Long-term Antibiotic Treatment Research Articles

Ultrasound-Triggered Piezoelectric Catalysis of Zinc Oxide@Glucose Derived Carbon Spheres for the Treatment of MRSA Infected Osteomyelitis.

Currently, methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis is a clinically life-threatening disease, however, long-term antibiotic treatment can lead to bacterial resistance, posing a huge challenge to treatment and public health. In this study, glucose-derived carbon spheres loaded with zinc oxide (ZnO@HTCS) are successfully constructed. This composite demonstrates the robust ability to generate reactive oxygen species (ROS) under ultrasound (US) irradiation, eradicating 99.788% ± 0.087% of MRSA within 15min and effectively treating MRSA-induced osteomyelitis infection. Piezoelectric force microscopy tests and finite element method simulations reveal that the ZnO@HTCS composite exhibits superior piezoelectric catalytic performance compared to pure ZnO, making it a unique piezoelectric sonosensitizer. Density functional theory calculations reveal that the formation of a Mott-Schottky heterojunction and an internal piezoelectric field within the interface accelerates the electron transfer and the separation of electron-hole pairs. Concurrently, surface vacancies of the composite enable the adsorption of a greater amount of oxygen, enhancing the piezoelectric catalytic effect and generating a substantial quantity of ROS. This work not only presents a promising approach for augmenting piezoelectric catalysis through construction of a Schottky heterojunction interface but also provides a novel, efficient therapeutic strategy for treating osteomyelitis.

Infection after Anterior Cruciate Ligament Reconstruction: A Narrative Review of the Literature.

Infection is an uncommon side effect of arthroscopic surgery, and this percentage is higher in anterior cruciate ligament reconstruction (ACLR) surgery, where graft and fixation devices are used. Infections can not only lead to high re-admission rates and poor functional recovery of the knee but can also have a significant negative impact on the patient's psychological and economic health, especially in athletes, as it can affect their sports career. It is important to be aware of the many risk factors, especially the manifestation of symptoms. These may sometimes be non-specific to the infectious pathology and common to other situations, such as the presence of a significant intra-articular hematoma. Septic arthritis after ACLR can occur at any time after surgery but typically presents acutely, while late manifestation is relatively rare. Diagnosis of infection is based on patient history, physical examination, laboratory parameters, and analysis of synovial fluid after joint aspiration, which is the gold standard for diagnosing post-operative infection. Once symptoms appear and the diagnosis seems certain, it is necessary to intervene quickly with arthroscopic debridement and long-term antibiotic treatment to try to save the graft and resolve the infectious situation to avoid graft failure and arthrofibrotic sequelae. The aim of this paper is to provide an overview of the epidemiology, pathogenesis, risk factors, clinical presentation, diagnostic evaluation, and current treatment guidelines of septic arthritis after ACLR surgery by analyzing recent literature, in particular meta-analyses and systematic reviews.

The Epidemiology, Management and Therapeutic Outcomes of Subdural Empyema in Neonates with Acute Bacterial Meningitis.

Background: Subdural empyema is one of the more serious complications of bacterial meningitis and therapeutic challenges to clinicians. We aimed to evaluate the clinical characteristics, treatment, and outcome of subdural empyema in neonates with bacterial meningitis. Methods: A retrospective cohort study was conducted in two medical centers in Taiwan that enrolled all cases of neonates with subdural empyema after bacterial meningitis between 2003 and 2020. Results: Subdural empyema was diagnosed in 27 of 153 (17.6%) neonates with acute bacterial meningitis compared with cases of meningitis without subdural empyema. The demographics and pathogen distributions were comparable between the study group and the controls, but neonates with subdural empyema were significantly more likely to have clinical manifestations of fever (85.2%) and seizure (81.5%) (both p values < 0.05). The cerebrospinal fluid results of neonates with subdural empyema showed significantly higher white blood cell counts, lower glucose levels and higher protein levels (p = 0.011, 0.003 and 0.006, respectively). Neonates with subdural empyema had a significantly higher rate of neurological complications, especially subdural effusions and periventricular leukomalacia. Although the final mortality rate was not increased in neonates with subdural empyema when compared with the controls, they were often treated much longer and had a high rate of long-term neurological sequelae. Conclusions: Subdural empyema is not uncommon in neonates with acute bacterial meningitis and was associated with a high risk of neurological complications, although it does not significantly increase the final mortality rate. Close monitoring of the occurrence of subdural empyema is required, and appropriate long-term antibiotic treatment after surgical intervention may lead to optimized outcomes.

