Binding selectivity analysis of new delhi metallo-beta-lactamase-1 inhibitors using molecular dynamics simulations: Exploring possibilities for decoding antimicrobial drug resistance.

BACKGROUND: New Delhi metallo-beta-lactamase-1 (NDM1) confers resistance to several bacterial species against a broad range of beta-lactam antibiotics and turning them into superbugs that pose a significant threat to healthcare systems worldwide. As such, it is a potentially relevant biological target for counteracting bacterial infections. Given the lack of effective treatment options against NDM1 producing bacteria, finding a reliable inhibitor for the NDM1 enzyme is crucial. METHODS: Using molecular dynamics simulations, the binding selectivities and affinities of three ligands, viz. PNK, 3S0, and N1G were investigated against NDM1. RESULTS: The results indicate that N1G binds with more affinity to NDM1 than PNK and 3S0. The binding energy decomposition analysis revealed that residues I35, W93, H189, K211, and N220 showed significant binding energies with PNK, 3S0, and N1G, and hence are crucially involved in the binding of the ligands to NDM1. Molecular dynamics trajectory analysis further elicited that the ligands influence dynamic flexibility of NDM1 morphology, which contributes to the partial selectivities of PNK, 3S0, and N1G. CONCLUSIONS: This in silico study offers a vital information for developing potential NDM1 inhibitors with high selectivity. Nevertheless, in vitro and in vivo experimental validation is mandated to extend the possible applications of these ligands as NDM1 inhibitors that succor in combating antimicrobial resistance.

Synthesis, molecular docking study and biological evaluation of new pyrrole scaffolds as potential antitubercular agents for dual targeting of enoyl ACP reductase and dihydrofolate reductase.

In this study, new series of N'-(2-(substitutedphenoxy)acetyl)-4-(1H-pyrrol-1-yl)benzohydrazides (3a-j) 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-(2-(substitutedphenoxy)acetyl)benzohydrazides (5a-j) were synthesized, characterized and assessed as inhibitors of enoyl ACP reductase and DHFR. Most of the compounds exhibited dual inhibition against the enzymes enoyl ACP reductase and DHFR. Several synthesized substances also demonstrated significant antibacterial and antitubercular properties. A molecular docking analysis was conducted in order to determine the potential mechanism of action of the synthesized compounds. The results indicated that there were binding interactions seen with the active sites of dihydrofolate reductase and enoyl ACP reductase. Additionally, important structural details were identified that play a critical role in sustaining the dual inhibitory activity. These findings were useful for the development of future dual inhibitors. Therefore, this study provided strong evidence that several synthesized molecules could exert their antitubercular properties at the cellular level through multi-target inhibition. By shedding light on the mechanisms through which these compounds exert their inhibitory effects, this research opens up promising avenues for the future development of dual inhibitors with enhanced antibacterial and antitubercular properties. The study's findings underscore the importance of multi-target approaches in drug design, providing a strong foundation for the design and optimization of novel compounds that can effectively target bacterial infections at the cellular level.

Therapeutic Potential of Green-Engineered ZnO Nanoparticles on Rotenone-Exposed D. melanogaster (Oregon R+): Unveiling Ameliorated Biochemical, Cellular, and Behavioral Parameters.

