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People who inject drugs are frequently colonized with Staphylococcus aureus and have an increased risk for skin and soft tissue infections. This longitudinal study aims to describe S. aureus carriage in this group and the risk for infections during a 1-year follow-up. We included 61 participants from the Malmö Needle Exchange Program. Mapping of S. aureus carriage was conducted by screening cultures every third month and S. aureus growth was semi-quantified. Data regarding infections and living conditions were collected from structured interviews. Statistics included univariate analysis with the Fischer's exact test, univariate logistic regression and multivariate logistic regression. S. aureus carriage was detected in 46-63% of participants, and 75% reported one or more infections during the study period. Self-reported infections were associated with carriage in perineum (OR 5.08 [95% CI 1.45-17.73]), in skin lesions (OR 1.48 [95% CI 1.21-1.81]), and unstable housing situation (OR 12.83 [95% CI 1.56-105.81]). Thus, people who inject drugs are frequent carriers of S. aureus and report a surprisingly high prevalence of skin and soft tissue infections. Homeless people and those with skin carriage seem to be at highest risk. Effective clinical interventions are needed, aiming at preventing infections in this vulnerable group.
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Portador Sadio , Infecções dos Tecidos Moles , Staphylococcus aureus , Abuso de Substâncias por Via Intravenosa , Humanos , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/microbiologia , Masculino , Estudos Longitudinais , Feminino , Staphylococcus aureus/isolamento & purificação , Adulto , Prevalência , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Pessoa de Meia-Idade , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Fatores de RiscoRESUMO
Objectives: This study aimed to investigate the etiology, clinical features, and outcomes of community-acquired pneumonia (CAP) in adults. Understanding the causative pathogens is essential for effective treatment and prevention. Design: Between 2016-2018, 518 hospitalized adults with CAP and 241 controls without symptoms were prospectively enrolled. Urine samples were collected for pneumococcal urinary antigen tests and nasopharyngeal swabs for viral and bacterial analysis, combined with routine diagnostic care. Results: Among the included CAP patients, Streptococcus pneumoniae was the most common pathogen, detected in 28% of patients, followed by Haemophilus influenzae in 16%. Viruses were identified in 28%, and concurrent viruses and bacteria were detected in 15%. There was no difference in mortality, length of stay, or symptoms at hospitalization when comparing patients with bacterial, viral, or mixed etiologies. Among the control subjects without respiratory symptoms, S. pneumoniae, H. influenzae, or Moraxella catarrhalis were detected in 5-7%, and viruses in 7%. Conclusion: Streptococcus pneumoniae emerged as the predominant cause of CAP, followed closely by viruses and H. influenzae. Intriguingly, symptoms and outcome were similar regardless of etiology. These findings highlight the complexity of this respiratory infection and emphasize the importance of comprehensive diagnostic and treatment strategies.Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT03606135].
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Bacteriófagos , Infecções Comunitárias Adquiridas , Pneumonia Bacteriana , Infecções Respiratórias , Adulto , Humanos , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Hospitalização , Pneumonia Bacteriana/epidemiologia , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Streptococcus pneumoniae , Resultado do Tratamento , Estudos de Casos e ControlesRESUMO
[This corrects the article DOI: 10.3389/fimmu.2018.01988.].