Barriers and Facilitators Affecting Long-Term Antibiotic Prescriptions for Acne Treatment

Dermatologists prescribe more oral antibiotics per clinician than clinicians in any other specialty. Despite clinical guidelines that recommend limitation of long-term oral antibiotic treatments for acne to less than 3 months, there is little evidence to guide the design and implementation of an antibiotic stewardship program in clinical practice. To identify salient barriers and facilitators to long-term antibiotic prescriptions for acne treatment. This qualitative study assessed data collected from stakeholders (including dermatologists, infectious disease physicians, dermatology resident physicians, and nonphysician clinicians) via an online survey and semistructured video interviews between March and August 2021. Data analyses were performed from August 12, 2021, to January 20, 2024. Online survey and qualitative video interviews developed with the Theoretical Domains Framework. Thematic analyses were used to identify salient themes on barriers and facilitators to long-term antibiotic prescriptions for acne treatment. Among 30 participants (14 [47%] males and 16 [53%] females) who completed the study requirements and were included in the analysis, knowledge of antibiotic guideline recommendations was high and antibiotic stewardship was believed to be a professional responsibility. Five salient themes were to be affecting long-term antibiotic prescriptions: perceived lack of evidence to justify change in dermatologic practice, difficulty navigating patient demands and satisfaction, discomfort with discussing contraception, iPLEDGE-related barriers, and the absence of an effective system to measure progress on antibiotic stewardship. The findings of this qualitative study indicate that multiple salient factors affect long-term antibiotic prescribing practices for acne treatment. These factors should be considered in the design and implementation of any future outpatient antibiotic stewardship program for clinical dermatology.

Rectal malakoplakia simulating a locally advanced rectal cancer: a case report

Malakoplakia is a rare and chronic granulomatous disease, resulting from the accumulation of large granular macrophages containing basophilic inclusion bodies in the cytoplasm named Michaelis-Gutmann bodies. The gastrointestinal tract is the second most common site after the urinary tract, though malakoplakia has the potential to manifest in multiple organs. Rectal malakoplakia is difficult to diagnose due to its unspecific clinical and radiological presentation, usually mimicking a malignancy. Most report cases are associated with immunosuppressive diseases or chronic prolonged illness. We present the case of a 64-year-old male with a history of anal pain. A pelvic magnetic resonance imaging showed a rectal mass with 38 mm invading the mesorectum. Colonoscopy was performed confirming a mass-like lesion and biopsies were taken. Histopathological examination revealed features consistent with malakoplakia. The patient underwent long-term oral antibiotic treatment and during follow-up there was a regression of the lesion and resolution of symptoms.

A Multifunctional Scaffold for Bone Infection Treatment by Delivery of microRNA Therapeutics Combined With Antimicrobial Nanoparticles.

Treating bone infections and ensuring bone repair is one of the greatest global challenges of modern orthopedics, made complex by antimicrobial resistance (AMR) risks due to long-term antibiotic treatment and debilitating large bone defects following infected tissue removal. An ideal multi-faceted solution would will eradicate bacterial infection without long-term antibiotic use, simultaneously stimulating osteogenesis and angiogenesis. Here, a multifunctional collagen-based scaffold that addresses these needs by leveraging the potential of antibiotic-free antimicrobial nanoparticles (copper-doped bioactive glass, CuBG) to combat infection without contributing to AMR in conjunction with microRNA-based gene therapy (utilizing an inhibitor of microRNA-138) to stimulate both osteogenesis and angiogenesis, is developed. CuBG scaffolds reduce the attachment of gram-positive bacteria by over 80%, showcasing antimicrobial functionality. The antagomiR-138 nanoparticles induce osteogenesis of human mesenchymal stem cells in vitro and heal a large load-bearing defect in a rat femur when delivered on the scaffold. Combining both promising technologies results in a multifunctional antagomiR-138-activated CuBG scaffold inducing hMSC-mediated osteogenesis and stimulating vasculogenesis in an in vivo chick chorioallantoic membrane model. Overall, this multifunctional scaffold catalyzes killing mechanisms in bacteria while inducing bone repair through osteogenic and angiogenic coupling, making this platform a promising multi-functional strategy for treating and repairing complex bone infections.

