Methicillin-resistant Strains Research Articles

A Comprehensive Study on Antibiotic Resistance among Coagulase-Negative Staphylococci (CoNS) Strains Isolated from Ready-to-Eat Food Served in Bars and Restaurants.

The present study aimed to characterize and assess the diversity of CoNS strains as potential vectors for the spread of resistance to antimicrobial agents from RTE foods served in bars and restaurants. Eighty-five CoNS strains, obtained from 198 RTE food samples, were investigated. Sixty-seven CoNS isolates (78.8%) were resistant to at least one antibiotic tested, and 37 (43.5%) were multidrug resistant (MDR-CoNS). Moreover, CoNS strains contained genes conferring resistance to antibiotics critically important in medicine, i.e., β-lactams [mecA (29.4%); blaZ (84.7%)], aminoglycosides [aac(6')-Ie-aph(2″)-Ia (45.9%); aph(2″)-Ic (3.5%)], macrolides, lincosamides and streptogramin B-MLSB [msrA/B (68.2%); ermB (40%) and mphC (4.7%)], tetracyclines [tetK (31.8%); tetM (16.5%) and/or tetL (2.35%)]. We also found the fusB/C/D genes responsible for the acquired low-level fusidic acid resistance (17.6%) and streptogramin resistance determinant vgaA in 30.6% of isolates. In three linezolid resistant strains (2 S. epidermidis and 1 S. warneri), mutation was detected, as demonstrated by L101V and V188I changes in the L3 protein amino acid sequences. The high frequency in RTE food of MDR-CoNS including methicillin-resistant (MR-CoNS) strains constitutes a direct risk to public health as they increase the gene pool from which pathogenic bacteria can pick up resistance traits.

Portulaca oleracea L. organic acid extract inhibits persistent methicillin-resistant Staphylococcus aureus in vitro and in vivo.

Staphylococcus aureus continues to be one of the most important pathogens capable of causing a wide range of infections in different sites of the body in humans and livestock. With the emergence of methicillin-resistant strains and the introduction of strict laws on antibiotic usage in animals, antibiotic replacement therapy has become increasingly popular. Previous studies have shown that Portulaca oleracea L. extract exerts a certain degree of bacteriostatic effect, although the active ingredients are unknown. In the present study, the antibacterial activity of the organic acid of P. oleracea (OAPO) against S. aureus was examined using a series of experiments, including the minimum inhibitory concentration, growth curve, and bacteriostasis curve. In vitro antibacterial mechanisms were evaluated based on the integrity and permeability of the cell wall and membrane, scanning electron microscopy, and soluble protein content. A mouse skin wound recovery model was used to verify the antibacterial effects of OAPO on S. aureus in vivo. The results showed that OAPO not only improved skin wound recovery but also decreased the bacterial load in skin wounds. Moreover, the number of inflammatory cells and cytokines decreased in the OAPO-treated groups. In summary, this study reports a botanical extract that can inhibit S. aureus in vitro and in vivo, indicating the potential use of OAPO to prevent and control S. aureus infection in the near future.

MRSA compendium of epidemiology, transmission, pathophysiology, treatment, and prevention within one health framework.

Staphylococcus aureus is recognized as commensal as well as opportunistic pathogen of humans and animals. Methicillin resistant strain of S. aureus (MRSA) has emerged as a major pathogen in hospitals, community and veterinary settings that compromises the public health and livestock production. MRSA basically emerged from MSSA after acquiring SCCmec element through gene transfer containing mecA gene responsible for encoding PBP-2α. This protein renders the MRSA resistant to most of the β-lactam antibiotics. Due to the continuous increasing prevalence and transmission of MRSA in hospitals, community and veterinary settings posing a major threat to public health. Furthermore, high pathogenicity of MRSA due to a number of virulence factors produced by S. aureus along with antibiotic resistance help to breach the immunity of host and responsible for causing severe infections in humans and animals. The clinical manifestations of MRSA consist of skin and soft tissues infection to bacteremia, septicemia, toxic shock, and scalded skin syndrome. Moreover, due to the increasing resistance of MRSA to number of antibiotics, there is need to approach alternatives ways to overcome economic as well as human losses. This review is going to discuss various aspects of MRSA starting from emergence, transmission, epidemiology, pathophysiology, disease patterns in hosts, novel treatment, and control strategies.

