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MXene-based (nano)materials have recently emerged as promising solutions for antibiotic photodegradation from aquatic environments, yet they are limited by scalability, stability, and selectivity challenges in practical settings. We formulated Fe 2 O 3 -SiO 2 /MXene ternary nano-photocomposites via coupled wet impregnation and sonochemistry approach for optimised tetracycline (TC) removal (the second most used antibiotic worldwide) from water using response surface methodology-central composite design (RSM-CCD). The photocatalysts containing various loading of Fe 2 O 3 /SiO 2 (5-45 wt%) on the MXene with a range of calcination temperatures (300-600 °C) via RSM optimisation were synthesised, characterised regarding crystallinity properties, surface morphology, binding energy, and light absorption capability, and analysed for TC degradation efficiency. The 25FeS/MX-450 composite among all samples demonstrated a superior efficiency in TC photocatalytic removal (98%) under optimised conditions (TC degradation: 39.75 mg/L, time: 68.28 min, pH: 5.57, catalyst dosage: 0.75 g/L). The developed surface area, with a reduced band gap due to FeS nanoparticles incorporation with improved light absorption within the visible spectrum, played a crucial role in the 25FeS/MX-450 heterostructure matrix, enhancing photogenerated carriers' separation and transportation capabilities. The tetracycline photoreduction mechanism involved electron transfer from FeS to the surface of MXene, engaging with O 2 to produce •O 2 -, attributed to the high electron mobility of MXene. Our findings for such nano-photocomposites materials can underscore the considerable potential of MXene-based nanomaterials for pharmaceutical removal from waterways., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Rising methicillin-resistant Staphylococcus aureus (MRSA) poses a global health threat, contributing to serious infections with high mortality rates. Integrons are recognized as significant genetic elements in disseminating multidrug-resistant (MDR) strains. This study focuses on assessing the prevalence of integron classes 1, 2, and 3 in S. aureus strains from four major cities in Iran., Methods: This cross-sectional study analyzed 183 S. aureus isolates from Shiraz, Tehran, Isfahan, and Yazd in Iran. The isolates were identified using specific biochemical and molecullar tests. The Kirby-Bauer disc diffusion method and microbroth dilution method were employed to determine the susceptibility of the isolates to relevant antibiotics and vancomycin, respectively. The macrolide-lincosamide-streptogramin B (MLS B ) resistance phenotype was also evaluated using the D-test. All isolates were sought for presence of the intI1, intI2, and intI3 genes., Results: Among 183 S. aureus isolates, high resistance rates were noted: 86.3% for erythromycin, 66.1% for ciprofloxacin, and 61.7% for clindamycin, while all isolates were susceptible to linezolid and vancomycin. Of the 183 isolates, 59.6% were identified as MRSA and 78.1% as MDR. According to the D-test results, 112/183 (61.2%), 29/183 (15.8%), 25/183 (13.7%), and 17/183 (9.7%) of S. aureus isolates showed constitutive resistance-MLS B , inducible resistance-MLS B , sensitive, and resistance to macrolide-streptogramin B (MS) phenotypes, respectively. The intI1 gene was found in 14 out of 183 S. aureus isolates (7.6%), while none were positive for the intI2 or intI3 genes. Notably, 11/14 (78.5%) and 13/14 (92.8%) intI1-positive isolates were MRSA and MDR, respectively., Conclusions: The distribution of MRSA and MDR S. aureus isolates in Iran seems concerning. Although the prevalence of intI1 was not as high as in prior studies, almost all S. aureus harbored the intI1 gene were MRSA and MDR., Competing Interests: Declarations. Ethics approval and consent to participate: The Ethics Committee of Jahrom University of Medical Sciences gave their approval for this study with the code number IR.JUMS.REC.1402.057. The informed consent was signed by each participant. Parents or legal guardians provided informed permission for individuals under the age of sixteen. We adhered to all of the World Medical Association Declaration of Helsinki's ethical guidelines for doing research on human subjects in medicine. Participants received assurances that the confidentiality of their data will be protected by Iran's data protection laws during processing. Consent of publication: Not applicable. Competing intrests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Carbon dots (CDs) are the research hotspots in antimicrobial applications. Also, due to the importance of calcium ions in skin regeneration, mesoporous hydroxyapatite nanoparticles (mHAP NPs) were prepared. This study aimed to evaluate the wound healing efficiency of both CD and mHAP NPs simultaneously., Methods: We doped Fluorine (F) and Copper (Cu) in CDs to prepare Cu*F-doped CDs (Cu.CDs). For the rapid release of calcium ions, a novel double-surfactant system (CTAB/F-127) was used for the synthesis of mHAP NPs. Then, we loaded both Cu.CDs and mHAP NPs simultaneously into the chitosan (CTS) gel., Results: The released calcium for mHAP NPs prepared using CTAB/F-127 was proved about 30 % higher than that prepared using only CTAB, after one day. The BET-specific surface area for mHAP NPs prepared using CTAB/F-127 was 23.17 % more than that prepared using only CTAB. This high porosity improves wound exudate absorption. Rheological analysis showed that the addition of both mHAP NPs and Cu.CD decreases the viscosity of CTS gel and thereby makes it suitable for topical applications. CTS gel containing mHAP + Cu.CDs indicated exceptional antibacterial properties even without light and/or H 2 O 2 with an inhibition zone diameter of 35 and 17 mm for E. coli and S. aureus species, respectively. CTS gel containing mHAP + Cu.CDs also showed significantly higher wound closure efficacy, greater inflammation inhibition, and better re-epithelialization than the other groups in rats with full-thickness skin wounds., Conclusion: The CTS gel containing both Cu.CD and mHAP NPs can be proposed as a new therapeutic gel for wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In order to mitigate the risk of antibiotic resistance in poultry, scientists nowadays consider plant secondary metabolites to be a major organic antibacterial substitute. This study aimed to characterize and investigate the in silico, in vitro, and in vivo antibacterial effects of peppermint essential oil (PEO) in the form of a nanoemulsion (NE), termed PEONE. Menthol as a major compound of PEO has been identified by gas chromatography and mass spectroscopy (GCMS) analysis as 32.3 %, while lower droplet size, polydispersity Index (PDI), and optimum zeta potential values depicted the stability of PEONE have been observed and validated by transmission electron microscopy (TEM) micrograph image. In silico antibacterial activity was studied by molecular docking of menthol and enrofloxacin with Topoisomerase IV protein (PDB: 1s16;) of Escherichia coli K12 MG1655 and this effect was validated by in vitro and in vivo analysis. In vitro analysis, sustained release of PEONE has been observed against Escherichia coli and Staphylococcus aureus. In this study for in vivo experiments (n = 90) day-old broiler chicks were distributed into 6 dietary treatments with 5 replicates of 3 birds per replication. Dietary treatments included 1) Negative control (basal diet), 2) Positive control (basal diet + 200 µl enrofloxacin), 3) 25 µl PEONE + basal diet, 4) 50 µl PEONE + basal diet, 5) 75 µl PEONE + basal diet, and 6) 100 µl PEONE + basal diet. Analyzed data by different statistical tools confirmed that PEONE significantly affected body weight gain (BWG) with an improved feed conversion ratio (FCR) compared to the control group. A significant increase in cecal Lactobacillus count and a decrease in total coliform was observed. Positive effects on physiological parameters, visceral organs, and meat quality characteristics have been observed. In conclusion, our experiments suggest that PEONE can be used in the broiler industry as a substitute for antibiotics to minimize bacterial resistance., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Medicinal plants have long been studied for their therapeutic benifits. The present research aims to unveil complex phytochemical profile and therapeutic properties of ethyl acetate fraction of Phlomis stewartii, an important medicinal plant. In this context, the Gas Chromatography-Mass Spectrometry (GC-MS) analysis of the fraction identified 26 compounds. Additionally, the fraction exhibited concentration dependent antioxidant activity with an IC50 value lower than the standard antioxidant butylated hydroxytoluene. The antifungal activity of the fraction examined against F. oxysporum, A. alternate, and R. solani resulted in almost complete inhibition (>90 %) of fungal growth. Furthermore, the fraction exhibited significant antibacterial potential against B. subtilus, S. aureus, E. coli, and S. dysenteriae, with inhibition zones of 18±0.22, 17±0.22, 12±0.11, and 10±0.12, respectively. Briefly, the plant extract was found to be highly potent, particularly in its antifungal action. Further studies, including natural products isolation coupled with bioassays, are recommended for promising drug candidates discovery., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

