Resistant MRSA Research Articles

P-665. Etiology of Pneumonia and Antibiotic Resistance in Adults with Cancer in the ICU of a Tertiary Care Centre in Eastern India: a Prospective Cohort Study

Abstract Background Cancer and its treatment cause immune-dysregulation which, along with frequent healthcare exposure, poses a higher risk of respiratory infections, frequently with unusual pathogens that can be highly drug-resistant. We assessed the etiology of pneumonia in adult cancer patients admitted to the ICU over one year and summarized the antibiotic resistance seen. Methods Pneumonia cases were identified from October 2022-September 2023. Sputum, endotracheal secretion, bronchoalveolar lavage (BAL), tracheal aspirate, nose and throat swab samples from -4 to +10 days of the date of event were considered. Microbiological diagnosis involved microscopy, culture, ELISA, PCRs, and CBNAATs. Antibiotic susceptibility was determined phenotypically by disc-diffusion and genotypically using PCR tests for MRSA, ESBL, carbapenemase, and polymyxin resistance genes. Results 355 cases of pneumonia were identified. 258 (72.7%) cases of had a positive microbiology, 123 were polymicrobial (47.7%) and termed “co-infections/ superadded infections". Table 1 summarizes the etiology of microbiology positive cases. Antibiotic susceptibility data was available for 191 isolates, 14 were Staphylococcus aureus (table 2) and 177 were Gram-negatives (table 3). S. aureus have fluoroquinolones. 30.4% were MRSA and 21.4% showed inducible clindamycin resistance. Gram negatives were resistant to third-generation cephalosporins, beta-lactam/beta-lactamase inhibitors, carbapenems, aminoglycosides, fluoroquinolones and cotrimoxazole, though variations exist across genera. 51% Gram negative isolates were positive for ESBL, 5.8% for AmpC, 9.7% were polymyxin resistant, and 49.5% were resistant to carbapenems. Carbapenem resistance genotypes are summarized in table 4. Conclusion Isolates from adult cancer patients with pneumonia showed high prevalence of resistance to all first-line antibiotics. Disclosures All Authors: No reported disclosures

Comprehensive safety and toxicity analysis of 2,2’-Bipyridine derivatives in combating MRSA biofilm formation and persistence

IntroductionMethicillin-resistant Staphylococcus aureus (MRSA) infections have become arduous to treat due to their capacity to form biofilms, develop persistence, and exhibit significant antimicrobial resistance. These factors contribute to the complexity of managing MRSA infections and highlight the urgent need for innovative treatment strategies.ObjectivesThis endeavor aims to evaluate the safety of 2,2’-Bipyridine (2,2’-Bipy) derivatives and their antimicrobial, anti-biofilm, and anti-persister activities in treating MRSA Infections.MethodsSix derivatives were screened for their ADMET properties and tested for minimum inhibitory concentrations against various bacterial strains using agar well diffusion and broth dilution. Safety studies were conducted through hemolysis tests, cell viability assays, and in vivo acute oral toxicity examinations. Bactericidal mechanisms and biofilm disruption effects were analyzed using crystal violet staining and confocal microscopy assays. The murine thigh infection model was also used to investigate the in vivo efficacy.ResultsAll derivatives exhibited favorable physicochemical profiles and ADMET properties and are predicted to be safe based on their drug-like properties. in vitro studies demonstrated that derivatives are non-toxic to 3T3 L1, and in vivo studies confirmed their safety in mice at a dose of 300 mg/kg and their non-hemolytic nature against rabbit red blood cells. All compounds showed potent antibacterial activity against the tested bacteria, including the resistant MRSA strain 831. They inhibited biofilm formation and eradicated biofilms in a dose-dependent manner against MTCC 737 and MRSA 831, and they effectively eliminated MRSA persister cells, outperforming the reference antibiotic vancomycin. These derivatives were found to depolarize the mitochondrial membrane and accumulate intracellular reactive oxygen species. These derivatives significantly reduced the bacterial load in the murine thigh infection model.ConclusionThe study concluded that 2,2’-Bipy derivatives possess significant antimicrobial activity, are non-toxic, and are effective in inhibiting biofilm formation and killing persister cells.

Lysine succinylome analysis of MRSA reveals critical roles in energy metabolism and virulence.

