Multidrug-resistant Pathogens Research Articles

Rapid design of bacteriophage cocktails to suppress the burden and virulence of gut-resident carbapenem-resistant Klebsiella pneumoniae

Antibiotic use can lead to the expansion of multi-drug-resistant pathobionts within the gut microbiome that can cause life-threatening infections. Selective alternatives to conventional antibiotics are in dire need. Here, we describe a Klebsiella PhageBank for the tailored design of bacteriophage cocktails to treat multi-drug-resistant Klebsiella pneumoniae. Using a transposon library in carbapenem-resistant K.pneumoniae, we identify host factors required for phage infection in major Klebsiella phage families. Leveraging the diversity of the PhageBank, we formulate phage combinations that eliminate K.pneumoniae with minimal phage resistance. Optimized cocktails selectively suppress the burden of K.pneumoniae in the mouse gut and drive the loss of key virulence factors that act as phage receptors. Phage-mediated diversification of bacterial populations in the gut leads to co-evolution of phage variants with higher virulence and broader host range. Altogether, the Klebsiella PhageBank charts a roadmap for phage therapy against a critical multidrug-resistant human pathogen.

Synergistic efficacy of ZnO quantum dots, Ag NPs, and nitazoxanide composite against multidrug-resistant human pathogens as new trend of revolutionizing antimicrobial treatment

Antibiotic resistance is currently becoming a more serious threat to global health, especially in severe nosocomial infections treatment by multidrug-resistant bacteria. This research provides a new way of synergizing green-synthesis for zinc oxide quantum dots (ZnO-QDs with hexagonal crystals) that are 7 nm in diameter and zero-valent Ag cubic crystals that are 67 nm in size embedded with nitazoxanide substrate (NAZ). Instrumental characterization like SEM, TEM, EDAX, and FT-IR and comprehensive antimicrobial studies were conducted to study the incorporation behavior of composites based on Ag NPs/ZnO QDs/NAZ. This combination has not been hitherto addressed anywhere else in the published literature, as well as commercial viability. In this context, we have precisely tuned nanoparticle to nitazoxanide ratio for designing the formulation demonstrating potent activity against MDR infections. By employing nitazoxanide as a scaffold and careful decoration thereof antimicrobial potency has been unlocked overriding conventional therapies. In addition, Ag NPs/ZnO-QDs/nitazoxanide (G6) formula exhibited a therapeutic efficacy span of 96.15 ± 1.68% to 99.57 ± 0.20% against MDR human infections post 48 h incubation; a breakthrough in therapeutic efficacy levels has been achieved by our method. Accordingly, ZnO QDs/Ag NPs/NAZ composite offered potential multidrug resistant human pathogens as a new trend of revolutionizing antimicrobial treatment.Graphical abstractSchematic diagram of synthesis routev ZnO quantum dots/Ag NPs/Nitazoxanide Triumphs composite NPs.

A-292 Validation of Aztreonam-Avibactam MIC Antimicrobial Susceptibility Test for MicroScan Dried Gram-Negative MIC Panels from a Multicenter Assessment of Enterobacterales, Pseudomonas species, and Stenotrophomonas maltophilia

Abstract Background Aztreonam-avibactam (AZA) is a novel antibiotic combination for treating Gram-negative bacterial infections, including metallo-β-lactamase-producing multidrug-resistant pathogens for which there are limited or no treatment options.1 Given the need for accurate antimicrobial susceptibility testing results, a study was conducted with clinical isolates of Enterobacterales, Pseudomonas species, and Stenotrophomonas maltophilia on an investigational MicroScan Dried Gram-negative MIC (MSDGN) panel with AZA.2 Methods Three clinical sites evaluated MSDGN MIC values to MICs from CLSI reference panels. The study included 602/671 Enterobacterales, 53/59 Pseudomonas species and 69/70 S. maltophilia isolates using Prompt or turbidity inoculation. MSDGN panels were incubated at 35 ± 1°C and read on the WalkAway, autoSCAN-4, and visually at 16-20 hours. Reference panels were prepared according to CLSI methodology, incubated 16-20 hours for Enterobacterales and Pseudomonas species, and 20-24 hours for S. maltophilia and read visually. Results Essential agreement was calculated comparing MSDGN panel MIC results against reference panel MIC results for all isolates (Table 1). Conclusions AZA MIC results for Enterobacterales, Pseudomonas species, and S. maltophilia from MSDGN panels correlate well with MICs obtained using reference panels in this study. 1Pending approval by US Food and Drug Administration (FDA); not available for in vitro diagnostic use in the US. Not for Distribution in the US. 2Pending submission and clearance by the US FDA; not yet available for in vitro diagnostic use in the US. For Investigational Use Only. The performance characteristics of this product have not been established. In development, pending achievement of CE compliance; not yet available for in vitro diagnostic use. © 2024 Beckman Coulter. All rights reserved. All other trademarks are the property of their respective owners. BEC, the stylized logo and the BEC product and service marks mentioned herein are trademarks or registered trademarks of BEC, Inc. in the US and other countries. 2023-12350

