities and gradually spread to acute hospitals. The majority of carriers were elderly people (median age 78 y). Fifty-two percent of new carriers had an infection with MRSA at the time of detection. CONCLUSIONS: The incidence of MRSA in Pirkanmaa HD is substantially higher than the incidence for all of Finland. Temporary projects to control MRSA have not proved sufficient to contain this large epidemic.

[Fever, skin rash and blood bullae of the ears in a middle-aged woman]. / Keski-ikäisen naisen kuume, ihottuma ja korvien veribullat.

A healthcare worker sought medical advice after four days of fever, muscle pains, occipital headache and blocked ears, and was diagnosed with a high CRP level and blood bullae in the outer ear canal. In addition, skin rash appeared during hospital care, and the fever did not seem to go down upon treatment with broad-spectrum antibiotics, during which the CRP rose to a level of 413 mg/L at the highest. Haemorragic bullous otisis was confirmed diagnosis caused by Mycoplasma Pneumoniae.

Effect of non-cephalosporin antibiotic prophylaxis on the risk of periprosthetic joint infection after total joint replacement surgery: a retrospective study with a 1-year follow-up.

Background: Cephalosporins are recommended as first-line antibiotic prophylaxis in total joint replacement surgery. Studies have shown an increased risk for periprosthetic joint infection (PJI) when non-cephalosporin antibiotics have been used. This study examines the effect of non-cephalosporin antibiotic prophylaxis on the risk for PJI. Methods: Patients with a primary hip or knee replacement performed from 2012 to 2020 were identified (27 220 joint replacements). The primary outcome was the occurrence of a PJI in a one-year follow-up. The association between perioperative antibiotic prophylaxis and the outcome was examined using logistic regression analysis. Discussion: Cefuroxime was used as prophylaxis in 26,467 operations (97.2%), clindamycin in 654 (2.4%) and vancomycin in 72 (0.3%). The incidence of PJI was 0.86% (228/26,467) with cefuroxime and 0.80% (6/753) with other prophylactic antibiotics. There was no difference in the risk for PJI with different prophylactic antibiotics in the univariate (OR 1.06, 95% CI 0.47-2.39) or multivariable analysis (OR 1.02, 95% CI 0.45-2.30). Conclusion: Non-cephalosporin antibiotic prophylaxis in primary total joint replacement surgery was not associated with an increased risk for PJI.

Presence of Streptococcus pyogenes in the throat in invasive Group A Streptococcal disease: a prospective two-year study in two health districts, Finland.

PURPOSE: Streptococcus pyogenes (Group A Streptococcus, GAS) is an important human pathogen that can cause severe invasive (iGAS) infections. Throat carriage has been assumed to possibly lead to hematogenous seeding. Retrospective studies may estimate the incidence of throat carriage in iGAS patients inaccurately. In this study we aimed to gather data on the presence of GAS in the throat among iGAS patients in a prospective setting. METHODS: We conducted a prospective clinical study covering iGAS infections in adult patients in two university hospitals in Finland from June 2018 to July 2020. Recruited patients' throats were swabbed for culture and isothermal amplification tests (IAT) to search for GAS. The study was registered at ClinicalTrials.gov as ID NCT03507101. RESULTS: We enrolled 45 patients. Throat swabs were obtained from 39/45 (87%) patients. Ten patients (22%) had a positive IAT for GAS. They were statistically significantly more likely to be male (9/10 [90%] vs 13/29 [45%], p = .024). Several different emm types caused the iGAS infections. CONCLUSIONS: GAS was frequently observed in throat swabs of patients with iGAS infection. This may suggest that hematogenous seeding from the nasopharynx is a possible portal of entry.

Nasal nitric oxide is decreased in acute mild COVID-19 and related to viral load.

