-
Medicine May 2024There are multiple mechanisms by which The Coronavirus-19 (COVID-19) infection can cause electrolyte abnormalities, which may not be the case for bacterial causes of... (Observational Study)
Observational Study
There are multiple mechanisms by which The Coronavirus-19 (COVID-19) infection can cause electrolyte abnormalities, which may not be the case for bacterial causes of pneumonia. This study aimed to assess the differences in electrolyte levels between patients suffering from COVID-19 and bacterial pneumonia. This is an original, retrospective study. Two cohorts of hospitalized patients were included, 1 suffering from COVID-19 and the other from bacterial pneumonia. Their day 1 and day 3 levels of sodium, potassium, magnesium, and phosphorus, as well as their outcomes, were extracted from the charts. Statistical analysis was subsequently performed. Mean admission levels of sodium, potassium, phosphorus, and magnesium were 135.64 ± 6.13, 4.38 ± 0.69, 3.53 ± 0.69, and 2.03 ± 0.51, respectively. The mean day 3 levels of these electrolytes were 138.3 ± 5.06, 4.18 ± 0.59, 3.578 ± 0.59, and 2.11 ± 0.64, respectively. Patients suffering from bacterial pneumonia were significantly older (N = 219, mean = 64.88 ± 15.99) than patients with COVID-19 pneumonia (N = 240, mean = 57.63 ± 17.87). Bacterial pneumonia group had significantly higher serum potassium (N = 211, mean = 4.51 ± 0.76), and magnesium (N = 115, mean = 2.12 ± 0.60) levels compared to COVID-19 group (N = 227, mean = 4.254 ± 0.60 for potassium and N = 118, mean = 1.933 ± 0.38 for magnesium). Only magnesium was significantly higher among day 3 electrolytes in the bacterial pneumonia group. No significant association between electrolyte levels and outcomes was seen. We found that COVID-19 patients had lower potassium and magnesium levels on admission, possibly due to the effect of COVID-19 on the renin-angiotensin-aldosterone system as well as patient characteristics and management. We did not find enough evidence to recommend using electrolyte levels as a determinator of prognosis, but more research is needed.
Topics: Humans; COVID-19; Male; Female; Retrospective Studies; Middle Aged; Aged; Hospitalization; Water-Electrolyte Imbalance; Pneumonia, Bacterial; Potassium; Magnesium; SARS-CoV-2; Electrolytes; Sodium; Phosphorus
PubMed: 38758907
DOI: 10.1097/MD.0000000000037749 -
JAMA Network Open May 2024β-lactam (BL) allergies are the most common drug allergy worldwide, but most are reported in error. BL allergies are also well-established risk factors for adverse drug...
IMPORTANCE
β-lactam (BL) allergies are the most common drug allergy worldwide, but most are reported in error. BL allergies are also well-established risk factors for adverse drug events and antibiotic-resistant infections during inpatient health care encounters, but the understanding of the long-term outcomes of patients with BL allergies remains limited.
OBJECTIVE
To evaluate the long-term clinical outcomes of patients with BL allergies.
DESIGN, SETTING, AND PARTICIPANTS
This longitudinal retrospective cohort study was conducted at a single regional health care system in western Pennsylvania. Electronic health records were analyzed for patients who had an index encounter with a diagnosis of sepsis, pneumonia, or urinary tract infection between 2007 and 2008. Patients were followed-up until death or the end of 2018. Data analysis was performed from January 2022 to January 2024.
EXPOSURE
The presence of any BL class antibiotic in the allergy section of a patient's electronic health record, evaluated at the earliest occurring observed health care encounter.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause mortality, derived from the Social Security Death Index. Secondary outcomes were defined using laboratory and microbiology results and included infection with methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, or vancomycin-resistant Enterococcus (VRE) and severity and occurrence of acute kidney injury (AKI). Generalized estimating equations with a patient-level panel variable and time exposure offset were used to evaluate the odds of occurrence of each outcome between allergy groups.
