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BACKGROUND: Revised diagnostic criteria for infective endocarditis (IE), the 2023 Duke-ISCVID criteria, were recently presented and need validation. Here, we compare the 2000 modified Duke criteria for IE with Duke-ISCVID among patients with bacteremia and relate the diagnostic classification to IE treatment. METHODS: We reanalyzed patient cohorts with Staphylococcus aureus, Staphylococcus lugdunensis, non-ß-hemolytic streptococci, Streptococcus-like bacteria, Streptococcus dysgalactiae, Enterococcus faecalis, and HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) bacteremia. Episodes were classified as definite, possible, or rejected IE with the modified Duke and Duke-ISCVID criteria. Reclassification included the microbiology criteria, positron emission tomography-computed tomography, and cardiac implanted electronic devices. To calculate sensitivity, patients treated for IE were considered as having IE. RESULTS: In 4050 episodes of bacteremia, the modified Duke criteria assigned 307 episodes (7.6%) as definite IE, 1190 (29%) as possible IE, and 2553 (63%) as rejected IE. Using the Duke-ISCVID criteria, 13 episodes (0.3%) were reclassified from possible to definite IE, and 475 episodes (12%) were reclassified from rejected to possible IE. With the modified Duke criteria, 79 episodes that were treated as IE were classified as possible IE, and 11 of these episodes were reclassified to definite IE with Duke-ISCVID. Applying the decision to treat for IE as a reference standard, the sensitivity of the Duke-ISCVID criteria was 80%. None of the 475 episodes reclassified to possible IE were treated as IE. CONCLUSIONS: The Duke-ISCVID criteria reclassified a small proportion of episodes to definite IE at the expense of more episodes of possible IE. Future criteria should minimize the possible IE group while keeping or improving sensitivity.
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Bacteriemia , Doenças Transmissíveis , Endocardite Bacteriana , Endocardite , Humanos , Estudos Retrospectivos , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/microbiologia , Endocardite/diagnóstico , Endocardite/microbiologia , Bacteriemia/diagnóstico , Bacteriemia/microbiologiaRESUMO
PURPOSE: Patients with non-beta-hemolytic streptococcal bacteremia (NBHSB) are at risk of infective endocarditis (IE). Patients with cardiac implantable electronic device (CIED) have been described to have an increased risk of IE. The aim of the study was to describe a population-based cohort of patients with NBHSB and CIED and variables associated with IE and recurrent NBHSB. METHODS: All episodes with NBHSB in blood culture from 2015 to 2018 in a population of 1.3 million inhabitants were collected from the Clinical Microbiology Laboratory, Lund, Sweden. Through medical records, patients with CIED during NBHSB were identified and clinical data were collected. Patients were followed 365 days after NBHSB. RESULTS: Eighty-five episodes in 79 patients with CIED and NBHSB constituted the cohort. Eight patients (10%) were diagnosed with definite IE during the first episode, five of whom also had heart valve prosthesis (HVP). In 39 patients (49%) transesophageal echocardiography (TEE) was performed of which six indicated IE. Four patients had the CIED extracted. Twenty-four patients did not survive (30%) the study period. Four patients had a recurrent infection with NBHSB with the same species, three of whom had HVP and had been evaluated with TEE with a negative result during the first episode and diagnosed with IE during the recurrency. CONCLUSION: The study did not find a high risk of IE in patients with NBHSB and CIED. Most cases of IE were in conjunction with a simultaneous HVP. A management algorithm is suggested.
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Rothia, Kocuria, Arthrobacter, and Pseudoglutamicibacter are bacterial species within the family Micrococcaeae. Knowledge of human infections due to these bacteria is limited. This study aimed to examine features of infections caused by non-Micrococcus Micrococcaeae (NMM). Findings of NMM from blood cultures and other sterile cultures from 2012 to 2021 were identified from the records of the Department of Clinical Microbiology in Region Skåne, Lund, Sweden. Medical records were retrospectively reviewed. True infection was defined as having signs of infection, no other more likely pathogen, and no other focal infection, together with two positive blood cultures or one positive blood culture and an intravascular device. A total of 197 patients with findings of NMM in blood cultures were included. Among adult patients with bacteremia, 29 patients (22%) were considered to have a true infection. Adults with true infection were significantly more likely to have malignancy (69%), leukopenia (62%), and treatment with chemotherapeutics (66%) compared to patients with contaminated samples (24%, 3%, and 8%, respectively) (P < 0.001). A total of 31 patients had findings of NMM in other sterile cultures, and infections were considered true in joints (n = 4), a pacemaker (n = 1), and peritoneal dialysis fluid (n = 1). Infections due to NMM occur but are rare. Growth of NMM in blood cultures should be suspected to be a true infection mainly in immunocompromised patients.
