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Clinical Infectious Diseases : An... Aug 2023Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of...
BACKGROUND
Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort.
METHODS
Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture.
RESULTS
Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non-MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non-MBL-Ec was 62% (95% CI: 48.2-74.3%). Among infected patients, non-MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec.
CONCLUSIONS
Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non-MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations.
Topics: Humans; Prospective Studies; beta-Lactamases; Escherichia coli; Bacterial Proteins; Carbapenem-Resistant Enterobacteriaceae; Anti-Bacterial Agents; Microbial Sensitivity Tests
PubMed: 37154071
DOI: 10.1093/cid/ciad288 -
Proceedings of the National Academy of... Oct 2023The pathogenic bacteria and cause pertussis (whooping cough) and pertussis-like disease, respectively, both of which are characterized by paroxysmal coughing. We...
The pathogenic bacteria and cause pertussis (whooping cough) and pertussis-like disease, respectively, both of which are characterized by paroxysmal coughing. We previously reported that pertussis toxin (PTx), which inactivates heterotrimeric GTPases of the G family through ADP-ribosylation of their α subunits, causes coughing in combination with Vag8 and lipid A in infection. In contrast, the mechanism of cough induced by , which produces Vag8 and lipopolysaccharide (LPS) containing lipid A, but not PTx, remained to be elucidated. Here, we show that a toxin we named deacylating autotransporter toxin (DAT) of inactivates heterotrimeric G GTPases through demyristoylation of their α subunits and contributes to cough production along with Vag8 and LPS. These results indicate that DAT plays a role in infection in place of PTx.
Topics: Humans; Bordetella parapertussis; Whooping Cough; Type V Secretion Systems; Cough; Lipid A; Lipopolysaccharides; Bordetella pertussis; Pertussis Toxin; Toxins, Biological
PubMed: 37748060
DOI: 10.1073/pnas.2308260120 -
Emerging Infectious Diseases May 2024To determine changes in Bordetella pertussis and B. parapertussis detection rates, we analyzed 1.43 million respiratory multiplex PCR test results from US facilities...
To determine changes in Bordetella pertussis and B. parapertussis detection rates, we analyzed 1.43 million respiratory multiplex PCR test results from US facilities from 2019 through mid-2023. From mid-2022 through mid-2023, Bordetella spp. detection increased 8.5-fold; 95% of detections were B. parapertussis. While B. parapertussis rates increased, B. pertussis rates decreased.
Topics: Bordetella parapertussis; United States; Humans; Bordetella Infections; Communicable Diseases, Emerging; Bordetella pertussis; History, 21st Century; Child; Child, Preschool; Whooping Cough; Adult; Adolescent; Infant; Multiplex Polymerase Chain Reaction; Young Adult
PubMed: 38666607
DOI: 10.3201/eid3005.231278 -
Microbiology Spectrum Jun 2023The classical species infect the respiratory tract of mammals. While B. bronchiseptica causes rather chronic respiratory infections in a variety of mammals, the...
The classical species infect the respiratory tract of mammals. While B. bronchiseptica causes rather chronic respiratory infections in a variety of mammals, the human-adapted species B. pertussis and cause an acute respiratory disease known as whooping cough or pertussis. The virulence factors include a type III secretion system (T3SS) that translocates effectors BteA and BopN into host cells. However, the regulatory mechanisms underlying the secretion and translocation activity of T3SS in bordetellae are largely unknown. We have solved the crystal structure of BopN of B. pertussis and show that it is similar to the structures of gatekeepers that control access to the T3SS channel from the bacterial cytoplasm. We further found that BopN accumulates at the cell periphery at physiological concentrations of calcium ions (2 mM) that inhibit the secretion of BteA and BopN. Deletion of the gene in B. bronchiseptica increased secretion of the BteA effector into calcium-rich medium but had no effect on secretion of the T3SS translocon components BopD and BopB. Moreover, the Δ mutant secreted approximately 10-fold higher amounts of BteA into the medium of infected cells than the wild-type bacteria, but it translocated lower amounts of BteA into the host cell cytoplasm. These data demonstrate that BopN is a T3SS gatekeeper required for regulated and targeted translocation of the BteA effector through the T3SS injectisome into host cells. The T3SS is utilized by many Gram-negative bacteria to deliver effector proteins from bacterial cytosol directly into infected host cell cytoplasm in a regulated and targeted manner. Pathogenic bordetellae use the T3SS to inject the BteA and BopN proteins into infected cells and upregulate the production of the anti-inflammatory cytokine interleukin-10 (IL-10) to evade host immunity. Previous studies proposed that BopN acted as an effector in host cells. In this study, we report that BopN is a T3SS gatekeeper that regulates the secretion and translocation activity of T3SS.