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BACKGROUND: In Sweden, vaccine uptake is exceptionally high due to an efficient child immunization program. More than 97% of Swedish children were vaccinated at child health care centers (CHCs) according to the schedule at 2 years of age in 2021. From the age of 6 years, vaccinations are given within the school health care. Maintaining high vaccination coverage over time is one of the central motives to explore and understand drivers for vaccine acceptance. The current study aimed to assess parental vaccine acceptance concerning the national immunization program and explore factors contributing to the high vaccine acceptance in Sweden. METHODS: Parents of children aged 1-2 years and 8-12 years were recruited through purposive sampling and asked to participate in focus groups held in three cities in Sweden, in February and March 2019. In total, 47 parents participated in two focus groups per city, one session for parents of younger (1-2 years) and older (8-12 years) children respectively. The focus group discussions were analyzed using qualitative content analysis. RESULTS: Parents of children aged 1-2 years expressed the themes; strong compliance to and protection of the value of vaccinations; parents feel safe with an attentive relationship with their nurse; the spectrum of communication needs is essential to meet. For parents to children aged 8-12 years, the themes expressed were; vaccinate to do good for the individual and society; a foundation of trust is built at CHCs for decisions later on; decisions for vaccination become more complex as children get older; communication changes as children get older and need to be explicit and tailored to the situation. CONCLUSION: Both individual and societal perspectives were shown to influence the vaccination decision for childhood immunizations, as manifested in parental reflections and experiences. As nurses have a key role, it is important to provide them with continued support and tools to facilitate their support for parents in making informed decisions. Continuous work for supporting driving factors for vaccination over time is needed to maintain high vaccine acceptance in Sweden.
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Enfermeiras e Enfermeiros , Vacinas , Criança , Humanos , Pré-Escolar , Suécia , Grupos Focais , PaisRESUMO
Non-typeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes a wide range of airway diseases. NTHi has a plethora of mechanisms to colonize while evading the host immune system for the establishment of infection. We previously showed that the outer membrane protein P5 contributes to bacterial serum resistance by the recruitment of complement regulators. Here, we report a novel role of P5 in maintaining bacterial outer membrane (OM) integrity and protein composition important for NTHi-host interactions. In silico analysis revealed a peptidoglycan-binding motif at the periplasmic C-terminal domain (CTD) of P5. In a peptidoglycan-binding assay, the CTD of P5 (P5CTD) formed a complex with peptidoglycan. Protein profiling analysis revealed that deletion of CTD or the entire P5 changed the membrane protein composition of the strains NTHi 3655Δp5CTD and NTHi 3655Δp5, respectively. Relative abundance of several membrane-associated virulence factors that are crucial for adherence to the airway mucosa, and serum resistance were altered. This was also supported by similar attenuated pathogenic phenotypes observed in both NTHi 3655Δp5 CTD and NTHi 3655Δp5. We found (i) a decreased adherence to airway epithelial cells and fibronectin, (ii) increased complement-mediated killing, and (iii) increased sensitivity to the ß-lactam antibiotics in both mutants compared to NTHi 3655 wild-type. These mutants were also more sensitive to lysis at hyperosmotic conditions and hypervesiculated compared to the parent wild-type bacteria. In conclusion, our results suggest that P5 is important for bacterial OM stability, which ultimately affects the membrane proteome and NTHi pathogenesis.
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Bactérias , Peptidoglicano , Humanos , Membranas , Parede Celular , Haemophilus influenzae/genéticaAssuntos
Infecções por Bactérias Gram-Negativas , Humanos , Ucrânia/epidemiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Testes de Sensibilidade MicrobianaRESUMO
Objectives: In Sweden, pneumococcal serotype distribution in adults with community-acquired pneumonia (CAP) and potential coverage of currently licensed pneumococcal conjugate vaccines (PCVs) is unknown. Methods: During 2016-2018, patients aged ≥18 years hospitalized with radiologically confirmed (RAD+) CAP were enrolled at Skåne University Hospital in a study on the etiology of CAP in Sweden (ECAPS). Urine samples and blood cultures were collected per-protocol. Streptococcus pneumoniae (Spn) culture isolates were serotyped and urine samples tested for the pan-pneumococcal urinary antigen (PUAT) and multiplex urine antigen detection (UAD) assay, detecting 24 serotypes. Results: Analyses included 518 participants with RAD+CAP; 67.4% were ≥65 years of age, 73.4% were either immunocompromised or had an underlying chronic medical condition. The proportion of CAP due to Spn identified by any method was 24.3% of which 9.3% was detected by UAD alone. The most frequently identified serotypes were 3 (26 cases, 5.0% of all CAP), and 8, 11A and 19A (10 cases each, 1.9%). In individuals aged 18-64 and ≥65 years, respectively, PCV20 serotypes contributed to 35 of 169 (20.7%) and 53 of 349 cases of all CAP (15.2%), and PCV13 serotypes caused 21 of 169 (12.4%) and 35 of 349 (10.0%) cases. PCV15 coverage was 23 of 169 (13.6%) and 42 of 349 (12.0%) in individuals aged 18-64 and ≥65 years, respectively. Overall, PCV20 increases the coverage of all CAP from 10.8% (PCV13) to 17.0%. Conclusion: Compared to earlier pneumococcal vaccines, PCV20 expands the coverage of all-cause CAP. Routine diagnostic tests underestimate the proportion of CAP caused by Spn.