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Arthrobacter , Bacteriemia , Micrococcaceae , Adulto , Humanos , Micrococcus , Estudos Retrospectivos , Bacteriemia/microbiologiaRESUMO
Infective endocarditis (IE) caused by bacteria within Haemophilus (excluding Haemophilus influenzae), Aggregatibacter, Cardiobacterium, Eikenella and Kingella (HACEK) is rare. This study aimed to describe clinical features of IE caused by HACEK genera in comparison with IE due to other pathogens. Cases of IE due to HACEK were identified through the Swedish Registry of Infective Endocarditis (SRIE). Clinical characteristics of IE cases caused by HACEK were compared with cases of IE due to other pathogens reported to the same registry. Ninety-six patients with IE caused by HACEK were identified, and this corresponds to 1.8% of all IE cases. Eighty-three cases were definite endocarditis, and the mortality rate was 2%. The median age was 63 years, which was lower compared to patients with IE caused by other pathogens (66, 70 and 73 years respectively, p ≤ 0.01). Patients with IE caused by Haemophilus were younger compared to patients with IE due to Aggregatibacter (47 vs 67 years, p ≤ 0.001). Patients with IE due to HACEK exhibited longer duration from onset of symptoms to hospitalization and had more prosthetic valve endocarditis compared to patients with IE due to Staphylococcus aureus (10 vs 2 days, p ≤ 0.001, and 35 vs 14%, p ≤ 0.001). This is, to date, the largest study on IE due to HACEK. Aggregatibacter was the most common cause of IE within the group. The condition has a subacute onset and often strikes in patients with prosthetic valves, and the mortality rate is relatively low.
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Bactérias/classificação , Bactérias/isolamento & purificação , Endocardite Bacteriana/microbiologia , Endocardite/microbiologia , Sistema de Registros , Adulto , Idoso , Bactérias/patogenicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Suécia , Fatores de TempoRESUMO
SARS-CoV-2 has spread rapidly worldwide, causing the COVID-19 pandemic. Platelet activation and platelet-leukocyte complex formation are proposed to contribute to disease progression. Here, we report platelet and leukocyte activation during acute and convalescent COVID-19 in patients recruited between May-July 2020. Blood samples were analyzed by flow cytometry and ELISA using paired comparison between inclusion (day 0) and 28 days later. The majority of patients were mildly or moderately ill with significantly higher cytokine levels (IL-6 and IL-10) on day 0 as compared with day 28. Platelet activation and granule release were significantly higher on day 0 compared with day 28, as determined by ADP- or thrombin-induced surface CD62P expression, baseline released CD62P, and thrombin-induced platelet-monocyte complex formation. Monocyte activation and procoagulant status at baseline and post activation were heterogeneous but generally lower on day 0 compared with day 28. Baseline and thrombin- or fMLF-induced neutrophil activation and procoagulant status were significantly lower on day 0 compared with day 28. We demonstrate that during the acute phase of COVID-19 compared with the convalescent phase, platelets are more responsive while neutrophils are less responsive. COVID-19 is associated with thromboembolic events where platelet activation and interaction with leukocytes may play an important role.