Instant Protection Spray for Anti-Infection and Accelerated Healing of Empyrosis.

Distinct from common injuries, deep burns often require a chronic recovery cycle for healing and long-term antibiotic treatment to prevent infection. The rise of drug-resistant bacteria has caused antibiotics to no longer be perfect, and continuous drug use can easily lead to repeated infection and even death. Inspired by wild animals that chew plants to prevent wound infection, probiotic extracts with a structure similar to the tailspike of phage are obtained from Lactobacillus casei and combined with different flavones to design a series of nonantibiotic bactericides. These novel antibacterial agents are combined with a rapid gelation spray with a novel cross-angle layout to form an instant protection spray (IPS) and provide a physical and anti-infectious barrier for burns within 30 s. This IPS is able to sterilize 100.00% and 96.14% of multidrug-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, respectively. In addition, it is found to effectively reduce inflammation in MRSA-infected burns in rats and to promote tissue healing.

The Role of Antigranulocyte Scintigraphy in Diagnosis of Aortic Graft Infection and Evaluation of Treatment Outcome

The aim of this study was to assess the eventual added benefit of anti- granulocyte monoclonal antibodies scintigraphy to the diagnostic imaging of aortic graft infection and its role in evaluation of treatment outcome. A population-based, retrospective, register-based analysis was carried out of all patients with infected aortic grafts after treatment for aneurysmal or aortoiliac occlusive disease (AIOD) at Karolinska University Hospital, covering the greater Stockholm area during Nov-2012-Dec-2020. Cases were based on the definitions in the 2016 MAGIC (Management of Aortic Graft Infection Collaborations) consensus. Using the in-hospital electronic patient registry (Take Care®) and the Swedish National Registry for Vascular Surgery (Swedvasc), 835 patients who had been treated for aortic aneurysms or AIOD were identified. The diagnostic arsenal of laboratory tests, CT and clinical signs has been supplemented by anti-G mAb scintigraphy. Data were analyzed using SPSS Statistics. Eighteen cases of AGI out of 835 operations incorporating aortic grafts during the period were identified. Fourteen patients (78%) were categorized as diagnosed AGI (AGI-D) and the remaining four (22%) were classified as suspected AGI (AGI-S). In the AGI-D group (n=14), ten patients (71%) had positive CTs and four (29%) had low probability CTs. In the group of ten positive CTs nine patients had also positive scintigraphy scans with only one negative scintigraphy scan. There were no negative scintigraphy scans without ongoing antibiotic treatment at the time of investigation. In 15 of 18 cases a culprit agent was identified, either pre-operatively or perioperatively. Thirteen of the 18 patients were treated solely by antibiotics whereas five patients underwent surgical treatment in addition to antibiotic treatment. The outcome has been divided into three groups: infection free (n=6; 33%); life-long antibiotic treatment (n=7; 39%) and deceased (n=5; 28%). The imaging modalities in AGI diagnostics are a cornerstone of the investigative work up, complemented by clinical signs and laboratory methods. The main advantage conveyed by anti-G mAb scintigraphy is in postoperative imaging and its ability to differentiate between infection and general postoperative changes in the areas of concern. We have identified six patients in our cohort in whom antibiotic therapy was discontinued after a negative anti-G mAb scintigraphy scan. Anti-G mAb scintigraphy may fulfill a unique need for diagnosis in suspected cases, evaluation of therapeutic efficacy in patients requiring long-term antibiotic treatment and aiding in the decision to discontinue antibiotic therapy.