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Vacinas Pneumocócicas , Pneumonia , Humanos , Adulto , Adolescente , Idoso , Sorogrupo , Suécia , Hospitais UniversitáriosRESUMO
The human pathogen Haemophilus influenzae causes respiratory tract infections and is commonly associated with prolonged carriage in patients with chronic obstructive pulmonary disease. Production of outer membrane vesicles (OMVs) is a ubiquitous phenomenon observed in Gram-negative bacteria including H. influenzae. OMVs play an important role in various interactions with the human host; from neutralization of antibodies and complement activation to spread of antimicrobial resistance. Upon vesiculation certain proteins are found in OMVs and some proteins are retained at the cell membrane. The mechanism for this phenomenon is not fully elucidated. We employed mass spectrometry to study vesiculation and the fate of proteins in the outer membrane. Functional groups of proteins were differentially distributed on the cell surface and in OMVs. Despite its supposedly periplasmic and outer membrane location, we found that the peptidoglycan synthase-activator Lipoprotein A (LpoA) was accumulated in OMVs relative to membrane fractions. A mutant devoid of LpoA lost its fitness as revealed by growth and electron microscopy. Furthermore, high-pressure liquid chromatography disclosed a lower concentration (55%) of peptidoglycan in the LpoA-deficient H. influenzae compared to the parent wild type bacterium. Using an LpoA-mNeonGreen fusion protein and fluorescence microscopy, we observed that LpoA was enriched in "foci" in the cell envelope, and further located in the septum during cell division. To define the fate of LpoA, C-terminally truncated LpoA-variants were constructed, and we found that the LpoA C-terminal domain promoted optimal transportation to the OMVs as revealed by flow cytometry. Taken together, our study highlights the importance of LpoA for H. influenzae peptidoglycan biogenesis and provides novel insights into cell wall integrity and OMV production.
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Anti-Infecciosos , Haemophilus influenzae , Humanos , Haemophilus influenzae/metabolismo , Domínios Proteicos , Proteínas da Membrana Bacteriana Externa/metabolismo , Lipoproteína(a)/metabolismo , Peptidoglicano/metabolismo , Parede Celular/metabolismo , Anti-Infecciosos/metabolismoRESUMO
Background/Objective: The frequencies of non-susceptibility against common antibiotics among pneumococci vary greatly across the globe. When compared to other European countries antibiotic resistance against penicillin and macrolides has been uncommon in Sweden in recent years. Multidrug resistance (MDR) is, however, of high importance since relevant treatment options are scarce. The purpose of this study was to characterize the molecular epidemiology, presence of resistance genes and selected virulence genes of extensively drug-resistant (XDR) (n=15) and MDR (n=10) Streptococcus pneumoniae detected in clinical respiratory tract samples isolated from patients in a southern Swedish county 2016-2018. With the aim of relating them to global MDR pneumococci. Methods: Whole genome sequencing (WGS) was performed to determine molecular epidemiology, resistance genes and presence of selected virulence factors. Antimicrobial susceptibility profiles were determined using broth microdilution testing. Further analyses were performed on isolates from the study and from the European nucleotide archive belonging to global pneumococcal sequence cluster (GPSC) 1 (n=86), GPSC9 (n=55) and GPSC10 (n=57). Bacteria were analyzed regarding selected virulence determinants (pilus islet 1, pilus islet 2 and Zinc metalloproteinase C) and resistance genes. Results: Nineteen of 25 isolates were related to dominant global MDR lineages. Seventeen belonged to GPSC1, GPSC9 or GPSC10 with MDR non-PCV serotypes in GPSC9 (serotype 15A and 15C) as well as GPSC10 (serotype 7B, 15B and serogroup 24). Pilus islet-1 and pilus islet-2 were present in most sequence types belonging to GPSC1 and in two isolates within GPSC9 but were not detected in isolates belonging to GPSC10. Zinc metalloproteinase C was well conserved within all analyzed isolates belonging to GPSC9 but were not found in isolates from GPSC1 or GPSC10. Conclusions: Although MDR S. pneumoniae is relatively uncommon in Sweden compared to other countries, virulent non-PCV serotypes that are MDR may become an increasing problem, particularly from clusters GPSC9 and GPSC10. Since the incidence of certain serotypes (3, 15A, and 19A) found among our MDR Swedish study isolates are persistent or increasing in invasive pneumococcal disease further surveillance is warranted.
