Treatment Of Bacterial Infections Research Articles

Colistin-niclosamide effervescent dry suspension combats colistin-resistant Salmonella in vitro and in vivo

The increasing incidence of bacterial infections caused by multidrug-resistant (MDR) Gram-negative bacteria has deepened the need for new effective treatments. It has been reported that niclosamide (NIC) can restore the sensitivity of Gram-negative bacteria to colistin (COL). However, NIC is practically insoluble in water and sparingly soluble in organic solvents, leading to limited therapeutic applications. This study aims to prepare a COL-NIC effervescent dry suspension (CNEDS) and evaluate its antibacterial effect against COL-resistant Salmonella both in vitro and in broiler chickens. With the sedimentation volume ratio as an index, suitable suspending agent, wetting agent, filler and effervescent agent were screened through a single-factor method. The preparation conditions were optimized using the Box-Behnken response surface method to obtain the formulation for CNEDS. The quality evaluation results showed that the successfully prepared CNEDS had a sedimentation volume ratio of 0.99, a drying weight loss of 1.3%, and a re-dispersion capability of 1-2 times, all of which met pharmacopoeial requirements. In terms of pharmacological evaluation, we first demonstrated that CNEDS substantially restored COL sensitivity against COL-resistant bacteria. Subsequently, time-killing analysis, scanning electron microscopy (SEM) and live/dead assays confirmed the antibacterial activity of CNEDS against COL-resistant bacteria. Finally, a Salmonella infection model in broiler chickens was established to further assess the therapeutic effect of CNEDS in vivo. CNEDS improved the survival rate of broiler chickens, reduced the bacterial burden on organs. These findings suggest that CNEDS effectively overcome COL resistance, indicating its potential for the treatment of COL-resistant bacterial infections in broiler chickens.

Copper peroxide-decorated Prussian blue for effective bacterial elimination via photothermal-enhanced and H2O2-releasing chemodynamic therapy

Bacterial infection is a major impediment towards wound healing and threaten human health worldwide. Traditional antibiotic therapy poses a high risk of inducing bacterial resistance, thus nanomaterial-based synergistic bactericidal strategy as effective alternatives have received tremendous attention. Herein, a NIR/pH-dual responsive nanoplatform was fabricated for synergistic photothermal and chemodynamic therapy (PTT/CDT). Prussian blue (PB) were employed as supporting material, while copper peroxide (CP) were growth in situ on PB surface, resulting in a core-shell structured nanoplatform (designated as PC). PB core served as photothermal/Fenton catalyst dual agents, and CP shell could co-release Cu2+ and H2O2 under acidic bacterial infection environment, realizing synergistic PTT and H2O2-releasing CDT. Under NIR irradiation, PC exhibited photothermal-enhanced Fenton-like reaction feature and the hyperthermia facilitated Cu2+ release, leading to the rapid conversion of H2O2 into toxic •OH to effectively kill Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus), eradicating S. aureus biofilm. Moreover, the released Cu2+ could improve the bactericidal effect of CDT via the depletion of GSH and significantly promote cell migration. Furthermore, in vivo experiments demonstrated PC with good biocompatibility exhibited robust bactericidal effect and promoted wound healing. Overall, this versatile nanoplatform offered an efficacious and safe antibiotic-free strategy for bacterial infection treatments.

Magnetic Field/Ultrasound-Responsive Fe3O4 Microbubbles for Targeted Mechanical/Catalytic Removal of Bacterial Biofilms