MRSA's resistance poses a global health challenge. This study investigates lysine succinylation in MRSA using proteomics and bioinformatics approaches to uncover metabolic and virulence mechanisms, with the goal of identifying novel therapeutic targets. Mass spectrometry and bioinformatics analyses mapped the MRSA succinylome, identifying 8 048 succinylation sites on 1 210 proteins. These analyses included Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) network construction (e.g. using the STRING database), providing a comprehensive functional and interactive landscape of succinylated proteins. The succinylated proteins were predominantly involved in cytoplasmic metabolic processes, with enrichment in glycolysis/gluconeogenesis and the tricarboxylic acid (TCA) cycle. Both of these pathways are critical for MRSA's energy production, growth, and virulence, supplying the necessary metabolic intermediates and energy to support bacterial survival and pathogenicity. Motif analysis revealed 13 conserved motifs, while PPI analysis highlighted FnbA as a central virulence factor. Succinylation significantly influences MRSA's metabolism and virulence, potentially impacting biofilm by modifying key proteins such as FnbA, bifunctional autolysin, and LuxS. These findings provide new avenues for developing antibiofilm strategies and therapeutic interventions against MRSA.

Epidemiology and Resistance Profiles of Bacteria Isolated from Blood Samples in Septic Patients at Emergency Department Admission: A 6-year Single Center Retrospective Analysis from Northern Italy.

This study aimed to investigate the microbiological and clinical heterogeneity of community-onset bloodstream infections (BSIs) and identify features to support targeted empirical antibiotic therapy in the Emergency Department (ED). Clinical and microbiological data from 992 BSI cases (1,135 isolates) diagnosed within 24 hours of ED admission at IRCCS Humanitas Research Hospital, Milan, Italy (January 2015-June 2022), were analyzed. Drug resistance was interpreted using EUCAST-2023. Clinical features included age, sex, comorbidities (e.g., cancer, diabetes), infection source, presence of central venous catheters (CVC), ongoing therapies, and sepsis severity. Microbiological data included pathogen identification and antimicrobial susceptibility. Antibiotic-susceptible Escherichia coli (29.5%) was the most common isolate, including extended-spectrum beta-lactamase (ESBL)-producing strains (11.3%), followed by methicillin-susceptible Staphylococcus aureus (MSSA, 8.4%). BSIs due to E. coli were more frequent in patients >60 years (43.9% vs. 27.3%, p<0.001) and associated with ESBL production (OR=2.202, p=0.031) and urosepsis (OR=1.688, p=0.006). Younger patients (≤60 years) had more S. aureus-associated BSIs (22.4% vs. 10.8%, p<0.001) and methicillin resistance (7.9% vs. 3.6%, p=0.021). Carbapenem-resistant Enterobacterales were rare (2.1%-2.8%), predominantly involving Klebsiella pneumoniae. Onco-hematological patients had a lower multidrug-resistance prevalence (9.5% vs. 21.1%, p<0.001). Community-onset BSIs demonstrated substantial prevalence of resistant pathogens, including ESBL and MRSA, emphasizing the need for robust surveillance systems. Age is a critical factor in guiding empirical antibiotic therapy in the ED.

Detection of multidrug-resistant methicillin-resistant Staphylococcus aureus from healthy black Bengal goat in Bangladesh.

The emergence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is a growing public health concern. The objective of this study was to determine the prevalence and multi-drug resistant (MDR) profiles of MRSA in goats in Bangladesh. A total of 150 samples from goats comprised of rectal swab (n = 50), nasal swab (n = 50), and milk (n = 50) were collected. Isolation of S. aureus from samples was conducted onto mannitol salt agar (MSA). Identification of S. aureus was performed by cultural characteristics, Gram staining, biochemical tests (catalase, coagulase, indole, methyl red, and Voges-Proskaur), and nuc gene-specific PCR assay. The MRSA was identified by cefoxitin disc diffusion test and mecA gene-specific PCR assay. The MDR profiles of MRSA were performed against ampicillin, amoxicillin, gentamicin, cefoxitin, vancomycin, azithromycin, cefotaxime, ciprofloxacin and nalidixic acid by disc diffusion method. The overall prevalence of S. aureus was 35.3% and MRSA was 7.3%. The prevalence of MRSA was 12% in rectal swabs, 8% in nasal swabs, and 2% in milk. The highest resistance of MRSA was against ampicillin (91%) followed by azithromycin (55%), amoxycillin (36%), nalidixic acid (27%), ciprofloxacin (18%) and cefotaxime (9%). Most MRSA isolates (90.9%) exhibited resistance to at least three classes of antibiotics and were MDR. This study shows that goats may harbor MDR-MRSA, posing a risk to public health.