A-254 Increase of Stenotrophomonas maltophilia Isolates Non-Susceptible to Trimethoprim-Sulfamethoxazole and/or Levofloxacin at Brazilian Hospitals

Abstract Background Stenotrophomonas maltophilia is an emerging multidrug-resistant pathogen that exhibits intrinsic and acquired resistance to a wide variety of antimicrobial agents such as β-lactams, aminoglycosides, quinolone, tetracyclines and disinfectants. In addition to that, the increased resistance to sulfamethoxazole/trimethoprim (SMX/TMP) and Levofloxacin has been reported in the past few years, leading to few therapeutic options. This study aimed to describe the increase of Stenotrophomonas maltophilia clinical isolates recovered from Brazilian hospitals over a 6-year analysis (January 2018 to December 2023). Methods This study design was a retrospective, observational analysis based on microbiological data of emergent BGN-NF isolates detected in several Brazilian tertiary hospitals. The bacterial identification was performed by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF/MS) and the antimicrobial susceptibility profile to trimethoprim-sulfamethoxazole and levofloxacin was determined using disk-diffusion method and epsilometer method, respectively. Only one sample per patient was considered in this analysis. Results During the 6 year period, a total of 1,706 (2018; 221), (2019; 203), (2020; 294), (2021; 276), (2022; 294) and (2023; 418) Stenotrophomonas maltophilia strains were isolated from blood (n=626), respiratory tract (n=365), fluid and secretion (n=235), skin and soft tissue (n=162), urine (n=132), catheter tip (n=112), swab (n=36), bone fragment (n=29) and cerebrospinal fluid (n=9). The major frequency of S. maltophilia isolation occurred among man (52.6%) and the main age range was over 60 years (42.7%), while 0-10 comprised 16.6% of cases. Compared the 6-years period, the resistance rate to trimethoprim-sulfamethoxazole was 2.7%; 5.4%; 5.8%; 2.2%; 5.8%; 7.9% and levofloxacin was 3.6%; 3.4%; 3.1%; 3.3%; 1.7%; 2.9%, respectively. The resistance rate to trimethoprim-sulfamethoxazole and levofloxacin, simultaneously, was 0.23%. Conclusions The incidence rate of S. maltophilia infections has increased significantly, especially in the last year, followed by an increase in the pattern of resistance to trimethoprim-sulfamethoxazole. Regarding trimethoprim-sulfamethoxazole and levofloxacin co-resistance, very low rates were detected in our analysis. Our data point to a scenario wherein the presence of S. maltophilia may have been intensified by the covid-19 pandemic. Regional surveillance reports are extremely important and should be out to understand some aspects of the dynamics of bacterial resistance in both hospital and community settings.

A multiantigenic antibacterial nanovaccine utilizing hybrid membrane vesicles for combating Pseudomonas aeruginosa infections.

Bacterial infections, especially those caused by multidrug-resistant pathogens, pose a significant threat to public health. Vaccines are a crucial tool in fighting these infections; however, no clinically available vaccine exists for the most common bacterial infections, such as those caused by Pseudomonas aeruginosa. Herein, a multiantigenic antibacterial nanovaccine (AuNP@HMV@SPs) is reported to combat P. aeruginosa infections. This nanovaccine utilizes the hybrid membrane vesicles (HMVs) created by fusing macrophage membrane vesicles (MMVs) with bacterial outer membrane vesicles (OMVs). The HMVs mitigate the toxic effects of both OMVs and bacterial secreted toxins (SP) adsorbed on the surface of MMVs, while preserving their stimulating properties. Gold nanoparticles (AuNPs) are utilized as adjuvant to enhance immune response without comprising safety. The nanovaccine AuNP@HMV@SPs induces robust humoral and cellular immune responses, leading to destruction of bacterial cells and neutralization of their secreted toxins. In murine models of septicemia and pneumonia caused by P. aeruginosa, AuNP@HMV@SPs exhibits superior prophylactic efficacy compared to control groups including OMVs, or MMVs@SPs and HMV@SPs, achieving 100% survival in septicemia and>99.9% reduction in lung bacterial load in pneumonia. This study highlights AuNP@HMV@SPs as a safe and effective antibacterial nanovaccine, targeting both bacteria and their secreted toxins, and offers a promising platform for developing multiantigenic antibacterial vaccines against multidrug-resistant pathogens.

