Treatment Of Methicillin-resistant Staphylococcus Aureus Infections Research Articles

Norwogonin aids in fighting MRSA-induced pneumonia by targeting agrAC to inhibit α-hemolysin production.

The increasing prevalence of infections related to methicillin-resistant Staphylococcus aureus (MRSA) necessitates the exploration of innovative therapeutic strategies that diverge from conventional antibiotic treatments. This is imperative to effectively combat resistance and manage these infections. The adoption of antivirulence strategies has emerged as a particularly promising avenue. This approach applies a heightened selective pressure on pathogens, thereby diminishing the likelihood of bacteria evolving resistance to antibiotics. In our pursuit of novel therapeutics for treating MRSA infections, we have focused on agents that inhibit the virulence of S. aureus without impeding its growth, aiming to minimize the development of drug resistance. α-Hemolysin, a critical virulence factor encoded by the hla gene, is a cytotoxin that forms pores in host cell membranes and plays a pivotal role in the progression of disease during bacterial infections. Herein, we identified that norwogonin could effectively inhibit Hla production via targeting agrAC, a crucial protein in quorum sensing, resulting in dose-dependent inhibition of hemolytic activity without suppressing S. aureus growth. In vitro assays illustrated that norwogonin decreased the thermal stability of agrAC, providing evidence of interaction between norwogonin and agrAC. Meanwhile, norwogonin alleviated Hla-mediated A549 cell damage and reduced lactate dehydrogenase release. In vivo studies suggested that norwogonin treatment blocked the establishment of a mouse model of pneumonia caused by S. aureus USA300. Notably, norwogonin enhanced the antibacterial potency of oxacillin. In conclusion, norwogonin is a promising candidate for treating S. aureus infections, offering a novel alternative to traditional antibiotics by targeting virulence factors and enhancing the efficacy of existing treatments.

Plant Flavonoids with Antimicrobial Activity against Methicillin-Resistant Staphylococcus aureus (MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) has become a serious threat to human public health and global economic development, and there is an urgent need to develop new antimicrobial agents. Flavonoids are the largest group of plant secondary metabolites, and the anti-S. aureus and anti-MRSA activities of flavonoids have now been widely reported. The aim of this Review is to describe plant-derived flavonoid active ingredients and their effects and mechanisms of inhibitory activity against MRSA in order to provide insights for screening novel antimicrobial agents. Here, 85 plant-derived flavonoids (14 flavones, 21 flavonols, 26 flavanones, 9 isoflavones, 12 chalcones, and 3 other classes) with anti-MRSA activity are reviewed. Among these flavonoids, flavones and isoflavones generally showed the most significant anti-MRSA activity (MICs: 1-8 μg/mL). The results of the present Review display that most of the flavonoids with excellent anti-MRSA activity were derived from Morus alba L. and Paulownia tomentosa (Thunb.) Steud. The antibacterial mechanism of flavonoids against MRSA is mainly achieved by disruption of membrane structures, inhibition of efflux pumps, and inhibition of β-lactamases and bacterial virulence factors. We hope this Review can provide insights into the development of novel antimicrobials based on natural products for treating MRSA infections.

Nanocomposite alginate hydrogel loaded with propranolol hydrochloride kolliphor® based cerosomes as a repurposed platform for Methicillin-Resistant Staphylococcus aureus-(MRSA)-induced skin infection; in-vitro, ex-vivo, in-silico, and in-vivo evaluation.

