Long-term Antibiotic Research Articles

Epidemiology of bronchiectasis at a single center in Japan: a retrospective cohort study

BackgroundThe characteristics of bronchiectasis (BE) in Asia, including Japan, remain largely unknown. We aimed to provide insights into the clinical characteristics and treatment outcomes of BE, especially regarding nontuberculous mycobacteria (NTM) infection and its poorly understood impact on prognosis. We also aimed to clarify the effect of long-term macrolide antibiotic use in patients with BE, who had no history of exacerbations.MethodsIn this single-center, retrospective study, the medical records of patients who satisfied the BE criteria between January 1, 2012, and August 31, 2023, were reviewed. Severe exacerbations and mortality during the observation period were recorded. Baseline characteristics and overall survival of patients with and without NTM infection, and factors influencing the time to the first exacerbation and death were analyzed. Additionally, the effects of long-term macrolide antibiotic use in patients without a history of severe exacerbations were estimated.ResultsIn a cohort of 1044 patients with BE, the rate of severe exacerbation was 22.3%, with mortality rates of 3.2% over 3 years. Notably, the high prevalence of NTM infection (n = 410, 39.3%) in this cohort was distinctive. NTM infection was not associated with either the time to first severe exacerbation (p = 0.5676, adjusted hazard ratio = 1.11) or mortality (p = 0.4139, adjusted hazard ratio = 0.78). Compared with the NTM group, the non-NTM group had a higher proportion of elevated inflammatory markers, with significant differences in C-reactive protein levels (p = 0.0301) and blood neutrophil counts (p = 0.0273). Pseudomonas aeruginosa colonization was more frequent in the non-NTM group (p = 0.0003). Among patients with non-NTM infection and without a history of exacerbation in the past 2 years, 38.2% received long-term macrolide antibiotics that did not invariably prolong the time to first severe exacerbation (p = 0.4517, IPW p = 0.3555).ConclusionsThis study highlights BE epidemiology in Japan, noting that the presence of NTM infection may not necessarily worsen the prognostic outcomes and advising caution in the casual use of macrolides for milder cases without a history of exacerbations.Clinical trial registrationUMIN Clinical Trials Registry Number: UMIN000054726 (Registered on 21 June 2024).

Antibiotics for surgical site infections in patients undergoing orthognathic surgery.

PubMed, Embase, Web of Science and Scopus. Randomized Controlled Trials (RCTs) for patients undergoing orthognathic surgery of any type, which evaluated surgical site infections (SSI) in either: long-term (at least 2 days) post-surgical antibiotic dosing versus short term (one day) post-surgical dosing for the same drug; or Orthognathic surgery patients administered a post-surgical single-day antibiotic versus a singular pre-operative dosing of any antibiotic in the post-surgical phase. Singe-arm studies, retrospective studies, unpublished data, studies which were not peer-reviewed, editorials and trials not dealing with patients undergoing orthognathic surgery specifically were not included. Data for the publication year, primary author name, location of the study, antibiotic type, antibiotic protocol with its type, dosing and timing, sample size, protocol of the control group, male gender, age, diagnosis and rates of SSIs were extracted from the included studies. Pooled rates of SSIs were utilized to produce risk ratio (RR). A total of eleven RCTs met the inclusion criteria. As per the meta-analysis, post-orthognathic surgery SSI risk was reduced significantly as a result of long-term prophylactic antibiotic usage when compared to short-term utilization. Further, the meta-analysis demonstrated that there was a significant reduction of SSI risk in patients on a single day prophylactic antibiotic regimen in comparison to those on a single preoperative antibiotic dose. The study observed that long-term (2-7 days) prophylactic antibiotics reduce SSI risk when compared to antibiotic administration over a single day. In turn, it was also found that the latter was of greater benefit over a pre-operative single antibiotic dosage.

Dalbavancin-resistant Staphylococcus epidermidis in vivo selection following a prosthetic joint infection: phenotypic and genomic characterization.