Conventional antibiotics are limited by drug resistance, poor penetration, and inadequate targeting in the treatment of bacterial biofilm-associated infections. Microbubble-based ultrasound (US)-responsive drug delivery systems can disrupt biofilm structures and enhance antibiotic penetration through cavitation effects. However, currently developed US-responsive microbubbles still depend on antibiotics and lack targeting capability. In this work, magnetic field/ultrasound (MF/US)-responsive Fe3O4 microbubbles (FMB) were constructed based on Fe3O4 nanoparticles (NPs) with superparamagnetic and peroxidase-like catalytic properties. In vitro experiments demonstrated that FMB can be targeted to methicillin-resistant Staphylococcus aureus (MRSA) biofilms by the direction of MF. Upon US irradiation, FMB collapse due to inertial cavitation and generate mechanical forces to disrupt the structure of MRSA biofilms and releases Fe3O4 NPs, which catalyze the generation of reactive oxygen species (ROS) from H2O2 in the biofilm microenvironment and kill the bacteria within the biofilm. In a mouse biofilm infection model, FMB efficiently destroyed MRSA biofilms grown in subcutaneous catheters with the MF and US. Magnetic-targeted mechanical/catalytic therapy based on FMB provides a promising strategy for effectively combating bacterial biofilm infection.

Using digital health technologies to optimise antimicrobial use globally.

Digital health technology (DHT) describes tools and devices that generate or process health data. The application of DHTs could improve the diagnosis, treatment, and surveillance of bacterial infection and the prevention of antimicrobial resistance (AMR). DHTs to optimise antimicrobial use are rapidly being developed. To support the global adoption of DHTs and the opportunities offered to optimise antimicrobial use consensus is needed on what data are required to support antimicrobial decision making. This Series paper will explore bacterial AMR in humans and the need to optimise antimicrobial use in response to this global threat. It will also describe state-of-the-art DHTs to optimise antimicrobial prescribing in high-income and low-income and middle-income countries, and consider what fundamental data are ideally required for and from such technologies to support optimised antimicrobial use.

Synthetic indole derivatives as an antibacterial agent inhibiting respiratory metabolism of multidrug-resistant gram-positive bacteria.

The survival of modern medicine depends heavily on the effective prevention and treatment of bacterial infections, are threatened by antibacterial resistance. The increasing use of antibiotics and lack of stewardship have led to an increase in antibiotic-resistant pathogens, so the growing issue of resistance can be resolved by emphasizing chemically synthesized antibiotics. This study discovered SMJ-2, a synthetic indole derivative, is effective against all multidrug-resistant gram-positive bacteria. SMJ-2 has multiple targets of action, but the primary mechanism inhibits respiratory metabolism and membrane potential disruption. SMJ-2 was discovered to interfere with the mevalonate pathway, ultimately preventing the synthesis of farnesyl diphosphate, a precursor to the antioxidant staphyloxanthin, eventually releasing reactive oxygen species, and leading phagocytic cells to destroy pathogens. Additionally, no discernible biochemical and histopathological alterations were found in the mouse acute toxicity model. This study emphasizes mechanistic insights into SMJ-2 as a potential antibacterial with an unusual method of action.

Prevalence of blaOXA-48 and other carbapenemase encoding genes among carbapenem-resistant Pseudomonas aeruginosa clinical isolates in Egypt.

Resistance to carbapenem, the last line of treatment for gram-negative bacterial infections has been increasing globally and becoming a public health threat. Since integrons may aid in the transmission of resistance genes, the purpose of this study was to detect the frequency of class 1, 2, and 3 integrons as well as carbapenem-resistant genes in clinical isolates of P. aeruginosa that are resistant to carbapenem. This study was carried out on 97 clinical isolates of P. aeruginosa isolated from wound and urine samples. The antimicrobial susceptibility for all isolates was tested by the disc diffusion method. The presence of integrons and carbapenem-resistant genes among carbapenem-resistant P. aeruginosa isolates was evaluated by conventional PCR. The antimicrobial resistance rate among P. aeruginosa clinical isolates was high, with imipenem resistance in 58.8% of the studied isolates. In this study, 86% of the carbapenem-resistant P. aeruginosa isolates carry carbapenemase genes, with blaVIM being the most common gene followed by the blaOXA-48 gene. Class 1 and class 2 integrons were reported in 37 (64.9%) and 10 (17.5%) of the tested carbapenem-resistant P. aeruginosa isolates, respectively. Our data reported a high prevalence of class 1 integrons in carbapenem-resistant P. aeruginosa clinical isolates, suggesting the important role of integrons in carbapenem-resistant gene transfer among such isolates.

Development of Cyclometalated Iridium(III) Complexes of 2-Phenylbenzimidazole and Bipyridine Ligands for Selective Elimination of Gram-Positive Bacteria.