Unveiling the Potential of Bergenia Phenolics: Vitexin's Role in Allosteric Modulation of PBP2a as a Strategy against MRSA Resistance.

For cell wall biosynthesis, drug-resistant S. aureus uses a special protein called PBP2a, even when antibiotics are present and stop its natural processes from working. To combat this, novel therapies are required to specifically target PBP2a with greater efficacy. Using computational approaches, we screened nine phenolic compounds from other Bergenia species, including Bergenia ciliata, Begenia ligulata, Bergenia purpurascens, and Bergenia stracheyi, against the PBP2a allosteric site to explore the potential interaction between phenolic compounds and a specific region of PBP2a known as the allosteric site. Based on interaction patterns and estimated affinity, vitexin has been found to be the most prominent phenolic compound. We performed MD simulations on vitexin and ceftazidime as control molecules based on the docking results. The binding free energy estimates of vitexin (-94.48 +/- 17.92 kJ/mol) using MM/PBSA were lower than those of the control (-67.61 +/- 12.29 kJ/mol), which suggests that vitexin may be able to inhibit PBP2a activity in MRSA. It has been intriguing to observe a correlation between the affinity of the lead vitexin at the allosteric site and the modification of Tyr446, the active site gatekeeper residue in PBP2a. Our findings have implied that lead vitexin can either directly or indirectly decrease PBP2a activity by inducing allosteric site change in conventional medicine.

Evaluation of Antibiotic Sensitivity in Methicillin-Resistant Staphylococcus aureus Isolates From Clinical Specimens in a Tertiary Care Hospital.

Common Gram-positive bacteria Staphylococcus aureus can cause infections ranging from minor skin conditions to serious illnesses like sepsis.Methicillin-resistant S. aureus (MRSA) emerged in the 1960s and now causes over 50% of hospital infections. In India, MRSA prevalence ranges from 25% in the west to 50% in the south. Contributing factors include prolonged hospital stays and indiscriminate antibiotic use. This study investigates the prevalence and antibiotic resistance patterns of MRSA in clinical isolates from a hospital in Karad. MRSA's resistance to multiple antibiotics, including vancomycin, poses significant treatment challenges, with limited therapeutic options such as vancomycin, linezolid, daptomycin, and teicoplanin remaining effective. The antibiotics mentioned provide a broader context for understanding MRSA resistance. In this study, only those specifically relevant to the hospital's data have been included in detail in the result table antibiogram of MRSA. A two-year laboratory-based analysis of MRSA strains in a hospital that provides tertiary care was conducted to assess their antibiotic susceptibility profiles. In all, 100 isolates of MRSA were examined for patterns of antibiotic susceptibility in various clinical specimens. Among these 41 (41%) were from pus samples, 18 (18%) from wound swabs/discharge, 15 (15%) from urine, 13 (13%) from blood, 4% fromsputum, and 3% fromtips were found to have smaller percentages than umbilical swabs (2 (2%)) and tissue (1 (1%)) and vaginal swabs( 1 (1%)) and sinus tract samples (1 (1%)). The frequency of MRSA strains was more in males (59%). Linezolid showed the highest sensitivity at 86%. This studyhighlights the growing challenge of MRSAand other resistant bacteria in hospital settings, complicating treatment choices. Effective MRSA​​​​​​​ management requires stringent antibiotic policy, infection control procedures, and thorough susceptibility testing. These strategies are critical to preserving viable treatment options and combating antibiotic resistance in healthcare environments.

Resilience Against Resistance: Exploring Cutting-edge Therapies for Methicillin-resistant Staphylococcus aureus (MRSA).