Assessment of synergistic activity of rhamnolipid and linezolid against methicillin-resistant Staphylococcus aureus in-vitro and in-vivo with Galleria mellonella larvae model.

Antibiotic resistance, one of the most crucial public health problems, has increased the interest in synergy studies of antibiotics with existing antibiotics and natural compounds to make current treatment more effective in addition to new drug development. In this study, the effectiveness of rhamnolipid and linezolid on the Galleria mellonella larvae model in-vitro and in-vivo against Methicillin-resistant Staphylococcus aureus isolates, which are problematic in treatment, were investigated. Four S.aureus (One ATCC 29213 strain and three methicillin-resistant strains) were used in the study. Two MRSA isolates were resistant to linezolid, and one was susceptible. Partial synergy was observed in one resistant strain, and although no synergy was observed in the other resistant strain, the minimum inhibitory concentration of the resistant strain decreased from 16 to 4μg/mL with a four-fold decrease and reached the susceptibility limit. No change was observed in the MIC of linezolid-susceptible strains. The G.mellonella larval model demonstrated that combined therapy was more effective than monotherapy by survival function tests and CFU determination. RML/LNZ combination improved survival compared to monotherapy and decreased the bacterial burden from 108 to 103.

Распространенность бессимптомного носительства метициллин-резистентных Staphylococcus spp. на слизистой оболочке носовой полости и ротоглотки

Staphylococci are widely distributed in the environment. Most species of the genus Staphylococcus are opportunistic resident representatives of the human and animal microbiota, capable of causing diverse clinical manifestations of varying severity. The situation is aggravated by the widespread distribution of representatives of the genus Staphylococcus, which are resistant to methicillin – the first semi-synthetic penicillin – and are causative agents of community-acquired infections posing a danger to immuno-compromised people. The purpose of our study was to identify methicillin-sensitive and methicillin-resistant strains of Staphylococcus spp. on the mucous membrane of the nasal cavity and oropharynx by polymerase chain reaction. The study involved 588 people who, as part of their professional activities, should be examined for carriage of Staphylococcus aureus in the nasopharynx. As a result of the study, staphylococcus DNA was detected in 273 (46.42%) of the subjects, and methicillin-resistant strains predominated, they were detected in 227 (83.15%) people. Among them, DNA of methicillin-resistant coagulase-negative Staphylococcus spp. was found in 148 (54.21%) people, a combination of different types of methicillin-resistant staphylococci, including methicillin-resistant S. aureus and methicillin-resistant coagulase-negative Staphylococcus spp., was detected in 53 (19.41%) subjects, DNA of methicillin-resistant S. aureus in monoculture was detected in 26 (9.52%) people. DNA of methicillin-sensitive S. aureus was found in 46 (16.84%) people.

Antimicrobial Susceptibility Profile of Methicillin Resistant Staphylococcus Aureus (MRSA) Isolates in a Tertiary Care Hospital, Mysuru, India

Antimicrobial medications have become a significant issue in the healthcare sector as a result of the increaseddeath rate from Staphylococcus aureus infections, the appearance of methicillin-resistant and other multi-drugresistant strains. The study’s goals and objectives were determining the prevalence of MRSA and assessing theantibiotic efficacy of MRSA isolates from various clinical samples.Materials and Methods: A total of 395 MRSA were isolated from various clinical specimens and identified byusing standard microbiological techniques at tertiary care hospital of Mysore, South India. Methicillin resistancewas determined by standard Kirby-Bauer disc diffusion test using cefoxitin 30μg disk.Antimicrobial resistance patterns were determined by automated Vitek2 system.Results: A total of 246 (62.27%) isolates were identified as MRSA out of 395 S. aureus isolates collected from variousclinical samples such as pus samples (86.17%), blood (3.65%), Et swabs (3.65%), ear swabs (2.84%), sputum (1.6%),urine (0.81%), and other sterile body fluids (1.21%). All MRSA isolates were susceptible (100%) to vancomycin,linezolid and daptomycin followed by other antibiotics like rifampicin (99%), tigecycline (96.74%), tetracycline(95.93%), teicoplanin (95.5%), gentamicin (73.17%). Most of the MRSA isolates were resistant to oxacillin (97.15%),trimethoprim/sulfamethoxazole (95.12%), Levofloxacin (93.49%), ciprofloxacin (92.68%), clindamycin (87.80%),erythromycin (63.41%).Conclusion: In our study, we found MRSA isolates were susceptible to most active and reliable routinely usedantibiotics. Good infection control procedures like thorough hand washing, identifying and treating MRSAcarriers, and prudent use of antimicrobial medicines are advised to prevent the formation of drug-resistantisolates. In addition to the Vitek 2 approach, we may conclude that cefoxitin disc diffusion is an essential test todiagnose MRSA.