RESULTS
A total of 20 092 patients (mean [SD] age, 62.9 [19.7] years; 12 231 female [60.9%]), of whom 4211 (21.0%) had BL documented allergy and 15 881 (79.0%) did not, met the inclusion criteria. A total of 3513 patients (17.5%) were Black, 15 358 (76.4%) were White, and 1221 (6.0%) were another race. Using generalized estimating equations, documented BL allergies were not significantly associated with the odds of mortality (odds ratio [OR], 1.02; 95% CI, 0.96-1.09). BL allergies were associated with increased odds of MRSA infection (OR, 1.44; 95% CI, 1.36-1.53), VRE infection (OR, 1.18; 95% CI, 1.05-1.32), and the pooled rate of the 3 evaluated antibiotic-resistant infections (OR, 1.33; 95% CI, 1.30-1.36) but were not associated with C difficile infection (OR, 1.04; 95% CI, 0.94-1.16), stage 2 and 3 AKI (OR, 1.02; 95% CI, 0.96-1.10), or stage 3 AKI (OR, 1.06; 95% CI, 0.98-1.14).
CONCLUSIONS AND RELEVANCE
Documented BL allergies were not associated with the long-term odds of mortality but were associated with antibiotic-resistant infections. Health systems should emphasize accurate allergy documentation and reduce unnecessary BL avoidance.
Topics: Humans; Drug Hypersensitivity; Female; Male; beta-Lactams; Retrospective Studies; Middle Aged; Aged; Anti-Bacterial Agents; Longitudinal Studies; Pennsylvania; Adult; Urinary Tract Infections; Risk Factors; Electronic Health Records
PubMed: 38758551
DOI: 10.1001/jamanetworkopen.2024.12313 -
Research Square May 2024Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation...
Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of open-access bioinformatics tools capable of simultaneously analyzing both microbial and AMR gene sequences. To address this need, we developed the CZ ID AMR module, an open-access, cloud-based workflow designed to integrate detection of both microbes and AMR genes in mNGS and whole-genome sequencing (WGS) data. It leverages the Comprehensive Antibiotic Resistance Database and associated Resistance Gene Identifier software, and works synergistically with the CZ ID short-read mNGS module to enable broad detection of both microbes and AMR genes. We highlight diverse applications of the AMR module through analysis of both publicly available and newly generated mNGS and WGS data from four clinical cohort studies and an environmental surveillance project. Through genomic investigations of bacterial sepsis and pneumonia cases, hospital outbreaks, and wastewater surveillance data, we gain a deeper understanding of infectious agents and their resistomes, highlighting the value of integrating microbial identification and AMR profiling for both research and public health. We leverage additional functionalities of the CZ ID mNGS platform to couple resistome profiling with the assessment of phylogenetic relationships between nosocomial pathogens, and further demonstrate the potential to capture the longitudinal dynamics of pathogen and AMR genes in hospital acquired bacterial infections. In sum, the new AMR module advances the capabilities of the open-access CZ ID microbial bioinformatics platform by integrating pathogen detection and AMR profiling from mNGS and WGS data. Its development represents a critical step toward democratizing pathogen genomic analysis and supporting collaborative efforts to combat the growing threat of AMR.
PubMed: 38746293
DOI: 10.21203/rs.3.rs-4271356/v1 -
BioRxiv : the Preprint Server For... May 2024(Kpn) is the fourth leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive Kpn. In this study, we sought to...
BACKGROUND
(Kpn) is the fourth leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive Kpn. In this study, we sought to determine whether the O-specific polysaccharide (OPS) antigen, a vaccine candidate, is immunogenic in humans with Kpn bloodstream infection (BSI). We also sought to define the cross-reactivity of human antibody responses among structurally related Kpn OPS subtypes and to assess the impact of capsule production on OPS-targeted antibody binding and function.
METHODS
We measured plasma antibody responses to OPS (and MrkA, a fimbrial protein) in a cohort of patients with Kpn BSI and compared these with controls, including a cohort of healthy individuals and a cohort of individuals with BSI. We performed flow cytometry to measure the impact of Kpn capsule production on whole cell antibody binding and complement deposition, utilizing patient isolates with variable levels of capsule production and isogenic capsule-deficient strains derived from these isolates.
FINDINGS
We enrolled 69 patients with Kpn BSI. Common OPS serotypes accounted for 57/69 (83%) of infections. OPS was highly immunogenic in patients with Kpn BSI, and peak OPS-IgG antibody responses in patients were 10 to 30-fold higher than antibody levels detected in healthy controls, depending on the serotype. There was significant cross-reactivity among structurally similar OPS subtypes, including the O1v1/O1v2, O2v1/O2v2 and O3/O3b subtypes. Physiological amounts of capsule produced by both hyperencapsulated and non-hyperencapsulated Kpn significantly inhibited OPS-targeted antibody binding and function.