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Infecções Pneumocócicas , Streptococcus pneumoniae , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Testes de Sensibilidade Microbiana , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas , Sistema Respiratório , Sorogrupo , Sorotipagem , Suécia/epidemiologia , Fatores de Virulência/genética , ZincoRESUMO
Otitis media (OM) is an inflammatory disorder in the middle ear. It is mainly caused by viruses or bacteria associated with the airways. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the three main pathogens in infection-related OM, especially in younger children. In this review, we will focus upon the multifaceted gene regulation mechanisms that are well-orchestrated in S. pneumoniae, H. influenzae, and M. catarrhalis during the course of infection in the middle ear either in experimental OM or in clinical settings. The sophisticated findings from the past 10 years on how the othopathogens govern their virulence phenotypes for survival and host adaptation via phase variation- and quorum sensing-dependent gene regulation, will be systematically discussed. Comprehensive understanding of gene expression regulation mechanisms employed by pathogens during the onset of OM may provide new insights for the design of a new generation of antimicrobial agents in the fight against bacterial pathogens while combating the serious emergence of antimicrobial resistance.
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Otite Média , Regulação da Expressão Gênica , Haemophilus influenzae/genética , Humanos , Moraxella catarrhalis/genética , Otite Média/genética , Otite Média/microbiologia , Streptococcus pneumoniae/genéticaRESUMO
Gram-negative bacteria from the genus Acinetobacter are responsible for life-threating hospital-related infections such as pneumonia, septicemia, and meningitis, especially in immunocompromised patients. Worryingly, Acinetobacter have become multi- and extensively drug resistant (MDR/XDR) over the last few decades. The complement system is the first line of defense against microbes, thus it is highly important to increase our understanding of evasion mechanisms used by Acinetobacter spp. Here, we studied clinical isolates of Acinetobacter spp. (n=50), aiming to characterize their recognition by the complement system. Most isolates tested survived 1 h incubation in 30% serum, and only 8 isolates had a lower survival rate, yet none of those isolates were fully killed. Intriguingly, four isolates survived in human whole blood containing all cell component. Their survival was, however, significantly reduced. Flow cytometry analyses revealed that most of the isolates were detected by human IgG and IgM. Interestingly, we could not detect any significant concentration of deposited C1q, despite observing C4b deposition that was abolished in C1q-deficient serum, indicating transient binding of C1q to bacteria. Moreover, several isolates were recognized by MBL, with C4b deposition abolished in MBL-deficient serum. C3b was deposited on most isolates, but this was not, however, seen with respect to C5b and formation of the membrane attack complex (MAC), indicating that many isolates could avoid complement-mediated lysis. India ink staining showed that isolates were capsulated, and capsule thickness varied significantly between isolates. Studies performed on a wild-type strain and capsule mutant strains, demonstrated that the production of a capsular polysaccharide is one mechanism that mediates resistance to complement-mediated bactericidal activity by preventing MAC deposition and lysis. Our data showed that most clinical Acinetobacter spp. isolates are highly serum resistant despite being efficiently recognized by the complement system.