Dalbavancin is a lipoglycopeptide antibiotic with a wide spectrum of activity against Gram-positive bacteria, including MDR isolates. Its pharmacokinetic properties and administration patterns could be useful for the treatment of bone and joint infections, especially prosthetic joint infections (PJIs). We report the case of an 80-year-old man who experienced an acute periprosthetic joint infection of his right total knee arthroplasty (TKA). A DAIR procedure was done with tissue sampling, which allowed identification of a linezolid-resistant MDR S. epidermidis (LR-MDRSE) strain. The patient was then treated with dalbavancin (four injections). We studied the phenotypic and genomic evolution of the strains and plasma through concentrations of dalbavancin at different points in time. After four injections (1500 mg IV) of dalbavancin over a 6 month period, the dalbavancin MIC increased 4-fold. Calculated fAUC0-24/MIC ratios were 945, 1239 and 766.5, respectively, at Days 49, 71 and 106, assuming an MIC of 0.032 mg/L. The PFGE dendrogram revealed 97% similarity among all the isolates. These results suggest acquisition by the S. epidermidis strain of dalbavancin resistance when the patient underwent dalbavancin treatment. A 4-amino-acid deletion in the walK gene coinciding with the emergence of phenotypic resistance was revealed by WGS without any other relevant indels. Despite dalbavancin treatment with pharmacokinetic management, emerging dalbavancin resistance in S. epidermidis was observed, resulting in treatment failure. This outcome led to a prosthesis revision and long-term suppressive antibiotic therapy, with no recurrence of PJI after an 18 month follow-up.

ROLE OF FUNGI IN COVID-19 PATIENTS WITH CHRONIC LUNG DISEASE IN RANI DURGAVATI MEDICAL COLLEGE, BANDA (FORMERLY GOVERNMENT ALLOPATHIC MEDICAL COLLEGE, BANDA 210001 (UP) INDIA.)

Background: Fungal infections of the lung have gained increasing recognition in the field of infectious disease and they are difficult to diagnosis. Advances in modern treatment like antibiotics corticosteroids, Immunosupressants and anticancer drugs have lead to increase in opportunistic fungal infections including bronchopulmonary Candidiasis and Bronchopulmonary aspergillosis has also increased, commonly occurs in COVID-19 patients of pre existing bronchial asthma. In India there is high prevalence of chronic lung diseases including bronchial Asthma, yet the diagnosis of aspergillosis and Candidiasis. An association between asthma and aspergillosis was noted and confirmed by isolation of Aspergillus species more commonly in sputum of Asthma patients (Lum et al., 2020 Singla, N. et al., 2019). Subject and Methods: To find out the role of fungi in 50 Corona virus (RTPCR test) positive patients of chronic lung disease (non tubercular) like COPD, Chronic Bronchitis with or without emphysema, Broncheichtasis, Bronchial Asthma were included. Patients were attended and admitted in Rani Durgavati Medical College (RDMC) and Hospital, Banda (UP) India, in a one year period was taken up from December 2020 till December 2021. The diagnosis of these cases v/as established by clinical features, radiological examination of chest, ECG, pulmonary function tests. Laboratory procedure for isolation and identification of fungi in bronchoalveoiar lavage. Each specimen of Bronchoalveloar Lavage (BAL) was subjected to various laboratory procedures for isolation and identification of fungi. Result: Different fungal species were cultured in 26% total cases. 20% isolates were positive for fungi alone whereas rest 6% cases showed both bacterial and fungal pathogens amongst fungi Candida was the predominant isolate in 16% cases followed by Aspergillus in 8% cases and Histopfasms capsulatum in just1(2%) case. Fungal isolates in bronchial aspirates were sensitive to Amphotericin B, Fluconazole, etc. Conclusion: COVID-19 Patients which are already containing chronic lung diseases especially COPD, bronchiectasis is more common in elderly males. The Bronchiectatic patients are also at risk of getting, fungal infections Patients of chronic lung disease who are on long-term antibiotic therapy, and or steroids are more predisposed to get these opportunistic infections. Another conclusion from it is clear that there is great need better and judicious use of antibiotics in patients to prevent drug resistance, to prevent further progression of the diseases.

