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International Journal of Molecular... Sep 2023The recurrence of bacterial infectious diseases is closely associated with bacterial persisters. This subpopulation of bacteria can escape antibiotic treatment by... (Review)
Review
The recurrence of bacterial infectious diseases is closely associated with bacterial persisters. This subpopulation of bacteria can escape antibiotic treatment by entering a metabolic status of low activity through various mechanisms, for example, biofilm, toxin-antitoxin modules, the stringent response, and the SOS response. Correspondingly, multiple new treatments are being developed. However, due to their spontaneous low abundance in populations and the lack of research on in vivo interactions between persisters and the host's immune system, microfluidics, high-throughput sequencing, and microscopy techniques are combined innovatively to explore the mechanisms of persister formation and maintenance at the single-cell level. Here, we outline the main mechanisms of persister formation, and describe the cutting-edge technology for further research. Despite the significant progress regarding study techniques, some challenges remain to be tackled.
Topics: Humans; Bacteria; Bacterial Infections; Anti-Bacterial Agents
PubMed: 37762613
DOI: 10.3390/ijms241814311 -
International Journal of Molecular... Jun 2023Interferons are a group of immunomodulatory substances produced by the human immune system in response to the presence of pathogens, especially during viral and... (Review)
Review
Interferons are a group of immunomodulatory substances produced by the human immune system in response to the presence of pathogens, especially during viral and bacterial infections. Their remarkably diverse mechanisms of action help the immune system fight infections by activating hundreds of genes involved in signal transduction pathways. In this review, we focus on discussing the interplay between the IFN system and seven medically important and challenging viruses (herpes simplex virus (HSV), influenza, hepatitis C virus (HCV), lymphocytic choriomeningitis virus (LCMV), human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), and SARS-CoV coronavirus) to highlight the diversity of viral strategies. In addition, the available data also suggest that IFNs play an important role in the course of bacterial infections. Research is currently underway to identify and elucidate the exact role of specific genes and effector pathways in generating the antimicrobial response mediated by IFNs. Despite the numerous studies on the role of interferons in antimicrobial responses, many interdisciplinary studies are still needed to understand and optimize their use in personalized therapeutics.
Topics: Humans; Interferons; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Signal Transduction; Bacterial Infections
PubMed: 37373262
DOI: 10.3390/ijms241210115 -
Journal of Clinical Laboratory Analysis Feb 2024Procalcitonin (PCT) is a critical biomarker that is released in response to bacterial infections and can be used to differentiate the pathogenesis of the infectious... (Review)
Review
BACKGROUND
Procalcitonin (PCT) is a critical biomarker that is released in response to bacterial infections and can be used to differentiate the pathogenesis of the infectious process.
OBJECTIVE
In this article, we provide an overview of recent advances in PCT biosensors, highlighting different approaches for biosensor construction, different immobilization methods, advantages and roles of different matrices used, analytical performance, and PCT biosensor construction. Also, we will explain PCT biosensors sensible limits of detection (LOD), linearity, and other analytical characteristics. Future prospects for the development of better PCT biosensor systems are also discussed.
METHODS
Traditional methods such as capillary electrophoresis, high-performance liquid chromatography, and mass spectrometry are effective in analyzing PCT in the medical field, but they are complicated, time-consuming sample preparation, and require expensive equipment and skilled personnel.
RESULTS
In the past decades, PCT biosensors have emerged as simple, fast, and sensitive tools for PCT analysis in various fields, especially medical fields.
CONCLUSION
These biosensors have the potential to accompany or replace traditional analytical methods by simplifying or reducing sample preparation and making field testing easier and faster, while significantly reducing the cost per analysis.
Topics: Humans; Procalcitonin; Bacterial Infections; Biosensing Techniques; Biomarkers; Limit of Detection
PubMed: 38268233
DOI: 10.1002/jcla.25006 -
Emerging Infectious Diseases Aug 2023Few data are available on incidence of multidrug-resistant organism (MDRO) colonization and infections in mechanically ventilated patients, particularly during the...