Herein, we have reported a series of cationic aggregation-induced emission (AIE) active iridium(III) complexes (Ir1-Ir5) of the type [Ir(C^N)2(N^N)]Cl, wherein C^N is a cyclometalating 2-phenylbenzimidazole ligand with varying alkyl chain lengths and N^N is a 2,2'-bipyridine ligand attached to bis-polyethylene glycol chains, for the treatment of bacterial infections. The AIE phenomenon of the complexes leveraged for detecting bacteria by fluorescence microscopy imaging that displayed a strong red emission in Gram-positive bacteria. The antibacterial activity of the complexes assessed against Gram-positive methicillin-sensitive S. aureus, methicillin-resistant S. aureus, E.faecium and E.faecalis and Gram-negative E. coli and P.aeruginosa bacteria of clinical interest. The complexes Ir2-Ir4 exerted potent antibacterial activity towards Gram-positive strains with low minimum inhibitory concentrations (MICs) values in the range of 1-9 μM, which is comparable to clinically approved antibiotic vancomycin. In contrast, these complexes were found to be inactive towards Gram-negative bacterial strains (MICs > 100 µM). The mechanism of antibacterial activity of the complexes implies that ROS generation, membrane depolarization and rupture are responsible for bacterial cell death. Further, the complexes Ir1-Ir3 were found to be low-toxic against human red blood cells and human embryonic kidney (HEK293) cells, indicating their potential for use as antibacterial agents.

Surface-functionalized UIO-66-NH2 for dual-drug delivery of vancomycin and amikacin against vancomycin-resistant Staphylococcus aureus

BackgroundConventional antibacterial compounds can inhibit the growth of microorganisms, but their adverse effects and the development of drug limit their widespread use. The current study aimed to synthesize PEG-coated UIO-66-NH2 nanoparticles loaded with vancomycin and amikacin (VAN/AMK-UIO-66-NH2@PEG) and evaluate their antibacterial and anti-biofilm activities against vancomycin-resistant Staphylococcus aureus (VRSA) clinical isolates.MethodsThe VAN/AMK-UIO-66-NH2@PEG were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) to determine their size, polydispersity index (PDI), encapsulation efficiency (EE%), zeta-potential, drug release profile, and physical stability. Antibacterial activity was evaluated using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill assays. Biofilm formation by VRSA was assessed using the crystal violet (CV) and minimum biofilm eradication concentration (MBEC) assays. The effect of sub-MIC concentrations of the formulations on the expression of biofilm-related genes (icaA, icaD) and resistance-related genes (mecA, vanA) was investigated using quantitative real-time polymerase chain reaction (RT-qPCR).ResultsAs demonstrated by MIC, MBC and time-kill assay, the VAN/AMK-UIO-66-NH2@PEG nanoparticles exhibited enhanced antibacterial activity against VRSA isolates compared to free drugs and prepared formulations. Furthermore, CV and MBEC tests indicated that the VAN/AMK-UIO-66@NH2/PEG can reduce biofilm formation dramatically compared to VAN/AMK and VAN/AMK-UIO-66@NH2, due to its great drug release properties. This study also found that the expression level of the mecA, vanA, icaA, and icaD genes in VAN/AMK-UIO-66@NH2/PEG treated VRSA isolates was substantially decreased compared to other groups.ConclusionsThese findings highlighted the efficiency of VAN/AMK-UIO-66@NH2/PEG in combating antimicrobial resistance and biofilm formation in VRSA isolates. Future studies, particularly in vivo models, are necessary to evaluate the safety, efficacy, and clinical applicability of these nanoparticles for the treatment of bacterial infections.