Retrospective description of the clinical use of chloramphenicol in client-owned cats: 12 cases (2015-2023).

The study aimed to describe the clinical use of chloramphenicol in client-owned cats, examining the patient population, sites of infection, targeted pathogens, prescribed dosing regimen, outcomes and adverse effects. Between 2015 and 2023, a retrospective medical record review was undertaken to identify a case series of cats treated with chloramphenicol. Twelve client-owned cats with complicated infections were treated with chloramphenicol at a median dose of 13.3 mg/kg (range 9.1-34.7) administered orally every 12 h for a median duration of 14.5 days. Within 30 days before starting chloramphenicol, 11/12 cats had received treatment with at least one antibiotic. The sites of infection included skin, urinary tract and multisystemic. Multidrug-resistant pathogens, for which no alternative oral antibiotic therapy was available, were commonly targeted. These included meticillin-resistant Staphylococcus species and multidrug-resistant Enterococcus faecium. Of the 12 cats treated with chloramphenicol, nine effectively achieved either bacteriologic or clinical cure. Chloramphenicol adverse effects were uncommon and limited to gastrointestinal upset, which was self-limiting or manageable with supportive treatment in two cats. In these cats, the decision to treat with chloramphenicol was made because an alternative oral antibiotic was not available to target the multidrug-resistant pathogens. Infections of the skin or urinary tract were common. Overall, chloramphenicol was well tolerated, and treatment success was possible for most cats.

Multi Drug Resistant (MDR) Klebsiella pnuemoniae Isolated from Different Sources

Background: Multidrug-resistant pathogens are a significant cause of morbidity globally. The recent rise in resistant bacterial strains is largely attributed to the extensive use of antibiotics in human and animal treatment. In recent years, there has been a notable increase in drug-resistant Klebsiella pneumoniae strains, posing a major challenge for clinicians worldwide. Methods: In the current study, 121 samples were obtained from bovine mastitis milk and faeces, dairy cattle farm premises, chicken cloacal swabs, poultry farm litter and water. The samples were processed for the isolation and identification of Klebsiella species. Klebsiella isolates were identified by cultural, morphological and biochemical characteristics and were subsequently confirmed by PCR assays that targeted species-specific genes. The isolates were subjected to in vitro antibiotic sensitivity test. The DNA from all the isolates was extracted and subjected to PCR to identify the presence of 10 different Antibiotic Resistance Genes (ARG) using published primers. The ARGs targeted were blaTEM, blaSHV, blaOXA, blaIMP, DHAM, MOXM, tetA, tetB, sul1 and aadA. Result: Out of 121 samples, twenty-six (21.4%) samples were identified as Klebsiella pnuemoniae isolates. The occurence of Klebsiella pnuemoniae in samples from different sources was- 3/33 (09%) from mastitis milk, 8/27 (29.6%) from faecal samples and 04/14 (28.5%) from environmental samples collected from dairy farms. Similarly, Klebsiella pnuemoniae prevalence was recorded to be 6/33 (18.1%) in cloacal swabs and 5/14 (35.7%) from environmental samples collected from poultry farms. On in vitro antibiotic sensitivity test, all the Klebsiella pneumoniae isolates were found to be resistant to penicillin, amoxicillin, cefuroxime and ampicillin/ sulbactam (100% each), followed by cefalexin (65.3%), streptomycin (53.8%), tetracycline (38.4%), imipenum and co-trimoxazole (34.6% each), ofloxacin (30.7%), norfloxacin (27%), ceftriaxone (23%), amikacin (15.38%) and gentamicin (11.5%). All the K. pneumoniae isolates were found to be Multi Drug Resistant (MDR). Out of 26 isolates, 25 (96%) were positive for Sul1, 22 (84.6%) for blaTEM, 19 (73%) for blaSHV, 19 (3%) for tetA, 16 (61.5%) for aadA, 10 (38.4%) for OXA, 9 (34.6%) for tetB and 2 (7.6%) for DHAM and MOXM each. None of the isolates harboured blaIMP gene.