Repositioning of FDA-approved drugs for the treatment of methicillin-resistant Staphylococcus aureus infection: Structure-based virtual screening and in vitro assay

Background: Computer-aided repositioning of approved drugs is an increasingly popular strategy for the discovery of effective therapies. The potency of the newly repositioned drugs can be optimized using them as a component of an effective drug combination, thereby achieving the desired therapeutic effect at a lower and more tolerable drug concentration. Aim and Objectives: The aim of the study was to perform structure-based virtual screening and repurposing of FDA-approved drugs for the treatment of methicillin resistance by Staphylococcus aureus (SA) and perform an in vitro validation of the prediction. Materials and Methods: Following ethical clearance at the Department of Pharmacology and Therapeutics, College of Health Sciences, Usmanu Danfodiyo University Sokoto, molecular docking was performed against 5 validated protein targets involved in the development of methicillin resistance by SA and an in vitro validation of the prediction was done using 3 of the top-ranking drug candidates against methicillin-resistant vancomycin-susceptible strain of the pathogen (ATCC 43300). Results: Desmopressin and docetaxel, two of the 20 top-ranking repurposed drugs discovered through virtual screening, enhanced the inhibitory effect of oxacillin against the ATCC 43300 SA strain in a ratio-dependent manner, although each of the two drugs singly was only weakly effective against the bacterial strain. The standard drug, vancomycin (also among the top-scoring candidates), alone, was effective against ATCC 43300 strain and in combination with oxacillin, the two drugs produced a ratio-dependent synergistic effect against the bacterial strain. Conclusion: These findings suggest that oxacillin-based combinations with desmopressin, docetaxel, and the standard drug vancomycin, three of the 20 top-ranking drugs, at optimum ratios, may be beneficial in reversing the resistance of the ATCC 43300 SA strain to oxacillin, thus supporting the prediction of the molecular docking results.

Bacteria-mediated synthesis of silver nanoparticles under photo-irradiation and their efficacy against methicillin-resistant Staphylococcus aureus

ABSTRACT Over the last few decades, morbidity and mortality rates from infectious diseases have increased due to antibiotic resistance. Community-acquired and nosocomial-related methicillin-resistant bacterial strains are proliferating, which makes the discovery of new antibiotics and the search for new approaches to fight pathogenic bacteria an urgent task. One of the new promising classes of antimicrobials is silver nanoparticles (AgNPs). The goal of this study was to investigate the bacteria-mediated synthesis of AgNPs and evaluate their antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Indigenous bacteria from soil samples from Multan (Pakistan) were isolated and three strains – Klebsiella spp., Citrobacter freundii, and Bacillus cereus – were selected for the synthesis of AgNPs under photo-irradiation. The biosynthesis of AgNPs was confirmed by UV-visible spectroscopy. The AgNPs obtained in our experiments showed strong antibacterial activity against MRSA isolated from patients with community-acquired skin infections (from the dermatology ward of Jinnah Hospital Lahore) with 15 mm to 25 mm zones of inhibition (ZOI) according to the well diffusion method. The results of this project showed that microbial reduction of AgNO3 under photo-irradiation produces AgNPs that are highly active against MRSA.

Multicenter Antimicrobial Resistance Surveillance of Clinical Isolates from Major Hospitals - China, 2022.

