Secondary Infections in Patients with Extremely Severe COVID-19 During ECMO Therapy.

Up to 70% of patients hospitalized for COVID-19 need respiratory support, up to 10% need high-flow oxygen therapy, non-invasive and invasive ventilation. However, standard methods of respiratory support are ineffective in 0.4-0.5% of patients. In case of potentially reversible critical refractory respiratory failure that patients may require ECMO. Management of patients with extremely severe COVID-19 associates with numerous clinical challenges, including critical illness, multiple organ dysfunction, blood coagulation disorders, requiring prolonged ICU stay and care, use of multiple pharmacotherapies including immunosuppressive drugs. Pharmacological suppression of immunity is associated with a significant increase in the risk of secondary bacterial and fungal infections. Currently, data on epidemiology of secondary infections in patients with COVID-19 undergoing ECMO is limited. Aim. To study the prevalence and etiology of secondary infections associated with positive blood cultures in patients with extremely severe COVID-19 requiring ECMO. Materials and methods. A single-center retrospective non-interventional epidemiological study including 125 patients with extremely severe COVID-19 treated with ECMO in April 2020 to December 2021. Results. Out of 700 blood culture tests performed in 125 patients during the study, 250 tests were positive confirming bacteremia/fungemia. Isolated pathogens varied depending on the duration of ECMO: gram-positive bacteria (primarily coagulase-negative staphylococci) dominated from the initiation of ECMO support;increased duration of ECMO associated with an increasing the proportion of pathogens common in ICU (Klebsiella pneumoniae and/or Acinetobacter baumannii with extensively drug resistant and pan-drug resistant phenotypes, and vancomycin-resistant Enterococcus faecium). When ECMO lasted more than 7-14 days, opportunistic pathogens (Candida species, Stenotrophomonas maltophilia, Providencia stuartii, non-diphtheria corynebacteria, Burkholderia species and others) prevailed as etiological agents. Conclusion. Longer duration of ECMO resulted in increasing the rates of infectious complications. In patients undergoing ECMO for more than 14 days, the microbiological landscape becomes extremely diverse, which hampers choosing an empirical antimicrobial therapy. Since potential pathogens causing secondary infections in patients during ECMO are difficult to predict, rapid identification of rare opportunistic pathogens and their sensitivity profile, followed by targeted administration of antimicrobials, seems most beneficial.Copyright © 2023, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

Patient and carer perspectives on the use of video consultations in the management of the ketogenic diet for epilepsy.

BACKGROUND: The COVID-19 pandemic resulted in a significant change in the way healthcare was delivered worldwide. During this time, a survey of Ketogenic Dietitians Research Network (KDRN) members found that all respondents expected digital platforms for clinics and/or education to continue post-pandemic. As a follow-up to this, we surveyed views about video consultations (VCs) of patients and carers of those following the ketogenic diet for drug-resistant epilepsy. METHODS: The SurveymonkeyTM survey was distributed on Matthews' Friends and KDRN social media platforms and emailed from five United Kingdom ketogenic diet centers to their patients/carers. RESULTS: Forty eligible responses were received. More than half of the respondents (23, 57.5%) had attended a VC. Eighteen respondents (45%) would like to have VCs for most (categorized as approximately 75%) or all of their consultations. Half as many (9, 22.5%) would not like video consultations. The most common benefits selected were saving travel time (32, 80%), less stress of finding somewhere to park and not having to take time off work (22, 55% each). Twelve (30%) responded that VCs lessened environmental impact. The most common disadvantages selected were not being able to get blood tests/having to make a separate consultation for blood tests (22, 55% overall), not being able to get weight or height checked/having to make a separate consultation for this and it is less personal/preferring face-to-face (17, 42.5% each). Three-quarters (30 respondents) felt it would be very easy or easy to accurately weigh the patient when not attending an in-person consultation. CONCLUSION: Our results suggest that many patients and carers would welcome the option of VCs as well as face-to-face consultations. Where possible and appropriate patients and their families should be offered both options. This is in line with the NHS Long-Term Plan and the NHS response to climate change.

Antimicrobial Resistance in Ventilator-Associated Pneumonia: Predictive Microbiology and Evidence-Based Therapy.