INTERPRETATION
OPS was highly immunogenic in patients with Kpn BSI, supporting its potential as a candidate vaccine antigen. The strong cross-reactivity observed between similar OPS subtypes in humans with Kpn BSI suggests that it may not be necessary to include all subtypes in an OPS-based vaccine. However, these observations are tempered by the fact that capsule production, even in non-highly encapsulated strains, has the potential to interfere with OPS antibody binding. This may limit the effectiveness of vaccines that exclusively target OPS.
FUNDING
National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
RESEARCH IN CONTEXT
Despite the potential of O-specific polysaccharide (OPS) as a vaccine antigen against (Kpn), the immunogenicity of OPS in humans remains largely unstudied, creating a significant knowledge gap with regard to vaccine development. A search of PubMed for publications up to March 18, 2024, using the terms " " and "O-specific polysaccharide" or "O-antigen" or "lipopolysaccharide" revealed no prior studies addressing OPS antibody responses in humans with Kpn bloodstream infections (BSI). One prior study evaluated antibody response to a single lipopolysaccharide (which contains one subtype of OPS) in humans with invasive Kpn infection; however, in this study OPS typing of the infecting strains and target antigen were not described. Our investigation into OPS immunogenicity in a human cohort marks a significant advance. Analyzing plasma antibody responses in 69 patients with Kpn BSI, we found OPS to be broadly immunogenic across all the types and subtypes examined, and there was significant cross-reactivity among structurally related OPS antigens. We also demonstrated that Kpn capsule production inhibit OPS antibody binding and the activation of complement on the bacterial surface, even in classical Kpn strains expressing lower levels of capsule. While the immunogenicity and broad cross-reactivity of OPS in humans with Kpn BSI suggests it is a promising vaccine candidate, the obstruction of OPS antibody binding and engagement by physiologic levels of Kpn capsule underscores the potential limitations of an exclusively OPS-antigen based vaccine for Kpn. Our study provides insights for the strategic development of vaccines aimed at combating Kpn infections, an important antimicrobial resistant pathogen.
PubMed: 38746292
DOI: 10.1101/2024.05.01.591958 -
Drugs in Context 2024Antibiotics are drugs of natural or synthetic origin used to treat various infections. The practice of excessive and inappropriate antibiotics use is the main global...
BACKGROUND
Antibiotics are drugs of natural or synthetic origin used to treat various infections. The practice of excessive and inappropriate antibiotics use is the main global cause of bacterial resistance, which is one of the most serious global public health threats. It is estimated that about 50% of global antibiotic prescriptions are inappropriate. This study assesses the prevalence and pattern of inappropriate prescriptions of antibiotics amongst ambulatory care visits in Ethiopia.
METHODS
A facility-based, cross-sectional study with a quantitative approach was conducted amongst randomly selected prescriptions issued for outpatients from May to June 2022 at Debre Markos Specialized Comprehensive Hospital, Northwest Ethiopia. Descriptive statistics, such as frequencies and percentages, were computed. For group comparisons, χ and independent sample -tests were computed. The statistical significance of the association was considered at <0.05.
RESULTS
A total of 2640 antibiotics were prescribed for patients in the outpatient setting with various bacterial infections via 911 prescriptions, of which 49.5% were non-compliant with the national treatment guideline. Guideline non-compliant prescriptions increased remarkably amongst patients in the outpatient setting diagnosed with community-acquired pneumonia (38.8% 30.1%; =0.006) and peptic ulcer disease (14.9% 9%; =0.006). Moreover, inappropriate prescription was significantly higher amongst patients taking amoxicillin/clavulanic acid (33.2% 48.2%; <0.001) and cephalexin (17.8% 24.3%; =0.016).
CONCLUSION
Large proportions of antibiotic prescriptions for outpatients were non-compliant with the national treatment guideline, suggesting that prescribers need to give special attention to outpatients whilst ordering antibiotics such as amoxicillin/clavulanic acid and cephalexin. Antibiotic stewardship efforts to optimize outpatient antibiotic prescriptions and reduce the use of potentially inappropriate antibiotics are needed in Ethiopia.
PubMed: 38742144
DOI: 10.7573/dic.2023-12-2 -
Journal of Inflammation Research 2024Community-acquired pneumonia (CAP) is a global health concern due to its high rates of morbidity and mortality. Bacterial pathogens are common causes of CAP. It is one...