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Plaquetas , COVID-19 , Convalescença , Monócitos , Ativação de Neutrófilo , Neutrófilos , Ativação Plaquetária , SARS-CoV-2/metabolismo , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/metabolismo , Plaquetas/patologia , COVID-19/sangue , COVID-19/patologia , Feminino , Citometria de Fluxo , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Monócitos/patologia , Neutrófilos/metabolismo , Neutrófilos/patologiaRESUMO
Knowledge of infective endocarditis (IE) caused by Streptococcus dysgalactiae (SD) is limited. This study aimed to identify the clinical and microbiological features of SD-caused IE and to investigate any possible synergy between penicillin and gentamicin on SD isolates. Cases of IE 2008-2016 due to SD reported to the Swedish Registry of Infective Endocarditis (SRIE) were identified. Isolates were emm typed and synergy between antibiotics was determined in time-kill experiments. Medical records were reviewed and SD-cases were compared to cases of IE due to other pathogens reported to the SRIE. Fifty cases of SD-caused IE were confirmed. emm types stC74a, stG62647, and stG643 were most commonly encountered. The patients had a median age of 74 years (range 38-93) and were significantly older compared to patients with Staphylococcus aureus-caused IE, (65 years (p = 0.003)). The median time to diagnosis from symptom onset was 1 day for patients with SD-caused IE which was less compared to patients with IE due to the other pathogens (2-15 days). Embolization was seen in 46% and the in-hospital mortality was 8%. Etest-based methods did not indicate any synergy between penicillin and gentamicin whereas synergy was noted for four out of nine isolates applying time-kill assays. This is the largest study of SD-caused IE, a condition with an acute onset predominantly affecting elderly people. Synergy between penicillin and gentamicin against some SD isolates was distinguished but the potential benefit of this must be weighed against the risk of aminoglycoside side effects.
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Endocardite Bacteriana/epidemiologia , Endocardite/microbiologia , Streptococcus/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Transporte/genética , Sinergismo Farmacológico , Endocardite/mortalidade , Feminino , Gentamicinas/uso terapêutico , Mortalidade Hospitalar , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Penicilinas/uso terapêutico , Sistema de Registros , Staphylococcus aureus , Streptococcus/efeitos dos fármacos , Streptococcus/genética , Suécia/epidemiologiaRESUMO
BACKGROUND: Erysipelas is a common and severe infection where the aetiology and optimal management is not well-studied. Here, we investigate the clinical features, bacteriological aetiology, and treatment of erysipelas. METHODS: Episodes of erysipelas in a seven-years period in our institution were studied retrospectively using a pre-specified protocol and is presented with descriptive and comparative statistics. RESULTS: 1142 episodes of erysipelas were identified in 981 patients. Patients had a median age of 61 years, 59 % were male, a majority had underlying diseases or predisposing conditions, and the leg was most often affected. Wound cultures were taken in 343 episodes and 56 grew group A streptococci (GAS), 53 grew group G streptococci (GGS), 11 grew group C streptococci (GCS), and 153 grew Staphylococcus aureus. Blood cultures were drawn in 49 % of episodes and 50 cultures were positive with GGS as the most common finding (21 cultures) followed by GAS in 13, group B streptococci in 5, S. aureus in 4, and GCS in 3 cultures. In 45 % of episodes, patients received antibiotics with activity against S. aureus. CONCLUSIONS: GGS is the most common streptococcus isolated in erysipelas and the role of S. aureus in erysipelas remains elusive.
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Erisipela/microbiologia , Staphylococcus aureus/isolamento & purificação , Streptococcus/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Erisipela/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Streptococcus pyogenes/isolamento & purificação , Adulto JovemRESUMO
BACKGROUND: Swift identification and diagnosis of gastrointestinal infections are crucial for prompt treatment, prevention of complications, and reduction of the risk of hospital transmission. The radiological appearance on computed tomography could potentially provide important clues to the etiology of gastrointestinal infections. We aimed to describe features based on computed tomography of patients diagnosed with Campylobacter, Salmonella or Shigella infections in South Sweden. METHODS: This was a retrospective observational population-based cohort study conducted between 2019 and 2022 in Skåne, southern Sweden, a region populated by 1.4 million people. Using data from the Department of Clinical Microbiology combined with data from the Department of Radiology, we identified all patients who underwent computed tomography of the abdomen CTA two days before and up to seven days after sampling due to the suspicion of Campylobacter, Salmonella or Shigella during the study period. RESULTS: A total of 215 CTAs scans performed on 213 patients during the study period were included in the study. The median age of included patients was 45 years (range 11-86 years), and 54% (114/213) of the patients were women. Of the 215 CTAs, 80% (n = 172) had been performed due to Campylobacter and 20% (n = 43) due to Salmonella enteritis. CTA was not performed for any individual diagnosed with Shigella during the study period. There were no statistically significant differences in the radiological presentation of Campylobacter and Salmonella infections. CONCLUSION: The most common location of Campylobacter and Salmonella infections was the cecum, followed by the ascending colon. Enteric wall edema, contrast loading of the affected mucosa, and enteric fat stranding are typical features of both infections. The CTA characteristics of Campylobacter and Salmonella are similar, and cannot be used to reliably differentiate between different infectious etiologies.