Impeding microbial biofilm formation and Pseudomonas aeruginosa virulence genes using biologically synthesized silver Carthamus nanoparticles

Long-term antibiotic treatment results in the increasing resistance of bacteria to antimicrobials drugs, so it is necessary to search for effective alternatives to prevent and treat pathogens that cause diseases. This study is aimed for biological synthesis of silver Carthamus nanoparticles (Ag-Carth-NPs) to combat microbial biofilm formation and Pseudomonas aeruginosa virulence genes. Ag-Carth-NPs are synthesized using Carthamus tenuis aqueous extract as environmentally friendly method has no harmful effect on environment. General factorial design is used to optimize Ag-Carth-NPs synthesis using three variables in three levels are Carthamus extract concentration, silver nitrate concentration and gamma radiation doses. Analysis of response data indicates gamma radiation has a significant effect on Ag-Carth-NPs production. Ag-Carth-NPs have sharp peak at λ max 425 nm, small and spherical particles with size 20.0 ± 1.22 nm, high stability up to 240 day with zeta potential around − 43 ± 0.12 mV, face centered cubic crystalline structure and FT-IR spectroscopy shows peak around 620 cm−1 that corresponding to AgNPs that stabilized by C. tenuis extract functional moiety. The antibacterial activity of Ag-Carth-NPs against pathogenic bacteria and fungi was determined using well diffusion method. The MIC values of Ag-Carth-NPs were (6.25, 6.25, 3.126, 25, 12.5, 12.5, 25 and 12.5 µg/ml), MBC values were (12.5, 12.5, 6.25, 50, 25, 25, 50 and 25 µg/ml) and biofilm inhibition% were (62.12, 68.25, 90.12, 69.51, 70.61, 71.12, 75.51 and 77.71%) against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Candida tropicalis and Candida albicans respectively. Ag-Carth-NPs has bactericidal efficacy and significantly reduced the swarming, swimming motility, pyocyanin and protease production of P. aeruginosa. Furthermore, P. aeruginosa ToxA gene expression was significantly down regulated by 81.5%, while exoU reduced by 78.1%, where lasR gene expression reduction was 68%, while the reduction in exoU was 66% and 60.1% decrease in lasB gene expression after treatment with Ag-Carth-NPs. This activity is attributed to effect of Ag-Carth-NPs on cell membrane integrity, down regulation of virulence gene expression, and induction of general and oxidative stress in P. aeruginosa. Ag-Carth-NPs have no significant cytotoxic effects on normal human cell (Hfb4) but have IC50 at 5.6µg/mL against of HepG-2 cells. Limitations of the study include studies with low risks of silver nanoparticles for in vitro antimicrobial effects and its toxicity.

PH-responsive and nanoenzyme-loaded artificial nanocells relieved osteomyelitis efficiently by synergistic chemodynamic and cuproptosis therapy

Osteomyelitis is an osseous infectious disease that primarily affects children and the elderly with high morbidity and recurrence. The conventional treatments of osteomyelitis contain long-term and high-dose systemic antibiotics with debridements, which are not effective and lead to antibiotic resistance with serious side/adverse effects in many cases. Hence, developing novel antibiotic-free interventions against osteomyelitis (especially antibiotic-resistant bacterial infection) is urgent and anticipated. Here, a bone mesenchymal stem cell membrane-constructed nanocell (CFE@CM) was fabricated against osteomyelitis with the characteristics of acid-responsiveness, hydrogen peroxide self-supplying, enhanced chemodynamic therapeutic efficacy, bone marrow targeting and cuproptosis induction. Notably, mRNA sequencing was applied to unveil the underlying biological mechanisms and found that the biological processes related to copper ion binding, oxidative phosphorylation, peptide biosynthesis and metabolism, etc., were disturbed by CFE@CM in bacteria. This work provided an innovative antibiotic-free strategy against osteomyelitis through copper-enhanced Fenton reaction and distinct cuproptosis, promising to complement the current insufficient therapeutic regimen in clinic.

The True Impact of Voiding Dysfunctions after Transobturator Sub-Urethral Tape Procedures: A Systematic Review of Literature.

Introduction: Transobturator techniques are frequently used for the surgical treatment of female stress urinary incontinence (SUI), due to their high success rates and few intraoperative complications. However, controversial results have been reported in the literature regarding their incidence. The aim of this study is to analyze the real incidence and trend over time of such complications, especially voiding dysfunctions and overactive bladder (OAB) symptoms. Methods: A comprehensive search using PubMed/MEDLINE, Scopus, and Cochrane databases was performed. The search string used was the following: (female stress urinary incontinence) AND (complication) AND ((midurethral sling) OR (transobturator tape) OR (TVT-O) OR (voiding dysfunctions) OR (de novo OAB) OR (recurrent UTI) OR (vaginal erosion)). We included randomized controlled trials, prospective controlled studies, prospective and retrospective observational studies. All selected articles were screened based on titles and abstracts. Relevant data were extracted and tabulated. Results: A total of 39 studies were included in our analysis. Transobturator tape procedures show a high objective cure rate for SUI, from 76.9% to 100%. Postoperative voiding dysfunctions are shown to be quite common, ranging from 0-22% of cases. Despite that, this percentage decreases to 0-1% after 12 months. De novo OAB incidence ranges from 3% to 14% at 12 months, with variability over time due to multiple factors. Tape-related complications usually occur after 12 months, with a variable incidence up to 7%. Urinary tract infections (UTIs) are quite common in the immediate postoperative period but sometimes can be recurrent, requiring long-term prophylactic antibiotic treatment. Conclusions: Voiding dysfunctions are generally transient complications, while de novo OAB may persist over time. An adequate preoperative counseling, along with accurate written informed consent, could enhance patient tolerance of these issues and contribute to long-term patient satisfaction.