Ventilator-associated pneumonia (VAP) is a serious intensive care unit (ICU)-related infection in mechanically ventilated patients that is frequent, as more than half of antibiotics prescriptions in ICU are due to VAP. Various risk factors and diagnostic criteria for VAP have been referred to in different settings. The estimated attributable mortality of VAP can go up to 50%, which is higher in cases of antimicrobial-resistant VAP. When the diagnosis of pneumonia in a mechanically ventilated patient is made, initiation of effective antimicrobial therapy must be prompt. Microbiological diagnosis of VAP is required to optimize timely therapy since effective early treatment is fundamental for better outcomes, with controversy continuing regarding optimal sampling and testing. Understanding the role of antimicrobial resistance in the context of VAP is crucial in the era of continuously evolving antimicrobial-resistant clones that represent an urgent threat to global health. This review is focused on the risk factors for antimicrobial resistance in adult VAP and its novel microbiological tools. It aims to summarize the current evidence-based knowledge about the mechanisms of resistance in VAP caused by multidrug-resistant bacteria in clinical settings with focus on Gram-negative pathogens. It highlights the evidence-based antimicrobial management and prevention of drug-resistant VAP. It also addresses emerging concepts related to predictive microbiology in VAP and sheds lights on VAP in the context of coronavirus disease 2019 (COVID-19).

Placing Antimicrobial Resistance in the Context of Competing Public Health Priorities in Sub-Saharan Africa, a Perspective from Malawi

Antimicrobial resistance is a major threat to human health that is predicted to impact most heavily on sub-Saharan Africa, however there is a lack of clinical outcome data from drug-resistant infections in this setting. There are reasons to expect the COVID-19 pandemic to have both positive and negative impacts on AMR in Africa. We have recruited a series of prospective longitudinal cohorts from Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi and the surrounding communities in the Southern Region of Malawi. The data from these cohorts has been used to describe the aetiology of febrile illness, the burden of antimicrobial resistance in this setting and the distribution of extended spectrum beta-lactamase producing bacteria in humans, animals and the environment. Amongst a cohort of patients presenting to QECH unwell with febrile illness, 67% were living with human immunodeficiency virus (HIV). We identified a diagnosis in 145 of 225 (64%) participants, most commonly tuberculosis (TB;34%) followed by invasive bacterial infections (17%), arboviral infections (13%), and malaria (9%). In a second cohort with drug resistant infection, resistance to third-generation cephalosporins was associated with an increased probability of in-hospital mortality (hazard ratio [HR] 1.44, 95% CI 1.02-2.04), longer hospital stays (1.5 days, 1.0-2.0) and decreased probability of discharge alive (HR 0.31, 0.22-0.45). In the community cohorts, a paucity of environmental health infrastructure and materials for safe sanitation was identified across all sites and ESBL-Enterobacterales were isolated from 41.8% of human stool, 29.8% of animal stool and 66.2% of river water samples and was associated with the wet season, living in urban areas, advanced age and in household-animal interactions. Life threatening febrile illness is common in Blantyre however, diagnostics are few, however the COVID-19 pandemic has led to rapid expansion of diagnostic capacity. We are, however frequently treating the wrong bugs with ceftriaxone, further there was significant expansion of azithromycin demand and usage during the pandemic. Current management of sepsis has not been optimised and ceftriaxone use is promoting carriage of ESBL bacteria out of the hospital and ESBL E. coli and K. pneumoniae are ubiquitous in the community, where environmental hygiene infrastructure and community antimicrobial stewardship are critically lacking.Copyright © 2023

Chalcone-based Ferrocenyl-Derivatives as an Antimicrobial Drug

The lack of development of new antibiotics is the major concern at the present scenario. One key factor contributing to the rise of antibiotic-resistant bacteria is the widespread movement of people throughout the world. The world has seen the consequences of the migration in the case of COVID-19 very recently. To tackle or cope with the situation, development of new antibiotics is very essential, which can be inhibited multidrug-resistant bacteria. In this framework, chalcone-based ferrocenyl containing compounds showed a diversity of pharmacological properties and its derivatives possess a high degree of structural diversity and it is helpful for the discovery of new therapeutic agents. Thus, there is a need for new antibacterial drug candidates with increased strength, new targets, low cost, superior pharmacokinetic properties and minimum side effects. The present review concluded and focuses on the recent developments in the area of medicinal chemistry to explore the diverse chemical structures of potent antibacterial agents and also describes its structure-activity relationship studies (SAR). This review will help to the researchers in the medical field to find out the future generation potential drug discovery and development. © 2023 Chemical Publishing Co.. All rights reserved.

