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PloS One 2024Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial... (Observational Study)
Observational Study
Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial identification, we developed a molecular assay and evaluated its performance compared with bacterial culture. Our multiplex-quantitative PCR to detect Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae was assessed using bacterial genomic DNA and laboratory-prepared samples (n = 267). To evaluate clinical performance, we conducted the Molecular Assessment of Thoracic Empyema (MATE) observational study, enrolling children hospitalised with empyema. Pleural fluids were tested by bacterial culture and multiplex-qPCR, and performance determined using a study gold standard. We determined clinical sensitivity and time-to-organism-identification to assess the potential of the multiplex-qPCR to reduce the duration of empiric untargeted antibiotic therapy. Using spiked samples, the multiplex-qPCR demonstrated 213/215 (99.1%) sensitivity and 52/52 (100%) specificity for all organisms. During May 2019-March 2023, 100 children were enrolled in the MATE study; median age was 3.9 years (IQR 2-5.6). A bacterial pathogen was identified in 90/100 (90%) specimens by multiplex-qPCR, and 24/100 (24%) by bacterial culture (P <0.001). Multiplex-qPCR identified a bacterial cause in 68/76 (90%) culture-negative specimens. S. pneumoniae was the most common pathogen, identified in 67/100 (67%) specimens. We estimate our multiplex-qPCR would have reduced the duration of untargeted antibiotic therapy in 61% of cases by a median 20 days (IQR 17.5-23, range 1-55). Multiplex-qPCR significantly increased pathogen detection compared with culture and may allow for reducing the duration of untargeted antibiotic therapy.
Topics: Humans; Child, Preschool; Empyema, Pleural; Male; Female; Multiplex Polymerase Chain Reaction; Child; Haemophilus influenzae; Staphylococcus aureus; Streptococcus pneumoniae; Streptococcus pyogenes; Infant; Hospitalization; Anti-Bacterial Agents; Sensitivity and Specificity; DNA, Bacterial
PubMed: 38917227
DOI: 10.1371/journal.pone.0304861 -
PloS One 2024During the COVID-19 pandemic, acute respiratory infection (ARI) antibiotic prescribing in ambulatory care markedly decreased. It is unclear if antibiotic prescription...
BACKGROUND
During the COVID-19 pandemic, acute respiratory infection (ARI) antibiotic prescribing in ambulatory care markedly decreased. It is unclear if antibiotic prescription rates will remain lowered.
METHODS
We used trend analyses of antibiotics prescribed during and after the first wave of COVID-19 to determine whether ARI antibiotic prescribing rates in ambulatory care have remained suppressed compared to pre-COVID-19 levels. Retrospective data was used from patients with ARI or UTI diagnosis code(s) for their encounter from 298 primary care and 66 urgent care practices within four academic health systems in New York, Wisconsin, and Utah between January 2017 and June 2022. The primary measures included antibiotic prescriptions per 100 non-COVID ARI encounters, encounter volume, prescribing trends, and change from expected trend.
RESULTS
At baseline, during and after the first wave, the overall ARI antibiotic prescribing rates were 54.7, 38.5, and 54.7 prescriptions per 100 encounters, respectively. ARI antibiotic prescription rates saw a statistically significant decline after COVID-19 onset (step change -15.2, 95% CI: -19.6 to -4.8). During the first wave, encounter volume decreased 29.4% and, after the first wave, remained decreased by 188%. After the first wave, ARI antibiotic prescription rates were no longer significantly suppressed from baseline (step change 0.01, 95% CI: -6.3 to 6.2). There was no significant difference between UTI antibiotic prescription rates at baseline versus the end of the observation period.
CONCLUSIONS
The decline in ARI antibiotic prescribing observed after the onset of COVID-19 was temporary, not mirrored in UTI antibiotic prescribing, and does not represent a long-term change in clinician prescribing behaviors. During a period of heightened awareness of a viral cause of ARI, a substantial and clinically meaningful decrease in clinician antibiotic prescribing was observed. Future efforts in antibiotic stewardship may benefit from continued study of factors leading to this reduction and rebound in prescribing rates.