ASSESSMENT OF ANTIBIOTIC STEWARDSHIP IN TERTIARY HEALTH CARE TEACHING MEDICAL INSTITUTION IN CENTRAL INDIA

Objective: The objective of the study was to mitigate the impact of antimicrobial resistance and ensure continued access to effective treatments for bacterial infections. This study was undertaken to explore the hospital status of antibiotic prescription and evaluate the impact of antibiotic stewardship in clinical wards of tertiary health care settings. Methods: This is hospital-based observational prospective study carried out in a tertiary health care settings. All patients of either sex of any age who came in outpatient department and admitted in inpatient department of medicine, orthopedics, surgery, and pediatric departments and prescribed antibiotics were selected randomly in the study. Results: Study response rate was male predominance (57%). Empiric antimicrobials were mainly prescribed orally (47.3%), significantly higher than injectable route (22.8%) (p<0.001), while the majority were not given an empiric antibiotic by a clinical expert. A significantly high number of patients were prescribed injectable 1st Antimicrobial after surgery/culture, namely, injectable piperacillin+tazobactum (35.5%), followed by injectable cephalosporin (34.0%), amikacin injection/4.5%, and injection carbapenem/1.8% (p<0.001). Its frequency is significantly high with BD dose (66.8%) and the majority prescribed for period of 6–10 days (63.5%) followed by 1–6 days (19.5%) (p<0.001). Conclusion: As all prescriptions got optimal dose and duration of therapy, the stay of patients in the hospital was following Indian Council of Medical Research (2019) guideline therefore, it can thus be said that the results of this study revealed precise prescribing pattern of antibiotics. However, emphasis on information technology staff and patient education is vital in incorporating stewardship protocols. Emphasizing the importance of conducting antibiotic time-outs within 48–72 h is crucial for reassessing the necessity and choice of antibiotics. Such stewardship studies are instrumental in monitoring patterns of antibiotic usage and aid in future policy-making steps.

Investigating the hypothermic effects of fluoroquinolone antimicrobials on non-bacterial fever model mice

BackgroundFluoroquinolone (FQ) antimicrobials have antipyretic effects during the treatment of bacterial infections; however, it is not clear whether these are due to their antimicrobial activities or their hypothermic effects. In this study, we investigated the hypothermic effects of FQ antimicrobials (ciprofloxacin [CPFX], gatifloxacin [GFLX], and levofloxacin [LVFX]) on fever by evaluating rectal body temperature changes in a mouse model of non-bacterial fever.MethodsCPFX, GFLX, and LVFX were administered intraperitoneally to non-bacterial fever model mice induced by yeast. Rectal body temperature was measured up to 180 min after administration.ResultsA decrease in rectal body temperature of up to 1.2 °C for CPFX, 3.4 °C for GFLX, and 1.0 °C for LVFX was observed. The decrease in temperature was induced by an increase in the plasma concentration of FQ antimicrobials, suggesting that they are responsible for the temperature reduction. Focusing on glucocorticoids, one thermoregulation mechanism, we investigated the substances responsible for the reduction in rectal body temperature induced by FQ antimicrobials. Aminoglutethimide (an inhibitor of glucocorticoid production) were premedicated, followed by intraperitoneal administration of GFLX in the yeast-induced fever mouse model, resulting in attenuated GFLX-induced hypothermic effects.ConclusionsThese results suggest that certain antipyretic effects of CPFX, GFPX, and LVFX during fever may contribute to their hypothermic effects; certain mechanisms are glucocorticoid-mediated.

Antimicrobial Peptide Delivery Systems as Promising Tools Against Resistant Bacterial Infections

The extensive use of antibiotics during recent years has led to antimicrobial resistance development, a significant threat to global public health. It is estimated that around 1.27 million people died worldwide in 2019 due to infectious diseases caused by antibiotic-resistant microorganisms, according to the WHO. It is estimated that 700,000 people die each year worldwide, which is expected to rise to 10 million by 2050. Therefore, new and efficient antimicrobials against resistant pathogenic bacteria are urgently needed. Antimicrobial peptides (AMPs) present a broad spectrum of antibacterial effects and are considered potential tools for developing novel therapies to combat resistant infections. However, their clinical application is currently limited due to instability, low selectivity, toxicity, and limited bioavailability, resulting in a narrow therapeutic window. Here we describe an overview of the clinical application of AMPs against resistant bacterial infections through nanoformulation. It evaluates metal, polymeric, and lipid AMP delivery systems as promising for the treatment of resistant bacterial infections, offering a potential solution to the aforementioned limitations.