Early-life prophylactic antibiotic treatment disturbs the stability of the gut microbiota and increases susceptibility to H9N2 AIV in chicks

BackgroundAntibiotics are widely used for prophylactic therapy and for improving the growth performance of chicken. The problem of bacterial drug resistance caused by antibiotic abuse has previously attracted extensive attention; however, the influence of early-day use of prophylactic antibiotics on the gut microflora and on the disease resistance ability in chicks has not been explored. Here, we comprehensively evaluate the growth performance, gut microbial dynamics, level of antibiotic resistance genes (ARGs) in the gut microbial community, and resistance to H9N2 avian influenza virus (AIV) in chickens following long-term and short-term early-day prophylactic antibiotic treatment.ResultsUnexpectedly, long-term prophylactic enrofloxacin treatment slowed the growth rate of chickens, whereas short-term antibiotics treatments were found to increase the growth rate, but these changes were not statistically significant. Strikingly, expansions of Escherichia-Shigella populations were observed in early-life prophylactic antibiotics-treated groups of chickens, which is in contrast to the general perception that antibiotics should control their pathogenicity in chicks. The gut microbiota composition of chickens treated long term with antibiotics or received early-day antibiotics treatment tend to be more dramatically disturbed compared to the gut microbiome of chickens treated with antibiotics for a short term at a later date, especially after H9N2 AIV infection.ConclusionsOur data provide evidence that early-day and long-term antibiotic treatments have a more adverse effect on the intestinal microbiome of chickens, compared to short-term late age antibiotic treatment. Furthermore, our metagenomic data reveal that both long-term and short-term antibiotic treatment increase the relative abundance of ARGs. Our findings highlight the adverse effects of prophylactic antibiotic treatment and provide a theoretical basis for the cautious administration of antibiotics in food-producing animal management.Ao91n5eHkkQPyDkUXXsk_bVideo

Lung abscess: Clinical characteristics of 222 Danish patients diagnosed from 2016 to 2021

IntroductionLung abscess (LA) is a serious respiratory infection often followed by several weeks of antibiotic treatment. This study described the clinical presentation of LA, treatment duration and mortality in a contemporary Danish population. MethodsIn a retrospective multicenter cohort study at four Danish hospitals, patients diagnosed with LA were identified using the International Classification of Diseases and Related Health Problems 10th revision (ICD-10) between 2016 and 2021. A predefined data collection tool was used to extract data on demographics, symptoms, clinical findings and treatment. ResultsOf 302 patients, 222 with LA were included after review of patient records (76%). Mean age was 65 years (54–74), 62.9% was male and 74.9% were ever-smokers. Chronic obstructive pulmonary disease (COPD) (35.1%), use of sedatives (29.3%) and alcohol abuse (21.8%) were common risk factors. Dental status was reported in 51.4%, whereof 41.6% had poor dental status. Patients presented with cough (78.8%), malaise (61.3%) and fever (56.8%) Patients were hospitalized for a median of 14 days (interquartile ranges, IQR 7–21) and median duration of antibiotic treatment was 38 days (IQR 30–51). All-cause mortality after 1, 3 and 12 months was 2.7%, 7.7% and 15.8%, respectively. ConclusionRisk factors for LA include COPD and use of sedatives, alcohol abuse, and poor dental status. Despite long-term antibiotic treatment, long-term mortality is markedly high.

P267 In vitro efficacy of inhalative antibiotics against Pseudomonas aeruginosa using artificial sputum medium

Cystic fibrosis (CF) is characterized by a polymicrobial infection of the airways with Pseudomonas aeruginosa being the most common pathogen. Chronic infection with P. aeruginosa has been associated with accelerated lung function decline and premature death. In case P. aeruginosa early eradication therapy fails, long-term antibiotic maintenance treatment is required to reduce airway inflammation and irreversible structural lung damage. Most commonly, inhalative antibiotics (tobramycin, colistin, aztreonam lysine, levofloxacin), that generate high local concentrations with low systemic drug concentrations and low systemic side effects, are used. So far, no validated antimicrobial breakpoints to assess antipseudomonal activity of inhalative agents exist. Our study thus aims to investigate the in vitro efficacy of antipseudomonal inhalative antibiotics.