Recent Trends in Therapeutic Drug Monitoring of Peptide Antibiotics.

Antimicrobial peptides take a specific position in the field of antibiotics (ATBs), however, from a large number of available molecules only a few of them were approved and are used in clinics. These therapeutic modalities play a crucial role in the management of diseases caused by multidrug-resistant bacterial pathogens and represent the last-line therapy for bacterial infections. Therefore, there is a demand for a rationale use of such ATBs based on optimization of the dosing strategy to minimize the risk of resistance and ensure the sustainable efficacy of the drug in real clinical practice. Therapeutic drug monitoring, as a measurement of drug concentration in the body fluids or tissues, results in the optimization of the patient´s medication and therapy outcome. This strategy is beneficial and could result in tailored therapy for different types of infection and the prolongation of the use and efficacy of ATBs in hospitals. This review paper provides an actual overview of approved antimicrobial peptides used in clinical practice and covers current trends in their analysis by convenient and advanced methodologies used for their identification and/or quantitation in biological matrices for therapeutic drug monitoring purposes. Special emphasis is given to the methods with perspective clinical outcomes.

Bacillus Sp. as Potential Probiotics for Use in Tilapia Fish Farming Aquaculture – A Review

Abstract Aquaculture is a crucial and rapidly expanding industry in global food production. Fisheries are also an essential socio-economic activity, providing abundant resources and remarkable prospects. However, due to the deteriorating ecological environment, aquatic animals are often exposed to traumatic conditions and are susceptible to bacterial infections that pose significant challenges for aquaculture production. The indiscriminate use of antibiotics in the past has led to the emergence of multidrug-resistant pathogens and sudden outbreaks of infectious diseases, resulting in serious economic losses. Moreover, the use of expensive chemotherapeutic drugs and antibiotics has negative impacts on aquatic environments. Therefore, it is increasingly important to adopt alternative natural agents, such as probiotics and their metabolites, to enhance healthy fish production. Probiotics are microorganisms that have numerous beneficial effects on their hosts. They are environmentally friendly, non-toxic, and cost-effective. This review specifically focuses on the use of Bacillus sp. as probiotics to promote healthy tilapia production in the aquatic sector, while also examining their interactions with the immune system and gut micro-biota. The information presented in this review can guide future research and promote effective and healthy tilapia culture production.

Computational Exploration of Limonin as a Potential Inhibitor of DapB in Klebsiella pneumoniae.

Klebsiella pneumoniae has emerged as a significant multidrug-resistant pathogen, classified as a critical priority by the World Health Organization. The rising rates of antibiotic resistance have led to increased therapeutic failures, diminishing the effectiveness of existing antibiotics. Consequently, there is an urgent need for alternative treatments to effectively inhibit the growth of K. pneumoniae and mitigate associated diseases. Phytochemicals have demonstrated potential advantages over traditional antibiotics, prompting their exploration as innovative therapeutic agents. This study aimed to identify phytochemicals that can inhibit dapB, a vital enzyme in the lysine biosynthesis pathway of K. pneumoniae, which is essential for protein synthesis and the cross-linking of the bacterial peptidoglycan cell wall. We screened 17,934 phytochemicals based on Lipinski's Rule of Five, along with their Absorption, Distribution, Metabolism, Excretion properties and toxicological parameters. Next, we conducted triplicate docking studies against dapB to evaluate the library further. The most promising molecules then underwent 100 ns Molecular Dynamics simulations in triplicate, followed by binding free energy calculations to identify potential dapB inhibitors. This in silico analysis highlighted limonin as a promising inhibitor of dapB in K. pneumoniae. Further experimental validation is crucial to enhance limonin's potential as a novel therapeutic agent against K. pneumoniae-associated diseases.