Impact of COVID-19 on diagnosis of tuberculosis, multidrug-resistant tuberculosis, and on mortality in 11 countries in Europe, Northern America, and Australia. A Global Tuberculosis Network study.

OBJECTIVES: Although evidence is growing on the overall impact of the COVID-19 pandemic on tuberculosis (TB) services, global studies based on national data are needed to better quantify the extent of the impact and the countries' preparedness to tackle the two diseases. The aim of this study was to compare the number of people with new diagnoses or recurrence of TB disease, the number of drug-resistant (DR)-TB, and the number of TB deaths in 2020 vs 2019 in 11 countries in Europe, Northern America, and Australia. METHODS: TB managers or directors of national reference centers of the selected countries provided the agreed-upon variables through a validated questionnaire on a monthly basis. A descriptive analysis compared the incidence of TB and DR-TB and mortality of the pre-COVID-19 year (2019) vs the first year of the COVID-19 pandemic (2020). RESULTS: Comparing 2020 vs 2019, lower number of TB cases (new diagnosis or recurrence) was notified in all countries (except USA-Virginia and Australia), and fewer DR-TB notifications (apart from France, Portugal, and Spain). The deaths among TB cases were higher in 2020 compared to 2019 in most countries with three countries (France, The Netherlands, USA-Virginia) reporting minimal TB-related mortality. CONCLUSIONS: A comprehensive evaluation of medium-term impact of COVID-19 on TB services would benefit from similar studies in multiple settings and from global availability of treatment outcome data from TB/COVID-19 co-infected patients.

Drug-Resistant Tuberculosis Treatment Recommendation, and Multi-Class Tuberculosis Detection and Classification Using Ensemble Deep Learning-Based System.

This research develops the TB/non-TB detection and drug-resistant categorization diagnosis decision support system (TB-DRC-DSS). The model is capable of detecting both TB-negative and TB-positive samples, as well as classifying drug-resistant strains and also providing treatment recommendations. The model is developed using a deep learning ensemble model with the various CNN architectures. These architectures include EfficientNetB7, mobileNetV2, and Dense-Net121. The models are heterogeneously assembled to create an effective model for TB-DRC-DSS, utilizing effective image segmentation, augmentation, and decision fusion techniques to improve the classification efficacy of the current model. The web program serves as the platform for determining if a patient is positive or negative for tuberculosis and classifying several types of drug resistance. The constructed model is evaluated and compared to current methods described in the literature. The proposed model was assessed using two datasets of chest X-ray (CXR) images collected from the references. This collection of datasets includes the Portal dataset, the Montgomery County dataset, the Shenzhen dataset, and the Kaggle dataset. Seven thousand and eight images exist across all datasets. The dataset was divided into two subsets: the training dataset (80%) and the test dataset (20%). The computational result revealed that the classification accuracy of DS-TB against DR-TB has improved by an average of 43.3% compared to other methods. The categorization between DS-TB and MDR-TB, DS-TB and XDR-TB, and MDR-TB and XDR-TB was more accurate than with other methods by an average of 28.1%, 6.2%, and 9.4%, respectively. The accuracy of the embedded multiclass model in the web application is 92.6% when evaluated with the test dataset, but 92.8% when evaluated with a random subset selected from the aggregate dataset. In conclusion, 31 medical staff members have evaluated and utilized the online application, and the final user preference score for the web application is 9.52 out of a possible 10.

A Simplified Amplification-Free Strategy with Lyophilized CRISPR-CcrRNA System for Drug-Resistant Salmonella Detection.