Nanotechnology holds significant ameliorative potential against neurodegenerative diseases, as it can protect the therapeutic substance and allow for its sustained release. In this study, the reducing and capping agents of Urtica dioica (UD), Matricaria chamomilla (MC), and Murraya koenigii (MK) extracts were used to synthesize bio-mediated zinc oxide nanoparticles (ZnO-NPs) against bacteria (Staphylococcus aureus and Escherichia coli) and against rotenone-induced toxicities in D. melanogaster for the first time. Their optical and structural properties were analyzed via FT-IR, DLS, XRD, EDS, SEM, UV-Vis, and zeta potential. The antioxidant and antimicrobial properties of the fabricated ZnO-NPs were evaluated employing cell-free models (DPPH and ABTS) and the well diffusion method, respectively. Rotenone (500 µM) was administered to Drosophila third instar larvae and freshly emerged flies for 24-120 h, either alone or in combination with plant extracts (UD, MC, an MK) and their biogenic ZnO-NPs. A comparative study on the protective effects of synthesized NPs was undertaken against rotenone-induced neurotoxic, cytotoxic, and behavioral alterations using an acetylcholinesterase inhibition assay, dye exclusion test, and locomotor parameters. The findings revealed that among the plant-derived ZnO-NPs, MK-ZnO NPs exhibit strong antimicrobial and antioxidant activities, followed by UD-ZnO NPs and MC-ZnO NPs. In this regard, ethno-nano medicinal therapeutic uses mimic similar effects in D. melanogaster by suppressing oxidative stress by restoring biochemical parameters (AchE and proteotoxicity activity) and lower cellular toxicity. These findings suggest that green-engineered ZnO-NPs have the potential to significantly enhance outcomes, with the promise of effective therapies for neurodegeneration, and could be used as a great alternative for clinical development.

Isolation and Detection of Drug-Resistant Bacterial Pathogens in Postoperative Wound Infections at a Tertiary Care Hospital in Saudi Arabia.

Background: Surgical site infections (SSIs), especially when caused by multidrug-resistant (MDR) bacteria, are a major healthcare concern worldwide. For optimal treatment and prevention of antimicrobial resistance, it is important for clinicians to be aware of local drug-resistant bacterial pathogens that cause SSIs. Objective: To determine the frequency patterns of drug-resistant bacterial strains causing SSIs at a tertiary care hospital in Saudi Arabia. Methods: This retrospective study was conducted at the Microbiology laboratory of Al-Noor Specialist Hospital, Makkah, Saudi Arabia, and included wound swab samples from all cases of SSI between January 01, 2017, and December 31, 2021. The swabs were processed for the identification of bacterial strains and their resistance pattern to antibiotics according to the Clinical and Laboratory Standards Institute. Results: A total of 5409 wound swabs were analyzed, of which 3604 samples (66.6%) were from male. Most samples were from the Department of Surgery (43.3%). A total of 14 bacterial strains were isolated, of which 9 were Gram-negative bacteria. The most common isolates were Klebsiella pneumoniae, followed by Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and vancomycin-resistant S. aureus (VRSA). In terms of MDR in 2021, the highest rate of carbapenem-resistance was in A. baumannii (97%). MDR was as follows: A. baumannii, 97%; K. pneumoniae, 81%; E. coli, 71%; MRSA, 60%; P. aeruginosa, 33%; VRE, 22%; and VRSA, 2%. Conclusion: This study showed that in the city of Makkah, Saudi Arabia, the rates of MDR bacteria are high, with the majority being Gram-negative.

Integrated immunoinformatics and subtractive proteomics approach for multi-epitope vaccine designing to combat S. pneumoniae TIGR4.

Streptococcus pneumoniae is one of the major precarious pathogens accountable for over 1.2 million fatalities annually. The key drivers for pneumococcal vaccine development involve high morbidity and mortality in over one million cases, especially in very young children and the elderly. In this study, immunoinformatics was integrated with subtractive proteomics to find antigenic proteins for designing a multi-epitope vaccine against S. pneumoniae. As prospective vaccine targets, the developed pipeline identified two antigenic proteins, i.e., penicillin-binding protein and ATP synthase subunit. Several immunoinformatics and bioinformatics resources were used to forecast T- and B-cell epitopes from specific proteins. By employing a mixture of five cytotoxic T-cell lymphocytes, six helper T-cell lymphocytes, and seven linear B-cell lymphocyte epitopes, a 392 amino acid-long vaccine was designed. To enhance immune responses, the designed vaccine was coupled with a cholera enterotoxin subunit B adjuvant. The designed vaccine was highly antigenic, non-allergenic, and stable for human usage. The stability of the vaccine with toll-like receptor-4 was evaluated by molecular docking and molecular dynamic simulation. In addition, immunological simulation was performed to test its real-world potency. The vaccine codon was then cloned in silico. Overall, this study paves the way for the development of a multi-epitope S. pneumoniae vaccine under laboratory conditions. Furthermore, the current findings warrant for the experimental validation of the final multi-epitope vaccine construct to demonstrate its immunological reinforcing capability and clinical applicability.