Few data are available on incidence of multidrug-resistant organism (MDRO) colonization and infections in mechanically ventilated patients, particularly during the COVID-19 pandemic. We retrospectively evaluated all patients admitted to the COVID-19 intensive care unit (ICU) of Hub Hospital in Milan, Italy, during October 2020‒May 2021. Microbiologic surveillance was standardized with active screening at admission and weekly during ICU stay. Of 435 patients, 88 (20.2%) had MDROs isolated ≤48 h after admission. Of the remaining patients, MDRO colonization was diagnosed in 173 (51.2%), MDRO infections in 95 (28.1%), and non-MDRO infections in 212 (62.7%). Non-MDRO infections occurred earlier than MDRO infections (6 days vs. 10 days; p<0.001). Previous exposure to antimicrobial drugs within the ICU was higher in MDRO patients than in non-MDRO patients (116/197 [58.9%] vs. 18/140 [12.9%]; p<0.001). Our findings might serve as warnings for future respiratory viral pandemics and call for increased measures of antimicrobial stewardship and infection control.
Topics: Humans; Retrospective Studies; Drug Resistance, Multiple, Bacterial; Respiration, Artificial; Pandemics; COVID-19; Bacterial Infections
PubMed: 37486196
DOI: 10.3201/eid2908.230115 -
Ultrasonics Sonochemistry Nov 2023The rapid spread and uncontrollable evolution of antibiotic-resistant bacteria have already become urgent global to treat bacterial infections. Sonodynamic therapy... (Review)
Review
The rapid spread and uncontrollable evolution of antibiotic-resistant bacteria have already become urgent global to treat bacterial infections. Sonodynamic therapy (SDT), a noninvasive and effective therapeutic strategy, has broadened the way toward dealing with antibiotic-resistant bacteria and biofilms, which base on ultrasound (US) with sonosensitizer. Sonosensitizer, based on small organic molecules or inorganic nanoparticles, is essential to the SDT process. Thus, it is meaningful to design a sonosensitizer-loaded nanoplatform and synthesize the nanoplatform with an efficient SDT effect. In this review, we initially summarize the probable SDT-based antibacterial mechanisms and systematically discuss the current advancement in different SDT-based nanoplatform (including nanoplatform for organic small-molecule sonosensitizer delivery and nanoplatform as sonosensitizer) for bacterial infection therapy. In addition, the biomedical applications of SDT-involved multifunctional nanoplatforms are also discussed. We believe the innovative SDT-based nanoplatforms would become a highly efficient next-generation noninvasive therapeutic tool for combating bacterial infection.
Topics: Humans; Ultrasonic Therapy; Cell Line, Tumor; Bacterial Infections; Nanoparticles; Anti-Bacterial Agents; Reactive Oxygen Species
PubMed: 37769588
DOI: 10.1016/j.ultsonch.2023.106617 -
European Journal of Public Health Aug 2023We performed a nationwide population-based retrospective study to describe the epidemiology of bacterial co-infections in coronavirus disease 2019...
BACKGROUND
We performed a nationwide population-based retrospective study to describe the epidemiology of bacterial co-infections in coronavirus disease 2019 (COVID-19)-hospitalized patients in Spain in 2020. We also analyzed the risk factors for co-infection, the etiology and the impact in the outcome.
METHODS
Data were obtained from records in the Minimum Basic Data Set (MBDS) of the National Surveillance System for Hospital Data in Spain, provided by the Ministry of Health and annually published with 2 years lag. COVID-19 circulated in two waves in 2020: from its introduction to 31st June and from 1st July to 31st December. The risk of developing a healthcare-associated bacterial co-infection and the risk for in-hospital and intensive care unit (ICU) mortality in co-infected patients was assessed using an adjusted logistic regression model.