Topics: Animals; Humans; Type III Secretion Systems; Whooping Cough; Calcium; Bordetella pertussis; Virulence Factors; Bacterial Proteins; Mammals
PubMed: 37036369
DOI: 10.1128/spectrum.04112-22 -
Vaccines Feb 2024Pertussis, or whooping cough, is a global public health concern. Pertussis vaccines have demonstrated good protection against infections, but their effectiveness... (Review)
Review
BACKGROUND
Pertussis, or whooping cough, is a global public health concern. Pertussis vaccines have demonstrated good protection against infections, but their effectiveness against remains debated due to conflicting study outcomes.
METHODS
A systematic review and meta-analysis were conducted to assess the effectiveness of pertussis vaccines in protecting children against infection. A comprehensive search of PubMed, Web of Science, and Scopus databases was conducted, and randomized controlled trials (RCTs) and observational studies that met inclusion criteria were included in the analysis.
RESULTS
The meta-analysis, involving 46,533 participants, revealed no significant protective effect of pertussis vaccination against infection (risk ratio: 1.10, 95% confidence interval: 0.83 to 1.44). Subgroup analyses by vaccine type and study design revealed no significant protection. The dearth of recent data and a limited pool of eligible studies, particularly RCTs, underscore a critical gap that warrants future research in the domain.
CONCLUSIONS
These findings offer crucial insights into the lack of effectiveness of pertussis vaccines against . Given the rising incidence of cases and outbreaks, coupled with the lack of cross-protection by the existing vaccines, there is an urgent need to develop vaccines that include specific antigens to protect against .
PubMed: 38543887
DOI: 10.3390/vaccines12030253 -
PloS One 2023B. parapertussis is one of the etiological agents of whooping cough. Once inhaled, the bacteria bind to the respiratory epithelium and start the infection. Little is...
B. parapertussis is one of the etiological agents of whooping cough. Once inhaled, the bacteria bind to the respiratory epithelium and start the infection. Little is known about this first step of host colonization and the role of the human airway epithelial barrier on B. parapertussis infection. We here investigated the outcome of the interaction of B. parapertussis with a polarized monolayer of respiratory epithelial cells. Our results show that B. parapertussis preferentially attaches to the intercellular boundaries, and causes the disruption of the tight junction integrity through the action of adenylate cyclase toxin (CyaA). We further found evidence indicating that this disruption enables the bacterial access to components of the basolateral membrane of epithelial cells to which B. parapertussis efficiently attaches and gains access to the intracellular location, where it can survive and eventually spread back into the extracellular environment. Altogether, these results suggest that the adenylate cyclase toxin enables B. parapertussis to overcome the epithelial barrier and eventually establish a niche of persistence within the respiratory epithelial cells.
Topics: Humans; Bordetella parapertussis; Adenylate Cyclase Toxin; Bordetella pertussis; Intracellular Space; Whooping Cough; Epithelial Cells
PubMed: 38011105
DOI: 10.1371/journal.pone.0291331 -
Open Forum Infectious Diseases Dec 2023Shotgun and targeted metagenomic sequencing have been shown in separate studies to be potentially useful for culture-free pathogen identification in blood and/or plasma...
BACKGROUND
Shotgun and targeted metagenomic sequencing have been shown in separate studies to be potentially useful for culture-free pathogen identification in blood and/or plasma of patients with infective endocarditis (IE). However, the 2 approaches have not been directly compared. The aim of this study was to compare shotgun metagenomic sequencing with targeted metagenomic sequencing (tMGS) for organism identification in blood or plasma of patients with IE.
METHODS
Patients with possible or definite IE were prospectively enrolled from October 2020 to July 2021. Shotgun metagenomic sequencing was performed with the Karius test, which uses microbial cell-free DNA (mcfDNA) sequencing to detect, identify, and quantitate DNA-based pathogens in plasma. tMGS was performed using a 16S ribosomal RNA (rRNA) polymerase chain reaction assay targeting the V1 to V3 regions of the 16S rRNA gene. Results were compared using the McNemar test of paired proportions.
RESULTS
Samples from 34 patients were investigated. The Karius test was positive in 24/34 (71%), including 3/6 (50%) with blood culture-negative endocarditis (BCNE), which was not significantly different from the positivity rate of tMGS ( = .41). Results of the Karius test were concordant with tMGS in 75% of cases. The Karius test detected 2 cases of methicillin-resistant among the 7 detections, in accordance with results of phenotypic susceptibility testing. The combination of blood cultures, the Karius test, and tMGS found a potential causative pathogen in 33/34 (97%), including 5/6 with BCNE.
CONCLUSIONS
The Karius test and tMGS yielded comparable detection rates; however, beyond organism identification, the Karius test generated potentially useful antibiotic resistance data.