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Acinetobacter/imunologia , Acinetobacter/fisiologia , Atividade Bactericida do Sangue , Proteínas do Sistema Complemento/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Proteínas do Sistema Complemento/classificação , Citometria de Fluxo , Humanos , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Ligação ProteicaAssuntos
Sepse , Infecções Urinárias , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Biópsia , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Masculino , Próstata/patologia , Reto , Suécia/epidemiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologiaRESUMO
Pneumonia is a global cause of mortality, and this provides a strong incentive to improve the mechanistic understanding of innate immune responses in the lungs. Here, we characterized the involvement of the cytokine interleukin (IL)-26 in bacterial lung infection. We observed markedly increased concentrations of IL-26 in lower airway samples from patients with bacterial pneumonia and these correlated with blood neutrophil concentrations. Moreover, pathogen-associated molecular patterns (PAMPs) from both Gram-negative and -positive bacteria increased extracellular IL-26 concentrations in conditioned media from human models of alveolar epithelial cells, macrophages, and neutrophils in vitro. Stimulation with IL-26 inhibited the inherent release of neutrophil elastase and myeloperoxidase in unexposed neutrophils. This stimulation also inhibited the expression of activity makers in neutrophils exposed to Klebsiella pneumoniae. In addition, priming of human lung tissue ex vivo with exogenous IL-26 potentiated the endotoxin-induced increase in mRNA for other cytokines involved in the innate immune response, including the master Th17-regulator IL-23 and the archetype inhibitory cytokine IL-10. Finally, neutralization of endogenous IL-26 clearly increased the growth of Klebsiella pneumoniae in the macrophage culture. These findings suggest that IL-26 is involved in bacterial lung infection in a complex manner, by modulating critical aspects of innate immune responses locally and systemically in a seemingly purposeful manner and by contributing to the killing of bacteria in a way that resembles an antimicrobial peptide. Thus, IL-26 displays both diagnostic and therapeutic potential in pneumonia and deserves to be further evaluated in these respects.
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Citocinas/imunologia , Pneumonia Bacteriana/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Feminino , Humanos , Klebsiella pneumoniae , Elastase de Leucócito/imunologia , Pulmão/citologia , Pulmão/imunologia , Macrófagos Alveolares/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Peroxidase/imunologia , Adulto JovemRESUMO
Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes infections mainly in the upper and lower respiratory tract. The bacterium is associated with bronchitis and exacerbations in patients suffering from chronic obstructive pulmonary disease and frequently causes acute otitis media in preschool children. We have previously demonstrated that the binding of C4b binding protein (C4BP) is important for NTHi complement evasion. In this study, we identified outer membrane protein 5 (P5) of NTHi as a novel ligand of C4BP. Importantly, we observed significantly lower C4BP binding and decreased serum resistance in P5-deficient NTHi mutants. Surface expression of recombinant P5 on Escherichia coli conferred C4BP binding and consequently increased serum resistance. Moreover, P5 expression was positively correlated with C4BP binding in a series of clinical isolates. We revealed higher levels of P5 surface expression and consequently more C4BP binding in isolates from the lower respiratory tract of chronic obstructive pulmonary disease patients and tonsil specimens compared with isolates from the upper respiratory tract and the bloodstream (invasive strains). Our results highlight P5 as an important protein for protecting NTHi against complement-mediated killing.