This investigation examined the potential antibacterial and antidiabetic effects of wound dressings created using electrospun nanofibers containing Ziziphus jujuba fruit extract (ZJ). These nanofibers were composed of a combination of Polycaprolactone (PCL), Polyvinyl Alcohol (PVA), and Polyhexamethylene Biguanide (PHMB). The process of creating these nanofibers involved electrospinning. The nanofiber products, which included PCL, PCL/PVA, PCL/PVA/ZJ, PCL/PVA/PHMB, and PCL/PVA/PHMB/ZJ, underwent a morphology, physicochemical, and biological assessment. Incorporating PHMB into the nanofibers enhanced the antibacterial properties, effectively preventing bacterial infections in wounds. Furthermore, including ZJ fruit extract in the nanofibers provided antidiabetic properties, making these dressings suitable for diabetic patients. The PCL/PVA/PHMB/ZJ combination exhibited exceptional healing capabilities and superior antibacterial efficiency in MRSA-infected wounds. The histological assay confirmed complete wound healing by day 14, accompanied by reduced inflammation. Based on these findings, using PCL/PVA/PHMB/ZJ as innovative wound dressings is recommended, as they can expedite wound healing while offering significant antidiabetic and antibacterial features. Ultimately, these electrospun nanofibers possess the potential to serve as advanced wound dressings with enhanced antibacterial and anti-diabetes properties.

Carbapenem-resistant organisms (CRO) represent a significant threat because of their widespread in hospital settings, difficult-to-treat, and association with high morbidity and mortality rates. Data on the efficacy of ceftazidime/avibactam (CAZ-AVI) among patients infected with CRO in Iran are lacking. Herein, we report a case of a 91-year-old man with infection caused by extensively drug-resistant ST11 co-harbouring bla NDM and bla OXA-48-like strain from seven isolates. During ICU hospitalization, 10 different antibiotics were prescribed to the patient, and CAZ-AVI was experimentally prescribed in combination with tobramycin and tigecycline to the patient for the first time in the teaching hospitals of Isfahan City. The patient died on the 56th day of hospitalization. The present study revealed that the use of CAZ-AVI should be limited to targeted therapy after susceptibility results and minimum inhibitory concentration values are available to the treating clinicians and not be used for empirical therapy of patients with an infection caused by CRO, underscoring the urgent need for stringent policies for antibiotic stewardship to preserve the activity of novel β-lactam/β-lactamase inhibitors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study synthesized zinc oxide nanoparticles (ZnO NPs) using a novel green approach, with Sida acuta leaf extract as a capping and reducing agent to initiate nucleation and structure formation. The innovation of this study lies in demonstrating the originality of utilizing zinc oxide nanoparticles for antibacterial action, antioxidant potential, and catalytic degradation of Congo red dye. This unique approach harnesses eco-friendly methods to initiate nucleation and structure formation. The synthesized nanoparticles' structure and conformation were characterized using UV-vis (λ max  = 280 nm), X-ray, atomic force microscopy, SEM, HR-TEM and FTIR. The antibacterial activity of the Nps was tested against Pseudomonas sp, Klebsiella sp, Staphylococcus aureus, and E. coli, demonstrating efficacy. The nanoparticles exhibited unique properties, with a crystallite size of 20 nm (XRD), a surface roughness of 2.5 nm (AFM), and a specific surface area of 60 m 2 /g (SEM). A Convolutional Neural Network (CNN) was effectively employed to accurately classify and analyze microscopic images of green-synthesized zinc oxide nanoparticles. This research revealed their exceptional antioxidant potential, with an average DPPH scavenging rate of 80% at a concentration of 0.05 mg/mL. Additionally, zeta potential measurements indicated a stable net negative surface charge of approximately -12.2 mV. These quantitative findings highlight the promising applications of green-synthesized ZnO NPs in healthcare, materials science, and environmental remediation. The ZnO nanoparticles exhibited catalytic capabilities for dye degradation, and the degradation rate was determined using UV spectroscopy. Key findings of the study encompass the green synthesis of versatile zinc oxide nanoparticles, demonstrating potent antibacterial action, antioxidant capabilities, and catalytic dye degradation potential. These nanoparticles offer multifaceted solutions with minimal environmental impact, addressing challenges in various fields, from healthcare to environmental remediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Cefpodoxime, a third-generation cephalosporin, is a broad-spectrum antibiotic widely used to treat acute upper respiratory tract infections (RTI). This systematic review aims to present a comprehensive view of all the available pharmacokinetics (PK) data associated with the pharmacodynamics (PD) parameters of cefpodoxime in humans., Areas Covered: The PubMed, Google Scholar, Cochrane Library, and Science Direct, were systematically searched to identify studies on the PK of cefpodoxime. Out of 746 papers, 26 articles meeting the eligibility criteria were included that have reported the PK data. The drug exposure for the patients undergoing hemodialysis was 50% lower than healthy participants. The renal clearance was almost 27% less in pediatric patients than in adults. The plasma concentrations of cefpodoxime exceeded the minimum inhibitory concentration (MIC) for 90% of skin pathogens, including Streptococcus species and Staphylococcus species (i.e.) < 1 μg/mL and 2-4 μg/mL respectively., Expert Opinion: The current study includes detailed information on clinical PK of cefpodoxime in healthy, diseased, pediatric populations as well as drug-drug interactions and drug-food interactions. Moreover, this systematic review also explicated PK/PD properties of drug with a specific impact on MIC of drug. The present review will also assist clinicians in the development of PK models for cefpodoxime.

The current research studies the synergistic effect of Cydonia oblonga and its extracted nano bio‑silver as a natural and eco-friendly agent for the improvement of three-dimensional (3D)-printed alginate wound dressings. Therefore, Cydonia oblonga extract was first prepared and silver nanoparticles were extracted from it through a green and simple method. The Cydonia oblonga and its extracted bio-based nanoparticles were then added to 3D printing alginate-based ink. Subsequently, a 3D structural extrusion printer was employed to create the porous hydrogel-based wound dressings. The morphological investigation demonstrated that using the extraction method the bio-based silver nanoparticles were successfully prepared, having an average size of 17.95 ± 4.50 nm. The Cydonia oblonga extract showed comparable antioxidant activity to the commercial antioxidant and an excellent total phenol content. In addition, the results showed the combination of Cydonia oblonga extracts/silver nanoparticles significantly improved the antibacterial performance of alginate-based bioinks. In vivo, and in vitro studies confirmed their biocompatibility and significant efficacy in the treatment of burn wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major public health problem, requiring the use of last-resort antibiotics such as colistin. However, there is concern regarding the emergence of isolates resistant to this agent. The report describes two patients with urinary tract infection (UTI) and ventilator-associated pneumonia (VAP) infection caused by CRKP strains. The first case was a 23-year-old male with UTI caused by a strain of ST16 co-harboring bla CTX-M , bla TEM , bla SHV , bla NDM , bla OXA-48-like genes. The second case was a 39-year-old woman with VAP due to hypervirulent ST337-K2 co-harboring bla SHV , bla NDM , bla OXA-48-like, iucA, rmpA2 and rmpA . The patients' general condition improved after combination therapy with colistin (plus meropenem and rifampin, respectively) and both of them recovered and were discharged from the hospital. This study highlights the necessary prevention and control steps to prevent the further spread of CRKP strains should be a priority in our hospital., (© 2024. The Author(s).)