Drug resistance in pathogenic bacteria has become a major threat to global health. The misuse of antibiotics has increased the number of resistant bacteria in the absence of rapid, accurate, and cost-effective diagnostic tools. Here, an amplification-free CRISPR-Cas12a time-resolved fluorescence immunochromatographic assay (AFC-TRFIA) is used to detect drug-resistant Salmonella. Multi-locus targeting in combination crRNA (CcrRNA) is 27-fold more sensitive than a standalone crRNA system. The lyophilized CRISPR system further simplifies the operation and enables one-pot detection. Induction of nucleic acid fixation via differentially charged interactions reduced the time and cost required for flowmetric chromatography with enhanced stability. The induction of nucleic acid fixation via differentially charged interactions reduces the time and cost required for flowmetric chromatography with enhanced stability. The platform developed for the detection of drug-resistant Salmonella has an ultra-sensitive detection limit of 84 CFU mL-1 within 30 min, with good linearity in the range of 102 -106 CFU mL-1 . In real-world applications, spiked recoveries range from 76.22% to 145.91%, with a coefficient of variation less than 10.59%. AFC-TRFIA offers a cost-effective, sensitive, and virtually equipment-independent platform for preventing foodborne illnesses, screening for drug-resistant Salmonella, and guiding clinical use.

Phantom Plague: How Tuberculosis Shaped History

The author highlights many challenges ahead that limit achieving the World Health Organization (WHO) End TB strategy without substantial additional investments and development of new tools to combat TB (the WHO End TB strategy targets a 90% reduction in TB cases and 95% reduction in TB-related deaths by 2035). [...]perhaps the book ends prematurely, because after it was written, new treatments were developed for highly drug-resistant TB that shifted to all oral regimens (WHO recommendation);a ≈90% favorable outcome was recently reported for the BPaL regimen used to treat highly drug-resistant TB (2). Emory University School of Medicine and Rollins School of Public Health, Atlanta, Georgia, USA World Health Organization.

Evolution of tuberculosis diagnostics: From molecular strategies to nanodiagnostics.

Tuberculosis has remained a global concern for public health affecting the lives of people for ages. Approximately 10 million people are affected by the disease and 1.5 million succumb to the disease worldwide annually. The COVID-19 pandemic has highlighted the role of early diagnosis to win the battle against such infectious diseases. Thus, advancement in the diagnostic approaches to provide early detection forms the foundation to eradicate and manage contagious diseases like tuberculosis. The conventional diagnostic strategies include microscopic examination, chest X-ray and tuberculin skin test. The limitations associated with sensitivity and specificity of these tests demands for exploring new techniques like probe-based assays, CRISPR-Cas and microRNA detection. The aim of the current review is to envisage the correlation between both the conventional and the newer approaches to enhance the specificity and sensitivity. A significant emphasis has been placed upon nanodiagnostic approaches manipulating quantum dots, magnetic nanoparticles, and biosensors for accurate diagnosis of latent, active and drug-resistant TB. Additionally, we would like to ponder upon a reliable method that is cost-effective, reproducible, require minimal infrastructure and provide point-of-care to the patients.

Cefiderocol-Based versus Colistin-Based Regimens for Severe Carbapenem-Resistant Acinetobacter baumannii Infections: A Propensity Score-Weighted, Retrospective Cohort Study during the First Two Years of the COVID-19 Pandemic.