Bacterial resistance surveillance is crucial for monitoring and understanding the trends and spread of drug-resistant bacteria. The number of strains collected in 2022 increased compared to 2021. The top five bacteria, including Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, remained largely unchanged. The detection rate of methicillin-resistant strains continued to decrease. Among clinical Enterobacterales isolates, the resistance rate to carbapenems was generally below 13%, except for Klebsiellaspp., which had a resistance range of 20.4% to 21.9%. Most clinical Enterobacterales isolates were highly susceptible to tigecycline, colistin, and polymyxin B, with resistance rates ranging from 0.1% to 12.6%. The detection rate of meropenem-resistant P. aeruginosa and meropenem-resistant Acinetobacter baumannii showed a decreasing trend for the fourth consecutive year. Multidrug-resistant bacteria remain a significant public health challenge in clinical antimicrobial treatment. To effectively address bacterial resistance, it is essential to enhance both bacterial resistance surveillance and the prudent use of antimicrobial agents.

Biofilm Formation by Staphylococcus aureus in the Specific Context of Cystic Fibrosis

Staphylococcus aureus is a major human pathogen whose characteristics support its success in various clinical settings including Cystic Fibrosis (CF). In CF, S. aureus is indeed the most commonly identified opportunistic pathogen in children and the overall population. S. aureus colonization/infection, either by methicillin-susceptible or methicillin-resistant strains, will become chronic in about one third of CF patients. The persistence of S. aureus in CF patients' lungs, despite various eradication strategies, is favored by several traits in both host and pathogen. Among the latter, living in biofilm is a highly protective way to survive despite deleterious environmental conditions, and is a common characteristic shared by the main pathogens identified in CF. This is why CF has earned the status of a biofilm-associated disease for several years now. Biofilm formation by S. aureus, and the molecular mechanisms governing and regulating it, have been extensively studied but have received less attention in the specific context of CF lungs. Here, we review the current knowledge on S. aureus biofilm in this very context, i.e., the importance, study methods, molecular data published on mono- and multi-species biofilm and anti-biofilm strategies. This focus on studies including clinical isolates from CF patients shows that they are still under-represented in the literature compared with studies based on reference strains, and underlines the need for such studies. Indeed, CF clinical strains display specific characteristics that may not be extrapolated from results obtained on laboratory strains.

Antimicrobial Polyketides from the Marine-Derived Fungus Spiromastix sp. SCSIO F190.

Three diphenyl ethers (1-3) and a cyclopentenone (4), together with seven known compounds (5-11), were isolated from the fermentation broth of the marine sediment-derived fungus Spiromastix sp. SCSIO F190. Compounds 3 and 4 were found to exist as a pair of atropisomers (3a, 3b) and racemates (4a, 4b), respectively. The planar structures of compounds 1-4 were elucidated on the basis of NMR and HRESIMS data sets. The absolute configurations of 2 and 3 were determined by spectroscopic and single-crystal X-ray diffraction analyses, whereas the configuration of 4 was determined by spectroscopic and chiral analyses. All compounds, except for 4 and 11, displayed activities against various pathogenic bacteria. Notably, compounds 1-4, especially 1, exhibited strong activity against Gram-positive bacteria, including methicillin-resistant bacterial strains of Staphylococcus aureus (MRSA), Enterococcus faecalis ATCC 29212, and Bacillus subtilis BS01, with MIC values ranging from 0.5 to 4 μg/mL. Moreover, the structure-activity relationship analyses of the active compounds and their analogues revealed the critical structural features correlating to the observed antimicrobial activities, herein providing insights for antimicrobial drug development.

Green Synthesis of Copper Nanoparticles Using Leaf Extract of Ocimum sanctum and its Antimicrobial Activity

Objectives: We reported a non-toxic, low-cost and environmentally friendly green synthesis technique for the manufacture of copper nanoparticles (Cu NPs) utilizing Ocimum sanctum (O. sanctum) leaf extract to prevent hospital-acquired and Methicillin-resistant pathogenic bacterial infections strains. Materials and Methods: The biogenic synthesis of Cu NPs via chemical precipitation method using O. sanctum phytochemical extract as stabilizing and reducing agent. Cu NPs syntheses are characterized using UV-visible spectroscopy (UV-vis spectroscopy), X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) to analyze and confirm size and nature of Cu NPs. Results: UV-vis spectroscopy of Cu NPs showed an absorption peak at 528 nm with calculated band gap 2.1 eV. XRD analysis indicates crystallite nature of Cu NPs having an average size 48 nm. FTIR showed involvement of O. sanctum extract biomolecules in capping process Cu NPs. The hexagonal morphology structure of Cu NPs nanoparticles is observed by SEM analysis. Cu NPs showed antibacterial activity against Staphylococcus aureus (38.66 ± 1.15 mm), Escherichia coli (43.33 ± 1.15 mm), Pseudomonas aeruginosa (21.66 ± 0.57 mm) and Proteus vulgaris (42.66± 0.57 mm). Conclusion: We report synthesis of simple, inexpensive and eco-friendly O. sanctum mediated Cu NPs. The biophysical characterization techniques used for analyze size, shape and nature of nanoparticles. The 32 ug/ml Cu NPs concentration showed excellent antimicrobial activity against Gram positive and Gram-negative bacteria. Cu NPs efficiently used to prevent Proteus vulgaris mediated infection.