Emphysematous Prostatitis with an Abscess in a Hemodialysis-Dependent Patient with End-Stage Kidney Disease: A Case Report

Emphysematous prostatitis with an abscess is an extremely rare but lethal infection, characterized by the accumulation of gas and purulent exudates. Due to its rarity, severity, and nonspecific presentation, prompt diagnosis and treatment are crucial to achieve favorable clinical outcomes. This report presents a 43-year-old male with hemodialysis-dependent end-stage kidney disease who reported a 3-day history of fever, urinary incontinence, dysuria, and dyspnea. His condition rapidly deteriorated due to septic shock caused by emphysematous prostatitis with an abscess. Following extensive treatment including long-term parenteral antibiotics, polymyxin B hemoperfusion filter treatment, abscess drainage via transurethral resection of the prostate, and suprapubic cystostomy, the patient successfully recovered.

Diagnosis of an atypical fever in a 55-year-old man.

The paper describes a diagnostically challenging case of recurrent fever with an atypical course in a 55-year-old man. The authors highlight the significant difficulty in reaching a correct diagnosis, as well as the doubts and problems associated with the diagnostics. They suggest considering brucellosis as a diagnosis based on the patient's history and the course of the disease characterized by fluctuating, intermittent, and nocturnal fever. The aim of the study was to present an atypical and diagnostically challenging case of recurrent febrile episodes in a 55-year-old man. A comprehensive diagnostic workup, including laboratory tests, imaging, and specialist consultations, was conducted. The patient's medical history, physical examination, and various diagnostic tests were analyzed. In a patient with recurrent episodes of fever, an infection with Brucella spp. was detected, which was effectively treated with long-term antibiotic therapy. Imaging and laboratory diagnostics, along with specialist consultations, helped rule out other potential causes of the symptoms. The patient achieved lasting improvement following the treatment. There is a high probability that the patient was infected with Brucella bacteria. Diagnostic challenges and the rarity of the disease, considered non-existent in Poland, hinder prompt confirmation or exclusion of infection. The authors aimed to highlight the possibility of a higher frequency of brucellosis in Poland. They suggest that Brucella bacteria may still be present, causing chronic, unrecognized, recurrent fevers. Based on the case analysis, the authors indicate that the frequent occurrence of this disease in Poland might be higher than reported by statistics.

Use of Topical Minocycline for Treatment of Confluent and Reticulated Papillomatosis

Confluent and reticulated papillomatosis (CRP) is a rare dermatosis initially that typically affects young adults and is characterized by scaly, hyperpigmented macules or papillomatous papules combining into patches typically involving the upper trunk and neck. Herein, we report two cases of CRP successfully treated with topical minocycline. The most widely accepted treatment of CRP to date is oral minocycline. Due to the chronic nature of CRP, topical minocycline could be considered a better first-line treatment option. This alternative treatment offers the advantage of a targeted, local application for enhanced skin bioavailability and efficacy. This case supports the possibility of topical minocycline use as an alternative to long-term oral antibiotics for treatment of CRP.

Bacteriophage therapy and infective endocarditis - is itrealistic?