Gaseous nitric oxide levels from the lungs (FeNO) and from the nose (nNO) have been demonstrated to react to acute infection or influenza vaccination. There are no published data on nNO levels during acute COVID-19, but normal levels of FeNO have been reported in one study. Our aim was to assess if acute mild COVID-19 alters nasal or bronchial NO output at the time of acute infection and at a two-month follow up, and if this is related to symptoms or viral load. This study included 82 subjects with mild acute airway infection who did not need hospitalization: 43 cases (reverse transcription polymerase chain reaction (RT-PCR)-positive for SARS-CoV-2 in routine testing from nasopharynx) and 39 age- (±5 years) and gender-matched controls (RT-PCR-negative for SARS-CoV-2). During acute infection, the cases had lower nNO compared to controls (158 [104-206] vs. 232 [203-279] nl min-1;p< 0.001), but after two months, there was no significant difference between the groups (230 [179-290] vs. 268 [222-320] nl min-1;p= 0.162). There was no difference in FeNO between the groups at either of the visits. Nasal NO correlated with the cycle threshold (Ct) value of the nasopharyngeal RT-PCR test for SARS-CoV-2 (Spearman'srs= 0.550;p< 0.001), that is, nNO was lower with a higher viral load. Nasal NO output was decreased in acute COVID-19 in relation to higher viral load, suggesting that the type and intensity of inflammatory response affects the release of NO from airway mucosa. In these subjects without significant lower airway involvement, there were no clinically relevant findings regarding FeNO.

Population-Based Assessment of Contact Tracing Operations for Coronavirus Disease 2019 in Pirkanmaa Hospital District, Finland.

Background: The coronavirus disease 2019 (COVID-19) epidemic overwhelmed local contact tracing (CT) efforts in many countries. In Finland, severe acute respiratory syndrome coronavirus 2 incidence and mortality were among the lowest in Europe during 2020-2021. We evaluated CT efficiency, effectiveness, and transmission settings. Methods: Polymerase chain reaction (PCR) test-positive COVID-19 cases and high-risk contacts in the population-based CT database of Pirkanmaa Hospital District (population 540 000) during June 2020-May 2021 were interviewed. Results: Altogether 353 926 PCR tests yielded 4739 (1.3%) confirmed cases (average 14-day case notification rate, 34 per 100 000 population); about 99% of confirmed cases and high-risk contacts were reached by a CT team. Of 26 881 high-risk contacts who were placed in quarantine, 2275 subsequently tested positive (48% of new cases), 825 (17%) had been in quarantine ≥48 hours before symptoms, and 3469 (77%) of locally acquired cases were part of transmission chains with an identified setting. The highest secondary attack rates were seen in households (31%), healthcare patients (18%), and private functions (10%). Among the 311 hospitalized patients, COVID-19 diagnosis or exposure was known in 273 (88%) before emergency room admission (identified patients). Healthcare workers had the highest proportion of work-related infections (159 cases [35%]). The source of infection was classifiable in 65% and was most commonly a coworker (64 cases [62%]). Conclusions: Our data demonstrate the role of effective testing and CT implementation during the cluster phase of COVID-19 spread. Although half of newly diagnosed cases were already in quarantine, targeted public health measures were needed to control transmission. CT effectiveness during widespread community transmission should be assessed.

Alcohol Consumption and Its Influence on the Clinical Picture of Puumala Hantavirus Infection.

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. Characteristic clinical findings include acute kidney injury (AKI), thrombocytopenia, and capillary leakage. Smoking increases the risk of severe AKI, but it is not known whether alcohol consumption predisposes patients to a more severe infection. Liver and pancreatic enzymes, as well as biomarkers of alcohol consumption (gamma-glutamyl transferase, GGT; carbohydrate-deficient transferrin, CDT; GGT-CDT combination; and ethyl glucuronide, EtG), were measured from 66 patients with acute PUUV infection during hospitalization and at the convalescence phase. Alcohol consumption was present in 41% of the study population, 15% showing signs of heavy drinking. Alcohol use did not affect the severity of PUUV induced AKI nor the overall clinical picture of the infection. Liver enzyme levels (GGT or alanine aminotransferase, ALT) were elevated in 64% of the patients, but the levels did not associate with the markers reflecting the severity of the disease. Serum amylase activities at the convalescent stage were higher than those at the acute phase (p < 0.001). No cases with acute pancreatitis were found. In conclusion, our findings indicate that alcohol consumption does not seem to affect the clinical course of an acute PUUV infection.