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Science Bulletin Nov 2023Although hypervirulent Klebsiella pneumoniae (hvKP) can produce community-acquired infections that are fatal in young and adult hosts, such as pyogenic liver abscess,... (Review)
Review
Although hypervirulent Klebsiella pneumoniae (hvKP) can produce community-acquired infections that are fatal in young and adult hosts, such as pyogenic liver abscess, endophthalmitis, and meningitis, it has historically been susceptible to antibiotics. Carbapenem-resistant K. pneumoniae (CRKP) is usually associated with urinary tract infections acquired in hospitals, pneumonia, septicemias, and soft tissue infections. Outbreaks and quick spread of CRKP in hospitals have become a major challenge in public health due to the lack of effective antibacterial treatments. In the early stages of K. pneumoniae development, HvKP and CRKP first appear as distinct routes. However, the lines dividing the two pathotypes are vanishing currently, and the advent of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) is devastating as it is simultaneously multidrug-resistant, hypervirulent, and highly transmissible. Most CR-hvKP cases have been reported in Asian clinical settings, particularly in China. Typically, CR-hvKP develops when hvKP or CRKP acquires plasmids that carry either the carbapenem-resistance gene or the virulence gene. Alternatively, classic K. pneumoniae (cKP) may acquire a hybrid plasmid carrying both genes. In this review, we provide an overview of the key antimicrobial resistance mechanisms, virulence factors, clinical presentations, and outcomes associated with CR-hvKP infection. Additionally, we discuss the possible evolutionary processes and prevalence of CR-hvKP in China. Given the wide occurrence of CR-hvKP, continued surveillance and control measures of such organisms should be assigned a higher priority.
Topics: Humans; Cross Infection; Klebsiella pneumoniae; China; Anti-Bacterial Agents; Carbapenems; Hospitals
PubMed: 37821268
DOI: 10.1016/j.scib.2023.09.040 -
Ugeskrift For Laeger Dec 2023Acute bacterial meningitis (ABM) is associated with increased intracranial pressure (ICP) caused by bacterial invasion and the host response to infection. Antibiotic... (Review)
Review
Acute bacterial meningitis (ABM) is associated with increased intracranial pressure (ICP) caused by bacterial invasion and the host response to infection. Antibiotic therapy is a sine qua non, and adjunct dexamethasone decreases mortality. The ICP increase may have a rapid course and death due to herniation is most often seen within the first week. Evidence regarding treatment of increased ICP in ABM is limited; this review summarises observational studies which point towards reduced mortality by applying a structured approach towards normalization of ICP in ABM.
Topics: Humans; Intracranial Pressure; Meningitis, Bacterial; Anti-Bacterial Agents; Intracranial Hypertension
PubMed: 38105735
DOI: No ID Found -
Asia Pacific Allergy Sep 2023(pneumococcus) is a significant cause of bacterial infections ranging from mild infections affecting the respiratory tract such as otitis media and sinusitis to severe... (Review)
Review
(pneumococcus) is a significant cause of bacterial infections ranging from mild infections affecting the respiratory tract such as otitis media and sinusitis to severe diseases including bacteremia, pneumonia, and invasive pneumococcal disease (IPD) (eg, meningitis, septic arthritis, and endocarditis). Pneumococcal vaccines were first developed in the 1970s as capsular pneumococcal polysaccharide vaccines, which were T-cell independent and hence lacked immunologic memory. Subsequently in the year 2000, pneumococcal conjugate vaccines (PCV) conjugated to a protein to increase immunogenicity were developed and made commercially available. The increasing number of pneumococcal serotypes identified and the expanding pipeline of PCV vaccines with improved immunogenicity have significantly reduced the morbidity and mortality associated with IPD in high-risk patients. Pneumococcal vaccines also play an important role in the diagnosis and immunophenotyping of children and adults with inborn errors of immunity (IEI) given the increasing diversity/heterogeneity of IEI presenting with primary and/or specific antibody deficiency. Other than the quantitation of serotype levels in routine clinical care, other measurements of immune response including the functional activity of antibodies, antibody avidity, cell-mediated immunity, and immunological memory remain limited to clinical trials during vaccine development.
PubMed: 37744960
DOI: 10.5415/apallergy.0000000000000114 -
Proceedings of the National Academy of... Jun 2023M family proteins are critical virulence determinants of Streptococci. subsp. (SEZ) are Group C streptococci that cause meningitis in animals and humans. SzM, the M...
M family proteins are critical virulence determinants of Streptococci. subsp. (SEZ) are Group C streptococci that cause meningitis in animals and humans. SzM, the M protein of SEZ, has been linked to SEZ brain invasion. Here, we demonstrate that SzM is important in SEZ disruption of the blood-brain barrier (BBB). SEZ release SzM-bound membrane vesicles (MVs), and endocytosis of these vesicles by human brain endothelial microvascular cells (hBMECs) results in SzM-dependent cytotoxicity. Furthermore, administration of SzM-bound MVs disrupted the murine BBB. A CRISPR screen revealed that SzM cytotoxicity in hBMECs depends on PTEN-related activation of autophagic cell death. Pharmacologic inhibition of PTEN activity prevented SEZ disruption of the murine BBB and delayed mortality. Our data show that MV delivery of SzM to host cells plays a key role in SEZ pathogenicity and suggests that MV delivery of streptococcal M family proteins is likely a common streptococcal virulence mechanism.