Coexistence of seven different carbapenemase producers in a single hospital admission screening confirmed by whole-genome sequencing

ObjectiveTo molecularly characterize several extensively drug-resistant isolates from a single hospital admission screening of a war injured patient from the Ukraine. MethodsAdmission screening included swabs from skin, wounds, catheters, nasopharyngeum and rectum. Bacterial identification, antimicrobial susceptibility testing (AST) and rapid multiplex PCR assays targeting resistance genes were performed during routine diagnostics. Isolates positive by PCR had their genomes sequenced using short- and long read-platforms (MiSeq and MinION) to confirm species, identify resistance genes and plasmids and investigate clonality with core genome MLST (cgMLST). ResultsSeven Gram-negative pathogens (Acinetobacter baumannii (n=2; ST78, ST2), Klebsiella pneumoniae (n=2; ST395), Pseudomonas aeruginosa (n=1; ST1047), Escherichia coli (n=1; ST46), Enterobacter cloacae complex (n=1; ST231)) were molecularly confirmed non-identical. AST showed resistance to carbapenems (7/7 isolates) and last resort treatment options such as ceftazidime-avibactam (6/7 isolates) and cefiderocol (4/7 isolates). All isolates were colistin susceptible. Sequencing identified the E. cloacae complex as E. hormaechei subsp. xiangfangensis. Six acquired carbapenemase genes (blaIMP-1, blaNDM-1, blaOXA-48, blaNDM-5, blaOXA-23 and blaOXA-72) were detected. Both A. baumannii isolates differed in sequence type, carbapenemases and cefiderocol susceptibility. Both K. pneumoniae isolates shared sequence type and some resistance genes on an IncR plasmid but were different in cgMLST and carbapenemases (OXA-48 or NDM-1). One vancomycin-resistant Enterococcus faecium was also detected (VanA). ConclusionWar injured patients from Ukraine may carry different clones of multidrug-resistant pathogens with limited treatment options and diverse resistance genes at risk for dissemination. Infection control measures should include early molecular characterization of isolates for detection of routes of transmission.

Advances in the clinical treatment of multidrug-resistant pathogens using polymyxins.

Polymyxins are a vital class of antibiotics used to combat multidrug-resistant Gram-negative bacteria. However, their use is limited due to potential nephrotoxicity and the availability of alternative antibiotics. This review aims to examine the properties of polymyxins and the clinical advances in their use for treating infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB). This review analyses literature on polymyxin properties and various clinical approaches, including intravenous drip infusion, nebulized or dry powder inhalation, and ointment application. Treatment efficacy in terms of bacterial eradication, cure rate and mortality rate are reviewed and evaluated. Polymyxins have been reintroduced to treat critical infections due to the increasing prevalence of CR-GNB. Clinical trials and studies have confirmed that polymyxins can effectively treat CR-GNB infections when the formulation and administration are appropriate, with acceptable levels of nephrotoxicity. In the future, the development of polymyxin formulations will aim to improve their clinical effectiveness while reducing toxicity and side effects and preventing the emergence of polymyxin-resistant strains. Enhanced efficacy and minimized potential side effects can be achieved by developing new polymyxin-delivery systems that provide a smart and controlled release or customized patient administration.

Phage therapy: A novel approach against multidrug-resistant pathogens.

The rapid rise of multidrug-resistant (MDR) organisms has created a critical need for alternative treatment options. Phage therapy is gaining attention as an effective way to fight bacterial infections by using lytic bacteriophages to specifically target and kill harmful bacteria. This review discusses several phage therapeutic options and emphasizes new developments in phage biology. Phage treatment has proven to be successful against MDR bacteria, as evidenced by multiple human clinical trials that indicate favorable results in treating a range of diseases caused by these pathogens. Despite these promising results, challenges such as phage resistance, regulatory hurdles, and the need for standardized treatment protocols remain. To effectively combat MDR bacterial infections, future research must focus on enhancing phage effectiveness, guaranteeing safety for human usage and incorporating phage therapy into clinical practice.

Antibiotic-Loaded Hydrogel for the Treatment of Lower-Limb Fracture-Related Infections: A Single Center's Multidisciplinary Experience.