RESULTS
The incidence of bacterial co-infection in COVID-19 hospitalized patients was 2.3%. The main risk factors associated with bacterial co-infection were organ failure, obesity and male sex. Co-infection was associated with worse outcomes including higher in-hospital, in-ICU mortality and higher length of stay. Gram-negative bacteria caused most infections. Causative agents were similar between waves, although higher co-infections with Pseudomonas spp. were detected in the first wave and with Haemophilus influenzae and Streptococcus pneumoniae in the second.
CONCLUSIONS
Co-infections are not as common as those found in other viral respiratory infections; therefore, antibiotics should be used carefully. Screening for actual co-infection to prescribe antibiotic therapy when required should be performed.
Topics: Humans; Male; COVID-19; Coinfection; Spain; Retrospective Studies; Bacterial Infections; Anti-Bacterial Agents; Risk Factors
PubMed: 37087109
DOI: 10.1093/eurpub/ckad060 -
EMBO Reports Aug 2023Recalcitrant infections pose a serious challenge by prolonging antibiotic therapies and contributing to the spread of antibiotic resistance, thereby threatening the... (Review)
Review
Recalcitrant infections pose a serious challenge by prolonging antibiotic therapies and contributing to the spread of antibiotic resistance, thereby threatening the successful treatment of bacterial infections. One potential contributing factor in persistent infections is antibiotic persistence, which involves the survival of transiently tolerant subpopulations of bacteria. This review summarizes the current understanding of antibiotic persistence, including its clinical significance and the environmental and evolutionary factors at play. Additionally, we discuss the emerging concept of persister regrowth and potential strategies to combat persister cells. Recent advances highlight the multifaceted nature of persistence, which is controlled by deterministic and stochastic elements and shaped by genetic and environmental factors. To translate in vitro findings to in vivo settings, it is crucial to include the heterogeneity and complexity of bacterial populations in natural environments. As researchers continue to gain a more holistic understanding of this phenomenon and develop effective treatments for persistent bacterial infections, the study of antibiotic persistence is likely to become increasingly complex.
Topics: Humans; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Biological Evolution; Environment; Drug Resistance, Bacterial
PubMed: 37395716
DOI: 10.15252/embr.202357309 -
BMC Infectious Diseases Oct 2023Few studies on neonatal severe bacterial infection are available in LMICs. Data are needed in these countries to prioritize interventions and decrease neonatal...
BACKGROUND
Few studies on neonatal severe bacterial infection are available in LMICs. Data are needed in these countries to prioritize interventions and decrease neonatal infections which are a primary cause of neonatal mortality. The BIRDY project (Bacterial Infections and Antimicrobial Drug Resistant among Young Children) was initially conducted in Madagascar, Senegal and Cambodia (BIRDY 1, 2012-2018), and continued in Madagascar only (BIRDY 2, 2018-2021). We present here the BIRDY 2 project whose objectives were (1) to estimate the incidence of neonatal severe bacterial infections and compare these findings with those obtained in BIRDY 1, (2) to identify determinants associated with severe bacterial infection and (3) to specify the antibiotic resistance pattern of bacteria in newborns.
METHODS
The BIRDY 2 study was a prospective community-based mother and child cohort, both in urban and semi-rural areas. All pregnant women in the study areas were identified and enrolled. Their newborns were actively and passively followed-up from birth to 3 months. Data on clinical symptoms developed by the children and laboratory results of all clinical samples investigated were collected. A Cox proportional hazards model was performed to identify risk factors associated with possible severe bacterial infection.
FINDINGS
A total of 53 possible severe bacterial infection and 6 confirmed severe bacterial infection episodes were identified among the 511 neonates followed-up, with more than half occurring in the first 3 days. For the first month period, the incidence of confirmed severe bacterial infection was 11.7 per 1,000 live births indicating a 1.3 -fold decrease compared to BIRDY 1 in Madagascar (p = 0.50) and the incidence of possible severe bacterial infection was 76.3, indicating a 2.6-fold decrease compared to BIRDY 1 in Madagascar (p < 0.001). The 6 severe bacterial infection confirmed by blood culture included 5 Enterobacterales and one Enterococcus faecium. The 5 Enterobacterales were extended-spectrum β-lactamases (ESBL) producers and were resistant to quinolones and gentamicin. Enterococcus faecium was sensitive to vancomycin but resistant to amoxicillin and to gentamicin. These pathogns were classified as multidrug-resistant bacteria and were resistant to antibiotics recommended in WHO guidelines for neonatal sepsis. However, they remained susceptible to carbapenem. Fetid amniotic fluid, need for resuscitation at birth and low birth weight were associated with early onset possible severe bacterial infection.