Chronic wounds have become a growing concern as they can have a profound impact on individuals, potentially resulting in mortality. It is crucial to prevent and manage bacterial infections, particularly drug-resistant ones. Antimicrobial peptides, such as LL-37, can firmly eliminate pathogens. Additionally, the process of angiogenesis, facilitated by growth factors like VEGF, is essential for tissue repair and wound healing. To enhance the stability and bioavailability of therapeutic agents, targeted delivery strategies utilizing Chitosan-based carriers have been employed. Electrospun biopolymers in advanced wound dressings have revolutionized wound care by providing a more effective and efficient solution for promoting tissue regeneration and speeding up the healing process. The present investigation utilized Chitosan nanoparticles to encapsulate the recombinant LL37 peptide and VEGF. An in-depth investigation was carried out to analyze the biophysical and morphological traits of the LL37-CSNPs and VEGF-CSNPs. The first support layer consisted of PCL electrospun nanofiber, followed by the electrospinning of PVA/CsLL37, PVA/CsVEGF, and PVA/CsLL37/CsVEGF onto the PCL layer. An in vitro examination assessed the fabricated nanofibers' morphological, mechanical, and biological characteristics. The antimicrobial effects were tested on methicillin-resistant Staphylococcus aureus (MRSA). The in vivo experiments assessed the antibacterial and wound-healing capabilities of the nanofibers. The findings validated the continuous release of LL37 and VEGF. The composite material PCL/PVA/CsLL37/CsVEGF demonstrated potent bactericidal and antioxidant characteristics. The cytotoxic assay demonstrated the biocompatibility of the fabricated nano mats and their potential to accelerate fibroblast cell proliferation. The efficacy of PVA/CsLL37/CsVEGF in promoting wound healing was confirmed through an in vivo wound healing assay. Furthermore, the histological analysis provided evidence of faster epidermal formation and improved antibacterial activity in wounds covered with PVA/CsLL37/CsVEGF. Adding LL37 and VEGF to the composite material improves the immune response and promotes blood vessel formation, accelerating wound healing and decreasing inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mastitis is considered one of the most widespread infectious disease of cattle and buffaloes, affecting dairy herds. The current study aimed to characterize the Staphylococcus aureus isolates recovered from subclinical mastitis animals in Pothohar region of the country. A total of 278 milk samples from 17 different dairy farms around two districts of the Pothohar region, Islamabad and Rawalpindi, were collected and screened for sub clinical mastitis using California Mastitis Test. Positive milk samples were processed for isolation of Staphylococcus aureus using mannitol salt agar. The recovered isolates were analyzed for their antimicrobial susceptibility and virulence genes using disc diffusion and PCR respectively. 62.2% samples were positive for subclinical mastitis and in total 70 Staphylococcus aureus isolates were recovered. 21% of these isolates were determined to be methicillin resistant, carrying the mecA gene. S. aureus isolates recovered during the study were resistant to all first line therapeutic antibiotics and in total 52% isolates were multidrug resistant. SCCmec typing revealed MRSA SCCmec types IV and V, indicating potential community-acquired MRSA (CA-MRSA) transmission. Virulence profiling revealed high prevalence of key genes associated with adhesion, toxin production, and immune evasion, such as hla, hlb, clfA, clfB and cap5. Furthermore, the Panton-Valentine leukocidin (PVL) toxin, that is often associated with recurrent skin and soft tissue infections, was present in 5.7% of isolates. In conclusion, the increased prevalence of MRSA in bovine mastitis is highlighted by this study, which also reveals a variety of virulence factors in S. aureus and emphasizes the significance of appropriate antibiotic therapy in combating this economically burdensome disease., (© 2024. The Author(s).)

Background: Spontaneous bacterial peritonitis (SBP) is a fatal complication of ascites fluid infection. The causes of SBP in children differ from those in adults, and these bacteria are frequently resistant to antibiotics. Therefore, this study investigated the clinical findings, bacterial etiology, and antimicrobial resistance in children with SBP., Methods: This study was conducted on all new pediatric ascites patients, who were admitted to the Department of Pediatric Gastroenterology, Namazi Hospital, affiliated with Shiraz University of Medical Sciences (Shiraz, Iran) from 2021 to 2022. Required data such as demographic information, and clinical information such as complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Gram staining, blood culture by Automated Blood Culture System (BACTEC), and antibiogram of ascites fluids by disc diffusion method were all collected. Finally, the data were statistically analyzed using SPSS Software (version 26). Besides, the t test, Fisher's exact, Mann-Whitney, and Chi square tests were used for data analysis. In all tests, P≤0.05 was considered statistically significant., Results: The present study examined 62 children with ascites of which 18 (29%) had SBP. The median (IQR) age was 2.5 (8.1) years. Thirty-four (54.8%) of the participants were girls. Abdominal pain was the most common clinical manifestation in patients (54%), and there was a significant association between abdominal pain and SBP (P=0.02). In 12 positive ascites fluid cultures, coagulase-negative staphylococci had the highest frequency (25%), followed by Escherichia coli (16.7%). Third-generation cephalosporins had a 25% sensitivity in the total positive cultures. This sensitivity was 33.3% for Gram-negative cultures and 16.6% for Gram-positive cultures., Conclusion: Although third-generation cephalosporins are recommended as the primary antibiotic for the empirical treatment of SBP, the present study found high bacterial resistance. Finally, empirical therapy should be tailored to each region's bacterial resistance features., Competing Interests: Mohammad Hadi Imanieh and Gholamreza Pouladfar, as the Editorial Board Members, were not involved in any stage of handling this manuscript. A team of independent experts was formed by the Editorial Board to review the article without their knowledge., (Copyright: © Iranian Journal of Medical Sciences.)

Cefaclor is a bactericidal antibiotic recommended for treating diverse types of infections. This review aims to comprehensively assess the pharmacokinetic (PK) data on cefaclor in humans.Google Scholar, PubMed, Cochrane Library, and EBSCO databases were systematically performed to identify all the relevant studies containing at least one reported PK parameter of cefaclor.Cefaclor shows the linear PK profile as the area under the plasma concentration-time curve from 0 to t (AUC 0-t ) and maximum plasma concentration (C max ) increase in a dose-dependent manner. The AUC 0-t of cefaclor in the rice diet was found to be higher than that of bread food, i.e. 19.9 ± 2.6 ug/ml.hr vs 15.4 ± 4 ug/ml.hr. The AUC in paediatrics during the fed state was significantly higher compared to that in adults. Patients with renal impairments showed a C max 2.2 times higher than that of normal subjects. A significant increase in C max was depicted among individuals following a vegetarian diet in comparison with the non-vegetarian diet. Moreover, cefaclor exhibits time-dependent killing above the minimum inhibitory concentration (MIC < 2 ug), favouring its use in treating infections caused by specific pathogens.This systematic review summarises all the reported PK parameters of cefaclor in healthy and diseased subjects in the literature. This data can help practitioners in adjusting cefaclor doses among different diseases and populations to avoid drug interactions and adverse effects.

This work aimed at tailoring of different properties of antibacterial drug delivery Ca-phosphate cements by incorporation of bioactive glass (BG). The cements were prepared from beta-tricalcium phosphate cement (β-TCP) and BG based on 50 SiO 2 -20 CaO-15 Na 2 O-7 B 2 O 3 -4 P 2 O 5 -4 Al 2 O 3  wt% with different percentages of BG [5, 10, 15, and 20% (w/w)]. The composite cements were characterized by XRD, FTIR, and TEM. Moreover, in vitro bioactivity and biodegradation were evaluated in the simulated body fluid (SBF) at 37 °C. In addition, physical properties and mechanical strength were determined. Also, the effect of glass addition on the drug release profile was examined using gentamicin. Finally, the antimicrobial activity was studied against Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia bacteria, one unicellular fungal strain (Candida albicans), and one multicellular fungal strain (Mucor racemosus). The results showed that after soaking in SBF, the compression strength values ranged from 14 to 36 MPa, the bulk densities and porosities were within 1.35 to 1.49 g/cm 3 and 51.3 to 44.71%, respectively. Furthermore, gentamicin was released in a sustained manner, and BG decreased the released drug amount from ~ 80% (in pure β-TCP) to 47-53% in the composite cements. A drug release profile that is sustained by all samples was achieved. The antimicrobial test showed good activity of gentamicin-conjugated cements against bacteria and fungi used in this study. Additionally, cytotoxicity results proved that all samples were safe on MG-63 cells up to 50 µg/mL with no more than 7-12% dead cells. From the view of the physico-mechanical properties, bioactivity, biodegradation, and drug release rate, 20BG/β-TCP sample was nominated for practical bone grafting material, where it showed appropriate setting time and a relatively high mechanical strength suitable for cancellous bone., (© 2024. The Author(s).)