Mucoadhesive polyelectrolyte complexes of fucoidan and chitin nanowhiskers to prolong the antiprotozoal activity of metronidazole

The improvement of the specific pharmacological activity of agents with antimicrobial and antiprotozoal properties (e.g. metronidazole, MET) is of interest for clinical applications in the treatment of bacterial infections. In this work, we prepared the polyelectrolyte complexes (PEC) based on chitin nanowhiskers (CNW) and fucoidan (FUC) with hydrodynamic diameters of 244 and 816 nm, a ζ-potential of about −22 mV and good mucoadhesive properties. The incorporation of MET into PEC particles promoted the sustained release of MET for 10 h and maintained the antiprotozoal activity against clinical isolates of Trichomonas vaginalis for up to 10 h. At concentrations of 1–3 mg/mL (HeLa cell line), the CWN-FUC-MET particles showed no cytotoxicity. The sustained drug release rate, combined with pronounced mucoadhesive properties, improved pharmacological activity, and non-cytotoxicity makes the developed biopolymer delivery systems promising candidates for further clinical trials.

Cubosomes hydrogel containing silver based organometallic compounds for enhanced wound healing of burns: In vitro and in vivo studies

The aim of this study is to investigate the treatment of burn wounds and bacterial infections, specifically focusing on silver(I) N-heterocyclic carbene (Ag-NHC) loaded into cubosomes. Ag-NHC is an organometallic complex of silver (Ag) and can be considered an active pharmaceutical ingredient for the topical treatment of burns. A novel nanoparticle system, cubosome dispersions, was formulated using high pressure homogenization methods with different concentrations of lipid phase glyceryl monooleate (GMO), surfactants such as poloxamer 407 (F-127), and polyvinyl alcohol (PVA). The optimized formulation (U6) was characterized by in vitro drug release profile (90.54 ± 1.17 %), particle size (126.7 ± 0.98 nm), zeta potential (−21.6 ± 6.83 mV), entrapment efficiency (89.30 ± 1.46 %), and morphology as observed by transmission electron microscopy (TEM). The U6 formulation was incorporated into a hydrogel containing Carbopol 940 to form a cubosomal hydrogel (cubogel). The cubogel was characterized by the in vitro release of Ag-NHC (92 %), entrapment efficiency (>90 %), pH (5.3), viscosity (1.2 cP), spreadability, and TEM. From the in vitro drug release pattern, it was concluded that the U6 formulation showed slow and sustained drug release over 24 h, and demonstrated superior burn healing compared to marketed products. The in vivo wound healing study revealed that the cubogel demonstrated a superior burn healing rate compared to commercially available products (Quench® and Clotrimazole®). The in vivo histopathological results showed that the prepared cubogel was effective in treating second-degree burns, with no side effects or skin irritation, compared to commercial products. Additionally, Ag-NHC-loaded cubogel facilitated sustained release for treating burn wounds without any bacterial infections. The current findings provide a strong basis for the initiating phase 0 clinal trials, highlighting significant potential for the further research to benefit the pharmaceutical industry.

Evaluating omadacycline dosing regimens against drug-resistant pathogens including Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in adults: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

The objective of this study was to evaluate the efficacy of various dosing regimens of omadacycline against main drug-resistant pathogens in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to calculate cumulative fractions of response (CFRs) in terms of drug area under the concentration curve/minimum inhibition concentration targets.CFR ≥ 90% was considered optimal for a dosage regimen. CFR of any approved oral/intravenous regimen with loading-dose was ≥ 90% against methicillin-resistant Staphylococcus aureus (MRSA) for ABSSSI and penicillin-resistant Streptococcus pneumonia, tetracycline-resistant Streptococcus pneumonia, MRSA and β-lactamase positive Haemophilus influenzae for CABP. In conclusion, approved oral/intravenous loading and maintenance doses of omadacycline showed enough efficacy in the treatment of ABSSI and CABP caused by the main drug-resistant pathogens.