CONCLUSION
Our results suggest that the incidence of severe bacterial infection is still high in the community of Madagascar, even if it seems lower when compared to BIRDY 1 estimates, and that existing neonatal sepsis treatment guidelines may no longer be appropriate in Madagascar. These results motivate to further strengthen actions for the prevention, early diagnosis and case management during the first 3 days of life.
Topics: Child; Infant, Newborn; Humans; Female; Pregnancy; Child, Preschool; Neonatal Sepsis; Prospective Studies; Madagascar; Incidence; Bacterial Infections; Bacteria; Anti-Bacterial Agents; Communicable Diseases; Gentamicins; Risk Factors
PubMed: 37798644
DOI: 10.1186/s12879-023-08642-w -
The Lancet. Microbe Dec 2023Historically, epidemiological investigation and surveillance for bacterial antimicrobial resistance (AMR) has relied on low-resolution isolate-based phenotypic analyses... (Review)
Review
Historically, epidemiological investigation and surveillance for bacterial antimicrobial resistance (AMR) has relied on low-resolution isolate-based phenotypic analyses undertaken at local and national reference laboratories. Genomic sequencing has the potential to provide a far more high-resolution picture of AMR evolution and transmission, and is already beginning to revolutionise how public health surveillance networks monitor and tackle bacterial AMR. However, the routine integration of genomics in surveillance pipelines still has considerable barriers to overcome. In 2022, a workshop series and online consultation brought together international experts in AMR and pathogen genomics to assess the status of genomic applications for AMR surveillance in a range of settings. Here we focus on discussions around the use of genomics for public health and international AMR surveillance, noting the potential advantages of, and barriers to, implementation, and proposing recommendations from the working group to help to drive the adoption of genomics in public health AMR surveillance. These recommendations include the need to build capacity for genome sequencing and analysis, harmonising and standardising surveillance systems, developing equitable data sharing and governance frameworks, and strengthening interactions and relationships among stakeholders at multiple levels.
Topics: Humans; Public Health; Anti-Bacterial Agents; Drug Resistance, Bacterial; Genomics; Anti-Infective Agents; Bacterial Infections; Bacteria
PubMed: 37977162
DOI: 10.1016/S2666-5247(23)00283-5 -
Journal of Critical Care Dec 2023Mortality in acute infections is mostly associated with sepsis, defined as 'life-threatening organ dysfunction caused by a dysregulated host response to infection'. It... (Review)
Review
Mortality in acute infections is mostly associated with sepsis, defined as 'life-threatening organ dysfunction caused by a dysregulated host response to infection'. It remains challenging to identify the patients with increased mortality risk due to the high heterogeneity in the dysregulated host immune response and disease progression. Biomarkers reflecting different pathways involved in the inflammatory response might improve prediction of mortality risk (prognostic enrichment) among patients with acute infections by reducing heterogeneity of the host response, as well as suggest novel strategies for patient stratification and treatment (predictive enrichment) through precision medicine approaches. The predictive value of inflammatory biomarkers has been extensively investigated in bacterial infections and the recent COVID-19 pandemic caused an increased interest in inflammatory biomarkers in this viral infection. However, limited research investigated whether the prognostic potential of these biomarkers differs between bacterial and viral infections. In this narrative review, we provide an overview of the value of various inflammatory biomarkers for the prediction of mortality in bacterial and viral infections.
Topics: Humans; Pandemics; COVID-19; Biomarkers; Prognosis; Sepsis; Infections; Bacterial Infections
PubMed: 37343422
DOI: 10.1016/j.jcrc.2023.154360