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Infecções por Campylobacter , Infecções por Salmonella , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Adulto , Infecções por Campylobacter/diagnóstico por imagem , Infecções por Campylobacter/epidemiologia , Infecções por Campylobacter/diagnóstico , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Idoso , Infecções por Salmonella/diagnóstico por imagem , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/microbiologia , Adolescente , Suécia/epidemiologia , Idoso de 80 Anos ou mais , Criança , Adulto Jovem , Campylobacter/isolamento & purificação , Salmonella/isolamento & purificaçãoRESUMO
BACKGROUND: Human infections due to Eubacterium are rare and knowledge of the condition is limited. This study aimed to describe clinical characteristics and outcome in patients with Eubacterium bacteremia. METHODS: Episodes of Eubacterium bacteremia were identified through the clinical microbiology laboratory in Lund, Sweden. Medical records were retrospectively reviewed. Blood isolates of Eubacterium were collected and antibiotic susceptibility testing was performed with agar dilution. RESULTS: Seventeen patients with Eubacterium bacteremia were identified of whom six had monomicrobial bacteremia. The incidence was 1.7 cases of Eubacterium bacteremia per million inhabitants and year. The median age was 67 years (interquartile range 63-79 years), and six patients had some form of malignancy. Most of the patients an abdominal focus of infection and the 30-day mortality was low (n = 1). CONCLUSIONS: Invasive infections with Eubacterium have a low incidence. The condition has a low mortality and an abdominal focus of infection, and malignancy, is common.
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Bacteriemia , Neoplasias , Humanos , Pessoa de Meia-Idade , Idoso , Eubacterium , Estudos Retrospectivos , Anaerobiose , Bacteriemia/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Background: Bacteremia with species in the genus Campylobacter is rare, and knowledge of the disease course in comparison with Campylobacter enteritis is limited. Methods: This is a retrospective population-based study. Episodes of Campylobacter bacteremia and Campylobacter enteritis with a concurrent negative blood culture result that occurred between 2015 and 2022 in southern Sweden were identified through the laboratory database. Medical records were reviewed, and clinical features between patients with bacteremic Campylobacter infections were compared with patients with Campylobacter spp found in feces. Results: The study included 29 bacteremic infections with Campylobacter and 119 cases of Campylobacter spp found in feces. Patients with Campylobacter bacteremia were significantly older than those with enteritis (72 years [IQR, 58-62] vs 58 years [IQR, 33-67], P < .0001). Eleven patients with bacteremia developed sepsis within 48â hours from blood culturing, and no patient died within 30 days from hospital admission. Conclusions: Campylobacter bacteremia is rare and occurs mainly in the elderly with comorbidities. In comparison with Campylobacter infections limited to the gastrointestinal tract, patients with bacteremic Campylobacter infections are older and seem more prone to develop sepsis. Classical gastroenteritis symptoms in bacteremic cases with Campylobacter may be absent.
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PURPOSE: Invasive infections with Streptococcus dysgalactiae predominantly occur in persons of older age with substantial morbidity and mortality. Time to positivity from blood cultures (TTP) has been shown to be a prognostic indicator in bloodstream infections caused by other beta-haemolytic streptococci. This study aimed to determine any possible association between TTP and outcome in invasive infections due to S. dysgalactiae. MATERIALS AND METHODS: Episodes of S. dysgalactiae bacteraemia, that occurred during 2015-2018 in the Region of Skåne, Sweden, were identified through the laboratory database and retrospectively studied. Any association with TTP and the primary outcome, death within 30 days and the development of sepsis or disease deterioration within 48 hours from blood culturing as secondary outcomes were investigated. RESULTS: Among the 287 episodes of S. dysgalactiae bacteraemia, 30-day mortality rate was 10% (n = 30). Median TTP was 9.3 h (interquartile range 8.0-10.3 h). Median TTP was statistically significantly shorter in patients who died within 30 days compared to surviving patients (7.7 vs 9.3 h, p = .001, Mann-Whitney U test). Short TTP(≤ 7.9 h) was still associated with 30-day mortality when adjusting for age, (OR 4.4, 95% CI 1.6-12.2, p = .004). Associations between secondary outcomes and levels of TTP were not observed. CONCLUSION: TTP may be an important prognostic indicator for 30-day mortality in patients with bloodstream infections due to S. dysgalactiae.