Ethylendiaminetetrakis(1,10-phenanthroline)dicopper(II) chlorided: Synthesis and application for voltammetric determination of doxycycline in real samples

The study describes on the preparation of a new homobinuclear mixed ligand complex µ-ethylendiaminetetrakis(1,10-phenanthroline)dicopper(II) chloridedihydrate (EP4Cu2CH2) from a previously reported complex chlorobis(1,10-phenanthroline)copper(II) chloridemonohydrate (CP2CuCH). The synthesis was checked by spectroscopy (UV–Vis, FT IR), CHN elemental analysis, Cu determination using ICP-OES, electrolytic conductivity, qualitative and quantitative chloride estimation, and melting point measurements. The new complex was applied for the modification of a glassy carbon electrode (poly(EP4Cu2CH2)/GCE) for determination of doxycycline (Doxy), (which belongs to a tetracycline antibiotic, mainly used for the treatment of a wide bacterial infections) by selective, accurate, and precise differential pulse voltammetric method. Electrode characterization revealed modification of the electrode surface by a conductive, and electroactive polymer film (poly(EP4Cu2CH2)/GCE) leading to improved effective electrode surface area. In contrast to the bare electrode, the appearance of two well-resolved irreversible oxidative peaks at much reduced potential with sevenfold current enhancement at poly(EP4Cu2CH2)/GCE showed the catalytic effect of the modifier towards Doxy. Differential pulse voltammetric current response of poly(EP4Cu2CH2)/GCE showed a linear dependence on the concentration of Doxy in the range 5 × 10−8 – 3.5 × 10−4 M with a detection limit of 3.5 × 10−9. The Doxy levels in four tablet brands were in the range 96.00–101.30 % of their labeled values. Spike recovery results in tablet, cow milk, and human urine samples were 98.90–100.73 %, 98.30–100.00 %, and 98.50–100.54 %, respectively. Based on the innovative mixed ligand poly(EP4Cu2CH2)/GCE, the interference recovery results about 4.79 % error, lesser LoD, and a broader concentrationrange than most previously published methods validated the present method’s potential applicability with excellent accuracy and sensitivity for Doxy determination in various real samples with complex matrix.

Precise photothermal treatment of bacterial infection mediated by charge-switchable nanoplatform with acylsulfonamide betaine surface

Photothermal therapy (PTT) offers a promising approach for the treatment of drug-resistant bacterial-infected wounds, yet it requires precise targeting of thermal damage to bacteria rather than healthy tissues. Herein, ultrasmall CuS NPs modified with polyzwitterion containing acylsulfonamide betaine (PCBSA@CuS), which provides a sensitive and reversible charge conversion around pH 6.8, are used to enhance the healing of bacteria-infected wounds. In the acidic infection microenvironment, the majority of PCBSA@CuS can electrostatically adsorb onto bacterial cells through cationic exposure, resulting in direct damage and death of bacteria upon NIR irradiation. Additionally, the photothermal NPs rapidly return to a zwitterionic nature in normal physiological environments, ensuring lower affinity and avoiding thermal damage to healthy tissues during continuous PTT. Compared to inert photothermal systems such as PEG-modified CuS NPs, the NPs used in this study exhibited higher bactericidal and wound healing efficacy. Therefore, this nano-antibacterial agent with highly sensitive thermal-targeting function provides a novel photothermal strategy for efficient and biosafe treatment of infected wounds.

Guanethidine Enhances the Antibacterial Activity of Rifampicin Against Multidrug-Resistant Bacteria

The escalating global threat of antibiotic resistance necessitates innovative strategies, such as the combination of antibiotics with adjuvants. Monotherapy with rifampicin is more likely to induce resistance in pathogens compared to other antibiotics. Herein, we found that the antihypertensive drug guanethidine enhanced the activity of rifampicin against certain clinically resistant Gram-negative bacteria, resulting in a reduction of up to 128-fold in the minimum inhibitory concentration. In infected animal models, this combination has achieved treatment benefits, including increased survival and decreased bacterial burden. The antimicrobial mechanism of guanethidine in synergy with rifampicin involves the disruption of the outer membrane of Gram-negative bacteria, leading to dissipation of the proton motive force. This results in an increase in reactive oxygen species and a reduction in ATP synthesis, severely disturbing energy metabolism and ultimately increasing bacterial mortality. In summary, guanethidine has the potential to become a novel adjuvant for rifampicin, offering a new option for the treatment of clinical Gram-negative bacterial infections.