Threat of Antimicrobial Resistance among Pilgrims with Infectious Diseases during Hajj: Lessons Learnt from COVID-19 Pandemic.

Hajj pilgrimage is a large mass gathering global event that may facilitate the spread and emergence of various infectious diseases as well as antimicrobial resistance (AMR) in a local and global scenario. Planning and preparing for these public health issues is a challenging and complex process for the Kingdom of Saudi Arabia (KSA) health authorities. Despite multiple efforts for the prevention and treatment of infectious diseases through longtime funding in education and medical care, the prevalence of infectious disease is still high among Hajj pilgrims. The commonly observed infectious diseases during Hajj include respiratory tract infections (influenza and pneumonia), urinary tract infections and skin infections that may necessitate the use of antimicrobials. Beta-lactams are used as a first-line treatment for hospital acquired infections as well as community acquired infections due to their broad-spectrum activity. However, most of the bacterial isolates such as Staphylococcus spp., Pseudomonas spp. and E. coli are resistant to beta-lactams. Irrational use of antimicrobials, lack of infection prevention practices and suboptimal healthcare access further exacerbate the risk of spreading AMR among Hajj pilgrims. Enhanced collaboration between countries, sharing of best practices and international cooperation are crucial in addressing AMR threats among pilgrims. Consequently, robust surveillance systems for early detection and monitoring of AMR, collaboration with national as well as international healthcare agencies, effective infection prevention and control measures, public awareness and rational use of antimicrobials via antimicrobial stewardship programs are required to mitigate the risk of AMR and ensure the health and well-being of pilgrims during Hajj.

Antimicrobial Resistance Pattern of Pseudomonas aeruginosa: An 11-Year Experience in a Tertiary Care Hospital in Makkah, Saudi Arabia.

Purpose: Pseudomonas aeruginosa (P. aeruginosa) is a common causative pathogen in healthcare settings and displays increasing levels of resistance to common antimicrobial drugs. Its capacity to resist has been reported in multiple locations across the world. This study evaluates current levels of antibiotic resistance and seeks to understand antibiotic resistance patterns in the context of the clinical isolates of P. aeruginosa. Methods: All clinical isolates were cultured at 37 °C for 24 h in different media: blood sheep agar, McConkey agar, and cystine-lactose-electrolyte-deficient agar (CLED), bacterial identification and antibiotic susceptibility patterns were determined using the Vitek-2 (bioMérieux) automated system. Results: In total, there were 61,029 patient specimens, of which 5534 were identified as non-duplicated P. aeruginosa clinical isolates, most being from males aged over 60 years. The research findings revealed that the maximum antibiotic resistance associated with P. aeruginosa isolates was found in colistin (97%), which was followed by piperacillin/tazobactam (75.8%). The maximum resistance rates in P. aeruginosa isolates were found in relation to cefepime (42.7%,) which was followed by ciprofloxacin (34.3%). Conclusion: The antibiotic resistance rate during the first six years of the research period was notably higher than in the last years, due to the application of infection control protocols and strict policies to control antibiotic prescriptions in all Saudi hospitals.

Dose optimization of vancomycin in obese patients: A systematic review.

Background: Dose optimization of vancomycin plays a substantial role in drug pharmacokinetics because of the increased incidence of obesity worldwide. This systematic review was aimed to highlight the current dosing strategy of vancomycin among obese patients. Methods: This systematic review was in concordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The literature search was carried out on various databases such as Scopus, PubMed/MEDLINE, ScienceDirect and EMBASE using Keywords and MeSH terms related to vancomycin dosing among obese patients. Google Scholar was also searched for additional articles. The English language articles published after January, 2000 were included in this study. The quality of the study was assessed using different assessment tools for cohort, and case reports. Results: A total of 1,029 records were identified. After screening, 18 studies were included for the final review. Of total, twelve studies are retrospective and remaining six are case-control studies. A total of eight studies were conducted in pediatrics while remaining studies were conducted in adult population. Most of the studies reported the dosing interval every 6-8 h. Differences in target trough concentration exist with respect to target ranges. The administration of loading dose (20-25 mg/kg) followed by maintenance dose (15-25 mg/kg) of vancomycin is recommended in adult patients to target therapeutic outcomes. Moreover, a dose of 40-60 mg/kg/day appears appropriate for pediatric patients. Conclusion: The initial dosing of vancomycin based on TBW could be better predictor of vancomycin trough concentration. However, the clinical significance is uncertain. Therefore, more studies are needed to evaluate the dosing strategy of vancomycin in overweight or obese patients.