BACKGROUND: A large increase in multi-drug-resistant Acinetobacter baumannii, especially carbapenem-resistant strains, occurred during the first two years of the COVID-19 pandemic, posing important challenges in its treatment. Cefiderocol appeared to be a good option for the treatment of Carbapenem-resistant Acinetobacter baumannii (CR-Ab), but to date, the guidelines and evidence available are conflicting. METHODS: We retrospectively included a group of patients with CR-Ab infections (treated with colistin- or cefiderocol-based regimens) at Padua University Hospital (August 2020-July 2022) and assessed predictors of 30-day mortality, and differences in microbiological and clinical treatment. To evaluate the difference in outcomes, accounting for the imbalance in antibiotic treatment allocation, a propensity score weighting (PSW) approach was adopted. RESULTS: We included 111 patients, 68% males, with a median age of 69 years (IQR: 59-78). The median duration of antibiotic treatment was 13 days (IQR:11-16). In total, 60 (54.1%) and 51 (45.9%) patients received cefiderocol- and colistin-based therapy, respectively. Notably, 53 (47.7%) patients had bloodstream infections, while 58 (52.3%) had pneumonia. Colistin was combined in 96.1%, 80.4%, and 5.8% of cases with tigecycline, meropenem, and fosfomycin, respectively. Cefiderocol was combined in 13.3%, 30%, and 18.3% of cases with fosfomycin, tigecycline, and meropenem, respectively. At the baseline, the two treatment groups significantly differed in age (patients treated with colistin were significantly older), the prevalence of diabetes and obesity (more frequent in the group treated with colistin), length of stay (longer in the group receiving cefiderocol), and type of infection (BSI were more frequent in the group receiving cefiderocol). The proportion of patients who developed acute kidney injury was significantly higher in the colistin group. By using PSW, no statistically significant differences emerged for mortality or clinical and microbiological cure between the two groups. No independent predictors were detected for hospital mortality or clinical cure, while for the length of stay, the only selected predictor was age, with a non-linear effect (p-value 0.025 for non-linearity) on the prolongation of hospital stay of 0.25 days (95% CI 0.10-0.39) at increasing ages (calculated over the IQR). CONCLUSIONS: Cefiderocol treatment did not differ in terms of main outcomes and safety profile from colistin-based regimens. More prospective studies with a larger number of patients are required to confirm our results.

Recent Advances in Strategies to Combat Bacterial Drug Resistance: Antimicrobial Materials and Drug Delivery Systems.

Bacterial infection is a common clinical disease. Antibiotics have saved countless lives since their discovery and are a powerful weapon in the fight against bacteria. However, with the widespread use of antibiotics, the problem of drug resistance now poses a great threat to human health. In recent years, studies have investigated approaches to combat bacterial resistance. Several antimicrobial materials and drug delivery systems have emerged as promising strategies. Nano-drug delivery systems for antibiotics can reduce the resistance to antibiotics and extend the lifespan of novel antibiotics, and they allow targeting drug delivery compared to conventional antibiotics. This review highlights the mechanistic insights of using different strategies to combat drug-resistant bacteria and summarizes the recent advancements in antimicrobial materials and drug delivery systems for different carriers. Furthermore, the fundamental properties of combating antimicrobial resistance are discussed, and the current challenges and future perspectives in this field are proposed.

Nanomedicine for drug resistant pathogens and COVID-19 using mushroom nanocomposite inspired with bacteriocin - A review.

Multidrug resistant (MDR) pathogens have become a major global health challenge and have severely threatened the health of society. Current conditions have become worse as a result of the COVID-19 pandemic, and infection rates in the future will rise. It is necessary to design, respond effectively, and take action to address these challenges by investigating new avenues. In this regard, the fabrication of metal NPs utilized by various methods, including green synthesis using mushroom, is highly versatile, cost-effective, eco-compatible, and superior. In contrast, biofabrication of metal NPs can be employed as a powerful weapon against MDR pathogens and have immense biomedical applications. In addition, the advancement in nanotechnology has made possible to modify the nanomaterials and enhance their activities. Metal NPs with biomolecules composite prevent the microbial adhesion and kills the microbial pathogens through biofilm formation. Bacteriocin is an excellent antimicrobial peptide that works well as an augmentation substance to boost the antimicrobial effects. As a result, we concentrate on the creation of new, eco-compatible mycosynthesized metal NPs with bacteriocin nanocomposite via electrostatic, covalent, or non-covalent bindings. The synergistic benefits of metal NPs with bacteriocin to combat MDR pathogens and COVID-19, as well as other biomedical applications, are discussed in this review. Moreover, the importance of the adverse outcome pathway (AOP) in risk analysis of manufactured metal nanocomposite nanomaterial and their future possibilities were also discussed.

Rapid tissue prototyping with micro-organospheres.