Topics: Humans; Anti-Bacterial Agents; COVID-19; Respiratory Tract Infections; Male; Ambulatory Care; Female; Retrospective Studies; Middle Aged; Drug Prescriptions; Aged; Practice Patterns, Physicians'; Adult; SARS-CoV-2; Pandemics; Wisconsin; Utah; New York
PubMed: 38917147
DOI: 10.1371/journal.pone.0306195 -
Critical Care Explorations Jul 2024Amid the COVID-19 pandemic, this study delves into ventilator shortages, exploring simple split ventilation (SSV), simple differential ventilation (SDV), and... (Comparative Study)
Comparative Study
CONTEXT
Amid the COVID-19 pandemic, this study delves into ventilator shortages, exploring simple split ventilation (SSV), simple differential ventilation (SDV), and differential multiventilation (DMV). The knowledge gap centers on understanding their performance and safety implications.
HYPOTHESIS
Our hypothesis posits that SSV, SDV, and DMV offer solutions to the ventilator crisis. Rigorous testing was anticipated to unveil advantages and limitations, aiding the development of effective ventilation approaches.
METHODS AND MODELS
Using a specialized test bed, SSV, SDV, and DMV were compared. Simulated lungs in a controlled setting facilitated measurements with sensors. Statistical analysis honed in on parameters like peak inspiratory pressure (PIP) and positive end-expiratory pressure.
RESULTS
Setting target PIP at 15 cm H2O for lung 1 and 12.5 cm H2O for lung 2, SSV revealed a PIP of 15.67 ± 0.2 cm H2O for both lungs, with tidal volume (Vt) at 152.9 ± 9 mL. In SDV, lung 1 had a PIP of 25.69 ± 0.2 cm H2O, lung 2 at 24.73 ± 0.2 cm H2O, and Vts of 464.3 ± 0.9 mL and 453.1 ± 10 mL, respectively. DMV trials showed lung 1's PIP at 13.97 ± 0.06 cm H2O, lung 2 at 12.30 ± 0.04 cm H2O, with Vts of 125.8 ± 0.004 mL and 104.4 ± 0.003 mL, respectively.
INTERPRETATION AND CONCLUSIONS
This study enriches understanding of ventilator sharing strategy, emphasizing the need for careful selection. DMV, offering individualization while maintaining circuit continuity, stands out. Findings lay the foundation for robust multiplexing strategies, enhancing ventilator management in crises.
Topics: Humans; Respiration, Artificial; COVID-19; Ventilators, Mechanical; Tidal Volume; SARS-CoV-2; Positive-Pressure Respiration
PubMed: 38916647
DOI: 10.1097/CCE.0000000000001113 -
International Journal of... Apr 2024Bedaquiline is one of the core drugs used to treat multidrug-resistant TB (MDR-TB). Delamanid is one of the companion drugs in group C which is used to complete the... (Observational Study)
Observational Study Comparative Study
Comparison of Individual Regimen Containing Bedaquiline with Delamanid and Bedaquiline without Delamanid on Efficacy and Safety in Multidrug-resistant Tuberculosis Patients: Implementation in Dr. Soetomo General Academic Hospital, Indonesia.
BACKGROUND
Bedaquiline is one of the core drugs used to treat multidrug-resistant TB (MDR-TB). Delamanid is one of the companion drugs in group C which is used to complete the treatment regimen when drugs in groups A and B can not be used. This study was conducted to analyze the efficacy and safety between individual regimens containing bedaquiline with delamanid and bedaquiline without delamanid.
METHODS
This was an observational analytic study with a retrospective design in MDR-TB patients treated with individual regimens containing bedaquiline with delamanid (bedaquiline-delamanid group) and bedaquiline without delamanid (bedaquiline group). Efficacy was measured according to the time to Acid Fast Bacilli (AFB) conversion and Mycobacterium tuberculosis culture conversion, while safety was measured specifically on QTc interval prolongation.