Infective endocarditis (IE) is a severe infection of the inner heart. Even with current standard treatment, the mean in-hospital mortality is as high as 15-20%, and 1-year mortality is up to 40% for left-sided IE. Importantly, IE mortality rates have not changed substantially over the past 30 years, and the incidence of IE is rising. The treatment is challenging due to the bacterial biofilm mode of growth inside the heart valve vegetations, resulting in antibiotic tolerance. Achieving sufficient antibiotic anti-biofilm concentrations in the biofilms of the heart valve vegetations is problematic, even with high-dose and long-term antibiotic therapy. The increasing prevalence of IE caused by antibiotic-resistant bacteria adds to the challenge. Therefore, adjunctive antibiotic-potentiating drug candidates and strategies are increasingly being investigated. Bacteriophage therapy is a reemerging antibacterial treatment strategy for difficult-to-treat infections, mainly biofilm-associated and caused by multidrug-resistant bacteria. However, significant knowledge gaps regarding the safety and efficacy of phage therapy impede more widespread implementation in clinical practice. Hopefully, future preclinical and clinical testing will reveal whether it is a viable treatment. The objective of the present review is to assess whether bacteriophage therapy is a realistic treatment for IE.

Circumferential correction of spinal deformity and instability secondary to bacterial spondylodiscitis

BackgroundSpinal deformity as a sequela of non-tuberculous spondylodiscitis is a rarely discussed clinical entity. Sagittal plane deformity, segmental instability, and persistently active infection overlap in these patients resulting in severe restriction in activity and quality of life. The presence of multiple medical co-morbidities restricts surgical options but nonoperative care may be ineffective and result in persistent, refractory discitis for years. We describe our experience with vertebrectomy and long-segment fixation for patients with post-infectious thoracic or lumbar deformity. MethodsA retrospective chart review of 23 consecutive patients who underwent vertebrectomy and long-segment fixation for thoracic or lumbar deformity secondary to nontuberculous bacterial spondylodiscitis was performed. Pre-, peri- and postoperative data is compiled and analyzed with a focus on the perioperative management algorithm to safely perform an extensive reconstruction in this very sick patient population. ResultsExtremely low preoperative quality of life was evident with 87% (20/23) of patients bedridden primarily due to pain despite 70% (16/23) of patients being strong enough to ambulate (Frankel D or E). Most patients (87%) already had an identified infection under adequate treatment either through blood cultures, prior biopsy or decompressive surgery. A single-stage posterior-only was the primary surgical approach utilized in the majority (83%) of cases. Complications were present in 100% of patients, most commonly perioperative anemia and hypotension requiring vasopressor support and aggressive blood product replacement. One in-hospital mortality occurred secondarily to pulmonary embolism. Mean preoperative segmental angle was 18±10 degrees of kyphosis which was corrected to 1±9 degrees of lordosis (p=0.001). The mean correction of the segmental angle was 19 degrees (standard deviation 23 degrees). Visual analogue scale scores improved from a pre-operative value of 8.8±0.9 to a post-operative value of 2.5±1.4 (p<0.001), which was obtained at the last outpatient follow-up (mean 631 days after surgery). Full self-care including ambulation was achieved in 18/23 (78%) patients, and the infection was successfully treated in 22/23 (96%) patients after long-term antibiotics. ConclusionsPatients with refractory spondylodiscitis on appropriate care and antibiotics are typically considered extremely poor surgical candidates despite non-operative care often being ineffective. Post-infectious deformity may also be so severe as to preclude a limited surgical treatment strategy. This study suggests that extensive circumferential reconstruction for deformity secondary to bacterial spondylodiscitis can be effective in restoring these extremely sick patients to self-care and ambulatory status.

A secondary abdominal aorta-duodenal fistula accompanied with acquired Immune Deficiency Syndrome presented with recurrent sepsis: a case report

BackgroundAbdominal aorta-duodenal fistulas are rare abnormal communications between the abdominal aorta and duodenum. Secondary abdominal aorta-duodenal fistulas often result from endovascular surgery for aneurysms and can present as severe late complications.Case presentationA 50-year-old male patient underwent endovascular reconstruction for an infrarenal abdominal aortic pseudoaneurysm. Prior to the operation, he was diagnosed with Acquired Immune Deficiency Syndrome and Syphilis. Two years later, he was readmitted with lower extremity pain and fever. Blood cultures grew Enterococcus faecium, Salmonella, and Streptococcus anginosus. Sepsis was successfully treated with comprehensive anti-infective therapy. He was readmitted 6 months later, with blood cultures growing Enterococcus faecium and Escherichia coli. Although computed tomography did not show contrast agent leakage, we suspected an abdominal aorta-duodenal fistula. Esophagogastroduodenoscopy confirmed this suspicion. The patient underwent in situ abdominal aortic repair and received long-term antibiotic therapy. He remained symptom-free during a year and a half of follow-up.ConclusionsThis case suggests that recurrent infections with non-typhoidal Salmonella and gut bacteria may be an initial clue to secondary abdominal aorta-duodenal fistula.