In vitro tissue models hold great promise for modeling diseases and drug responses. Here, we used emulsion microfluidics to form micro-organospheres (MOSs), which are droplet-encapsulated miniature three-dimensional (3D) tissue models that can be established rapidly from patient tissues or cells. MOSs retain key biological features and responses to chemo-, targeted, and radiation therapies compared with organoids. The small size and large surface-to-volume ratio of MOSs enable various applications including quantitative assessment of nutrient dependence, pathogen-host interaction for anti-viral drug screening, and a rapid potency assay for chimeric antigen receptor (CAR)-T therapy. An automated MOS imaging pipeline combined with machine learning overcomes plating variation, distinguishes tumorspheres from stroma, differentiates cytostatic versus cytotoxic drug effects, and captures resistant clones and heterogeneity in drug response. This pipeline is capable of robust assessments of drug response at individual-tumorsphere resolution and provides a rapid and high-throughput therapeutic profiling platform for precision medicine.

New advances in management and treatment of multidrug-resistant Klebsiella pneumoniae.

INTRODUCTION: The management of multidrug-resistant (MDR) Klebsiella pneumoniae (KP) represents a major challenge in the field of infectious diseases. It is associated with a high rate of nosocomial infections with a mortality rate that reaches approximately 50%, even when using an effective antimicrobial therapy. Therefore, combined actions addressing infection control and antibiotic stewardship are required to delay the emergence of resistance. Since new antimicrobial agents targeting MDR-GNB bacteria have been produced during the last years and are now available for physicians to treat MDR, it is fundamental to choose appropriate antimicrobial therapy for K. pneumoniae infection. AREAS COVERED: The PubMed database was searched to review the most significant recent literature on the topic, including data from articles coming from endemic areas and from the current European and American Guidelines. EXPERT OPINION: We explore the most effective strategies for prevention of MDR-KP spread and the currently available treatment options, focusing on comparing old strategies and new compounds. We reviewed data concerning newly developed drugs that could play an important role in the future; we also propose a treatment algorithm that could be useful for physicians in daily clinical practice.

The chamber of secretome in Mycobacterium tuberculosis as a potential therapeutic target.

Mycobacterium tuberculosis (MTB) causes one of the ancient diseases, Tuberculosis, affects people around the globe and its severity can be understood by its classification as a second infectious disease after COVID-19 and the 13th leading cause of death according to a WHO report. Despite having advanced diagnostic approaches and therapeutic strategies, unfortunately, TB is still spreading across the population due to the emergence of drug-resistance MTB and Latent TB infection (LTBI). We are seeking for effective approaches to overcome these hindrances and efficient treatment for this perilous disease. Therefore, there is an urgent need to develop drugs based on operative targeting of the bacterial system that could result in both efficient treatment and lesser emergence of MDR-TB. One such promising target could be the secretory systems and especially the Type 7 secretory system (T7SS-ESX) of Mycobacterium tuberculosis, which is crucial for the secretion of effector proteins as well as in establishing host-pathogen interactions of the tubercle bacilli. The five paralogous ESX systems (ESX-1 to EXS-5) have been observed by in silico genome analysis of MTB, among which ESX-1 and ESX-5 are substantial for virulence and mediating host cellular inflammasome. The bacterium growth and virulence can be modulated by targeting the T7SS. In the present review, we demonstrate the current status of therapeutics against MTB and focus on the function and cruciality of T7SS along with other secretory systems as a promising therapeutic target against Tuberculosis.

Pathogen Distribution, Drug Resistance Risk Factors, and Construction of Risk Prediction Model for Drug-Resistant Bacterial Infection in Hospitalized Patients at the Respiratory Department During the COVID-19 Pandemic.