Exploration of New Drug Candidate Derived from Antioxidants of Korean Native Halophytes: Control of Acinetobacter baumannii with Antipathogenic Activity

The rise of antibiotic-resistant bacteria poses a significant challenge to the treatment of bacterial infections, necessitating the development of novel antibiotics or strategies to preserve the efficacy of existing ones. This study investigates the role of oxidative stress modulation in the pathogenicity of multidrug-resistant (MDR) bacterial strains, aiming to identify potential avenues for new drug design. Specifically, the anti-biofilm effects of crude extracts and fractions from seven halophyte species native to Jeju Island, South Korea, were evaluated against Acinetobacter baumannii ATCC 17978. Notably, the 85% aqueous methanol fraction of Peucedanum japonicum Thunb. (Pj) and the n-hexane fraction of Lysimachia mauritiana Lam. (Lm) demonstrated significant anti-biofilm activity. Further assessments revealed that these fractions also exhibited notable antioxidant and anti-inflammatory properties, with the Pj fraction showing a lifespan extension effect in the Caenorhabditis elegans model. These findings suggest that Pj and Lm hold promise as potential candidates for the development of new therapeutic agents targeting MDR bacteria.

Experience with expanded use of oritavancin in a tertiary hospital: indications, tolerability and outcomes.

Oritavancin is a lipoglycopeptide antibacterial agent used to treat infections caused by Gram-positive organisms. It is FDA-approved for the treatment of acute bacterial skin and soft tissue infections (ABSSIs) but is increasingly being used off-label to treat invasive bacterial infections such as osteomyelitis, prosthetic joint infection and infective endocarditis. This study describes the clinical outcomes and adverse reactions related to oritavancin. This was a retrospective study conducted over a 5 year period at a tertiary care medical centre. Ninety-five adult patients were included in this study and were followed for 1 year after the last dose of oritavancin. The most common indication for oritavancin at our institution was osteomyelitis, followed by ABSSI. Other indications were vertebral infection, hardware-associated infection, bacteraemia and infective endocarditis. Fourteen percent (13/95) of patients developed an adverse reaction to oritavancin during the study period. Cure with no recurrence up to 1 year after the last dose of oritavancin was achieved in 74% (53/71) of patients, and the treatment failure rate was 19% (14/71 patients). Oritavancin is an effective agent that can be used to treat invasive Gram-positive bacterial infections other than ABSSI. Adverse events requiring drug discontinuation were common.

Self-assembly antimicrobial peptide for treatment of multidrug-resistant bacterial infection

The wide-spreading of multidrug resistance poses a significant threat to human and animal health. Although antimicrobial peptides (AMPs) show great potential application, their instability has severely limited their clinical application. Here, self-assembled AMPs composed of multiple modules based on the principle of associating natural marine peptide N6 with ß-sheet-forming peptide were designed. It is noteworthy that one of the designed peptides, FFN could self-assemble into nanoparticles at 35.46 µM and achieve a dynamic transformation from nanoparticles to nanofibers in the presence of bacteria, resulting in a significant increase in stability in trypsin and tissues by 1.72–57.5 times compared to that of N6. Additionally, FFN exhibits a broad spectrum of antibacterial activity against multidrug-resistant (MDR) gram-positive (G+) and gram-negative (G−) bacteria with Minimum inhibitory concentrations (MICs) as low as 2 µM by membrane destruction and complemented by nanofiber capture. In vivo mouse mastitis infection model further confirmed the therapeutic potential and promising biosafety of the self-assembled peptide FFN, which can effectively alleviate mastitis caused by MDR Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and eliminate pathogenic bacteria. In conclusion, the design of peptide-based nanomaterials presents a novel approach for the delivery and clinical translation of AMPs, promoting their application in medicine and animal husbandry.Graphical