Chronic Suppressive Antibiotic Treatment for Staphylococcal Bone and Joint Implant-Related Infections.

Prosthetic joint infection (PJI) and fracture-related infection (FRI) are difficult-to-treat conditions in patients with severe comorbidity or significant surgical risk. In cases not eligible for standard strategy, debridement procedures with the retention of prosthesis or internal fixation device, combined with long-term antibiotic treatment and subsequent indefinite chronic oral antimicrobial suppression (COAS), can be the only reasonable choice. The aim of this study was to investigate the role of COAS and its follow-up in the management of these cases. We retrospectively analyzed a cohort of 16 patients with a follow-up of at least 6 months (mean age 75 yo, 9F, 7M, 11 PJI, 5 FRI). All microbiological isolates were tetracycline-susceptible staphylococci and for this reason a minocycline-based COAS was adopted after debridement and 3 months of antibiogram-guided antibiotic treatment. Patient monitoring was carried out on a clinical basis, with bimonthly execution of the inflammation indices and serial radiolabeled leukocyte scintigraphy (LS). The overall median time of COAS follow-up was 15 months (min 6-max 30). Moreover, 62.5% of patients were still taking COAS with no relapse after cure at the last evaluation available. Clinical failure with a relapse of the infection was observed in 37.5% of patients; interestingly, 50% of them had previously stopped COAS due to side effects of the antibiotic used. In the COAS follow-up, a combination of clinical, laboratory and LS evaluation seems to monitor the infection properly. COAS can be considered as an interesting approach in patients not suitable for standard treatments of PJI or FRI but it requires careful monitoring.

Incidence and Risk Factors for Fracture-Related Infection After Peri-Prosthetic Femoral Fractures: A Multicenter Retrospective Study (TRON Group Study).

Background: Fracture-related infection (FRI) sometimes occurs with peri-prosthetic femoral fracture (PPF) treatment. Fracture-related infection often leads to multiple re-operations, possible non-union, a decreased clinical function, and long-term antibiotic treatment. In this multicenter study, we aimed to clarify the incidence of FRI, the causative organisms of wound infection, and the risk factors associated with post-operative infection for PPF. Patients and Methods: Among 197 patients diagnosed with peri-prosthetic femoral fracture who received surgical treatment in 11 institutions (named the TRON group) from 2010 to 2019, 163 patients were included as subjects. Thirty-four patients were excluded because of insufficient follow-up (less than six months) or data loss. We extracted the following risk factors for FRI: gender, body mass index, smoking history, diabetes mellitus, chronic hepatitis, rheumatoid arthritis, dialysis, history of osteoporosis treatment, injury mechanism (high- or low-energy), Vancouver type, and operative information (waiting period for surgery, operation time, amount of blood loss, and surgical procedure). We conducted a logistic regression analysis to investigate the risk factors for FRI using these extracted items as explanatory variables and the presence or absence of FRI as the response variable. Results: Fracture-related infection occurred after surgery for PPF in 12 of 163 patients (7.3%). The most common causative organism was Staphylococcus aureus (n = 7). The univariable analysis showed differences for dialysis (p = 0.001), Vancouver type (p = 0.036), blood loss during surgery (p = 0.001), and operative time (p = 0.001). The multivariable logistic-regression analysis revealed that the patient background factor of dialysis (odds ratio [OR], 22.9; p = 0.0005), and the operative factor of Vancouver type A fracture (OR, 0.039-1.18; p = 0.018-0.19) were risk factors for FRI. Conclusions: The rate of post-operative wound infection in patients with a PPF was 7.3%. Staphylococcus was the most frequent causative organism. The surgeon should pay attention to infection after surgery for patients with Vancouver type A fractures and those undergoing dialysis.