BACKGROUND
Community-acquired pneumonia (CAP) is a global health concern due to its high rates of morbidity and mortality. Bacterial pathogens are common causes of CAP. It is one of the most common causes of acute respiratory distress syndrome (ARDS), a common severe respiratory system manifestation threatening human health. This study aimed to establish a predictive model for ARDS in patients with bacterial pneumonia, which was conducive to early identification of the occurrence and effective prevention of ARDS.
METHODS
We collected the clinical data of hospitalized patients with bacterial pneumonia in Affiliated Huzhou Hospital of Zhejiang University School of Medicine from January 2022 to November 2022. The independent risk factors for ARDS in patients with bacterial pneumonia were determined by univariate and multivariate binary logistic regression analyses. The nomogram was constructed to display the predictive model, and the receiver-operating characteristic curve was plotted to evaluate the predictive value of ARDS.
RESULTS
This study included 254 patients with bacterial pneumonia, of which 114 developed ARDS. The multivariate logistic regression analysis revealed age [odds ratio (OR) = 1.041, = 0.003], heart rate (OR = 1.020, = 0.028), lymphocyte count (OR = 0.555, = 0.033), white blood cell count (OR = 1.062, = 0.033), bilateral lung lesions (OR = 7.352, = 0.011) and pleural effusion (OR = 2.512, = 0.002) as the independent risk factors for ARDS. The predictive model was constructed based on the six independent factors, which was valuable in predicting ARDS with area under the curve of 0.794.
CONCLUSION
The predictive model was beneficial to evaluate the disease progression in patients with bacterial pneumonia and identify ARDS. Further, our nomogram might help doctors predict the incidence of ARDS and conduct treatment as early as possible.
PubMed: 38737109
DOI: 10.2147/JIR.S458690 -
The Journal of Biological Chemistry May 2024FOXK2 is a crucial transcription factor implicated in a wide array of biological activities and yet understanding of its molecular regulation at the level of protein...
FOXK2 is a crucial transcription factor implicated in a wide array of biological activities and yet understanding of its molecular regulation at the level of protein turnover is limited. Here we identify that FOXK2 undergoes degradation in lung epithelia in the presence of the virulent pathogens P. aeruginosa and K. pneumoniae through ubiquitin-proteasomal processing. FOXK2 through its carboxyl-terminus (aa 428-478) binds the Skp-Cullin-F-box ubiquitin E3 ligase subunit FBXO24 that mediates multisite polyubiquitylation of the transcription factor resulting in its nuclear degradation. FOXK2 was detected within mitochondria and targeted depletion of the transcription factor or cellular expression of FOXK2 mutants devoid of key carboxyl-terminal domains significantly impaired mitochondrial function. In experimental bacterial pneumonia, Fbxo24 heterozygous mice exhibited preserved mitochondrial function and Foxk2 protein levels compared to wild-type littermates. The results suggest a new mode of regulatory control of mitochondrial energetics through modulation of FOXK2 cellular abundance.
PubMed: 38735474
DOI: 10.1016/j.jbc.2024.107359 -
International Journal of Molecular... May 2024New antimicrobial molecules effective against , known as an antibiotic-resistant "high-priority pathogen", are urgently required because of its ability to develop...
New antimicrobial molecules effective against , known as an antibiotic-resistant "high-priority pathogen", are urgently required because of its ability to develop biofilms related to healthcare-acquired infections. In this study, for the first time, the anti-biofilm and anti-virulence activities of a polyphenolic extract of extra-virgin olive oil as well as purified oleocanthal and oleacein, toward clinical isolates were investigated. The main result of our study was the anti-virulence activity of the mixture of oleacein and oleocanthal toward multidrug-resistant and intermediately resistant strains of isolated from patients with ventilator-associated pneumonia or surgical site infection. Specifically, the mixture of oleacein (2.5 mM)/oleocanthal (2.5 mM) significantly inhibited biofilm formation, alginate and pyocyanin production, and motility in both strains ( < 0.05); scanning electron microscopy analysis further evidenced its ability to inhibit bacterial cell adhesion as well as the production of the extracellular matrix. In conclusion, our results suggest the potential application of the oleacein/oleocanthal mixture in the management of healthcare-associated infections, particularly in the era of increasing antimicrobial resistance.
Topics: Biofilms; Pseudomonas aeruginosa; Olive Oil; Cyclopentane Monoterpenes; Phenols; Aldehydes; Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Pseudomonas Infections; Bacterial Adhesion
PubMed: 38732269
DOI: 10.3390/ijms25095051 -
Molecules (Basel, Switzerland) Apr 2024Functional Lyocell fibers gain interest in garments and technical textiles, especially when equipped with inherently bioactive features. In this study, Lyocell fibers...