Methicillin-resistant Staphylococcus aureus [MRSA] stands as an enduring threat within healthcare landscapes, characterized by its ability to rapidly evolve and develop resistance to conventional antibiotics. This comprehensive review embarks on a journey through the historical landscape of MRSA, elucidating its initial emergence and subsequent evolution of resistance mechanisms over time. The narrative unfolds to underscore the profound impact of MRSA on patient outcomes and healthcare systems globally. Current trends in MRSA therapies come under meticulous scrutiny, spotlighting the limitations and challenges associated with existing treatment modalities. This analysis underscores the critical need for transformative and innovative therapeutic strategies to effectively combat the ever-growing spectre of drug resistance in MRSA from the exploration of novel antibiotics designed to overcome resistance mechanisms to the promising potential of phage therapy and immunotherapies. Amidst the exploration of innovative therapies, the review identifies and discusses emerging issues and challenges in MRSA management. Insights are provided into the intricate web of obstacles hindering the adoption and implementation of new therapeutic strategies. Furthermore, the socio-economic implications of MRSA and drug resistance are brought to the forefront, emphasizing the broader impact on public health and healthcare systems. In parallel, historical perspectives on MRSA research illuminate key milestones in scientific understanding and technological advancements. The evolution of research strategies and their impact on our ability to comprehend and combat MRSA is examined, providing context for the current state of the field. In conclusion, this review summarizes major findings and drawing implications for the future of MRSA treatment. Recommendations for further research and clinical practice are outlined, encapsulating a holistic overview of the resilient efforts against resistance in the ongoing battle against MRSA.

Green synthesis of cerium oxide nanoparticles usingTribulus terrestris: characterization and evaluation of antioxidant, anti-inflammatory and antibacterial efficacy against wound isolates.

Multi-drug resistance (MDR) infections are a significant global challenge, necessitating innovative and eco-friendly approaches for developing effective antimicrobial agents. This study focuses on the synthesis, characterization, and evaluation of cerium oxide nanoparticles (CeO2NPs) for their antioxidant, anti-inflammatory, and antibacterial properties. The CeO2NPs were synthesized using aTribulus terrestrisaqueous extract through an environmentally friendly process. Characterization techniques included UV-visible spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), x-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Energy Dispersive x-ray (EDX) analysis. The UV-vis spectroscopy shows the presence of peak at 320 nm which confirms the formation of CeO2NPs. The FT-IR analysis of the CeO2NPs revealed several distinct functional groups, with peak values at 3287, 2920, 2340, 1640, 1538, 1066, 714, and 574 cm-1. These peaks correspond to specific functional groups, including C-H stretching in alkynes and alkanes, C=C=O, C=C, alkanes, C-O-C, C-Cl, and C-Br, indicating the presence of diverse chemical bonds within the CeO2NPs. XRD revealed that the nanoparticles were highly crystalline with a face-centered cubic structure, and SEM images showed irregularly shaped, agglomerated particles ranging from 100-150 nm. In terms of biological activity, the synthesized CeO2NPs demonstrated significant antioxidant and anti-inflammatory properties. The nanoparticles exhibited 82.54% antioxidant activity at 100 μg ml-1, closely matching the 83.1% activity of ascorbic acid. Additionally, the CeO2NPs showed 65.2% anti-inflammatory activity at the same concentration, compared to 70.1% for a standard drug. Antibacterial testing revealed that the CeO2NPs were particularly effective against multi-drug resistant strains, includingPseudomonas aeruginosa,Enterococcus faecalis, and MRSA, with moderate activity againstKlebsiella pneumoniae. These findings suggest that CeO2NPs synthesized viaT. terrestrishave strong potential as antimicrobial agents in addressing MDR infections.