Long COVID and risk of erectile dysfunction in recovered patients from mild to moderate COVID-19.

Patients with coronavirus disease 2019 (COVID-19) were shown to have reduced serum testosterone levels compared to healthy individuals. Low testosterone levels are linked with the development of erectile dysfunction (ED). In this case-controlled study, 20 healthy controls and 39 patients with ED 3 months after recovering from mild-to-moderate COVID-19 pneumonia were studied. The patients ranged in age from 31 to 47 years. To identify early and late COVID-19 infections, real-time polymerase-chain reaction (RT-PCR) and COVID-19 antibody testing were done. The levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), free testosterone (FT), free androgenic index (FAI), and sex hormone-binding globulin (SHBG) were measured. The sexual health inventory for patients (SHIM) score was used to measure the erectile function of the patients and controls. When compared to the controls, the TT serum level in long COVID-19 (LC) patients with ED was low (p = 0.01). In contrast to controls, FT and FAI were both lower in LC patients with ED. (p = 0.001). FSH serum levels did not significantly differ (p = 0.07), but in ED patients, LH serum levels were elevated. SHIM scores were associated with low TT (p = 0.30), FT (p = 0.09), and high LH (p = 0.76) in LC patients with ED. Male patients with decreased serum levels of LH and testosterone may have hypothalamic-pituitary-gonadal axis dysfunction, which could lead to the development of LC-induced ED. Therefore, an in-depth research is necessary to confirm the causal link between COVID-19 and ED in LC patients.

Comprehensive deep mutational scanning reveals the pH induced stability and binding differences between SARS-CoV-2 spike RBD and human ACE2.

The SARS-CoV-2 spike (S) glycoprotein with its mobile receptor-binding domain (RBD), binds to the human ACE2 receptor and thus facilitates virus entry through low-pH-endosomal pathways. The high degree of SARS-CoV-2 mutability has raised concern among scientists and medical professionals because it created doubt about the effectiveness of drugs and vaccinations designed specifically for COVID-19. In this study, we used computational saturation mutagenesis approach, including structure-based free energy calculations to analyse the effects of the missense mutations on the SARS-CoV-2 S-RBD stability and the S-RBD binding affinity with ACE2 at three different pH (pH 4.5, pH 6.5, and pH 7.4). A total of 3705 mutations in the S-RBD protein were analyzed, and we discovered that most of these mutations destabilize the RBD protein. Specifically, residues G404, G431, G447, A475, and G526 were important for RBD protein stability. In addition, RBD residues Y449, Y489, Y495, Q498, and N487 were critical for the RBD-ACE2 interaction. Next, we found that the distribution of the mean stability changes and mean binding energy changes of RBD due to mutations at both serological and endosomal pH correlated well, indicating the similar effects of mutations. Overall, this computational analysis is useful for understanding the effects of missense mutations in SARS-CoV-2 pathogenesis at different pH.Communicated by Ramaswamy H. Sarma.

Microbial cellulase production and stability investigations via graphene like carbon nanostructure derived from paddy straw.