Induction of protective interferon-β responses in murine osteoblasts following S. aureusinfection and the use of nucleic acid nanoparticles to enhance bacterial killing.

Abstract Staphylococcus aureusis the primary causative agent of osteomyelitis, a severe inflammatory bone infection. Treatment for osteomyelitis includes long-term antibiotic treatment, surgical debridement of necrotic bone, or even amputation. Treatment is challenging due to an inability of antibiotics to penetrate bone tissue and resident bone cells that harbor intracellular bacteria, and the increased incidence of infections associated with antibiotic-resistant S. aureusstrains. Following S. aureusinfection, resident bone cells including osteoblasts produce immune mediators and bone regulatory factors. While type I interferons (IFNs) are best known for their antiviral effects, it is becoming apparent that they impact susceptibility to many pathogens. Here, we report elevated IFN-β levels in infected femurs in a mouse model of osteomyelitis. RNA Tag-Seq analysis of S. aureusinfected osteoblasts showed elevated expression of mRNA encoding IFN-β and ISGs. We confirmed rapid and robust release of IFN-β protein production by osteoblasts following S. aureuschallenge. Furthermore, we showed increased protein expression of ISGs by infected osteoblasts and demonstrate that this occurs secondary to the release of IFN-β by these cells. Importantly, we have determined that exposure of S. aureus-infected osteoblasts to IFN-β markedly reduces the viable bacteria harbored by these cells. Finally, we have demonstrated delivery of immunomodulatory nucleic acid nanoparticle (NANPs) scaffolds using lipid-based carriers to murine osteoblasts. These NANPs are promising agents that could induce protective IFNs during S. aureusinfection of bone tissue and be further functionalized with antimicrobials to kill intracellular S. aureus. This work was supported by grant 1R01AI170012-01 to IM and MBJ from the National Institute for Arthritis and Musculoskeletal and Skin Diseases.

Analysis of Clinical Factors Associated with Medical Burden and Functional Status in Pyogenic Spine Infection

Pyogenic spinal infection (PSI) has recently been on the rise due to aging and increasing degenerative spinal disease related procedures. PSI requires long-term antibiotic treatment and is followed by sustained functional disability even after successful treatment. This study aimed to analyze the clinical factors associated with medical burden and functional status of PSI. This retrospective study involved patients with non-postoperative PSI of thoraco-lumbo-sacral area in a single tertiary hospital. The length/cost of hospitalization with an antibiotic therapy and severity of back pain using the short form 36 (SF-36) were defined as the medical burden and functional status, respectively. We analyzed the clinical factors associated with medical burden and functional status. We enrolled 142 patients (91 males and 51 females). The length and cost of hospitalization were 55.56 ± 27.09 (7-172) days and $14,070.17 ± 9289.39 (1611.87-48,722.35), respectively. A recurrence rate of 7.7% (11/142) and significant improvement of SF-36 at six months after completion of antibiotic treatment were noted (p < 0.05). Procedure-related (OR 2.702), C-reactive protein (CRP; OR 1.062), bacteremia (OR 4.966), additional surgical treatment (OR 6.524), recurrence (OR 12.453), and paraspinal abscess (OR 5.965) for above-average length of hospitalization were observed; female (OR 4.438), CRP (OR 1.071), bacteremia (OR 4.647), additional surgical treatment (OR 6.737), recurrence (OR 22.543), and extent of lesion (OR 1.431) for above-average cost of hospitalization; leg weakness (OR 15.966), white blood cell (WBC; OR 1.116), Charlson's comorbidity index (CCI, OR 1.485), and identification of causative bacteria (OR 2.913) for below-average initial SF-36 were observed; leg weakness (OR 7.975) and WBC (OR 1.094) for below-average 6-month SF-36 were the statistically significant clinical factors in the multivariable logistic regression analysis (p < 0.05). Recurrence and leg weakness were identified as the most important clinical factors for medical burden and functional status in PSI, respectively. We think that it is necessary to actively suppress recurrence and manage neurological deficits for decreasing medical burden and achieving favorable functional outcome in the treatment of PSI.