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Bacteriemia , Sepse , Infecções Estreptocócicas , Humanos , Hemocultura , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Pyogenic liver abscess (PLA) is a rare but potentially life-threatening disease, and estimates suggest a gradual increase in the incidence during the last decades. The primary aim of this study was to report the incidence, trend and aetiology of PLA during a decade in Southern Sweden. METHODS: This was a population-based observational cohort study between 2011 and 2020 in Skåne, Southern Sweden. Data were retrieved from the Swedish National Board of Health and Welfare for all individuals diagnosed with liver abscess (K750) according to ICD-10 (International Statistical Classification of Diseases, 10th revision). RESULTS: A total of 456 episodes of PLA occurred in 364 patients during the study period. The median age of the first PLA episode was 71 years (range 3-97) and 57% (n = 206) were men. The mean incidence of all patients was 3.4/100,000 person-years (range 1.8-5.2). The incidence increased almost three times, from 1.8/100,000 person-years in 2011 to 5.2/100,000 person-years in 2020. Streptococcus species, Escherichia coli and Klebsiella species accounted for the vast majority of both mono- and polymicrobial findings in both blood and local abscess cultures. 16s rDNA added information about aetiology in 37% of episodes. CONCLUSION: The incidence of PLA increased during the study period, and Streptococcus spp., Klebsiella spp. and E. coli dominated both blood and local cultures. Despite antimicrobial therapy, pathogens could be found in local abscess cultures several weeks into treatment. Increased use of 16s rDNA in the management of PLA could be beneficial.
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Abscesso Hepático Piogênico , Masculino , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Abscesso Hepático Piogênico/epidemiologia , Abscesso Hepático Piogênico/diagnóstico , Abscesso Hepático Piogênico/terapia , Suécia/epidemiologia , Escherichia coli , Incidência , Estudos Retrospectivos , StreptococcusRESUMO
Background: Pyogenic liver abscess (PLA) is a rare entity that is associated with substantial mortality and morbidity. Our objective was to investigate variables associated with mortality and subsequent PLA in patients diagnosed with PLA in southern Sweden. Methods: We conducted a population-based observational study comprising all episodes of PLA that occurred between 2011 and 2020 in the county of Skåne, southern Sweden. The primary outcome was defined as all-cause 90-day mortality and the secondary outcome was defined as the occurrence of a subsequent PLA. Results: A total of 452 episodes of PLA occurred in 360 patients during the study period. The 90-day mortality rate was 16% (n = 58) and the subsequent PLA rate was 20% (n = 92). In a multivariable logistic regression model, female sex (odds ratio [OR], 2.0 [95% confidence interval {CI}, 1.1-3.9]), malignancy (OR, 3.7 [95% CI, 1.9-7.1]), liver failure (OR, 6.3 [95% CI, 2.7-14.5]), and polymicrobial findings (OR, 3.8 [95% CI, 2.2-6.9]) were associated with death within 90 days (P < .05). Male sex (OR, 2.1 [95% CI, 1.2-3.6]), malignancy (OR, 2.1 [95% CI, 1.3-3.6]), age (64-74 years: OR, 2.5 [95% CI, 1.3-4.8]), and chronic liver disease (OR, 3.0 [95% CI, 1.4-6.5]) were associated with the risk of subsequent PLA (P ≤ .01). Conclusions: Identifying different clinical variables associated with an unfavorable outcome may improve the management and treatment of patients with PLA and thus prevent the risk of death and subsequent PLA.
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Background: Streptococcus pyogenes bacteremia is a severe condition with high mortality. Time to blood culture positivity (TTP) is known to predict the outcome in bacteremia with other pathogens. This study aimed to determine the association between TTP and outcome in S pyogenes bacteremia. Methods: This retrospective observational cohort study comprised adults with S pyogenes bacteremia, identified through the laboratory database between 2015 and 2018, in the Region of Skåne, Sweden. Correlations between TTP and outcomes were investigated. Primary outcome was death within 30 days, and secondary outcomes were presence of sepsis or disease deterioration within the first 48 hours. Results: A total of 347 episodes of S pyogenes bacteremia were identified, of which 61 were excluded, resulting in 286 included episodes. Median TTP was 10.4 (interquartile range, 8.4-11.4) hours. Thirty-day mortality was 10%. Median TTP was shorter in patients who died within 30 days compared to survivors (8.6 vs 10.4 hours; P < .001). In a multivariable logistic regression, shorter TTP was associated with 30-day mortality when adjusting for age, Charlson Comorbidity Index, and focus of infection (odds ratio, 3.7 [95% confidence interval, 1.2-11.3]; P = .02). There was no statistically significant difference in TTP between patients with sepsis within 48 hours and those who did not have sepsis. Additionally, there was no statistically significant difference in TTP between patients with disease deterioration compared to those who did not deteriorate. Conclusions: Knowledge on TTP might be a tool to determine the prognosis of a given patient with S pyogenes bacteremia.