Cellulases are among the most in-demand bioprocess enzymes, and the high cost of production, combined with their low enzymatic activity, is the main constraint, particularly in the biofuels industry. As a result, low-cost enzyme production modes with high activity and stability have emerged as the primary focus of research. Here, a method for producing a graphene like carbon nanostructure (GLCNs) has been investigated utilizing paddy straw (Ps), and its physicochemical characteristics have been examined using a variety of techniques including XRD, FT-IR, SEM and TEM. Further, the pretreatment of Ps feedstock for cellulase production was done using diluted waste KOH liquid collected during the preparation of the GLCNs. To increase the production and stability of the enzyme, newly prepared GLCNs is utilized as a nanocatalyst. Using 15 mg of GLCNs, 35 IU/gds FP activity was seen after 72 h, followed by 158 IU/gds EG and 114 IU/gds BGL activity in 96 h. This nanocatalyst supported enzyme was thermally stable at 70 °C up to 15 h and exhibited stability at pH 7.0 for 10 h by holding 66 % of its half-life.

Strengthening microbial cell factories for efficient production of bioactive molecules.

High demand of bioactive molecules (food additives, antibiotics, plant growth enhancers, cosmetics, pigments and other commercial products) is the prime need for the betterment of human life where the applicability of the synthetic chemical product is on the saturation due to associated toxicity and ornamentations. It has been noticed that the discovery and productivity of such molecules in natural scenarios are limited due to low cellular yields as well as less optimized conventional methods. In this respect, microbial cell factories timely fulfilling the requirement of synthesizing bioactive molecules by improving production yield and screening more promising structural homologues of the native molecule. Where the robustness of the microbial host can be potentially achieved by taking advantage of cell engineering approaches such as tuning functional and adjustable factors, metabolic balancing, adapting cellular transcription machinery, applying high throughput OMICs tools, stability of genotype/phenotype, organelle optimizations, genome editing (CRISPER/Cas mediated system) and also by developing accurate model systems via machine-learning tools. In this article, we provide an overview from traditional to recent trends and the application of newly developed technologies, for strengthening the systemic approaches and providing future directions for enhancing the robustness of microbial cell factories to speed up the production of biomolecules for commercial purposes.

Prospects of microbial cellulase production using banana peels wastes for antimicrobial applications.

Microorganisms have been extensively studied and used to produce a wide range of enzymes and bioactive substances for a number of uses. Cellulases have also been widely used for a variety of bioprocessing and biotransformation purposes and are acknowledged as the essential enzymes for industrial applications. Broad industrial applications and huge demand essentially require mass-scale and low-cost production of cellulase enzyme. Nevertheless, low-cost production of cellulase enzyme at industrial-level finds certain issues, and this may be mainly associated with the unavailability of cheap and effective substrate to be utilized in fermentation process. In this context, cellulosic wastes are counted as one of the suitable bioresources and have been well explored for low-cost and highly efficient cellulase enzyme productions. Further, banana peels waste is considered as the high cellulose & sugar containing food wastes which is renewable and hugely available worldwide. Therefore, the present review explores the possible utilizations of banana peels as a potential food waste to be employed as substrate to produce cellulase enzymes. Availability and compositional analysis of banana peels has been explored for the microbial cellulase production based on reported studies. Further, this review explores the applications of cellulase enzymes as antimicrobial agents. Based on the available studies and their evaluation, potential limitations and future suggestions for the production of cellulase enzymes and their applications as antibacterial agents have been provided, which have a high potential for numerous biomedical applications and may offer a new opportunity for industrial utility.

Prevalence and Antibiogram Pattern of Klebsiella pneumoniae in a Tertiary Care Hospital in Makkah, Saudi Arabia: An 11-Year Experience.