Phytoconstituent and In silico Screening of Active Compounds from Red Ginger (Zingiber officinale var. rubrum Theilade) Rhizome and Avocado (Persea americana Mill.) Leaves Extracts as Novel Inhibitors of MRSA

Red ginger rhizome (Zingiber officinale var. Rubrum) and avocado leaves (Persea americana Mill.) are empirically known as one of the medicinal plants used in Taro Village, Gianyar Regency, Bali which have great potential in treating infectious diseases caused by antibiotic resistance, such as MRSA. This study aims to analyze the phytoconstituents and anti-MRSA potential contained in red ginger rhizome and avocado leaves extracts by assessing their inhibitory effects on three proteins related to MRSA resistance and virulence (PBAP2a, transglycosylase, and glycosyltransferase). Phytoconstituents of avocado leaf and red ginger extracts were analyzed using GC-MS. Molecular docking was performed in silico to determine the similarity properties of predicted drugs, bioactivity, toxicity, identification of active sites and validation of protein structures, and docking simulations were performed between compounds found in the extract and their target proteins. Phytoconstituent analysis revealed that avocado leaves and red ginger extracts as a whole have 43 types of compounds and 10 bioactive compounds each with beneficial drug-like properties. The compound 6,11-hexadecadien-1-ol from avocado leaves extracts was predicted to have hepatotoxic properties. There were at least 3 compounds, namely beta-bisabolene from avocado leaves extract, zingiberenol and gamma-curcumene from red ginger rhizome extract, showing the lowest binding affinity for the target protein. Red ginger rhizome and avocado leaves extracts showed valuable potential as anti-MRSA agents through the mechanism of inhibition of three resistance-related proteins, as predicted by in silico analysis.

High Prevalence and Antibiotic Resistance of MRSA and Acinetobacter spp. among Healthcare Personnel and Neonatal Units: Implications for Infection Control and Hygiene Protocols

High Prevalence and Antibiotic Resistance of MRSA and Acinetobacter spp. among Healthcare Personnel and Neonatal Units: Implications for Infection Control and Hygiene Protocols

Pharmaceutical Innovations and Stewardship Programs in Combating Antimicrobial Resistance

This study evaluates the effectiveness of the UK’s AMR Strategy 2019-2024 in combating antimicrobial resistance (AMR), focusing on pharmaceutical innovations. By analyzing trends in human and veterinary antibiotic use alongside resistance rates, the research identifies improvements in reducing antibiotic consumption and resistance, with MRSA resistance declining from 10% in 2016 to 6% in 2023. Despite these positive trends, the research highlights ongoing challenges in the development and implementation of new antibiotics and alternative therapies. Semi-structured interviews with stakeholders, including policymakers and pharmaceutical experts, reveal barriers such as regulatory issues, slow innovation, and insufficient funding for new drug development. The study also examines case studies of pharmaceutical innovations, including β-lactamase inhibitors, bacteriophage therapies, and antimicrobial peptides, noting progress in some areas, but significant gaps in others. The research concludes that while the UK’s AMR Strategy has led to some positive outcomes, further efforts are needed to accelerate the development of novel therapies and address structural barriers in the pharmaceutical sector. Future research should focus on enhancing international collaboration, improving regulatory frameworks, and incentivizing innovation to combat AMR more effectively. Comparative analysis with other countries' strategies could also provide valuable insights for improving the UK’s response to the AMR crisis.

ConsensusPrime—A Bioinformatic Pipeline for Efficient Consensus Primer Design—Detection of Various Resistance and Virulence Factors in MRSA—A Case Study

Background: The effectiveness and reliability of diagnostic tests that detect DNA sequences largely hinge on the quality of the used primers and probes. This importance is especially evident when considering the specific sample being analyzed, as it affects the molecular background and potential for cross-reactivity, ultimately determining the test’s performance. Methods: Predicting primers based on the consensus sequence of the target has multiple advantages, including high specificity, diagnostic reliability, broad applicability, and long-term validity. Automated curation of the input sequences ensures high-quality primers and probes. Results: Here, we present a use case for developing a set of consensus primers and probes to identify antibiotic resistance and virulence genes in Staphylococcus (S.) aureus using the ConsensusPrime pipeline. Extensive qPCR experiments with several S. aureus strains confirm the exceptional quality of the primers designed using the pipeline. Conclusions: By improving the quality of the input sequences and using the consensus sequence as a basis, the ConsensusPrime pipeline pipeline ensures high-quality primers and probes, which should be the basis of molecular assays.

Increasing Antibiotic-Resistant Infections With Inpatient Endoscopic Retrograde Cholangioscopies (ERCP) Is Associated With Higher Mortality in the United States: A Cross-sectional Cohort Study.