RESULTS
The median (range) time to AFB conversion in bedaquiline-delamanid group was faster than bedaquiline group, although there was no significant difference (1.5 (1-4) months vs. 1 (1-6) months, P=0.429), the median time to culture conversion in bedaquiline-delamanid group also faster than bedaquiline group, although there was no significant difference (1 (1-6) months vs. 2 (1-6) months, P=0.089). The incidence of QTc interval prolongation in bedaquiline-delamanid group was less than bedaquiline group, although there was no significant difference (26.9% vs. 40.3%, P=0.223).
CONCLUSIONS
Individual regimens containing bedaquiline with delamanid was proven to provide similar efficacy and safety profiles with individual regimens containing bedaquiline without delamanid. Delamanid should be preferred when selecting drugs to complete the treatment regimen when drugs in groups A and B can not be used.
Topics: Humans; Nitroimidazoles; Diarylquinolines; Oxazoles; Tuberculosis, Multidrug-Resistant; Antitubercular Agents; Retrospective Studies; Female; Adult; Male; Middle Aged; Indonesia; Treatment Outcome; Young Adult; Drug Therapy, Combination; Mycobacterium tuberculosis; Adolescent; Aged
PubMed: 38916383
DOI: 10.4103/ijmy.ijmy_88_24 -
Microbiology Spectrum Jun 2024Elexacaftor/tezacaftor/ivacaftor (ETI) therapy has revolutionized the treatment of cystic fibrosis (CF) for most affected individuals but the effects of treatment on...
Elexacaftor/tezacaftor/ivacaftor (ETI) therapy has revolutionized the treatment of cystic fibrosis (CF) for most affected individuals but the effects of treatment on sinus microbiota are still unknown. Changes to the airway microbiota in CF are associated with disease state and alterations to the bacterial community after ETI initiation may require changes to clinical management regimens. We collected sinus swab samples from the middle meatus in an observational study of 38 adults with CF and chronic rhinosinusitis (CRS) from 2017 to 2021 and captured the initiation of ETI therapy. We performed 16S and custom amplicon sequencing to characterize the sinus microbiota pre- and post-ETI. Real-time quantitative PCR (RT-qPCR) was performed to estimate total bacterial abundance. Sinus samples from people with CF (pwCF) clustered into three community types, dependent on the dominant bacterial organism: a -dominant, -dominant, and mixed dominance cluster. Shannon's diversity index was low and not significantly altered post-ETI. Total bacterial load was not significantly lowered post-ETI. spp. abundance was significantly reduced post-ETI, but eradication was not observed. spp. became the dominant organism in most individuals post-ETI and we showed the presence of methicillin-resistant (MRSA) in the sinus both pre- and post-ETI. We also demonstrated that the sinus microbiome is predictive of the presence of spp., spp., and spp. in the sputum. spp. and spp., including MRSA, persist in the sinuses of pwCF after ETI therapy, indicating that these pathogens will continue to be important in CF airway disease management in the era of highly effective modulator therapies (HEMT).IMPORTANCEHighly effective modulator therapies (HEMT), such as elexacaftor/tezacaftor/ivacaftor (ETI), for cystic fibrosis (CF) have revolutionized patient care and quality of life for most affected individuals. The effects of these therapies on the microbiota of the airways are still unclear, though work has already been published on changes to microbiota in the sputum. Our study presents evidence for reduced relative abundance of spp. in the sinuses following ETI therapy. We also show that spp. becomes the dominant organism in the sinus communities of most individuals in this cohort after ETI therapy. We identified methicillin-resistant (MRSA) in the sinus microbiota both pre- and post-therapy. These findings demonstrate that pathogen monitoring and treatment will remain a vital part of airway disease management for people with cystic fibrosis (pwCF) in the era of HEMT.
PubMed: 38916354
DOI: 10.1128/spectrum.00787-24 -
Microbiology Spectrum Jun 2024is one of the most important pathogens worldwide. The intrinsic and acquired resistance of , coupled with the slow pace of novel antimicrobial drug development, poses...