Infectious disease is one of the greatest causes of morbidity and mortality worldwide, and with the emergence of antimicrobial resistance, the situation is worsening. In order to prevent this crisis, antimicrobial resistance needs to be monitored carefully to control the spread of multidrug-resistant bacteria. Therefore, in this study, we aimed to determine the prevalence of infection caused by Klebsiella pneumoniae and investigate the antimicrobial profile pattern of K. pneumoniae in the last eleven years. This retrospective study was conducted in a tertiary hospital in Makkah, Saudi Arabia. Data were collected from January 2011 to December 2021. From 2011 to 2021, a total of 61,027 bacterial isolates were collected from clinical samples, among which 14.7% (n = 9014) were K. pneumoniae. The antibiotic susceptibility pattern of K. pneumoniae revealed a significant increase in the resistance rate in most tested antibiotics during the study period. A marked jump in the resistance rate was seen in amoxicillin/clavulanate and piperacillin/tazobactam, from 33.6% and 13.6% in 2011 to 71.4% and 84.9% in 2021, respectively. Ceftazidime, cefotaxime, and cefepime resistance rates increased from 29.9%, 26.2%, and 53.9%, respectively, in 2011 to become 84.9%, 85.1%, and 85.8% in 2021. Moreover, a significant increase in the resistance rate was seen in both imipenem and amikacin, with an average resistance rate rise from 6.6% for imipenem and 11.9% for amikacin in 2011 to 59.9% and 62.2% in 2021, respectively. The present study showed that the prevalence and drug resistance of K. pneumoniae increased over the study period. Thus, preventing hospital-acquired infection and the reasonable use of antibiotics must be implemented to control and reduce antimicrobial resistance.

In silico identification of microRNAs targeting the PPARα/γ: promising therapeutics for SARS-CoV­2 infection.

The SARS-CoV-2 lifecycle is dependent on the host metabolism machinery. It upregulates the PPARα and PPARγ genes in lipid metabolism, which supports the essential viral replication complex including lipid rafts and palmitoylation of viral protein. The use of PPAR ligands in SARS-CoV-2 infection may have positive effects by preventing cytokine storm and the ensuing inflammatory cascade. The inhibition of PPARα and PPARγ genes may alter the metabolism and may disrupt the lifecycle of SARS-CoV-2 and COVID-19 progression. In the present work, we have identified possible miRNAs targeting PPARα and PPARγ in search of modulators of PPARα and PPARγ genes expression. The identified miRNAs could possibly be viewed as new therapeutic targets against COVID-19 infection.

Energetic and frustration analysis of SARS-CoV-2 nucleocapsid protein mutations.

The ongoing COVID-19 spreads worldwide with the ability to evolve in diverse human populations. The nucleocapsid (N) protein is one of the mutational hotspots in the SARS-CoV-2 genome. The N protein is an abundant RNA-binding protein critical for viral genome packaging. It comprises two large domains including the N-terminal domain (NTD) and the C-terminal domain (CTD) linked by the centrally located linker region. Mutations in N protein have been reported to increase the severity of disease by modulating viral transmissibility, replication efficiency as well as virulence properties of the virus in different parts of the world. To study the effect of N protein missense mutations on protein stability, function, and pathogenicity, we analyzed 228 mutations from each domain of N protein. Further, we have studied the effect of mutations on local residual frustration changes in N protein. Out of 228 mutations, 11 mutations were predicted to be deleterious and destabilized. Among these mutations, R32C, R191C, and R203 M mutations fall into disordered regions and show significant change in frustration state. Overall, this work reveals that by altering the energetics and residual frustration, N protein mutations might affect the stability, function, and pathogenicity of the SARS-CoV-2.

Knowledge, attitude, and perception of community pharmacists towards antimicrobial stewardship in Saudi Arabia: A descriptive cross-sectional study.

Background: Antimicrobial resistance is of paramount concern globally. Community pharmacists (CPs) play a vital role in supporting judicious antimicrobial use in the community as they are the key healthcare providers at a public level. This study aimed to assess the knowledge, attitude, and perception of CPs towards antimicrobial stewardship at the community level in Saudi Arabia. Methods: A self-administered questionnaire was distributed to all community pharmacies in four major cities of Saudi Arabia. A simple random sampling approach was used to select pharmacies in each chain. Results: A total of 520 CPs responded to the survey with a response rate of 98.6 %. Most of the pharmacists (n = 479, 92.1 %) accepted that antimicrobial stewardship programs are essential tools to limit injudicious usage of antimicrobials at the community level. Interestingly, very few (n = 105, 21 %) agreed to recommend antibiotics for common illnesses, including upper respiratory tract infections, cold, and flu without a valid prescription. Further, we found a significant role of Saudi health authorities, e.g., Saudi food & drug authorities and the Ministry of Health, in restricting antimicrobials sale in community pharmacies without a valid prescription. Conclusion: Our study findings revealed that CPs had good knowledge about antimicrobial stewardship in Saudi Arabia. The CPs play an active role in the optimization of antimicrobial therapy and infections caused by different microbes. Strict policies by the Saudi health care authority regarding the restricted dispensing of antimicrobials are welcomed by the CPs and thus may contribute toward lowering of antimicrobial resistance burden on the patients and Saudi health care authorities.