Background: Whether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear., Methods: In this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was assessed., Results: A total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group. At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P = 0.004). An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group., Conclusions: Among patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up. (Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640; EUDRA Clinical Trials number, 2016-001054-17.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Gram-negative bloodstream infections (GN-BSIs) are a significant clinical challenge. The utility of follow-up blood cultures (FUBCs) in GN-BSIs and their impact on mortality and antibiotic consumption are areas of debate. This study aimed to evaluate the effect of FUBCs on mortality and antibiotic consumption in patients with GN-BSIs., Methods: This single-center, retrospective study was conducted in aged > 18 years of patients with GN-BSIs. FUBC was defined as a blood culture performed 2-7 days after the first blood culture. Patients were grouped as FUBC and no FUBC and compared. A 1:1 match analysis was performed between the groups according to the SOFA score. The matched subgroup was compared for mortality risk factors with logistic regression models. The two groups were compared for the duration of effective antibiotic therapy and total antibiotic consumption (days of therapy per 1000 patient days (DOT/1000 PD))., Results: FUBC was performed in 564 (69.4%) of 812 patients. Persistent, positive and negative FUBC rates were 7.9%, 14%, and 78%, respectively. The frequency of persistent GN-BSI in patients with appropriate antibiotic therapy was 3.9%. SOFA score (OR:1.33; 95% CI, 1.23-1.44), Charlson comorbidity index score (OR:1.18; 95% CI, 1.08-1.28), hospital-acquired infections (OR:1.93; 95% CI, 1.08-3.46) and carbapenem-resistant GN-BSI (OR: 2.92; 95% CI, 1.72-4.96) were independent risk factors for mortality. No relationship was found between FUBC and mortality (p > 0.05). Duration of effective antibiotic therapy (10(4-16) vs. 15(9-20), p < 0.001) and DOT/1000 PD (1609 (1000-2178) vs. 2000 (1294-2769), p < 0.001) were longer in the FUBC group., Conclusion: Routine FUBC should not be recommended because of the low prevalence of persistent infections in patients under appropriate antibiotic therapy and FUBC increases antibiotic consumption., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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Actions that are taken to preserve effective antibacterial agents and eliminate transmission of resistant organisms are crucial to prevent a catastrophic postantibiotic era. In this systematic review, we searched and appraised relevant texts and expert opinions to determine effective strategies to tackle bacterial resistance worldwide. We considered expert opinions, consensus, current discourses, comments, assumptions or assertions and discussion papers published in English. We searched following databases for expert opinion-based literature: MEDLINE, CINAHL, ISI Web of Knowledge, SCOPUS, Cochrane Central Register of Controlled Trials and World Health Organization (WHO). We extracted the textual data from texts using a standardised data extraction tool. Textual pooling was not possible, so the conclusions were presented in a narrative form. Eighteen texts were included in this review. The findings show that, the most repeated policies and strategies include implementing and strengthening bacterial resistance surveillance, developing national guidelines, improving public awareness; enhancing home and everyday life hygiene; improving prescribing patterns, improving laboratories capacity, promoting innovation and research in new drugs and technology and strengthening coordination. This review systematically gathered strategies that were recommended by textual publications. To our knowledge, this was the first systematic review of text and opinion in the field of bacterial resistance. These results can be used by policymakers, hospital managers, and governments, alongside the results of quantitative and qualitative systematic reviews., (© 2023 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Cefixime is an antibiotic from the cephalosporin class used to treat various bacterial infections. The purpose of performing this review is to thoroughly evaluate the pharmacokinetic (PK) data on cefiximeFive databases were systematically searched to identify studies on the PK of cefixime.A total of 38 articles meeting the eligibility criteria were included that provide data on concentration-time profiles or PK parameters such as peak plasma and serum concentration ( C max ), area under the curve (AUC), clearance (CL), and time to reach C max ( t max ). A dose-dependent increase in AUC and C max of cefixime was depicted in healthy volunteers. The clearance of cefixime decreased according to the degree of renal insufficiency among haemodialysis patients. A significant difference in CL was found in comparing fasted and fed states. A biphasic decline in serum concentrations of cefixime was reported when it was taken without probenecid.This review compiles all the reports on the PK of cefixime in healthy and really impaired patients; the summarised information can be used to optimise cefixime dosing in different disease states. Moreover, cefixime has increased time above MIC value suggesting that it may be an effective treatment for infections caused by certain pathogens.

Introduction: Rational antibiotic prescription (RAP) refers to the purposeful and appropriate antibiotic prescription with correct dose and course to produce the most possible benefits and less possible side effects. Identification and management of the barriers to RAP can help promote RAP. The aim of the study was to explore the barriers to RAP in Iran., Methods: This descriptive qualitative study was conducted in 2021 on 46 physicians (including general physicians, specialists, and subspecialists), pharmacologists, microbiologists, and nurses. Participants were purposefully selected from five specialty and subspecialty hospitals in Isfahan, Iran, and the Treatment Administration of Isfahan University of Medical Sciences, Isfahan, Iran. Data were collected via semi-structured interviews and were analyzed via conventional content analysis., Results: The barriers to RAP in Iran came into sixteen subcategories and four main categories, namely physicians' limited professional competence (with six subcategories), poor informational and functional resources (with four subcategories), ineffective supervision of RAP (with three subcategories), and inappropriate context for RAP (with three subcategories). The subcategories of these categories were physicians' limited professional knowledge, physicians' poor attitude towards RAP, physicians' routine-based practice instead of evidence-based practice, physicians' limited accountability, physicians' fear over the legal consequences of not prescribing antibiotics, physicians' financial motives, limited access to quality educational materials, poor in-service training for physicians, lack of culturally appropriate guidelines, inefficiency of the stewardship committee, limited supervision of physicians' performance, ineffective managerial supervision, limited supervision of sampling for antimicrobial susceptibility testing, sociocultural factors contributing to irrational antibiotic prescription, poor adherence of insurance companies to their financial commitments, and financial incentives of pharmaceutical companies for physicians., Conclusion: The barriers to RAP are different and complex and include physician-related, resource-related, supervision-related, and contextual factors. Physicians with limited professional competence, limited access to resources, and limited supervision will have problems in RAP. Effective management of the barriers to RAP can promote RAP and minimize irrational antibiotic prescription and its consequences, chiefly antimicrobial resistance., (© 2022. The Author(s).)

Nanotechnology has become a dire need of the current era and the green synthesis of nanoparticles offers several advantages over other methods. Nanobiotechnology is an emerging field that contributes to many domains of human life, such as the formulation of nanoscale drug systems or nanomedicine for the diagnosis and treatment of diseases. Medicinal plants are the main sources of lead compounds, drug candidates and drugs. This work reports the green synthesis of Ag nanoparticles (AgNPs) using the aqueous bark extract of Zanthozylum armatum, which was confirmed by a UV absorption at 457 nm. XRD analysis revealed an average size of 18.27 nm and SEM showed the particles' spherical shape, with few irregularly shaped particles due to the aggregation of the AgNPs. FT-IR revealed the critical functional groups of phytochemicals which acted as reducing and stabilizing agents. The bark extract showed rich flavonoids (333 mg RE/g) and phenolic contents (82 mg GAE/g), which were plausibly responsible for its high antioxidant potency (IC 50 = 14.61 µg/mL). Extract-loaded AgNPs exhibited the highest but equal inhibition against E. coli and P. aeruginosa (Z.I. 11.0 mm), whereas methanolic bark extract inhibited to a lesser extent, but equally to both pathogens (Z.I. 6.0 mm). The aqueous bark extract inhibited P. aeruginosa (Z.I. 9.0 mm) and (Z.I. 6.0 mm) E. coli. These findings-especially the biosynthesis of spherical AgNPs of 18.27 nm-provide promise for further investigation and for the development of commercializable biomedical products.