On the Way to Curing Advanced-Stage Mycosis Fungoides/Sézary Syndrome

Advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS) have poor prognosis with median survivals of less than 5 years. Although a variety of treatments are approved for MF/SS patients, durable complete remissions (CR) are rare. Advanced-stage MF or SS patients who achieved CR and maintained in CR or stage IA for more than 10 years were identified by a retrospective search of the principal investigator's database. Of 2266 patients diagnosed with MF or SS, 23 patients with advanced-stage MF/SS (6 IIB, 1 IIIB, 5 IVA1, 3 IVA2, 8 IVB) who achieved CR and maintained in CR or stage IA for ≥ 10 years were identified. As final/curative treatment, 11 patients underwent allogeneic stem cell transplantation (SCT). Most patients presented at young age, underwent SCT with reduced intensity conditioning regimen, had matched related donors, and controllable post-transplant graft versus host disease. Eleven patients were treated with TSEB as part of combined modality protocol in 2 patients and debulking therapy before allogeneic SCT in 9 patients. Five stage IIB patients achieved CR with radiotherapy. Four patients with blood involvement were treated with extracorporeal photopheresis (ECP) in combination with long-term antibiotics and immunomodulatory agents. Long-term antibiotics were given to 14 patients. TSEB followed by allogeneic SCT, radiotherapy, ECP plus long-term antibiotics and immunomodulatory agents were the most common curative/final treatments found in our patients. We are reporting the details of our long-term complete responders' treatment course in the hopes of obtaining more cure responses in the future.

Rethinking bronchiectasis as an inflammatory disease.

Bronchiectasis is understood to be the result of a complex interaction between infection, impaired mucociliary clearance, inflammation, and lung damage. Current therapeutic approaches to bronchiectasis are heavily focused on management of infection along with enhancing mucus clearance. Long-term antibiotics have had limited success in clinical trials, suggesting a need to re-evaluate the concept of bronchiectasis as an infective disorder. We invoke the example of asthma, for which treatment paradigms shifted away from targeting smooth muscle constriction, towards permanently suppressing airway inflammation, reducing risk and ultimately inducing remission with precision anti-inflammatory treatments. In this Review, we argue that bronchiectasis is primarily a chronic inflammatory disease, requiring early identification of at-risk individuals, and we introduce a novel concept of disease activity with important implications for clinical practice and future research. A new generation of novel anti-inflammatory treatments are under development and repurposing of anti-inflammatory agents from other diseases could revolutionise patient care.

Improving Linkage for Patients With Injection-Drug-Use-Related Endocarditis and Osteomyelitis to Medications for Opioid Use Disorder Through a Telephone Intervention.

The opioid overdose crisis has continued to worsen, with a concomitant increase in serious injection-related infections, such as endocarditis and osteomyelitis. Usual care of these infections involves long-term intravenous antibiotics, typically administered via a peripherally inserted central venous catheter (PICC) at home. In patients with a history of opioid use disorder who inject drugs, a PICC has long been viewed as a high-risk intervention that may contribute to illicit substance use due to ease of venous access; thus, providers are often uncomfortable discharging these patients home to complete their antibiotics. As a result, many patients remain hospitalized or are discharge to skilled nursing facilities (SNFs) in order to complete their antibiotics. Challenges to this model include difficulty finding SNFs that will accept these patients, inability for these SNFs to continue their medication for opioid use disorder (MOUD), and inability to coordinate care with outpatient MOUD providers at SNF discharge. This quality improvement project sought to increase linkage to outpatient MOUD on SNF discharge via a telephone intervention. A total of 11 patients qualified for this intervention. Although patients were still in an SNF, 4/7 (57.1%) of patients were successfully contacted. Once they were discharged from the SNF, only 3/10 (30.0%) of patients were successfully reached. Of those 30.0% who were contacted, all of them had attended their outpatient MOUD appointment. We suggest that future linkage interventions in this population may benefit from utilizing existing care team members to facilitate linkage, to maximize the rapport built during an inpatient stay.

1-Minute Pearls/Pitfalls for the Clinician

This article describes a few pearls/pitfalls pertinent to the use of colchicine in patients with coronary artery disease and the use of long-term prophylactic antibiotics in patients with cirrhosis.