UNLABELLED
is one of the most important pathogens worldwide. The intrinsic and acquired resistance of , coupled with the slow pace of novel antimicrobial drug development, poses an unprecedented and enormous challenge to clinical anti-infective therapy of . Recent studies in the field of pathogenicity, antibiotic resistance, and biofilms of have focused on the model strains, including ATCC 17978, ATCC 19606, and AB5075. However, these model strains represent only a limited portion of the heterogeneity in . Furthermore, variants of these model strains have emerged that show significant diversity not only at the genotypic level but also reflected in differences at the phenotypic levels of capsule, virulence, pathogenicity, and antibiotic resistance. Research on , a key pathogen, would benefit from a standardized approach, which characterizes heterogeneous strains in order to facilitate rapid diagnosis, discovery of new therapeutic targets, and efficacy assessment. Our study provides and describes a standardized, genomically and phenotypically heterogeneous panel of 45 different strains for the research community. In addition, we performed comparative analyses of several phenotypes of this panel. We found that the sequence type 2 (ST2) group showed significantly higher rates of resistance, lower fitness cost for adaptation, and yet less biofilm formation. The Macrocolony type E (MTE, flat center and wavy edge phenotype reported in the literature) group showed a less clear correlation of resistance rates and growth rate, but was observed to produce more biofilms. Our study sheds light on the complex interplay of resistance fitness and biofilm formation within distinct strains, offering insights crucial for combating infection.
IMPORTANCE
is globally notorious, and in an effort to combat the spread of such pathogens, several emerging candidate therapies have already surfaced. However, the strains used to test these therapies vary across studies (the sources and numbers of test strains are varied and often very large, with little heterogeneity). The variation complicates the studies. Furthermore, the limited standardized resources of strains have greatly restricted the research on the physiology, pathogenicity, and antibiotic resistance. Therefore, it is crucial for the research community to acquire a standardized and heterogeneous panel of . Our study meticulously selected 45 diverse strains from a total of 2,197 clinical isolates collected from 64 different hospitals across 27 provinces in China, providing a scientific reference for the research community. This assistance will significantly facilitate scientific exchange in academic research.
PubMed: 38916336
DOI: 10.1128/spectrum.00086-24 -
Reumatismo Jun 2024Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently characterized disease associated with somatic mutations in the UBA1 gene, which...
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently characterized disease associated with somatic mutations in the UBA1 gene, which cause dysregulation of ubiquitin-mediated processes. This case describes a 71-year-old male patient with VEXAS syndrome who presented with refractory lung inflammation with a pattern similar to computed tomography hypersensitivity pneumonitis, a novel finding in VEXAS syndrome. The presented clinical case highlights the protean involvement of the lung in VEXAS syndrome and emphasizes the importance of considering interstitial lung disease in the differential diagnosis.
Topics: Humans; Male; Aged; Alveolitis, Extrinsic Allergic; Ubiquitin-Activating Enzymes; Syndrome; Vacuoles; Diagnosis, Differential; Tomography, X-Ray Computed; Genetic Diseases, X-Linked; Hereditary Autoinflammatory Diseases; Mutation; Lung Diseases, Interstitial; Lung
PubMed: 38916169
DOI: 10.4081/reumatismo.2024.1611 -
International Journal of Chronic... 2024Chronic Obstructive Pulmonary Disease (COPD) progression in the elderly is notably influenced by nutritional, immune, and inflammatory status. This study aimed to...
BACKGROUND
Chronic Obstructive Pulmonary Disease (COPD) progression in the elderly is notably influenced by nutritional, immune, and inflammatory status. This study aimed to investigate the impact of adequate energy supply on these indicators in COPD patients.
METHODS
COPD patients meeting specific criteria were recruited and categorized into energy-adequate and energy-deficient groups based on their energy supply. Comparable demographic factors such as age, gender, smoking and drinking history, COPD duration, inhaled drug classification, and home oxygen therapy application were observed. Notable differences were found in BMI and inhaled drug use between the two groups.
RESULTS
The energy-adequate group exhibited significant improvements in various health indicators, including lymphocyte count, hemoglobin, CRP, total cholesterol, prealbumin, albumin, PNI, SII, SIRI, CAR, and CONUT scores in the secondary auxiliary examination. These positive changes suggest a notable enhancement in nutritional, immune, and inflammatory status.