This study aims to investigate associated mortality with inpatient endoscopic retrograde cholangiopancreatography (ERCP) with and without resistant infections. The co-primary objective compares frequencies of inpatient ERCP with resistant infections to overall hospitalizations with resistant infections. The risks of inpatient antibiotic-resistant organisms are known, but the associated mortality for inpatient ERCP is unknown. We aim to use a national database of hospitalizations and procedures to understand trends and mortality for patients with antibiotic-resistant infections during inpatient ERCP. The largest publicly available all-payer inpatient database in the United States (National Inpatient Sample) was used to identify hospitalizations associated with ERCPs and antibiotic-resistant infections for MRSA, VRE, ESBL, and MDRO. National estimates were generated, frequencies were compared across years, and multivariate regression for mortality was performed. From 2017 to 2020, national weighted estimates of 835,540 inpatient ERCPs were generated, and 11,440 ERCPs had coincident resistant infections. Overall resistant infection, MRSA, VRE, and MDRO identified at the same hospitalization of inpatient ERCPs were associated with higher mortality (OR CI(95%): Overall: 2.2(1.77-2.88), MRSA: 1.90 (1.34-2.69), VRE: 3.53 (2.16-5.76), and MDRO: 2.52 (1.39-4.55)). While overall hospitalizations with resistant infections have been decreasing annually, there has been a yearly increase in admissions requiring ERCPs with simultaneous resistant infections ( P =0.001-0.013), as well as infections with VRE, ESBL, and MDRO ( P =0.001-0.016). Required Research Practices for Studies Using the NIS scoring was 0, or the most optimal. Inpatient ERCPs have increasing coincident resistant infections and are associated with higher mortality. These rising infections during ERCP highlight the importance of endoscopy suite protocols and endoscopic infection control devices.

Identification of CH2-linked quinolone-aminopyrimidine hybrids as potent anti-MRSA agents: Low resistance potential and lack of cross-resistance with fluoroquinolone antibiotics

The structural optimization of B14, an antibacterial agent we previously obtained, has led to the discovery of a new class of CH2-linked quinolone-aminopyrimidine hybrids with potent anti-MRSA activities. Surprisingly, the hybrids lacking a C-6 fluoro atom at the quinolone nucleus showed equal or even stronger anti-MRSA activities than their corresponding 6-fluoro counterparts, despite the well-established structure-activity relationships (SARs) indicating that the 6-fluoro substituent enhances the antibacterial activity in conventional fluoroquinolone antibiotics. Moreover, these new hybrids, albeit structurally related to conventional fluoroquinolones, showed no cross-resistance with fluoroquinolone drugs. The most active compound, 15m, exhibited excellent activities with a MIC value of 0.39 μg/mL against both fluoroquinolone-sensitive strain USA500 and -resistant MRSA isolate Mu50. Further resistance development studies indicated MRSA is unlikely to acquire resistance against 15m. Moreover, 15m displayed favorable in vivo half-life and safety profiles. These findings suggest a rationale for further evolution of quinolone antibiotics with a high barrier to resistance.

Charge adaptive phytochemical-based nanoparticles for eradication of methicillin-resistant staphylococcus aureus biofilms

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

Study on antimicrobial resistance and detection of MRSA of Staphylococcus aureus isolated from carcass in Daegu slaughterhouses

Study on antimicrobial resistance and detection of MRSA of <i>Staphylococcus aureus</i> isolated from carcass in Daegu slaughterhouses

Comparative structural analysis of MecA encoded beta-lactam resistance in MRSA

As the level of antibiotic resistance in bacteria rises, the threat of patients facing fatal consequences from a simple cut or infection grows dramatically. One example of an emerging antibiotic-resistant threat is MRSA, methicillin-resistant staphylococcus aureus, which is a growing cause of hospital-acquired pneumonia, skin infections, and even sepsis through cross-contamination in health care settings. However, methicillin resistance like that exploited by MRSA is also highly conserved with that of another species of staphylococcus bacteria, Staphylococcus sciuri which is the ancestral bacterium of S. aureus. S. sciuri is a typically animal-associated bacterium with increasing clinical relevance as the amount of human infections from it has grown. Both these bacteria share the commonality of having the mecA gene that determines methicillin resistance transported through the mobile Staphylococcal cassette chromosome. This study focuses on the relationship between the mecA mobile element in S. sciuri compared to S. aureus and explores the specific role of S. sciuri in the creation of the mecA cassette. Understanding the cassette evolution and similarities and differences between S. sciuri and S. aureus will enable the continued tracking of S. sciuri as an emerging clinical threat. To answer all these questions, BLAST analysis, InterProScan, and additional computational analysis were used to characterize differences in homology, structure, function, and effect on infectivity, robustness of antibiotic resistance, and morbidity. The overall goal of this analysis is to characterize the differences between mecA and methicillin-resistant genes in clinically relevant MRSA as well as environmental samples such as S. sciuri.