Evolution of antibiotic susceptibility profiles of staphylococci from osteoarticular infections: A 10-year retrospective study

BackgroundKnowledge of the antibiotic susceptibility profiles of the bacteria responsible for osteoarticular infections is crucial for choosing the appropriate empirical antibiotic regimen. Wide use of broad spectrum antibiotics in these infections may have lead to selection of resistant bacteria. The aim of our study was to answer to these questions: (1) Did the bacterial pathogens isolated from osteoarticular infections (OAIs) and their antibiotic susceptibility profile change over the 10-year period in our University Hospital, particularly for Staphylococcus aureus and Coagulase negative staphylococci? (2) Are the antibiotics used for post-operative antibiotic therapy still effective against staphylococci involved in OAIs? (3) Are the antibiotics used for documented therapy still effective against staphylococci involved in OAIs? HypothesisWe hypothetise that bacterial epidemiology and antibiotic resistance rates have changed little thanks to a reasoned prescription of antibiotics in our Center. Materials and methodsWe performed a retrospective study describing the antibiotic susceptibility profile of bacteria isolated from osteoarticular infections over 10years in our University Hospital, with a focus on the Staphylococcus genus. ResultsA total of 3474 staphylococci were included (2373 coagulase negative staphylococci and 1101 S. aureus), 34.8% (1207/3469) of which were resistant to methicillin. Antibiotic susceptibility profiles remained quite stable between 2010 and 2019, except for rifampicin (14.1% (45/318) versus 5.7% (23/401), p=0.0001) and fluoroquinolones (35.3% (109/309) versus 20.3% (81/399), p=0.000008) for which resistance rates significantly decreased even among methicillin-resistant strains. DiscussionIn spite of wide use of antibiotics in orthopaedic units, overall resistance rates did not increase over the last 10years. The prescription of these molecules in combination regimens guided by the antibiotic susceptibility patterns performed on reliable samples and on the basis of multidisciplinary discussions may explain these results. Level of evidenceIV, retrospective study.

Detection of PBP2a and PVL Genes among Staphylococcus aureus and Their Methicillin-Resistant Strains Isolated from a Hospital in Sokoto Town

Detection of PBP2a and PVL Genes among Staphylococcus aureus and Their Methicillin-Resistant Strains Isolated from a Hospital in Sokoto Town

ENDOPHTHALMITIS IN OPHTHALMOLOGICAL REFERRAL CENTRE IN COLOMBIA: AETIOLOGY AND MICROBIAL RESISTANCE.

To describe the aetiology and microbial susceptibility profile of endophthalmitis cases treated at an ophthalmological referral centre in Colombia. A retrospective descriptive study was carried out with all endophthalmitis cases referred to the Fundación Oftalmológica de Santander FOSCAL (Floridablanca, Colombia) from 1 January 2012 to 31 December 2015. 121 eyes of 121 patients were evaluated. 77.7% of them were male and the mean age was 42.9 years. Five of them (4.1%) corresponded to endogenous endophthalmitis, and 116 (95.9%) to exogenous endophthalmitis. Of the latter, 66.9% were associated with trauma (almost one-half of them associated with intraocular foreign body), and 29.5% with intraocular surgery. The most common isolated microorganisms in the exogenous endophthalmitis group corresponded to methicillin-resistant and methicillin-sensitive strains of Staphylococcus epidermidis and Staphylococcus aureus, which were mostly susceptible to imipenem, vancomycin and moxifloxacin and resistant to ceftazidime. Endophthalmitis is a potentially sight-threatening condition, especially in cases of inadequate treatment. Therefore, antimicrobial therapy should be guided by vitreous humour culture to assure that the causative microorganism is susceptible to the selected agent. The results of our study lead us to propose vancomycin, moxifloxacin or imipenem as first-line antimicrobial options.