Introduction: Antibiotic-associated diarrhea (AAD) is a major hospital problem and a common adverse effect of antibiotic treatment. The aim of this study was to investigate the prevalence of the most important bacteria that cause AAD in hospitalized patients., Materials and Methods: PubMed, Web of Science and Scopus databases were searched using multiple relevant keywords and screening carried out based on inclusion/exclusion criteria from March 2001 to October 2021. The random-effects model was used to conduct the meta-analysis., Results: Of the 7,377 identified articles, 56 met the inclusion criteria. Pooling all studies, the prevalence of Clostridioides (Clostridium) difficile, Clostridium perfringens, Klebsiella oxytoca, and Staphylococcus aureus as AAD-related bacteria among hospitalized patients were 19.6%, 14.9%, 27%, and 5.2%, respectively. The prevalence of all four bacteria was higher in Europe compared to other continents. The highest resistance of C. difficile was estimated to ciprofloxacin and the lowest resistances were reported to chloramphenicol, vancomycin, and metronidazole. There was no or little data on antibiotic resistance of other bacteria., Conclusions: The results of this study emphasize the need for a surveillance program, as well as timely public and hospital health measures in order to control and treat AAD infections., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The production of alternative novel antimicrobial agents is considered an efficient way to cope with multidrug resistance among pathogenic bacteria. E50-52 and Ib-AMP4 antimicrobial peptides (AMPs) have illustrated great proven antibacterial effects. The aim of this study was recombinant production of these AMPs and investigation of their synergistic effects on methicillin-resistant Staphylococcus aureus (MRSA)., Method: At first, the codon optimized sequences of the Ib-AMP4 (UniProt: 024006 (PRO&#95;0000020721), and E50-52 (UniProtKB: P85148) were individually ligated into the pET-32α vector and transformed into E. coli. After the optimization of production and purification steps, the MIC (Minimum inhibitory concentration), time kill and growth kinetic tests of recombinant proteins were determined against MRSA. Finally, the in vivo wound healing efficiency was tested., Results and Conclusion: The recorded MIC of recombinant Trx-Ib-AMP4, Trx-E50-52 against MRSA bacterium were 0.375 and 0.0875 mg/mL respectively. The combination application of the produced AMPs by the checkerboard method confirmed their synergic activity. The results of the time-kill showed sharply decrease of the number of viable cells with over five time reductions in log 10  CFU/mL by the combination of Trx-E50-52 and Trx-IbAMP4 at 2 × MIC within 240 min. The growth kinetic results confirmed the combination of Trx-E50-52 and Trx-IbAMP4 had much greater success in the reduction of over 50 % of MRSA suspensions' turbidity within the first hour. Wound healing assay and histological analysis of infected mice treated with Trx-Ib-AMP4 or Trx-E50-52 compared with those treated with a combination of Trx-Ib-AMP4 and Trx-E50-52 showed significant synergic effects., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Today, bacterial cellulose has received a great deal of attention for its medical applications due to its unique structural properties such as high porosity, good fluid uptake, good strength, and biocompatibility. This study aimed to fabricate and study bacterial cellulose/graphitic carbon nitride/nettles/trachyspermum nanocomposite by immersion and PVA/BC/g-C 3 N 4 /nettles/trachyspermum nanofiber by electrospinning method as a wound dressing. The g-C 3 N 4 and g-C 3 N 4 solution were synthesized and then were characterized using Fourier transform infrared, X-ray diffraction, Zeta Potential, and scanning electronic microscope analyzes. Also, the antibacterial properties of the synthesized materials were proved by gram-positive and gram-negative bacteria using the minimum inhibitory concentration method. Besides, the toxicity, migration, and cell proliferation results of the synthesized materials on NIH 3T3 fibroblasts were evaluated using MTT and scratch assays and showed that the BC/PVA/g-C 3 N 4 /nettles/trachyspermum composite not only had no toxic effect on cells but also contributed to cell survival, cell migration, and proliferation has done. To evaluate the mechanical properties, a tensile strength test was performed on PVA/BC/g-C 3 N 4 /nettles/trachyspermum nanofibers, and the results showed good strength of the nanocomposite. In addition, in vivo assay, the produced nanofibers were used to evaluate wound healing, and the results showed that these nanofibers were able to accelerate the wound healing process so that after 14 days, the wound healing percentage showed 95%. Therefore, this study shows that PVA/BC/g-C 3 N 4 /nettles/trachyspermum nanofibers effectively inhibit bacterial growth and accelerate wound healing., (© 2021 American Institute of Chemical Engineers.)

Background: Carbapenemase-producing Klebsiella pneumoniae (CP-KP) is becoming extensively disseminated in Iranian medical centers. Colistin is among the few agents that retains its activity against CP-KP. However, the administration of colistin for treatment of carbapenem-resistant infections has increased resistance against this antibiotic. Therefore, the identification of genetic background of co-carbapenem, colistin-resistance K. pneumoniae (Co-CCRKp) is urgent for implementation of serious infection control strategies., Methods: Fourteen Co-CCRKp strains obtained from routine microbiological examinations were subjected to molecular analysis of antimicrobial resistance (AMR) using whole genome sequencing (WGS)., Results: Nine of 14 K. pneumoniae strains belonged to sequence type (ST)-11 and 50% of the isolates had K-locus type 15. All strains carried bla OXA-48 except for P26. bla NDM-1 was detected in only two plasmids associated with P6 and P26 strains belonging to incompatibility (Inc) groups; IncFIB, IncHI1B and IncFII. No bla KPC , bla VIM and bla IMP were identified. Multi-drug resistant (MDR) conjugative plasmids were identified in strains P6, P31, P35, P38 and P40. MIC colistin of K. pneumoniae strains ranged from 4 to 32 µg/ml. Modification of PmrA, PmrB, PhoQ, RamA and CrrB regulators as well as MgrB was identified as the mechanism of colistin resistance in our isolates. Single amino acid polymorphysims (SAPs) in PhoQ (D150G) and PmrB (R256G) were identified in all strains except for P35 and P38. CrrB was absent in P37 and modified in P7 (A200E). Insertion of ISKpn72 (P32), establishment of stop codon (Q30*) (P35 and P38), nucleotides deletion (P37), and amino acid substitution at position 28 were identified in MgrB (P33 and P42). None of the isolates were positive for plasmid-mediated colistin resistance (mcr) genes. P35 and P38 strains carried iutA, iucD, iucC, iucB and iucA genes and are considered as MDR-hypervirulent strains. P6, P7 and P43 had ICEKp4 variant and ICEKp3 was identified in 78% of the strains with specific carriage in ST11., Conclusion: In our study, different genetic modifications in chromosomal coding regions of some regulator genes resulted in phenotypic resistance to colistin. However, the extra-chromosomal colistin resistance through mcr genes was not detected. Continuous genomic investigations need to be conducted to accurately depict the status of colistin resistance in clinical settings., (© 2021. The Author(s).)

Members of Hymenochaetaceae fungi are among well-known macromycetes with various medicinal properties. The aim of this study was to investigate the biological activities of Phellinus tuberculosus and Fuscoporia ferruginosa collected in Iran. The antimicrobial, antioxidant, and cytotoxic activities of the two species were examined, and their phenolic and polysaccharide contents were quantified. Compounds were characterized by HPLC-DAD chromatography and LC-ESI-MS/MS spectroscopy. According to our results, the antibacterial and antioxidant effects of P. tuberculosus extracts were stronger than F. ferruginosa. Also, the effect of hydroalcoholic extracts was higher than the aqueous extract. Gram-positive bacteria were more sensitive to all extracts, especially Streptococcus mutans with a MIC of 0.7 mg/mL and MBC of 6.25 mg/mL. HPLC-DAD analyses detected gallic acid, caffeic acid, and syringic acid in both fungi. The LC-ESI-MS/MS confirmed the detected compounds in HPLC-DAD and showed the presence of several phenolic compounds such as phellifuropyranone, phelligridin, and hispidin, besides others. This study showed that F. ferruginosa and P. tuberculosus are potent medicinal fungi with antibacterial and antioxidant properties, with no toxic effect on normal HDF cells, and possess various bioactive compounds including styrylpyrone-type phenols with well-known bioactivities., (© 2021. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

A composite based on hydroxyapatite (HA) and chitosan (CS) combined with ciprofloxacin (CIP) was formulated by the solid-liquid mixing method. The optimization of the solid to the liquid ratio and the use of chitosan in a small amount (≤5 wt%) promoted the preparation of stable and rigid monoliths. A synergistic effect of CS and CIP contents on the compressive strength of the CIP-loaded composite was evidenced. The compressive strength of the fabricated biocomposite ranged in values from 1 to 6 MPa, comparable to those reported for cancellous bone. The improvement of the mechanical properties with the increase of the rate of organic components was correlated with the diminution of the surface area and the reduction in the pore volume of the specimens. On the other hand, the in vitro release experiments of the antibiotic indicated a sustained and controlled release of CIP over 10 days. Moreover, in vitro antibacterial tests performed on the biocomposite HA-CS5-CIP showed significant inhibition of Staphylococcus aureus and Escherichia coli pathogens. According to the showed results, the formulated composite with three-phase components could be a promising material for bone repair and local antibiotic release for the treatment of bone infections., (© 2021 Wiley Periodicals LLC.)