Topics: Humans; Animals; Mice; Blood-Brain Barrier; Autophagic Cell Death; Antigens, Bacterial; Streptococcus; Streptococcus equi; Endothelial Cells; Streptococcal Infections
PubMed: 37276410
DOI: 10.1073/pnas.2219435120 -
The Journal of Infection Mar 2024Diagnostic tools to differentiate between community-acquired bacterial and viral meningitis are essential to target the potentially lifesaving antibiotic treatment to... (Review)
Review
Diagnostic tools to differentiate between community-acquired bacterial and viral meningitis are essential to target the potentially lifesaving antibiotic treatment to those at greatest risk and concurrently spare patients with viral meningitis from the disadvantages of antibiotics. In addition, excluding bacterial meningitis and thus decreasing antibiotic consumption would be important to help reduce antimicrobial resistance and healthcare expenses. The available diagnostic laboratory tests for differentiating bacterial and viral meningitis can be divided microbiological pathogen-focussed methods and biomarkers of the host response. Bacterial culture-independent microbiological methods, such as highly multiplexed nucleic acid amplification tests, are rapidly making their way into the clinical practice. At the same time, more conventional host protein biomarkers, such as procalcitonin and C-reactive protein, are supplemented by newer proteomic and transcriptomic signatures. This review aims to summarise the current state and the recent advances in diagnostic methods to differentiate bacterial from viral meningitis.
Topics: Humans; Proteomics; Diagnosis, Differential; Meningitis, Viral; Biomarkers; Meningitis, Bacterial; Anti-Bacterial Agents
PubMed: 38307149
DOI: 10.1016/j.jinf.2024.01.010 -
The Lancet Regional Health. Europe Sep 2023Bacterial meningitis is associated with significant morbidity and mortality worldwide. We aimed to describe the epidemiology, aetiology, trends over time and outcomes of...
BACKGROUND
Bacterial meningitis is associated with significant morbidity and mortality worldwide. We aimed to describe the epidemiology, aetiology, trends over time and outcomes of laboratory-confirmed bacterial meningitis in England during 2012-2019.
METHODS
UK Health Security Agency routinely receives electronic notifications of confirmed infections from National Health Service hospital laboratories in England. Data were extracted for positive bacterial cultures, PCR-positive results for or from cerebrospinal fluid and positive blood cultures in patients with clinical meningitis.
FINDINGS
During 2012-19, there were 6554 laboratory-confirmed cases. Mean annual incidence was 1.49/100,000, which remained stable throughout the surveillance period (p = 0.745). There were 155 different bacterial species identified, including 68.4% (106/1550) Gram-negative and 31.6% (49/155) Gram-positive bacteria. After excluding coagulase-negative staphylococci (2481/6554, 37.9%), the main pathogens causing meningitis were (811/4073, 19.9%), (497/4073, 12.2%), (467/4073, 11.5%), (314/4073, 7.7%) and group B streptococcus (268/4073, 6.6%). Pneumococcal meningitis incidence increased significantly during 2012-9, while meningococcal, group A streptococcal and tuberculous meningitis declined. Infants aged <3 months had the highest mean incidence (55.6/100,000; 95% CI, 47.7-63.5) driven mainly by group B streptococci, followed by 3-11 month-olds (8.1/100,000; 95% CI 7.1-9.0), where pneumococcal and meningitis predominated. The 30-day case-fatality rate (CFR) was 10.0% (71/6554). Group A streptococcal meningitis had the highest CFR (47/85, 55.3%). The probability of surviving at 30 days was 95.3% (95% CI, 93.4-97.3%) for infants and 80.0% for older adults (77-84%).
INTERPRETATION
The incidence of bacterial meningitis has remained stable. The high CFR highlights a need for prevention through vaccination.
FUNDING
PHE.
PubMed: 37538400
DOI: 10.1016/j.lanepe.2023.100692 -
Current HIV/AIDS Reports Dec 2023Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Inadequate diagnostic testing and treatment regimens adapted from pulmonary tuberculosis without... (Review)
Review
PURPOSE OF REVIEW
Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Inadequate diagnostic testing and treatment regimens adapted from pulmonary tuberculosis without consideration of the unique nature of TBM are among the potential drivers. This review focuses on the progress being made in relation to both diagnosis and treatment of TBM, emphasizing promising future directions.
RECENT FINDINGS
The molecular assay GeneXpert MTB/Rif Ultra has improved sensitivity but has inadequate negative predictive value to "rule-out" TBM. Evaluations of tests focused on the host response and bacterial components are ongoing. Clinical trials are in progress to explore the roles of rifampin, fluoroquinolones, linezolid, and adjunctive aspirin. Though diagnosis has improved, novel modalities are being explored to improve the rapid diagnosis of TBM. Multiple ongoing clinical trials may change current therapies for TBM in the near future.
Topics: Humans; Tuberculosis, Meningeal; Mycobacterium tuberculosis; HIV Infections; Rifampin; Tuberculosis, Pulmonary; Sensitivity and Specificity
PubMed: 37947980
DOI: 10.1007/s11904-023-00678-6