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The human pathogen Streptococcus pyogenes causes substantial morbidity and mortality. It is unclear if antibodies developed after infections with this pathogen are opsonic and if they are strain specific or more broadly protective. Here, we quantified the opsonic-antibody response following invasive S. pyogenes infection. Four patients with S. pyogenes bacteremia between 2018 and 2020 at Skåne University Hospital in Lund, Sweden, were prospectively enrolled. Acute- and convalescent-phase sera were obtained, and the S. pyogenes isolates were genome sequenced (emm118, emm85, and two emm1 isolates). Quantitative antibody binding and phagocytosis assays were used to evaluate isolate-dependent opsonic antibody function in response to infection. Antibody binding increased modestly against the infecting isolate and across emm types in convalescent- compared to acute-phase sera for all patients. For two patients, phagocytosis increased in convalescent-phase serum both for the infecting isolate and across types. The increase was only across types for one patient, and one had no improvement. No correlation to the clinical outcomes was observed. Invasive S. pyogenes infections result in a modestly increased antibody binding with differential opsonic capacity, both nonfunctional binding and broadly opsonic binding across types. These findings question the dogma that an invasive infection should lead to a strong type-specific antibody increase rather than a more modest but broadly reactive response, as seen in these patients. Furthermore, our results indicate that an increase in antibody titers might not be indicative of an opsonic response and highlight the importance of evaluating antibody function in S. pyogenes infections. IMPORTANCE The bacterium Streptococcus pyogenes is a common cause of both mild and severe human diseases resulting in substantial morbidity and mortality each year. No vaccines are available, and our understanding of the antibody response to this human pathogen is still incomplete. Here, we carefully analyzed the opsonic antibody response following invasive infection in four patients. Unexpectedly, the patients did not always generate opsonic antibodies against the specific infecting strain. Instead, we found that some patients could generate cross-opsonic antibodies, leading to phagocytosis of bacteria across strains. The emergence of cross-opsonic antibodies is likely important for long-term immunity against S. pyogenes. Our findings question the dogma that mostly strain-specific immunity is developed after infection and add to our overall understanding of how immunity to S. pyogenes can evolve.
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Bacteriemia , Infecções Estreptocócicas , Humanos , Infecções Estreptocócicas/microbiologia , Fagocitose , Streptococcus pyogenes/genética , Anticorpos Antibacterianos , Antígenos de Bactérias/genéticaRESUMO
BACKGROUND: Corynebacterium species are often dismissed as contaminants in blood cultures, but they can also cause infective endocarditis (IE), which is a severe condition. Antibiotic resistance of corynebacteria is increasing making treatment challenging. Reports on IE caused by Corynebacterium species are scarce and more knowledge is needed. METHODS: Cases of IE caused by Corynebacterium species were identified through the Swedish Registry of Infective Endocarditis. Isolates were collected for species redetermination by matrix-assisted laser desorption ionization-time of flight and for antibiotic susceptibility testing using Etests. RESULTS: Thirty episodes of IE due to Corynebacterium species were identified between 2008 and 2017. The median age of patients was 71 years (interquartile range, 60-76) and 77% were male. Corynebacterium striatum (n = 11) was the most common IE causing pathogen followed by Corynebacterium jeikeium (n = 5). Surgery was performed in 50% and in-hospital mortality rate was 13%. Patients with IE caused by Corynebacterium species were significantly more likely to have prosthetic valve endocarditis (70%), compared with patients with IE due to Staphylococcus aureus or non-beta-hemolytic streptococci (14% and 26%, respectively) (P < .0001). Vancomycin was active towards all Corynebacterium isolates, whereas resistance towards penicillin G was common. CONCLUSIONS: Corynebacterium species cause IE, where prosthetic valves are mainly affected and surgery is often performed. Corynebacterium striatum is an important causative agent of IE within the genus. Antibiotic resistance of corynebacteria is relatively common but resistance towards vancomycin could not be detected in vitro.