Based on the promising biomedical developments in wound healing strategies, herein, a new nanobiocomposite scaffold was designed and presented by incorporation of carboxymethyl cellulose hydrogels prepared using epichlorohydrin as a cross-linking agent (CMC hydrogel), a natural silk fibroin (SF) protein, and magnesium hydroxide nanoparticles (Mg(OH) 2 NPs). Biological evaluation of the CMC hydrogel/SF/Mg(OH) 2 nanobiocomposite scaffold was conducted via in vitro cell viability assays and in vivo assays, red blood cell hemolysis, and antibiofilm assays. Considering the cell viability percentage of Hu02 cells (84.5%) in the presence of the prepared nanobiocomposite after 7 days, it was indicated that this new nanoscaffold was biocompatible. The signs of excellent hemocompatibility and the high antibacterial activity were observed due to the low-point hemolytic effect (8.3%) and high-level potential in constraining the P. aeruginosa biofilm formation with a low OD value (0.13). Moreover, in vivo wound healing assay results indicated that the wound healing method was faster in mice treated with the prepared nanobiocomposite scaffold (82.29%) than the control group (75.63%) in 12 days. Apart from the structural characterization of the CMC hydrogel/SF/Mg(OH) 2 nanobiocomposite through FTIR, EDX, FESEM, and TG analyses, compressive mechanical tests, contact angle, porosity, and swelling ratio studies indicated that the combination of the CMC hydrogel structure with SF protein and Mg(OH) 2 NPs could significantly impact Young's modulus (from 11.34 to 10.14 MPa), tensile strength (from 299.35 to 250.78 MPa), elongation at break (12.52 to 12.84%), hydrophilicity, and water uptake capacity (92.5%).

The present research paper reports the convenient synthesis, successful characterization, in vitro antibacterial, antifungal, antioxidant potency and biocompatibility of N-acyl-morpholine-4-carbothioamides (5a-5j). The biocompatible derivatives were found to be highly active against the tested bacterial and fungal strains. Moreover, some of the screened N-acyl-morpholine-4-carbothioamides exhibited excellent antioxidant potential. Docking simulation provided additional information about possibilities of their inhibitory potential against RNA. It has been predicted by in silico investigation of the binding pattern that compounds 5a and 5j can serve as the potential surrogate for design of novel and potent antibacterial agents. The results for the in vitro bioassays were promising with the identification of compounds 5a and 5j as the lead and selective candidate for RNA inhibition. Results of the docking computations further ascertained the inhibitory potential of compound 5a. Based on the in silico studies, it can be suggested that compounds 5a and 5j can serve as a structural model for the design of antibacterial agents with better inhibitory potential. Binding mode of compound 5j inside the active site of RNA in 3D space. 5j displayed highest antibacterial potential than the reference drug ampicillin with ZOI 10.50 mm against Staphylococcus aureus. 5j also displayed highest antifungal potential than the reference drug amphotericin B with ZOI 18.20 mm against Fusarium solani.

In recent years, applying various wound dressings with antibacterial activities to expedite tissue repair stages has gained remarkable attention. The intertwined three-dimensional structure of nanofibers provides unique spaces for carrying drugs and repair agents during the wound healing process. In this research, a carbon quantum dot (CQD)/silica nanoparticle (Si NP)/silk fibroin (SF) nanocomposite was synthesized, and two novel wound dressings, a BC-CQD/Si NP/SF nanocomposite and a PVA-CQD/Si NP/SF nanofiber, were prepared by Spray Printing and Electrospinning methods and successfully characterized. The water-uptake capacity of the BC-CQD/Si NP/SF nanocomposite has been optimized to evaluate its swelling behavior. To determine the antibacterial effects of the synthesized materials both MIC and Optical Density (OD) methods were performed, and the results imply that materials have high antibacterial activity and could successfully inhibit the growth of both S. aureus and E. coli bacteria. Cell toxicity, viability, and proliferation on NIH 3T3 fibroblast cells with the MTT assay have proved that the CQD/Si NP/SF nanocomposite not only has no toxicity but also can accelerate cell viability and proliferation. To assess the effect of the CQD/Si NP/SF nanocomposite on cell migration and in vitro wound healing scratch, a wound assay was performed, and the nanocomposite exhibits the ability to promote wound healing. The PVA-CQD/Si NP/SF nanofiber was used to investigate wound healing in an animal model. The results show that the PVA-CQD/Si NP/SF nanofiber effectively accelerates the skin and hair follicle regeneration. Therefore, the PVA-CQD/Si NP/SF nanofiber is a promising wound dressing for inhibiting bacterial growth and promoting skin wound repair and hair regeneration.

Herein, a novel nanobiocomposite scaffold based on modifying synthesized cross-linked terephthaloyl thiourea-chitosan hydrogel (CTT-CS hydrogel) substrate using the extracted silk fibroin (SF) biopolymer and prepared Mg(OH) 2 nanoparticles was designed and synthesized. The biological capacity of this nanobiocomposite scaffold was evaluated by cell viability method, red blood cells hemolytic and anti-biofilm assays. According to the obtained results from 3 and 7 days, the cell viability of CTT-CS/SF/Mg(OH) 2 nanobiocomposite scaffold was accompanied by a considerable increment from 62.5 to 89.6% respectively. Furthermore, its low hemolytic effect (4.5%), and as well, the high anti-biofilm activity and prevention of the P. aeruginosa biofilm formation confirmed its promising hemocompatibility and antibacterial activity. Apart from the cell viability, blood biocompatibility, and antibacterial activity of CTT-CS/SF/Mg(OH) 2 nanobiocomposite scaffold, its structural features were characterized using spectral and analytical techniques (FT-IR, EDX, FE-SEM and TG). As well as, given the mechanical tests, it was indicated that the addition of SF and Mg(OH) 2 nanoparticles to the CTT-CS hydrogel could improve its compressive strength from 65.42 to 649.56 kPa.

A solid-phase extraction method combined with deep eutectic solvent-based dispersive liquid-liquid microextraction has been developed for the extraction of three antibiotics in honey samples prior to their determination by ion mobility spectrometry. In this method, first, a multiwall carbon nanotube/urea-formaldehyde nanocomposite was synthesized using co-precipitation polymerization method and then it was used as a sorbent for the analytes extraction from the samples. After that the adsorbed analytes were eluted from the sorbent using a water-miscible organic solvent. The collected elution solvent was mixed with tetrabutylammonium chloride:butanol deep eutectic solvent and the mixture was applied in the following microextraction method. The method provided low limits of detection and quantification in the ranges of 0.32-0.86 and 1.1-2.9 ng/g, respectively. The method had a proper repeatability expressed as relative standard deviation less than or equal to 9.1%. The validated method was successfully performed on different honey samples obtained from different producers., (© 2020 Wiley-VCH GmbH.)

Lipopolysaccharide (LPS) is a toxic and immunogenic agent for human. Additionally, LPS is a good target for some antimicrobial compounds, including antimicrobial peptides (AMPs). LPS-binding peptides (LBPs) can recognize and neutralize LPS. Rabbit and human cathelicidins are AMPs with LPS-binding activity. In this study, we designed and synthesized two new truncated LBPs from rabbit and human CAP18 peptides by in silico methods. After synthesis of peptides, the antimicrobial properties and LPS-binding activity of these peptides were evaluated. The parental rabbit and human CAP18 peptides were selected as positive controls. Next, the changes in the secondary structure of these peptides before and after treatment with LPS were measured by circular dichroism (CD). Human cytotoxicity of the peptides was evaluated by MTT and red blood cells (RBCs) hemolysis assays. Finally, field emission scanning electron microscopy (FE-SEM), confocal microscopy, and flow cytometry were performed to study the action mechanism of these peptides. Results indicated that the hCap18 and rCap18 had antibacterial activity (at a MIC of 4-128 μg/mL). The results of the quantitative LAL test demonstrated that LPS-binding activity of hCap18 peptide was better than rCap18, while rCap18 peptide had better antimicrobial properties. Furthermore, rCap18 had less cytotoxicity than hCap18. However, both peptides were nontoxic for normal human skin fibroblast cell in MIC range. In conclusion, rCap18 has good antibacterial properties, while hCap18 can be tested as a diagnostic molecule in our future studies.

Study Design: Retrospective database review., Objective: The aim of this study was to determine the incidence of Clostridium difficile infection (CDI) within 90 days following elective spine surgery; examine risk factors associated with its development; and evaluate the impact of CDI on postoperative outcomes., Summary of Background Data: Although previous studies provided valuable insight into the rate of CDI following spine surgery and associated risk factors, to date no study has evaluated the role preoperative antibiotics use plays in the development of CDI, as well as its impact on 90-day outcomes., Methods: A retrospective database review of Humana patients ages 20 to 84 years who underwent elective spine surgery between 2008 and 2016 was conducted. Following exclusion criteria, the population was divided into patients who developed CDI within 90 days of surgery and those who did not. All risk factors and outcomes were analyzed using multivariate regression., Results: A total of 63,667 patients met study criteria. Ninety-day incidence of CDI was 0.68%. Notable medical risk factors (P < 0.05) included preoperative fluoroquinolone use (odds ratio [OR] 1.40), advanced age (OR 1.86), chronic kidney disease stage I/II (OR 1.76) and III-V (OR 1.98), decompensated chronic liver disease (OR 3.68), and hypoalbuminemia (OR 3.15). Combined anterior-posterior cervical (OR 2.74) and combined anterior-posterior lumbar (OR 2.43) approaches and procedures spanning more than eight levels (OR 3.99) were associated with the highest surgical risk (P < 0.05) of CDI. CDI was associated with a 12.77-day increase in length of stay (P < 0.05) and increased risk of readmission (OR 6.08, P < 0.05) and mortality (OR 8.94, P < 0.05)., Conclusion: Following elective spine surgery, CDI increases risk of readmission and mortality. In addition to preoperative fluoroquinolone use, novel risk factors associated with the highest risk of CDI included decompensated chronic liver disease, posterior approaches, and multilevel involvement. Perioperative optimization of modifiable risk factors may help to prevent occurrence of CDI., Level of Evidence: 3.