Case report: Extravascular catheter migration in a child: A rare complication of the totally implantable venous access device

Totally implantable venous access devices (TIVADs) are widely used to gain intermittent central venous access, such as in patients who need long-term chemotherapy, total parenteral nutrition, and long-term antibiotic treatment. At present, there are many complications associated with the use of these devices. Complete extravascular migration of TIVADs via the internal jugular vein is a very rare and potentially serious condition, especially in children. A 1-year-old girl needed palliative chemotherapy because of hepatoblastoma complicated by inferior vena cava thrombosis. A TIVAD was implanted through the right internal jugular vein with a routine heparin flushing tube. On the second day after the operation, a pale bloody liquid was drawn out from the device and the chest X-ray was checked to confirm that the position of the catheter was normal. On the third day after the operation, however, the patient's right respiratory sound was weakened on physical examination and auscultation. Fluoroscopy showed that the tip of the catheter was located in the right thoracic cavity, and there was a large amount of effusion in the right thoracic cavity. The pleural effusion was removed, the TIVAD was replaced again, and the child was discharged 2 days later. Following TIVAD implantation, if abnormalities are found, in addition to chest X-ray, saline flush and echocardiography should be performed to determine the position of the catheter and rule out extravascular migration of the catheter to avoid irreparable consequences.

Dual red and near-infrared light-emitting diode irradiation ameliorates LPS-induced otitis media in a rat model.

Objective: Otitis media (OM) is an infectious and inflammatory disease of the middle ear (ME) that often recurs and requires long-term antibiotic treatment. Light emitting diode (LED)-based devices have shown therapeutic efficacy in reducing inflammation. This study aimed to investigate the anti-inflammatory effects of red and near-infrared (NIR) LED irradiation on lipopolysaccharide (LPS)-induced OM in rats, human middle ear epithelial cells (HMEECs), and murine macrophage cells (RAW 264.7). Methods: An animal model was established by LPS injection (2.0mg/mL) into the ME of rats via the tympanic membrane. A red/NIR LED system was used to irradiate the rats (655/842nm, intensity: 102mW/m2, time: 30min/day for 3 days and cells (653/842nm, intensity: 49.4mW/m2, time: 3h) after LPS exposure. Hematoxylin and eosin staining was performed to examine pathomorphological changes in the tympanic cavity of the ME of the rats. Enzyme-linked immunosorbent assay, immunoblotting, and RT-qPCR analyses were used to determine the mRNA and protein expression levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mitogen-activated protein kinases (MAPKs) signaling was examined to elucidate the molecular mechanism underlying the reduction of LPS-induced pro-inflammatory cytokines following LED irradiation. Results: The ME mucosal thickness and inflammatory cell deposits were increased by LPS injection, which were reduced by LED irradiation. The protein expression levels of IL-1β, IL-6, and TNF-α were significantly reduced in the LED-irradiated OM group. LED irradiation strongly inhibited the production of LPS-stimulated IL-1β, IL-6, and TNF-α in HMEECs and RAW 264.7 cells without cytotoxicity in vitro. Furthermore, the phosphorylation of ERK, p38, and JNK was inhibited by LED irradiation. Conclusion: This study demonstrated that red/NIR LED irradiation effectively suppressed inflammation caused by OM. Moreover, red/NIR LED irradiation reduced pro-inflammatory cytokine production in HMEECs and RAW 264.7 cells through the blockade of MAPK signaling.

Resilience and stability of the CF- intestinal and respiratory microbiome during nutritional and exercise intervention