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BACKGROUND: Serological response and association to clinical manifestation is important for understanding the pathogenesis of COVID-19. MATERIALS AND METHODS: A prospective observational study was conducted where antibody responses of IgG and IgA towards SARS-CoV-2 spike protein were studied over time in patients with COVID-19. Possible associations between antibody titers and outcome were analyzed. RESULTS: Forty patients with COVID-19, hospitalized at Skåne University hospital, Sweden, between April and June 2020 were included. IgG antibody responses were detected for all patients with the highest levels four weeks after COVID-19 diagnosis. Levels of IgA were generally higher at diagnosis and decreased towards baseline 4 weeks after confirmed COVID-19. Patients with severe COVID-19 had higher levels of antibodies directed against SARS-CoV-2 spike protein compared with patients with mild disease. CONCLUSION: IgG and IgA antibodies towards the spike protein follow different kinetics during COVID-19 and patients with severe disease develop higher antibody levels.
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Anticorpos Antivirais/sangue , COVID-19/patologia , Idoso , Formação de Anticorpos , COVID-19/virologia , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Cinética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia , SuéciaRESUMO
INTRODUCTION: Streptococcus dysgalactiae can cause severe recurrent infections. This study aimed to investigate antibody responses following S. dysgalactiae bacteraemia and possible development of protective immunity. MATERIALS AND METHODS: Patients with S. dysgalactiae bacteraemia in the county of Skåne between 2017 and 2018 were prospectively included. Acute and convalescent sera were obtained. All isolates were emm typed and enzyme-linked immunosorbent assay (ELISA) was utilised to analyse specific antibody responses to bacteria and antigens. Bactericidal- and phagocytosis assays were applied to further establish antibody function. RESULTS: Sixteen patients with S. dysgalactiae bacteraemia were included of whom one had recurrent episodes of bacteraemia. Using ELISA with S. dysgalactiae isolates and mutants, development of IgG antibodies was demonstrated in few patients. Type-specific antibodies were demonstrated in one patient when recombinant M proteins as antigens, were applied. The type-specific serum mediated a small increase in phagocytosis but did not facilitate increased killing of the S. dysgalactiae isolate, carrying that M protein, in blood or by phagocytic cells. CONCLUSION: S. dysgalactiae bacteraemia sometimes results in increased levels of antibodies to the infecting pathogen. We did not find evidence that these antibodies are effectively opsonising. Apparent failure to produce opsonising antibodies might partially explain why S. dysgalactiae can cause recurrent invasive infections in the same host.
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Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.
Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Opsonização/imunologia , Fagocitose/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Monoclonais/imunologia , Linhagem Celular , Células HEK293 , Humanos , Testes de Neutralização/métodosRESUMO
Stapylococcus aureus is a common infectious agent in e.g. sepsis, associated with both high mortality rates and severe long-term effects. The cytolytic protein α-hemolysin has repeatedly been shown to enhance the virulence of S. aureus. Combined with an unhindered spread of multi drug-resistant strains, this has triggered research into novel anti virulence (i.e. anti α-hemolysin) drugs. Their functionality will depend on our ability to identify infections that might be alleviated by such. We therefore saw a need for detection methods that could identify individuals suffering from S. aureus infections where α-hemolysin was a major determinant. Molecular imprinted polymers were subsequently prepared on gold coated sensor chips. Used in combination with a surface plasmon resonance biosensor, α-hemolysin could therethrough be quantified from septic blood samples (n = 9), without pre-culturing of the infectious agent. The biosensor recognized α-hemolysin with high affinity (KD = 2.75 x 10-7 M) and demonstrated a statistically significant difference (p < 0.0001) between the α-hemolysin response and potential sample contaminants. The detection scheme proved equally good, or better, when compared to antibody-based detection methods. This novel detection scheme constitutes a more rapid, economical, and user-friendly alternative to many methods currently in use. Heightening both reproducibility and sensitivity, molecular imprinting in combination with surface plasmon resonance (SPR)-technology could be a versatile new tool in clinical- and research-settings alike.