PubMed: 38075017
DOI: 10.1093/ofid/ofad546 -
Frontiers in Immunology 2023Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty surgery. Increased densities of activated mast cells have been predicted...
BACKGROUND
Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty surgery. Increased densities of activated mast cells have been predicted to be present in PJI compared to non-infectious arthroplasty failure based on analysis of transcriptomic data, but their presence in PJI-associated periprosthetic tissues has not been visually confirmed.
OBJECTIVE
This preliminary study investigated the presence and activation status of mast cells in periprosthetic tissues associated with PJI.
METHODS
Periprosthetic tissues from five PJI cases and three arthroplasty failures due to instability and one due to stiffness were immunohistochemically stained using tryptase and microscopically evaluated to enumerate mast cells and evaluate overall activation status within tissue samples. Mast cell activation was evidenced by the release of tryptase into the extracellular space surrounding mast cells.
RESULTS
Mast cells were found in all samples, with average cellular densities of 22 and 26 cells/mm tissue in PJI and uninfected samples, respectively (p, 0.6610). Apparent mast cell activation and degranulation was readily observed throughout each of the five PJI samples studied, but not in any of the uninfected samples studied.
CONCLUSION
While preliminary, these findings provide evidence for a role of mast cells in the immune response in PJI. Additional investigation of the role of mast cells during arthroplasty failure is warranted, providing a better understanding of underlying biology and informing potential diagnostic and treatment targets.
Topics: Humans; Mast Cells; Prosthesis-Related Infections; Tryptases; Antigen Presentation; Arthritis, Infectious
PubMed: 37654491
DOI: 10.3389/fimmu.2023.1183977 -
Medicine Jul 2023Bordetella parapertussis caused by a severe infection is rare in clinical practice. Here, we report a case of plastic bronchitis (PB).
RATIONALE
Bordetella parapertussis caused by a severe infection is rare in clinical practice. Here, we report a case of plastic bronchitis (PB).
PATIENT CONCERNS
A 4-year-old girl with a 2-day history of fever, paroxysmal cough, and subconjunctival hemorrhage.
DIAGNOSES
The diagnoses were (1) B parapertussis , (2) pulmonary atelectasis, and (3) PB.
INTERVENTIONS
The patient received azithromycin and underwent bronchoscopy.
OUTCOMES
Symptoms disappeared after treatment. The patient had an outpatient follow-up of 2 months without respiratory symptoms.
LESSONS
PB can lead to respiratory failure if not intervened in the early stages.
Topics: Female; Humans; Child, Preschool; Bordetella parapertussis; Bordetella pertussis; Bordetella Infections; Bronchitis; Plastics
PubMed: 37417634
DOI: 10.1097/MD.0000000000034239 -
Proteomics. Clinical Applications Sep 2023This pilot study aimed to use proteomic profiling of sonicate fluid samples to compare host response during Staphylococcus aureus-associated periprosthetic joint...
Mass spectrometry-based proteomic profiling of sonicate fluid differentiates Staphylococcus aureus periprosthetic joint infection from non-infectious failure: A pilot study.
PURPOSE
This pilot study aimed to use proteomic profiling of sonicate fluid samples to compare host response during Staphylococcus aureus-associated periprosthetic joint infection (PJI) and non-infected arthroplasty failure (NIAF) and identify potential novel biomarkers differentiating the two.
EXPERIMENTAL DESIGN
In this pilot study, eight sonicate fluid samples (four from NIAF and four from S. aureus PJI) were studied. Samples were reduced, alkylated, and trypsinized overnight, followed by analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) on a high-resolution Orbitrap Eclipse mass spectrometer. MaxQuant software suite was used for protein identification, filtering, and label-free quantitation.
RESULTS
Principal component analysis of the identified proteins clearly separated S. aureus PJI and NIAF samples. Overall, 810 proteins were identified based on their detection in at least three out of four samples from each group; 35 statistically significant differentially abundant proteins (DAPs) were found (two-sample t-test p-values ≤0.05 and log fold-change values ≥2 or ≤-2). Gene ontology pathway analysis found that microbial defense responses, specifically those related to neutrophil activation, to be increased in S. aureus PJI compared to NIAF samples.
CONCLUSION AND CLINICAL RELEVANCE
Proteomic profiling of sonicate fluid using LC-MS/MS differentiated S. aureus PJI and NIAF in this pilot study. Further work is needed using a larger sample size and including non-S. aureus PJI and a diversty of NIAF-types.
Topics: Humans; Staphylococcus aureus; Prosthesis-Related Infections; Pilot Projects; Chromatography, Liquid; Proteomics; Tandem Mass Spectrometry
PubMed: 36938941
DOI: 10.1002/prca.202200071