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Bacteriemia/imunologia , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteína de Ligação ao Complemento C4b/metabolismo , Infecções por Haemophilus/imunologia , Haemophilus influenzae/metabolismo , Doença Pulmonar Obstrutiva Crônica/imunologia , Tonsilite/imunologia , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/genética , Proteínas da Membrana Bacteriana Externa/genética , Criança , Proteínas do Sistema Complemento/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Feminino , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/genética , Humanos , Ligantes , Masculino , Pessoa de Meia-Idade , Organismos Geneticamente Modificados , Ligação Proteica/genética , Doença Pulmonar Obstrutiva Crônica/microbiologia , Proteínas Recombinantes/metabolismo , Transdução de Sinais/genética , Tonsilite/microbiologiaRESUMO
OBJECTIVES: Ventilator-associated pneumonia (VAP) is difficult to diagnose using clinical criteria and no biomarkers have yet been proved to be sufficiently accurate. The use of the neutrophil-derived Heparin-binding protein (HBP) as a biomarker for pneumonia was investigated in this exploratory case-control study in two intensive care units at a tertiary referral hospital. METHODS: Patients with clinical signs of pneumonia were recruited and bronchoalveolar lavage fluid (BALF) or bronchial wash (BW) samples were collected. Mechanically ventilated and lung healthy subjects were recruited as controls. HBP was measured with enzyme-linked immunosorbent assay. RESULTS: BALF was collected from 14 patients with pneumonia and 14 healthy controls. Median HBP in BALF pneumonia samples was 14,690 ng/ml and controls 16.2 ng/ml (p < 0.0001). BW was collected from 10 pneumonia patients and 10 mechanically ventilated controls. Median HBP in BW pneumonia was 9002 ng/ml and controls 7.6 ng/ml (p < 0.0001). CONCLUSIONS: These data indicate that HBP concentrations is significantly higher in lower airway samples from patients with pneumonia than control subjects and is a potentially useful biomarker for diagnosis of VAP.
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Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas Sanguíneas/metabolismo , Líquido da Lavagem Broncoalveolar/química , Pulmão/metabolismo , Pneumonia Associada à Ventilação Mecânica/metabolismo , Respiração Artificial/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To determine the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae associated with mucosal infections in patients of all ages, 2 to 4 years after the transition from a 10-valent pneumococcal conjugate vaccine (PCV10) to PCV13 in the childhood immunization programme. METHODS: Background information and antimicrobial susceptibility data regarding all respiratory tract, middle ear, and conjunctival samples positive for growth of S. pneumoniae (n = 2,131) were collected during 18 months in 2016-2018. Available corresponding bacterial isolates were serotyped by PCR and/or antisera (n = 1,858). RESULTS: In total, 17% of isolates were covered by PCV13, predominantly represented by serotypes 3 (9%) and 19A (5%). The most common nonvaccine serotypes were 11A (10%), 23B (10%), 15A (6%) and 35F (5%). Isolates exhibiting serotype 15A or 23B were often multidrug-resistant (21%) or penicillin nonsusceptible (38%), respectively. CONCLUSIONS: The overall proportion of serotype 19A was halved compared to a previous observation period when PCV10 was used (years 2011-2013), suggesting herd protection related to PCV13. The proportion of serotype 3 was, however, unchanged. Despite most nonvaccine serotypes causing mucosal infections have a low invasive potential, certain antibiotic resistant serotypes may pose a clinical problem.
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Infecções Pneumocócicas , Streptococcus pneumoniae , Antibacterianos/farmacologia , Criança , Pré-Escolar , Humanos , Lactente , Penicilinas , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/genética , Suécia/epidemiologiaRESUMO
The outer membrane protein A (OmpA) family contains an evolutionary conserved domain that links the outer membrane in Gram-negative bacteria to the semi-rigid peptidoglycan (PG) layer. The clinically significant pathogen Pseudomonas aeruginosa carries several OmpA family proteins (OprF, OprL, PA0833, and PA1048) that share the PG-binding domain. These proteins are important for cell morphology, membrane stability, and biofilm and outer membrane vesicle (OMV) formation. In addition to other OmpAs, in silico analysis revealed that the putative outer membrane protein (OMP) with gene locus PA1041 is a lipoprotein with an OmpA domain and, hence, is a potential virulence factor. This study aimed to evaluate PA1041 as a PG-binding protein and describe its effect on the phenotype. Clinical strains were confirmed to contain the lipoprotein resulting from PA1041 expression with Western blot, and PG binding was verified in enzyme-linked immunosorbent assay (ELISA). By using a Sepharose bead-based ELISA, we found that the lipoprotein binds to meso-diaminopimelic acid (mDAP), an amino acid in the pentapeptide portion of PGs. The reference strain PAO1 and the corresponding transposon mutant PW2884 devoid of the lipoprotein were examined for phenotypic changes. Transmission electron microscopy revealed enlarged periplasm spaces near the cellular poles in the mutant. In addition, we observed an increased release of OMV, which could be confirmed by nanoparticle tracking analysis. Importantly, mutants without the lipoprotein produced a thick, but loose and unorganized, biofilm in flow cells. In conclusion, the lipoprotein from gene locus PA1041 tethers the outer membrane to the PG layer, and mutants are viable, but display severe phenotypic changes including disordered biofilm formation. Based upon the phenotype of the P. aeruginosa PW2884 mutant and the function of the protein, we designate the lipoprotein with locus tag PA1041 as "peptidoglycan-binding anchor" (Pba).