Objective: To investigate the distribution and drug resistance of pathogens among hospitalized patients in the respiratory unit during the COVID-19 pandemic, analyze the risk factors of drug resistance, construct a risk prediction model. Methods: This study isolated 791 strains from 489 patients admitted to the Affiliated Hospital of Chengdu University, who were retrospectively enrolled between December 2019 and June 2021. The patients were divided into training and validation sets based on a random number table method (8:2). The baseline information, clinical characteristics, and culture results were collected using an electronic database and WHONET 5.6 software and compared between the two groups. A risk prediction model for drug-resistant bacteria was constructed using multi-factor logistic regression. Results: K. pneumoniae (24.78%), P. aeruginosa (17.19%), A. baumannii (10.37%), and E. coli (10.37%) were the most abundant bacterial isolates. 174 isolates of drug-resistant bacteria were collected, ie, Carbapenem-resistant organism-strains, ESBL-producing strains, methicillin-resistant S. aureus, multi-drug resistance constituting 38.51%, 50.57%, 6.32%, 4.60%, respectively. The nosocomial infection prediction model of drug-resistant bacteria was developed based on the combined use of antimicrobials, pharmacological immunosuppression, PCT>0.5 ng/mL, CKD stage 4-5, indwelling catheter, and age > 60 years. The AUC under the ROC curve of the training and validation sets were 0.768 (95% CI: 0.624-0.817) and 0.753 (95% CI: 0.657-0.785), respectively. Our model revealed an acceptable prediction demonstrated by a non-significant Hosmer-Lemeshow test (training set, p=0.54; validation set, p=0.88). Conclusion: K. pneumoniae, P. aeruginosa, A. baumannii, and E. coli were the most abundant bacterial isolates. Antimicrobial resistance among the common isolates was high for most routinely used antimicrobials and carbapenems. COVID-19 did not increase the drug resistance pressure of the main strains. The risk prediction model of drug-resistant bacterial infection is expected to improve the prevention and control of antibacterial-resistant bacterial infection in hospital settings.

Multidrug-Resistant TB (MDR-TB) and Extensively Drug-Resistant TB (XDR-TB) Among Children: Where We Stand Now.

Drug-resistant tuberculosis (DR-TB) has continued to be a global health cataclysm. It is an arduous condition to tackle but is curable with the proper choice of drug and adherence to the drug therapy. WHO has introduced newer drugs with all-oral shorter regimens, but the COVID-19 pandemic has disrupted the achievements and raised the severity. The COVID-19 controlling mechanism is based on social distancing, using face masks, personal protective equipment, medical glove, head shoe cover, face shield, goggles, hand hygiene, and many more. Around the globe, national and international health authorities impose lockdown and movement control orders to ensure social distancing and prevent transmission of COVID-19 infection. Therefore, WHO proposed a TB control program impaired during a pandemic. Children, the most vulnerable group, suffer more from the drug-resistant form and act as the storehouse of future fatal cases. It has dire effects on physical health and hampers their mental health and academic career. Treatment of drug-resistant cases has more success stories in children than adults, but enrollment for treatment has been persistently low in this age group. Despite that, drug-resistant childhood tuberculosis has been neglected, and proper surveillance has not yet been achieved. Insufficient reporting, lack of appropriate screening tools for children, less accessibility to the treatment facility, inadequate awareness, and reduced funding for TB have worsened the situation. All these have resulted in jeopardizing our dream to terminate this deadly condition. So, it is high time to focus on this issue to achieve our Sustainable Development Goals (SDGs), the goal of ending TB by 2030, as planned by WHO. This review explores childhood TB's current position and areas to improve. This review utilized electronic-based data searched through PubMed, Google Scholar, Google Search Engine, Science Direct, and Embase.

Biomaterial therapeutic strategies for treatment of bacterial lung infections.

Bacterial infections of the lung frequently occur as a secondary infection to many respiratory viral infections and conditions, including influenza, COVID-19, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). Currently, clinical standard treats bacterial infections of the lung with antibiotic drugs. However, the use of broad-spectrum antibiotics can disrupt host microbiomes, lead to patient discomfort, and current clinical settings face the constantly increasing threat of drug-resistant bacteria. Biofilms further obstruct effective treatment due to their protective matrix layer, which shields bacteria from both the host immune system and antimicrobial drugs and subsequently promotes drug resistance. Alternative antimicrobial agents, including bacteriophages and antimicrobial peptides, have been utilized to treat drug-resistant bacteria. However, these antimicrobial agents have significant limitations pertaining to their ability to arrive at infection sites without compromised function and ability to persist over an extended period to fully treat infections. Enhanced delivery strategies present great promise in addressing these issues by using micro/nanoparticle carriers that shield antimicrobial agents in transit and result in sustained release, enhancing subsequent therapeutic effect and can even be modulated to be multi-functional to further improve recovery following bacterial infection.