Development of a novel multi-epitope vaccine for brucellosis prevention

Brucellosis, a zoonotic disease caused by Brucella, presents a significant threat to both animal and human health. In animals, the disease can lead to infertility, miscarriage, and high fever, while in humans, symptoms may include recurrent fever, fatigue, sweating, hepatosplenomegaly, and joint and muscle pain following infection. Treatment often involves long-term antibiotic therapy, placing a substantial psychological and financial burden on patients. While vaccination is crucial for prevention, current animal vaccines have drawbacks such as residual virulence, and a safe and effective human vaccine is lacking. Hence, the development of a vaccine for brucellosis is imperative. In this study, we utilized bioinformatics methods to design a multi-epitope vaccine targeting Brucella. Targeting Heme transporter BhuA and polysaccharide export protein, we identified antigenic epitopes, including six cytotoxic T lymphocyte (CTL) dominant epitopes, six helper T lymphocyte (HTL) dominant epitopes, one conformation B cell dominant epitope, and three linear B cell dominant epitopes. By linking these epitopes with appropriate linkers and incorporating a Toll-like receptor (TLR) agonist (human beta-defensin-2) and an auxiliary peptide (Pan HLA-DR epitopes), we constructed the multi-epitope vaccine (MEV). The MEV demonstrated high antigenicity, non-toxicity, non-allergenicity, non-human homology, stability, and solubility. Molecular docking analysis and molecular dynamics simulations confirmed the interaction and stability of the MEV with receptors (MHCI, MHCII, TLR4). Codon optimization and in silico cloning validated the translation efficiency and successful expression of MEV in Escherichia coli. Immunological simulations further demonstrated the efficacy of MEV in inducing robust immune responses. In conclusion, our findings suggest that the engineered MEVs have the potential to stimulate both humoral and cellular immune responses, offering valuable insights for the future development of safe and efficient Brucella vaccines.

Pseudomonas aeruginosa Bacteriophages and Their Clinical Applications.

Antimicrobial resistance poses a serious risk to contemporary healthcare since it reduces the number of bacterial illnesses that may be treated with antibiotics, particularly for patients with long-term conditions like cystic fibrosis (CF). People with a genetic predisposition to CF often have recurrent bacterial infections in their lungs due to a buildup of sticky mucus, necessitating long-term antibiotic treatment. Pseudomonas aeruginosa infections are a major cause of CF lung illness, and P. aeruginosa airway isolates are frequently resistant to many antibiotics. Bacteriophages (also known as phages), viruses that infect bacteria, are a viable substitute for antimicrobials to treat P. aeruginosa infections in individuals with CF. Here, we reviewed the utilization of P. aeruginosa bacteriophages both in vivo and in vitro, as well as in the treatment of illnesses and diseases, and the outcomes of the latter.

Potential Probiotic Weizmannia coagulans WC10 Improved Antibiotic-Associated Diarrhea in Mice by Regulating the Gut Microbiota and Metabolic Homeostasis.

Antibiotic-associated diarrhea (AAD) is a common side effect of long-term and heavy antibiotic therapy. Weizmannia coagulans (W. coagulans) is an ideal probiotic because of its high viability, stability, and numerous health benefits to the host. In this study, the strains were first screened for W. coagulans WC10 (WC10) with a high combined ability based on their biological properties of gastrointestinal tolerance, adhesion, and short-chain fatty acid production ability. The effect of WC10 on mice with AAD was further evaluated. The results showed that WC10 was effective in improving the symptoms of AAD, effectively restoring antibiotic-induced weight loss, and reducing diarrhea status score and fecal water content. In addition, WC10 decreased the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines, alleviated intestinal tissue damage and inflammation, and improved intestinal epithelial barrier function by decreasing serum levels of enterotoxin, DAO, and D-lactic acid, and by increasing the expression of the intestinal mucosal immune factors sIgA and occludin. Importantly, the composition and function of the gut microbiota gradually recovered after WC10 treatment, increasing the number of SCFAs-producing Bifidobacterium and Roseburia. Subsequently, the short-chain fatty acid (SCFA) content was examined and WC10 significantly increased acetate, propionate, and butyrate production. Additionally, metabolomic analysis also showed that WC10 reversed the antibiotic interference with major metabolic pathways. These findings provide a solid scientific basis for the future application of W. coagulans WC10 in the treatment of AAD.