CONCLUSION
This research highlights the substantial benefits of adequate energy supply in elderly COPD patients. The observed improvements in nutritional, immune, and inflammatory markers underscore the importance of addressing energy needs to positively influence disease-related outcomes in this population. These findings have implications for developing targeted interventions to optimize the well-being of elderly individuals with COPD.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Female; Aged; Nutritional Status; Inflammation Mediators; Inflammation; Biomarkers; Energy Metabolism; Energy Intake; Age Factors; Lung; Aged, 80 and over; Middle Aged
PubMed: 38915774
DOI: 10.2147/COPD.S450209 -
Respirology Case Reports Jun 2024Bronchial Dieulafoy's disease (BDD), remains poorly understood, with only 88 cases reported globally. Herein, we present the largest case series ( = 7) from a single...
Bronchial Dieulafoy's disease (BDD), remains poorly understood, with only 88 cases reported globally. Herein, we present the largest case series ( = 7) from a single centre, between 2017 and 2023, retrospectively reviewed, detailing clinical presentations, diagnoses, management and up to 4-year follow-up outcomes. Diagnosis relied on characteristic lesions detected through white light bronchoscopy with or without endobronchial ultrasound (EBUS) or narrow band imaging (NBI), along with computed tomography (CT) scans or bronchial angiography. Identification of aberrant vessels beneath lesions and bronchoscopy details were documented. Treatment modalities and follow-up outcomes until December 2023 were noted. All patients were non-smokers. Review of imaging findings by an experienced radiologist was crucial in suspected cases due to risk of bleeding and often unconclusive results from biopsy. Management of BDD varied, with six patients undergoing bronchial artery embolization (BAE) and one requiring lobectomy; four patients received additional endobronchial therapy, one died due to malignancy, none experienced recurrence of haemoptysis. Identifying patients with large volume haemoptysis disproportionate to parenchymal disease in CT scans is important. A bronchoscopic surveillance is crucial to avoid biopsy; it can be confirmed using EBUS of NBI. While no established guidelines exist, BAE and endobronchial therapy emerge as valuable interventions, with surgical resection reserved for recurrent cases.
PubMed: 38915736
DOI: 10.1002/rcr2.1411 -
Frontiers in Bioengineering and... 2024Branched gold and silver nanoparticles coated with polydopamine (Au-Ag-PDA) demonstrate high photothermal conversion efficiency. Utilizing umbilical cord mesenchymal...
Unveiling the mechanism of photothermal therapy in acne man-agement: targeting sebaceous gland ferroptosis via umbilical cord mesenchymal stem cell membrane-encapsulated Au-Ag-PDA.
BACKGROUND
Branched gold and silver nanoparticles coated with polydopamine (Au-Ag-PDA) demonstrate high photothermal conversion efficiency. Utilizing umbilical cord mesenchymal stem cell membranes (MSCM) as an effective drug delivery system, our preliminary studies investigated the suppression of sebum secretion in sebaceous glands using MSCM-coated Au-Ag-PDA nano-particles (Au-Ag-PDA@MSCM) combined with 808 nm laser irradiation, showing potential for dermatological applications in acne treatment.
METHODS
This study employs proteomic analysis, complemented by subsequent techniques such as Western blotting (WB), small interfering RNA (siRNA), and transmission electron microscopy, to further investigate the differential mechanisms by which Au-Ag-PDA and Au-Ag-PDA@MSCM-mediated photothermal therapy (PTT) suppress sebum secretion.
RESULTS
Our proteomic analysis indicated mitochondrial respiratory chain damage in sebaceous gland tissues post-PTT, with further validation revealing ferroptosis in sebaceous cells and tissues. Acyl-CoA Synthetase Long-Chain Family Member 4 (Acsl4) has been identified as a critical target, with Au-Ag-PDA@MSCM demonstrating enhanced ferroptotic effects.
CONCLUSION
These findings significantly advance our understanding of how PTT mediated by Au-Ag-PDA@MSCM nanoparticles reduces sebum secretion and underscore the pivotal role of MSCM in inducing ferroptosis in sebaceous glands, thus providing a robust theoretical foundation for employing PTT via specific molecular pathways in acne treatment.
PubMed: 38915336
DOI: 10.3389/fbioe.2024.1426477