A fracture-related infection (FRI) is a severe complication of an orthopedic trauma, often leading to challenging treatments and poor outcomes. The surgical strategies are typically categorized into one-stage or two-stage procedures, with the use of systemic and local antibiotics being crucial for infection management. This study assessed the efficacy of an antibiotic-loaded hydrogel (ALH) applied over the internal fixation devices for treating FRIs, comparing the outcomes between the one-stage (OS) and two-stage (TS) reconstructions. This retrospective study included 17 patients with an FRI treated using the ALH at a single center. The patients were divided into OS and TS reconstruction groups. The data on demographics, surgical procedures, antibiotic regimens, and outcomes were collected. The primary and secondary outcomes included the infection cure rate, bone union, complications, and reoperation rates. Among the 17 patients (mean age 48.5 years, 16 males), infections were predominantly in the tibia, with 12 chronic and 5 acute cases. Seven patients had monomicrobial infections, and nine had multidrug-resistant pathogens. No significant differences were found between the OS and TS groups in terms of the infection cure rate, bone union, or complications. One patient in the OS group experienced an infection recurrence, and bone healing was achieved in all but one case. Additional complications included delayed wound closure in two cases and implant failure in one case, requiring a reoperation. The ALH demonstrated potential as an effective local antibiotic treatment for FRIs, particularly in the one-stage reconstructions, allowing for a safe application of internal fixation devices. However, further research with larger sample sizes and longer follow-ups is needed to validate these findings.

A rapid microwave approach for ‘one-pot’ synthesis of antibiotic conjugated silver nanoparticles with antimicrobial activity against multi-drug resistant bacterial pathogens

Deaths directly attributable to drug-resistant infections reached 1.27 million in 2019 and continue to rise. This escalating resistance to antibiotics has driven a resurgence in the exploration of ancient antimicrobials to develop efficacious alternatives. The modern field of nanomaterials is a promising area of research with silver nanoparticles performing well as antimicrobial agents due to their large surface area and multiple bacterial targets. In the current study antibiotic conjugated silver nanoparticles (3–35 nm) were synthesized using β-lactam antibiotic, ampicillin. The method of heating during synthesis either microwave (4 min) or convection (4 h) influenced the physical characteristics of the ampicillin coated silver nanoparticles, however both approaches produced nanomaterials with antimicrobial activity against a variety of multi-drug resistant (MDR) clinical isolates in physiologically relevant media (when present at <0.2–2.28 mg L−1 in defined media). Critically, the microwave method is five times faster than the traditional water bath method, allowing rapid synthesis of ampicillin-conjugated nanoparticles, which supports scale up processes for industry. We suggest that the combination of antibiotic and silver in these nanoparticles produces a synergistic effect that circumvents resistance mechanisms and has the potential to provide a new line of combinatorial agents able to treat multi-drug resistant infections.

Targeting the phosphatidylglycerol lipid: An amphiphilic dendrimer as a promising antibacterial candidate.

The rapid emergence and spread of multidrug-resistant bacterial pathogens require the development of antibacterial agents that are robustly effective while inducing no toxicity or resistance development. In this context, we designed and synthesized amphiphilic dendrimers as antibacterial candidates. We report the promising potent antibacterial activity shown by the amphiphilic dendrimer AD1b, composed of a long hydrophobic alkyl chain and a tertiary amine-terminated poly(amidoamine) dendron, against a panel of Gram-negative bacteria, including multidrug-resistant Escherichia coli and Acinetobacter baumannii. AD1b exhibited effective activity against drug-resistant bacterial infections in vivo. Mechanistic studies revealed that AD1b targeted the membrane phospholipids phosphatidylglycerol (PG) and cardiolipin (CL), leading to the disruption of the bacterial membrane and proton motive force, metabolic disturbance, leakage of cellular components, and, ultimately, cell death. Together, AD1b that specifically interacts with PG/CL in bacterial membranes supports the use of small amphiphilic dendrimers as a promising strategy to target drug-resistant bacterial pathogens and addresses the global antibiotic crisis.

Bioactive Curcuma aromatica-stabilized silver nanoparticles embedded chitosan dressing with improved antibacterial, anti-inflammatory, and wound healing properties