Development and validation of a predictive scoring system for in-hospital mortality in COVID-19 Egyptian patients: a retrospective study.

SARS-CoV-2 virus has rapidly spread worldwide since December 2019, causing COVID-19 disease. In-hospital mortality is a common indicator for evaluating treatment outcomes. Therefore, the developing and validating a simple score system from observational data could assist in modulating the management procedures. A retrospective cohort study included all data records of patients with positive PCR for SARS-CoV-2. The factors that associated with mortality were analyzed, then allocation of potential predictors of mortality was executed using different logistic regression modeling, subsequently scoring system was developed from the most weighted predictors. The mortality rate of patients with COVID-19 pneumonia was 28.5% and 28.74%, respectively. The most significant factors that affected in-hospital mortality were old age (> 60 years), delay in hospital admission (> 4 days), high neutrophil/lymphocyte ratio "NLR" (> 3); higher computed tomography severity score; and CT-SS (> 20), in addition to using remdesivir and tocilizumab in the treatment protocol (P < 0.001 for all). The validity of the newly performed score was significant; the AUC was 85%, P < 0.001, and its prognostic utility was good; the AUC was 75%, P < 0.001. The prognostic utility of newly developed score system (EGY.Score) was excellent and could be used to adjust the treatment strategy of highly at-risk patients with COVID-19 pneumonia.

Dose optimization of ß-lactams antibiotics in pediatrics and adults: A systematic review.

Background: ß-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of ß-lactams. Methods: Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of ß-lactams are included in this study. Results: A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used ß-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes. Conclusion: Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses.

Green Synthesis of Zn(OH)2/ZnO-Based Bionanocomposite using Pomegranate Peels and Its Application in the Degradation of Bacterial Biofilm.

The ability and potency of bacterial species to form biofilms, which show antibiotic resistance thereby avoiding antibiotic surfaces, is a major cause of prolonged infections. Various advanced approaches have been employed to prevent or damage bacterial biofilms, formed by a variety of bacterial strains, to help prevent the associated infectious disease. In this context, zinc-based nanostructures have been recognized as a potential antibiotic agent against a broad spectrum of bacterial communities. As a result, a sustainable and green synthesis method was adapted in the present study to synthesize a Zn(OH)2/ZnO-based bionanocomposite, in which aqueous extracts of waste pomegranate peels (Punica granatum) were employed as a natural bioreducing agent to prepare the bionanocomposite at room temperature. Furthermore, FT-IR, XRD, DLS, UV-Visible, PL spectroscopy, FE-SEM, and TEM were used to characterize the green route synthesized a Zn(OH)2/ZnO bionanocomposite. The average crystallite size was determined using the Scherrer relation to be 38 nm, and the DLS results indicated that the Zn(OH)2/ZnO bionanocomposite had a hydrodynamic size of 170 nm. On the other hand, optical properties investigated through UV-Vis and PL spectroscopy explored the energy bandgap between 2.80 and 4.46 eV, corresponding to the three absorption edges, and it covered the blue spectrum when the sample was excited at 370 nm. Furthermore, the impact of this green route synthesized a Zn(OH)2/ZnO bionanocomposite on the biofilm degradation efficiency of the pathogenic bacterial strain Bacillus subtilis PF_1 using the Congored method was investigated. The Congored assay clearly explored the biofilm degradation efficiency in the presence of a 50 mg/mL and 75 mg/mL concentration of the Zn(OH)2/ZnO bionanocomposite against the bacterial strain Bacillus subtilis PF_1 grown for 24 h. This study can be further applied to the preparation of bionanocomposites following a low-cost green synthesis approach, and thus prepared nanostructures can be exploited as advanced antimicrobial agents, which could be of great interest to prevent various infectious diseases.