Functional Lyocell fibers gain interest in garments and technical textiles, especially when equipped with inherently bioactive features. In this study, Lyocell fibers are modified with an ion exchange resin and subsequently loaded with copper (Cu) ions. The modified Lyocell process enables high amounts of the resin additive (>10%) through intensive dispersion and subsequently, high uptake of 2.7% Cu throughout the whole cross-section of the fiber. Fixation by NaCO increases the washing and dyeing resistance considerably. Cu content after dyeing compared to the original fiber value amounts to approx. 65% for reactive, 75% for direct, and 77% for HT dyeing, respectively. Even after 50 household washes, a recovery of 43% for reactive, 47% for direct and 26% for HT dyeing is proved. XRD measurements reveal ionic bonding of Cu fixation inside the cellulose/ion exchange resin composite. A combination of the fixation process with a change in Cu valence state by glucose/NaOH leads to the formation of CuO crystallites, which is proved by XRD. Cu fiber shows a strong antibacterial effect against and bacteria, even after 50 household washing cycles of both >5 log CFU. In nonwoven blends with a share of only 6% Cu fiber, a strong antimicrobial (CFU > log 5) and full antiviral effectiveness (>log 4) was received even after 50 washing cycles. Time-dependent measurements already show strong antiviral behavior after 30 s. Further, the fibers show an increased die off of the fungal isolate Candida auris with CFU log 4.4, and nonwovens made from 6% Cu fiber share a CFU log of 1.7. Findings of the study predestines the fiber for advanced textile processing and applications in areas with high germ loads.
Topics: Antifungal Agents; Anti-Bacterial Agents; Antiviral Agents; Copper; Cellulose; Staphylococcus aureus; Textiles; Microbial Sensitivity Tests; Klebsiella pneumoniae; Lignin; Humans
PubMed: 38731545
DOI: 10.3390/molecules29092054 -
Medicine May 2024This study aimed to investigate the expression and significance of serum procalcitonin (PCT), leukotriene B4 (LTB4), Serum amyloid A (SAA), and C-reactive protein (CRP)... (Observational Study)
Observational Study
Expression and significance of procalcitonin, leukotriene B4, serum amyloid A, and C-reactive protein in children with different types of pneumonia: An observational study.
This study aimed to investigate the expression and significance of serum procalcitonin (PCT), leukotriene B4 (LTB4), Serum amyloid A (SAA), and C-reactive protein (CRP) in children with different types of pneumonia caused by different pathogenic infections. One hundred and one children with pneumonia admitted to The Fifth People Hospital of Zhuhai from July 2019 to June 2020 were enrolled and divided into 38 cases in the bacterial group, 30 cases in the mycoplasma group, and 33 cases in the virus group according to the different types of pathogens. The patients were divided into 42 cases in the noncritical group, 33 cases in the critical group, and 26 cases in the very critical group according to the pediatric clinical illness score (PCIS), and 30 healthy children were selected as the control group during the same period. Comparison of serum PCT, SAA: bacterial group > mycoplasma group > viral group > control group with significant differences (P < .05). Receiver operator characteristic (ROC) analysis showed that the area under the curves (AUCs) of serum PCT, LTB4, SAA, and CRP for the diagnosis of bacterial pneumonia were 1.000, 0.531, 0.969, and 0.833, respectively, and the AUCs for the diagnosis of mycoplasma pneumonia were 0.653, 0.609, 0.547, and 0.652, respectively, and the AUCs for the diagnosis of viral pneumonia were 0.888, 0.570, 0.955, and 1.000, respectively. Comparison of serum PCT, LTB4, SAA: very critical group > critical group > noncritical group > control group, with significant differences (P < .05). Serum PCT, LTB4, and SAA were negatively correlated with PCIS score by Pearson analysis (P < .05). Serum PCT and SAA showed diagnostic value for bacterial pneumonia, and serum SAA and CRP showed diagnostic value for viral pneumonia; serum PCT, LTB4, and SAA correlate with severity of disease and show higher expression with worsening of the condition.
Topics: Humans; C-Reactive Protein; Serum Amyloid A Protein; Male; Female; Procalcitonin; Child, Preschool; Pneumonia, Bacterial; Child; Leukotriene B4; Biomarkers; ROC Curve; Pneumonia, Mycoplasma; Infant; Pneumonia, Viral; Pneumonia
PubMed: 38728486
DOI: 10.1097/MD.0000000000037817