Identification of isothiazolones analogues as potent bactericidal agents against antibiotic resistant CRE and MRSA strains

Carbapenem-resistant Enterobacterales (CRE) has emerged as a worldwide spread nosocomial superbug exhibiting antimicrobial resistance (AMR) to all current antibiotics, leaving limited options for treating its infection. To discovery novel antibiotics against CRE, we designed and synthesized a series of 14 isothiazol-3(2H)-one analogues subjected to antibacterial activity evaluation against Escherichia coli (E. coli) BL21 (NDM-1) and clinical strain E. coli HN88 for investigating their structure–activity relationships (SAR). The results suggested that 5-chloroisothiazolone core with an N-(4-chlorophenyl) substitution 5a was the most potent antibacterial activity against the E. coli BL21 (NDM-1) with MIC value of less than 0.032 μg/mL, which was at least 8000-fold higher than the positive control Meropenem (MRM). It also displayed 2048-fold potent than the positive control MRM against E. coli HN88. Additionally, SAR analysis supported the conclusion that compounds with a chloro-group substituted on the 5-position of the heterocyclic ring was much more potent than other positions. The board spectrum analysis suggested that compound 5a showed a promising antimicrobial activity on MRSA and CRE pathogens. Meanwhile, cytotoxicity study of compound 5a suggested that it had a therapeutic index value of 875, suggesting future therapeutic potential. In vivo efficacy study declared that compound 5a could also protect the BALB/c mice against American type culture collection (ATCC) 43,300. Further screening of our compounds against a collection of CRE strains isolated from patients indicated that compound 5 g displayed much stronger antibacterial activity compared with MRM. In conclusion, our studies indicated that isothiazolones analogues could be potent bactericidal agents against CRE and MRSA pathogens.

Recombination-mediated dissemination of Methicillin-resistant S. aureus clonal complex 1 in the Egyptian health care settings

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is a rapidly evolving pathogen that is frequently associated with outbreaks and sustained epidemics. This study investigated the population structure, resistome, virulome, and the correlation between antimicrobial resistance determinants with phenotypic resistance profiles of 36 representative hospital-acquired MRSA isolates recovered from hospital settings in Egypt.ResultsThe community-acquired MRSA lineage, clonal complex 1 (CC1) was the most frequently detected clone, followed by three other globally disseminated clones, CC121, CC8, and CC22. Most isolates carried SCCmec type V and more than half of isolates demonstrated multi-drug resistant phenotypes. Resistance to linezolid, a last resort antibiotic for treating multidrug resistant MRSA, was observed in 11.11% of the isolates belonging to different genetic backgrounds. Virulome analysis indicated that most isolates harboured a large pool of virulence factors and toxins. Genes encoding aureolysin, gamma hemolysins, and serine proteases were the most frequently detected virulence encoding genes. CC1 was observed to have a high pool of AMR resistance determinants including cfr, qacA, and qacB genes, which are involved in linezolid and quaternary ammonium compounds resistance, as well as high content of virulence-related genes, including both of the PVL toxin genes. Molecular clock analysis revealed that CC1 had the greatest frequency of recombination (compared to mutation) among the four major clones, supporting the role of horizontal gene transfer in modulating AMR and hypervirulence in this clone.ConclusionsThis pilot study provided evidence on the dissemination success of CA-MRSA clone CC1 among Egyptian hospitals. Co-detection of multiple AMR and virulence genes in this lineage pose a broad public health risk, with implications for successful treatment. The results of this study, together with other surveillance studies in Egypt, should be used to develop strategies for controlling MRSA infections in Egyptian health-care settings.