In this study, a nanobiocomposite scaffold was fabricated by combining sodium alginate, polyvinyl alcohol, silk fibroin and magnesium hydroxide nanorods. The structural characteristics and properties of the scaffold were identified by field emission scanning electron microscope (FE-SEM), thermogravimetric analysis (TGA), Fourier-transformed infrared (FT-IR) and energy dispersive X-Ray (EDX) analyses. To introduce the application, biocompatibility, mechanical properties and biological activity of the scaffold were obtained. The composite was found to have high porosity, no cytotoxicity, excellent cellular adaptation, and most importantly Mg(OH) 2 nanorod had antibacterial activity and inhibited the growth of bacteria. In addition, silk fibroin and alginate increased the scaffold strength due to mechanical tests. Hemolytic assay and cell metabolic activity of this novel nanobiocomposite showed that the hemolytic effect was less than 8% and about 92% of cells survived. Due to considerable biological activities and acceptable mechanical properties, the mentioned nanobiocomposite can be considered as a scaffold for possible use in wound dressing, tissue engineering and drug delivery systems., Competing Interests: Declaration of competing interest The authors whose names are listed in this article have no competing interests or other conflicts of interest that might be perceived to influence the results and/or discussion reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Callistemon lanceolatus (Sm.) Sweet grows all over the world and used to treat cough and bronchitis. The air-dried powder of the aerial parts was exhaustively extracted with methanol and the concentrated extract was adsorbed on silica gel for preparation of slurry. It was dried and subjected to silica gel column packed in petroleum ether. The column was eluted with organic solvents in order of increasing polarity to isolate 1-triacosanol ( 1 ), n -eicosanyl palmitate ( 2 ), n -heptadecanyl arachidate ( 3 ), n -tricosanyl palmitate, ( 4 ), 4-hydroxyphenethyl carbocerate ( 5 ), 4-hydroxyphenethyl gheddate ( 6 ), urs-12-en-3 α -acetoxy-18 β -H-28-oic acid ( 7 ) and stigmast-5-en-3 β -ol-3 β -D-glucuronopyranoside ( 8 ). Among them, compound 5 and 6 were new fatty acid ester isolated from this plant. Compound 7 showed MIC 32 µg/mL against E. coli which was comparable to amoxicillin having same MIC 32 µg/mL. Compound 5 and 6 showed significant antioxidant activity by inhibiting DPPH due to the presence of phenolic groups.

Development of antibiotic resistance in bacteria is one of the major issues in the present world and one of the greatest threats faced by mankind. Resistance is spread through both vertical gene transfer (parent to offspring) as well as by horizontal gene transfer like transformation, transduction and conjugation. The main mechanisms of resistance are limiting uptake of a drug, modification of a drug target, inactivation of a drug, and active efflux of a drug. The highest quantities of antibiotic concentrations are usually found in areas with strong anthropogenic pressures, for example medical source (e.g., hospitals) effluents, pharmaceutical industries, wastewater influents, soils treated with manure, animal husbandry and aquaculture (where antibiotics are generally used as in-feed preparations). Hence, the strong selective pressure applied by antimicrobial use has forced microorganisms to evolve for survival. The guts of animals and humans, wastewater treatment plants, hospital and community effluents, animal husbandry and aquaculture runoffs have been designated as "hotspots for AMR genes" because the high density of bacteria, phages, and plasmids in these settings allows significant genetic exchange and recombination. Evidence from the literature suggests that the knowledge of antibiotic resistance in the population is still scarce. Tackling antimicrobial resistance requires a wide range of strategies, for example, more research in antibiotic production, the need of educating patients and the general public, as well as developing alternatives to antibiotics (briefly discussed in the conclusions of this article).

Introduction : In view of increasing concerns with antimicrobial resistance (AMR), the World Health Organization (WHO) instituted a Global Action Plan (GAP) to address this. Area covered : One of the strategies to achieve the goals of GAP is to conduct regular surveillance of antimicrobial use through point prevalence surveys (PPS). In this review, PubMed, EBSCO, Proquest, Cinahl, and Scopus were searched for PPS of antimicrobial use published in English between January 2000 and December 2019. After systematic database screening of 2,893 articles, 60 PPS met the inclusion criteria and consequently were incorporated in this systematic review. Expert opinion : This review highlighted that most of the PPS were conducted in upper-middle and high-income countries. Prevalence of antimicrobial use was significantly higher in non-European hospitals compared with European hospitals. The domination of third-generation cephalosporin and fluoroquinolones use across all the regions suggests substantial use of broad-spectrum antimicrobials across countries. Among all identified regions around the world, India was the region where the highest use of antimicrobials was observed. Although PPS is a useful tool to assess the pattern of antimicrobial use and provides a robust baseline; however, a standardized surveillance method is needed. In order to optimize antimicrobial use, more efforts are required to improve antimicrobial use.

Objective:  Erythromycin (Ery) and leech saliva (LS) can inhibit Staphylococcus aureus growth in in vitro conditions. This study aimed to evaluate the activities and synergy between Ery and LS on chronic osteomyelitis in male Wistar rat's tibia induced by methicillin-resistant S. aureus (MRSA)., Materials and Methods:  Four weeks after osteomyelitis induction, rats were divided into four groups including no treatment (control), Ery monotherapy (orally), LS monotherapy, or Ery + LS twice daily for 2 weeks. Staphylococcus aureus growth, pathological signs and inflammatory cytokine tumour necrosis factor-alpha (TNF-α) levels were assessed., Results:  Rats tolerated all therapeutic strategies well during the experiment. The Ery treatment alone significantly decreased bacterial growth, pathological signs and TNF-α levels. Leech saliva alone reduced TNF-α level significantly, but did not produce a significant reduction in bacterial growth and pathological signs. Ery + LS treatment significantly decreased bacterial growth, considerably alleviated bone pathological signs and decreased TNF-α levels compared with other groups. Statistical analysis suggested that there was a stronger efficiency and synergistic action of Ery and LS when combined against MRSA-induced osteomyelitis in rats., Clinical Significance:  The present study suggests that LS may have clinical utility to treat MRSA-induced osteomyelitis when combined with Ery or other therapeutics., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

To estimate the antibiotic utilization and treatment compliance in URTIs reported to tertiary care hospitals of Lahore. A cross-sectional study was conducted by including 423 prescription files from public and private hospitals of Lahore. Descriptive statistics were used to estimate percentage frequencies. The reporting frequency of URTIs, tonsillitis, pharyngitis and otitis media, was higher in public hospitals (JH; 27.4%, LGH; 25.8%) compared to private (NHMC;16.3%, DHMC;15.1%) hospitals in patients aged 21-40 years. Patients aged 18-40 years (59%) received most antibiotics. Broad spectrum antibiotics (95%) were prescribed in both public (JH; 27.4%, LGH;25.9%) and private hospitals (NHMC;16.3%, DHMC;14.8%) - co-amoxiclave (30%) in penicillin class, ceftriaxone (15.4%) and cefixime (11.6%) in cephalosporin class, levofloxacin (11.3%) in quinolone class and clarithromycin (10.4%) in macrolide class, in tonsillitis, pharyngitis and otitis media. The diagnosis that received most antibiotics included tonsillitis (30%), pharyngitis (29.1%) and otitis media (11.1%). Superior treatment compliance was observed in public hospitals compared to private hospitals. The highest treatment non-compliance was observed in laryngitis (36.4%), otitis media (34%) and pharyngitis (26%). 1st line and over all treatment compliance was superior in public hospitals - sore throat, tonsillitis, sinusitis, otitis media and pharyngitis received the most appropriate choices.