BackgroundImpaired respiratory and intestinal microbiome composition is linked to cystic fibrosis lung disease severity. In people with cystic fibrosis (pwCF), regular exercise is recommended to delay disease progression and preserve a stable lung function. An optimal nutritional status is vital for best clinical outcomes. Our study investigated whether regular and monitored exercise and nutritional support promotes CF microbiome health.MethodsA personalized nutrition and exercise program promoted nutritional intake and physical fitness in 18 pwCF for 12 months. Throughout the study, patients performed strength and endurance training monitored by a sports scientist via an internet platform. After three months, food supplementation with Lactobacillus rhamnosus LGG was introduced. Nutritional status and physical fitness were assessed before the study started, after three and nine months. Sputum and stool were collected, and microbial composition was analyzed by 16S rRNA gene sequencing.ResultsSputum and stool microbiome composition remained stable and highly specific to each patient during the study period. Disease-associated pathogens dominated sputum composition. Lung disease severity and recent antibiotic treatment had the highest impact on taxonomic composition in stool and sputum microbiome. Strikingly, the long-term antibiotic treatment burden had only a minor influence.ConclusionDespite the exercise and nutritional intervention, respiratory and intestinal microbiomes proved to be resilient. Dominant pathogens drove the composition and functionality of the microbiome. Further studies are required to understand which therapy could destabilize the dominant disease-associated microbial composition of pwCF.

The Role of COVID-19 in Antibiotic Resistance in Pediatric Population

There is data on the irrational use of antimicrobial drugs in pediatric population during the COVID-19 pandemic. This could lead to potential development of antibiotic resistance and increased morbidity and mortality among this vulnerable population group. The aim of this review is to study the role of COVID-19 in antimicrobial drugs administration and antibiotic resistance development, as well as to determine a set of measures for its prevention. Recent studies results have shown that COVID-19 pandemic had both direct and indirect impact on antibiotic resistance development in pediatric population. The COVID-19 outbreak has revealed weaknesses in health systems around the world. Antibiotics administration in patients with coronavirus infection during this period exceeded the number of cases with bacterial co-infection or other diseases. Thus, it indicates irrational antibiotic treatment. There were cases of inappropriate antibiotics administration during the crisis caused by the COVID-19 pandemic even in regions with long-term rational antibiotic treatment programs. One of the most viable methods to combat antibiotic resistance is to improve approaches in health care and to increase preparedness to infectious outbreaks. Increasing clinical competence of medical workers, accessibility of medical facilities, permanent supply of high-quality and cheap antibiotics, vaccines, reducing COVID-19 testing time, and adequate administration of antibacterial agents are the measures that can prevent diseases caused by drug resistance. All stakeholders (health authorities, regulating authorities, politicians, scientific community, pharmaceutical companies) have to collaborate and achieve results to implement all the mentioned above protection measures.

Role of Surgery in Brucella Spondylodiscitis: An Evaluation of 28 Patients.

Background A limited number of studies are available in the literature on the surgical treatment of brucellosis-related spondylodiscitis. This study aimed to define and discuss the role of surgery in brucellosis-related spondylodiscitis. Methodology A total of 28 patients who underwent surgical treatment due to brucellosis-related spondylodiscitis between February 2021 and August 2022 were included in this study. Medical records, radiological images, and laboratory data were collected. Surgical results were evaluated according to the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels, clinical findings, postoperative radiological imaging findings, and complications were evaluated. Results In total, 16 of the patients included in the study were male and 12 were female, with a mean age of 56.4 ± 7.2 years. The mean follow-up duration was 11.8 ± 5.4 months. Brucellosis involvement was in the lumbosacral region in all patients. Overall, 21 patients had a neurological deficit in the preoperative period. Posterior stabilization and fusion were done in 20 (71.4%) patients, while simple laminectomy (decompression) and debridement were done in eight (28.6%) patients. There was a decrease in the pain in the lower back and leg in all patients in the postoperative period. Neurological recovery was achieved in 18 patients with a neurological deficit. Two patients underwent wound drainage in the postoperative period.The patient who had morbid obesity and comorbidities died in the postoperative period. ESR and CRP levels returned to normal at the end of the six-month follow-up. There was a significant recovery in VAS and ODI scores (p < 0.05). In total, 24 (85.4%) patients were considered fully recovered both radiologically and clinically at the end of the follow-up. Conclusions Although long-term and specific antibiotic treatment constitute the main treatment in brucellosis-related spondylodiscitis, debridement, decompression, and stabilization (when required) of infection with a focus on neurological deficits and instability formation and non-stop severe pain are effective and safe treatment options.