Chronic wounds, particularly those infected with multidrug-resistant (MDR) pathogens, present significant challenges for effective healing. Silver nanoparticles (CAAgNPs) were synthsized using aqueous rhizome extract of Curcuma aromatica (CA), known for its wound-healing properties. CAAgNPs were incorporated in a chitosan (CS) dressing (CAAgNPs/CS) and tested for their wound healing potential, expecting synergistic action of AgNPs and phytochemicals capped on it. The porous nature of the CAAgNPs was confirmed using Field emission scanning electron microscopy. Fourier-transform infrared spectroscopy demonstrated a shift in peak intensity from 1589.06 to 1575.54 cm-1 for CAAgNPs/CS dressing confirming crosslinking with glutaraldehyde. Antibacterial activity of the dressings was cofirmed against isolates of Pseudomonas aeruginosa and Staphylococcus aureus. Wound healing studies were carried out using Wistar rats (six groups)- wound control, CS, CAAgNPs256/CS, CAAgNPs512/CS, CAAgNPs1024/CS, and commercial dressings. Histological examination and direct red-80 staining demonstrated maximum epithelization and collagen deposition (58.02%) within CAAgNPs1024/CS groups on day 10. Increased hydroxyproline levels (76.51 µg/mL) on day 7 for CAAgNPs1024/CS indicated maximum collagen formation. Reduced levels of inflammatory cytokines IL-6 (17.38 pg/mL) and TNF-α (80.38 pg/mL) on day 10 indicated quick wound healing without scar formation and damaging effects. The present study highlights the antibacterial and anti-inflammatory properties of CAAgNPs1024/CS dressings with a potential for wound healing applications.

Study of Bacterial Contamination in the Operating Room and Newborn Intensive Care Unit: Effects of the Predominantly Used Antibiotics at Sabratha Teaching Hospital

Contamination by bacteria in the operating room (OR) and newborn intensive care units (NICU) has continued to increase the incidence of nosocomial infections and a center point of multidrug-resistant (MDR) pathogens. This study was to examine the spread of bacteria isolated from inanimate surfaces in the operating room and neonatal intensive care units at Sabratha Teaching Hospital and find out the effectiveness of the most antimicrobial used. Methods: At the Sabratha Teaching Hospital in Sabratha, Libya, a cross-sectional, descriptive study was conducted in the OR and NICU from February to May 2024. A total of 22 swab samples were collected from high-contact environmental surfaces. Isolation, identification, and antibiotic sensitivity patterns were performed via standard techniques. Results: After 48 hours of incubation, (54.5 %) of the swabbed surfaces showed positive bacterial growth and 45.5% showed no bacterial growth, of which 25% had gram-positive bacteria and 75% had gram-negative bacteria. Staphylococcus saprophyticus 3 (25%) was the identified gram-positive bacterial isolate, and Klebsiella spp. 5 (55.5%) and Pseudomonas aeruginosa 4 (44.4%) were the probable gram-negative bacterial isolates. The antimicrobial susceptibility pattern of clinical pathogens tested Staphylococcus epidermides and Klebsiella spp showed similar patterns which were sensitive to most antimicrobials used, while Pseudomonas aeruginosa was highly resistant to Cotrimoxazole, Cefatoxime, Cefixitin, Ceftazidime, Ceftricillin, and Calvu amoxicillin. Conclusion: This study confirms the need for rigorous disinfection protocols and hand hygiene to reduce the spread of these pathogens in the OR and NICU.

Does manipulation of phyto-based nanoparticles is a promising solution against multi-drug resistant (MDR) pathogens? A critical opinion towards tackling MDR pathogens

Does manipulation of phyto-based nanoparticles is a promising solution against multi-drug resistant (MDR) pathogens? A critical opinion towards tackling MDR pathogens

Comprehensive Exploration of Bromophenol Derivatives: Promising Antibacterial Agents against SA and MRSA.

The incidence of treatment failure due to multidrug-resistant pathogens elevated over the years; the rate is much higher than new antibiotic drug discovery. Therefore, bromophenol derivatives as potential antibacterial agents on Staphylococcus aureus and MRSA were explored in this research via integrating chemistry, microbiology, and pharmacology to address significant knowledge gaps pertaining to the antibacterial activity of bromophenols based on their functional groups. Surprisingly, a simple molecule, 3-bromo-2,6-dihydroxyacetophenone (2), exhibited good anti-S. aureus activity and even MRSA, a drug-resistant strain. In addition, compound 2 also inhibited a common resistant pathway of pathogens, biofilm formation of S. aureus and MRSA. Moreover, the therapeutic index of 2 is up to 598, which can be viewed as highly selective and having low toxicity to human HEK-293 cells. Although these compounds displayed less effectiveness for the Gram-negative bacterium, Pseudomonas aeruginosa, they still manifested some effects on the virulence properties of P. aeruginosa, such as biofilm formation, pyocyanin production, and swarming motility. In silico analyses of the structure-activity relationship as well as ADMET properties were discussed in the end. This study shed some light on the antibacterial activities of bromophenols.