Although viruses cause most of upper respiratory tract infections but still antibiotics are irrationally prescribed in mild infections, especially in upper respiratory tract infections. To identify gaps among prescribers, due to lack of standard guidelines and antimicrobial stewardship programs, it is needed to check knowledge, attitude, perception and current prescribing pattern of antibiotics. Based on the data recommendations can be specified to overcome the prescribing deficiencies and increasing rates of antimicrobial resistance. It is inevitable to educate patients about ineffectiveness of antibiotics in viral infections, and to develop guidelines for prescribing antibiotics, running continuing medical education and establishing antibiotic stewardship programs. We conducted a cross-sectional survey-based study by engaging physicians of public and private sector hospitals in Lahore, Pakistan. About 66% agreed for semi-structured interview and met the inclusion criteria. Fifty percent of physicians have an understanding that antibiotics should be prescribed in URTIs, otherwise symptoms may get worsen. The only encouraging thing is that 78.8% believe that antibiotics are being misused and are major cause of increasing rate of resistance. Most of prescribers have an understanding that antibiotics should be prescribed in upper respiratory tract infections. They are prescribing antibiotics ignoring Center for Disease Control guidelines for the treatment or prophylaxis of upper respiratory infections.

The frequency and antibiotic susceptibility of bacterial meningitis in children older than one month at Children's Medical Center during 2012-2017 were evaluated in this study. The CSF samples were cultured, and antibiotic sensitivity tests were performed. The samples were cultured on chocolate agar, blood agar (for gram positive) and Mkanky (for gram negative). The antimicrobial susceptibility of the isolates was determined using the disc diffusion method. In total, 72 samples were positive for bacterial infection where Staphylococcus epidermidis (20.8%) was seen most and Enterobacter (1.4%) and Pseudomonas aeruginosa (1.4%) was seen least. Most of these patients were under 1 year of the age and overall frequency of positive cultures of CSF in men (58.3%) was greater than women (41.7%). Bacterial meningitis has relatively diverse etiological factors that include; time of infection, geographical location and age. Most commonly seen bacteria were Staphylococcus aureus with S.epidermidis whereas, Escherichia coli and Pseudomonas aeruginosa was seen least. This result can be substantial in hospitalized patients, because these bacteria are also the result of nosocomial infections., Competing Interests: The other authors have no conflicts of interest to disclose., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: The objective of this study was to identify the genes involved in plantaricin synthesis and adaptive stress response in four Lactobacillus plantarum strains (AS-6, AS-8, AS-9 and AS-10) and one Lactobacillus paraplantarum strain (AS-7) for their usage in medicine and industry. Materials & methods: Whole genomes of these strains were sequenced by a high-throughput sequencing technique known as next-generation sequencing via Ilumina MiSeq platform and the genes were identified by using various bioinformatics tools and software. Results: Plantaricin genes ( plnD , plnE , plnF , plnG , plnI ) and genes regulating response to temperature, pH, bile salt, osmotic and oxidative stress were identified in all strains. Conclusion: Lactobacilli could be an option to combat antimicrobial resistance and might replace harmful antibiotics in future.

Klebsiella pneumoniae is a well-known pathogen and contributes to different types of infection. To investigate the antibiotic resistance profiles and prevalence of class I, II, and III integrons among clinical isolates of K. pneumoniae, a total of 142 non-duplicate clinical isolates were collected. Antibiotic susceptibility was assessed using Kirby-Bauer disk diffusion method and Clinical and Laboratory Standards Institute (CLSI) guidelines. Polymerase chain reaction (PCR) method was used to identify class I, II and III integrons. The isolates were mostly resistant against streptomycin (62 strains, 43.7 %) and ceftriaxone (42 strains, 29.6 %). Twenty-six (18.3%) isolates were found to be multi-drug resistant (MDR). Class I and II integrons were detected in 65 isolates (45.8%) and 1 (0.7%) isolate, respectively. The findings of this study revealed that the prevalence of streptomycin-resistant isolates is high, and its use must be restricted. Also, our results revealed that class I integrons are widely prevalent in clinical isolates of K. pneumoniae and a significant association was observed between resistance against imipenem, ciprofloxacin, gentamicin and streptomycin and the presence of integrons, necessitating appropriate infection control programs.

The present study reports the convenient synthesis, spectroscopic characterization, bio-assays and computational evaluation of a novel series of N-acyl-1H-imidazole-1-carbothioamides. The screened derivatives displayed excellent antioxidant activity, moderate antibacterial and antifungal potential. The screened derivatives were found to be highly biocompatible against hRBCs. Molecular docking ascertained the mechanism and mode of action towards the molecular target delineating that ligands and complexes were stabilized at the active site by electrostatic and hydrophobic forces in accordance to the corresponding experimental results. Docking simulation provided additional information about the possibilities of inhibitory potential of the compounds against RNA. Computational evaluation predicted that N-acyl-1H-imidazole-1-carbothioamides 5c and 5g can serve as potential surrogates for hit to lead generation and design of novel antioxidant and antibacterial agents., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

The present study was conducted to investigate the antimicrobial susceptibility profiles of Salmonella serotypes, especially fluoroquinolone-resistant strains, recovered from clinical samples in Iran. A full electronic search using related keywords was conducted in Persian and English languages in ISI Web of Knowledge, PubMed, Scopus, Google Scholar and the Scientific Information Database (SID) search engines to find papers published between 1983 and 1 July 2019. According to the inclusion and exclusion criteria, 46 eligible articles were selected for the final analysis out of the initial 13,186 studies retrieved. The pooled prevalence of quinolone-resistant Salmonella serotypes in clinical specimens in Iran was 2.9% to ciprofloxacin and 48.1% to nalidixic acid. Additional data on antibiotic resistance was as follows: 54.3% to tetracycline, 50.6% to ceftizoxime, 50.2% to streptomycin, 37.9% to ampicillin, 36.5% to kanamycin, 33.5% to trimethoprim-sulfamethoxazole, 27.2% to chloramphenicol, 19.1% to cephalothin, 8.8% to ceftriaxone, 7.6% to cefotaxime, 7.4% to aztreonam, 7.2% to gentamicin, 7% to cefepime, 6.8% to ceftazidime, 5.8% to cefixime, 2.7% to imipenem and 2.2% to meropenem. Findings of the present study showed a rising trend of resistance to the drugs of choice for the treatment of Salmonella infections, i.e. ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole in Iran. However, ciprofloxacin, third-generation cephalosporins and carbapenems are still effective antibiotics especially against multi-drug resistant strains in Iran.

This study aims to investigate the biological activities of endemic plant Anabasis aretioïdes harvested in eastern Morocco. Various extracts were prepared from aerial part by aqueous and organic extraction using a Soxhlet and cold maceration. Preliminary phytochemical analysis was carried out on the powder and on the different extracts by standard phytochemical tests, and was confirmed by a quantitative analysis based on the determination of total polyphenols and cathechic tannins. Antioxidant activity was evaluated in vitro by five methods: H 2 O 2 , DPPH, ABTS, FRAP, and RP, and the antibacterial activity was carried out by disc diffusion method and the determination of MIC and MBC. Phytochemical screening revealed the presence of cathechic tannins, saponins, and sterols and quantitative analysis showed that Ethyl acetate extract presented the high level of phenolic and cathechic tannins contents (46.79 ± 0.75  µ g GAE/mg E and 46.46 ± 0.67  µ g CE/mg E). A highest hydrogen peroxide activity was observed in aqueous macerated extract (7.84 ± 0.44%) and the macerated methanol extract has the highest rates for the other four antioxidant activity tests: It was able to reduce DPPH with an IC 50 of 52.91 ± 0.24  µ g/ml, the highest ABTS•+ radical scavenging capacity (48.99 ± 1.316  µ g TE/mg E), it showed also the highest antioxidant activity by the FRAP and reducing power test (99.73 ± 3.570  µ g TE/mg E and 72.176 ± 0.540  µ g AAE/mg E). Antibacterial screening showed that the maximum zone of inhibition was noted for ethyl acetate extract against Staphylococcus aureus (13.5 mm). The lowest MIC value was obtained with methanolic and macerated methanolic extracts against Protéus mirabilis strain (MIC = 3.125 mg/ml). Principal component analysis showed that the four methods ABTS, DPPH, FRAP, and RP are highly correlated and a correlation between the antioxidant activity and the total phenolic contents of the extracts indicated that phenolic compounds were the dominant contributors to the antioxidant activity of the plant., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Souad Senhaji et al.)