Size-dependent molecular interaction of nontraditional 2D antibiotics with Staphylococcus aureus

The application of nanomaterials for their antibacterial properties is the subject of many studies due to antibiotic resistance of pathogen bacteria and the necessity of omitting them from food and water resources. Graphene oxide (GO) is one of the most popular candidates for antibacterial application. However, the optimum condition for such an effect is not yet clear for practical purposes. To shed light on how GO and bacteria interaction depends on size, a wide range of GO flake sizes from hundreds of µm2 going down to nano-scale as low as 10 N m2 was produced. In an in-vitro systematic study to inhibit Staphylococcus aureus growth, the correlation between GO flake size, thickness, functional group density, and antibacterial activity was investigated. The GO suspension with the average size of 0.05 µm2, in the order of the size of the bacteria itself, had the best bacteriostatic effect on S. aureus with the minimum inhibitory concentration value of 8 μg ml−1, well within the acceptable range for practical use. The bacteriostatic effect was measured to be a 76.2% reduction of the colony count over 2 h of incubation and the mechanism of action was the wrapping and isolation of cells from the growth environment. Furthermore, in-vivo animal studies revealed that 16 μg ml−1 of the optimum GO has efficient antibacterial performance against the methicillin-resistant strains of the bacteria with an enhanced wound healing rate and tensiometrial parameters which is important for realized targets.

Ultrasound-assisted facile synthesis of Boron-Heck-coupled sclareol analogues as potential antibacterial agents against Staphylococcus aureus.

To evaluate the antimicrobial capability of sclareol and its derivatives against Staphylococcus aureus and its Methicillin-resistant strain (MRSA). A new series of Boron-Heck-coupled sclareol analogues were prepared by structural modifications at the C-15 terminal double bond of sclareol using ultrasonication. The structural modifications were designed to keep the stereochemistry of all the five chiral centres of sclareol intact. A two-step reaction scheme consisting of Boron-Heck coupling of sclareol followed by Wittig reaction was carried out to produce novel sclareol congeners for antimicrobial evaluation. Three compounds SAJ-1, SAJ-2 and SB-11 exhibited strong antibacterial activity against S. aureus and Methicillin-resistant strain (MRSA) with MIC values between 3 and 11 μM. Among all the screened compounds, SAJ-1 and SAJ-2 showed the best antibiofilm profiles against both strains. Moreover, SAJ-1 and SAJ-2 acted synergistically with streptomycin against S. aureus while creating varying outcomes in combination with ciprofloxacin, penicillin and ampicillin. SAJ-1 also acted synergistically with ampicillin against S. aureus, while SB-11 showed synergism with ciprofloxacin against both pathogens. Moreover, SAJ-1 and SAJ-2 also inhibited staphyloxanthin production in S. aureus and MRSA and induced postantibiotic effects against both pathogens. It can be inferred that SAJ-1, SAJ-2 and SB-11 may act as potential chemical entities for the development of antibacterial substances. The study revealed that SAJ-1 and SAJ-2 are the most suitable sclareol analogues for further studies towards the development of antibacterial substances. SAJ-1, SAJ-2 and SB-11 show promising antibacterial properties against Staphylococcus aureus. Efforts should be made and more research should be done utilizing in vivo models to determine their efficacy as antibiotics.

Smart composite antibacterial coatings with active corrosion protection of magnesium alloys

A new method of the formation of composite coatings with the function of active corrosion protection of magnesium alloys was developed using the plasma electrolytic oxidation (PEO) method. Susceptibility of PEO-layers to pitting formation was evaluated using localized electrochemical methods (SVET/SIET). The morphological features and electrochemical properties of composite coatings were studied using SEM/EDX, XRD, micro-Raman spectroscopy and EIS/PDP measurements, respectively. The effect of surface layers impregnation with corrosion inhibitor on their protective properties in a corrosive environment was established. Additional protection was achieved using controllable coating pore sealing with polymer. It was found that the polymer treatment of the PEO-layer does not reduce the inhibitor's efficiency. The formed protective composite inhibitor-and-polymer-containing layers decrease the corrosion current density of a magnesium alloy in a 3 wt.% NaCl solution to three orders of magnitude. This predetermines the prospect of new smart coatings formation that significantly expand the field of application of electrochemically active materials. The mechanism of smart composite coating corrosion degradation was established. The antibacterial activity of the inhibitor-containing coatings against S. aureus methicillin-resistant strain was proved using the in vitro model. These protective layers are promising for reducing the incidence of implant-associated infections.