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Naturally acquired opsonic antipneumococcal antibodies are commonly found in nonvaccinated adults and confer protection against infection and colonization. Despite this, only limited data exist regarding the adaptive immune response after pneumococcal exposure. To investigate the dynamics of naturally acquired antipneumococcal immunity in relation to an episode of infection, opsonic antibody activity was studied with paired acute-phase and convalescent-phase sera obtained from 54 patients with pneumococcal community-acquired pneumonia (CAP) using an opsonophagocytic assay (OPA). Results were compared with clinical characteristics and anticapsular immunoglobulin (Ig) concentrations. Interestingly, a nonfunctional opsonic antibody response (characterized by a decreased convalescent-phase serum OPA titer compared to that of the acute-phase serum or undetectable titers in both sera) was observed in 19 (35%) patients. The remaining individuals exhibited either an increased convalescent-phase OPA titer (n = 24 [44%]) or a detectable, but unchanged, titer at both time points (n = 11 [20%]). Invasive pneumococcal disease (i.e., bacteremia) was significantly more common among patients with a nonfunctional convalescent-phase response than in patients with other convalescent-phase responses. Anticapsular Ig concentrations were higher among patients with detectable convalescent-phase OPA titers (P = 0.003), and the greatest Ig concentration increase was observed among patients with an increased convalescent-phase response (P = 0.002). Our findings indicate that an episode of pneumococcal infection may act as an immunizing event. However, in some cases when patients with CAP also suffer from bacteremia, a nonfunctional opsonic antibody response may occur. Furthermore, the results suggest that factors other than anticapsular Ig concentrations determine opsonic antibody activity in serum.IMPORTANCE Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. This study provides valuable information that will contribute to fill this knowledge gap. Our main results indicate that a functional immune response may fail after CAP, predominantly among patients with simultaneous bacteremia.
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OBJECTIVES: The adaptive humoral immune response following clinical infection with extended spectrum beta-lactamase (ESBL)-producing Enterobacterales (EPE) has not been thoroughly investigated. The aim of this study was to investigate the presence of anti-CTX-M-15 and/or anti-CTX-M-27 IgG antibodies in bacteremia patients diagnosed with EPE compared to a control group consisting of patients suffering from bacteremia with third generation cephalosporin-susceptible Escherichia coli (3GCSE). METHODS: Patientswith EPE (nâ¯=â¯59) or 3GCSE (nâ¯=â¯42) bacteremia were recruited in this case control study in the Skåne County (South of Sweden). Sera were collected 1-26 months after bacteremia. Enzyme-linked immunosorbent assay (ELISA) was used for detection of specific IgG antibodies directed against recombinant beta-lactamases CTX-M-15 and CTX-M-27. The beta-lactamase resistance genes of the corresponding EPE blood isolates were determined by DNA sequencing. RESULTS: The majority (nâ¯=â¯47; 80 %) of the 59 EPE blood isolates carried blaCTX-M-15 or blaCTX-M-27 genes. IgG antibodies reacting to the corresponding CTX-M enzyme was seen in 28 % (13/47) of patients suffering from EPE-bacteremia, while antibodies were detected in only 9.5 % (4/42) of patients with 3GCSE (pâ¯=â¯0.03). Patients with EPE had a statistically significantly higher median Charlson comorbidity index and prevalence of renal disease (pâ¯=â¯0.01), compared to the 3GCSE control group. CONCLUSION: This study implies that EPE bacteremia can trigger production of IgG antibodies targeting ESBL. Further investigations are required to determine the functional role of anti-ESBL antibodies against EPE bacteremia.