Comparative In Vitro Activity of New Lipoglycopeptides and Vancomycin Against Ocular Staphylococci and Their Toxicity on the Human Corneal Epithelium.

The purpose of this study was to assess the potential of new lipoglycopeptides as novel topical therapies for improved treatment of recalcitrant ocular infections. We evaluated the in vitro antimicrobial activity of oritavancin, dalbavancin, and telavancin compared with vancomycin (VAN) against a large collection of ocular staphylococcal isolates and their cytotoxicity on human corneal epithelial cells (HCECs). Antimicrobial susceptibility testing was performed by broth microdilution against 223 Staphylococcus spp. clinical isolates. Time-kill kinetics were determined for methicillin-resistant strains of Staphylococcus aureus (MRSA) (n = 2) and Staphylococcus epidermidis (MRSE) (n = 1). In vitro cytotoxicity assays were performed with AlamarBlue and live/dead staining on HCECs. All new lipoglycopeptides showed strong in vitro potency against ocular staphylococci, including multidrug-resistant MRSA strains, with dalbavancin showing a slightly higher potency overall [minimum inhibitory concentration (MIC) 90 0.06 μg/mL] compared with telavancin and oritavancin (MIC 90 0.12 μg/mL), whereas VAN had the lowest potency (MIC 90 2 μg/mL). Oritavancin exerted rapid bactericidal activity within 1 h for MRSA and 2 h for MRSE. All other drugs were bactericidal within 24 h. At a concentration commonly used for topical preparations (25 mg/mL), cytotoxicity was observed for VAN after 5 min of incubation, whereas reduction in HCEC viability was not seen for telavancin and was less affected by oritavancin and dalbavancin. Cytotoxicity at 25 mg/mL was seen for all drugs at 30 and 60 min but was significantly reduced or undetected for lower concentrations. Our study demonstrates that new lipoglycopeptides have substantially better in vitro antimicrobial activity against ocular staphylococcal isolates compared with VAN, with a similar or improved toxicity profile on HCECs.

The Therapeutic Potential of 4-Methoxy-1-methyl-2-oxopyridine-3-carbamide (MMOXC) Derived from Ricinine on Macrophage Cell Lines Infected with Methicillin-Resistant Strains of Staphylococcus aureus.

The incidences of methicillin-resistant strains of Staphylococcus aureus (MRSA) and their survival inside the macrophages are the major attributes of the relapsed infections after antimicrobial therapy, and it is a global problem. In this context, we have previously demonstrated 4-methoxy-1-methyl-2-oxopyridine-3-carbamide (MMOXC), a Ricinine derivative exhibiting anti-S. aureus and anti-biofilm characteristics by competitively inhibiting uridine monophosphate kinase (UMPK), UDP-N-acetyl muramyl pentapeptide ligase (Mur-F), and peptidyl deformylase, (PDF). In the present study, the stability of this competitive inhibitor MMOXC was evaluated by showing its ability to remain bound to the active sites of UMPK, Mur-F, and PDF even after increasing the incubation time, temperature, pH, and substrate concentration. On growing MRSA in fewer concentrations of MMOXC, these strains could not attain resistance to MMOXC and at the same time distinct reductions in the expression of UMPK, Mur-F, and PDF genes were noted. In vitro, infective models were generated by infecting MRSA to RAW 264.7 and human monocyte-derived macrophage (hMDM) cell lines. In these infected cell lines, in spite of increased nitric oxide synthase (NOS), NADPH-P450 reductase, superoxide dismutase, catalase, and peroxidase activities, the MRSA survived. At 640µM/ml, the concentration of MMOXC penetrated into these infected cells and obliterated MRSA. While treating uninfected macrophage cell lines with MMOXC, no appreciable effect was observed indicating that MMOXC is the most suitable drug for the treatment of infections caused by MRSA.