Nanocomposite alginate hydrogel containing Propranolol hydrochloride (PNL) cerosomes (CERs) was prepared as a repurposed remedy for topical skin Methicillin-Resistant Staphylococcus aureus (MRSA) infection. CERs were formed via an ethanol injection technique using different ceramides, Kolliphores® as a surfactant, and Didodecyldimethylammonium bromide (DDAB) as a positive charge inducer. CERs were optimized utilizing 13. 22 mixed-factorial design employing Design-Expert® software, the assessed responses were entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP). The optimum CER, composed of 5mg DDAB, ceramide VI, and Kolliphor® RH40 showed tubular vesicles with EE% of 92.91 ± 0.98%, PS of 388.75 ± 18.99nm, PDI of 0.363 ± 0.01, and ZP of 30.36 ± 0.69 mV. Also, it remained stable for 90 days and manifested great mucoadhesive aspects. The optimum CER was incorporated into calcium alginate to prepare nanocomposite hydrogel. The ex-vivo evaluation illustrated that PNL was permeated in a more prolonged pattern from PNL-loaded CERs nanocomposite related to PNL-composite, optimum CER, and PNL solution. Confocal laser scanning microscopy revealed a perfect accumulation of fluorescein-labeled CERs in the skin. The in-silico investigation illustrated that the PNL was stable when mixed with other ingredients in the CERs and confirmed that PNL is a promising candidate for curing MRSA. Moreover, the PNL-loaded CERs nanocomposite revealed superiority over the PNL solution in inhibiting biofilm formation and eradication. The PNL-loaded CERs nanocomposite showed superiority over the PNL-composite for treating MRSA infection in the in-vivo mice model. Histopathological studies revealed the safety of the tested formulations. In conclusion, PNL-loaded CERs nanocomposite provided a promising, safe cure for MRSA bacterial skin infection.

Phage-antibiotic combinations in various treatment modalities to manage MRSA infections.

Introduction: The emergence of antibiotic resistance is a significant challenge in the treatment of bacterial infections, particularly in patients in the intensive care unit (ICU). Phage-antibiotic combination therapy is now being utilized as a preferred therapeutic option for infections that are multi-drug resistant in nature. Methods: In this study, we examined the combined impact of the staph phage vB_Sau_S90 and four antibiotics on methicillin-resistant Staphylococcus aureus (MRSA). We conducted experiments on three different treatment sequences: a) administering phages before antibiotics, b) administering phages and antibiotics simultaneously, and c) administering antibiotics before phages. Results: When the media was supplemented with sub-inhibitory concentrations of 0.25μg/mL and 1μg/mL, the size of the plaque increased from 0.5 ± 0.1mm (in the control group with only the phage) to 4 ± 0.2mm, 1.6 ± 0.1mm, and 1.6 ± 0.4mm when fosfomycin, ciprofloxacin, and oxacillin were added, respectively. The checkerboard analysis revealed a synergistic effect between the phages and antibiotics investigated, as indicated by a FIC value of less than 0.5. The combination treatment of phages and antibiotics demonstrated universal efficacy across all treatments. Nevertheless, the optimal effectiveness was demonstrated when the antibiotics were delivered subsequent to the phages. Utilizing the Galleria mellonella model, in vivo experiments showed that the combination of phage-oxacillin effectively eliminated biofilm-infected larvae, resulting in a survival rate of up to 80% in the treated groups. Discussion: Our findings highlight the advantages of using a combination of phage and antibiotic over using phages alone in the treatment of MRSA infections.

Antimicrobial and antibiofilm effect of cannabinoids from Cannabis sativa against methicillin-resistant Staphylococcus aureus (MRSA) causing bovine mastitis.

Antimicrobial resistance (AMR) poses a serious threat to human, animal, and plant health on a global scale. Search and elimination techniques should be used to effectively counter the spread of methicillin-resistant Staphylococcus aureus (MRSA) infections. With only a few novel drugs in clinical development, the quest for plant-based alternatives to prevent the spread of antibiotic resistance among bacteria has accelerated. Treatment of MRSA infections is challenging owing to rapidly emerging resistance mechanisms coupled with their protective biofilms. In the present research, we examined the antibacterial properties of ten plant-derived ethanolic leaf extracts. The most effective ethanolic leaf extract against MRSA in decreasing order of zone of inhibition, Cannabis sativa L. > Syzygium cumini > Murraya koenigii > Eucalyptus sp. > while Aloe barbadensis, Azadirachta indica, had very little impact. Mangifera indica, Curcuma longa, Tinospora cordifolia, and Carica papaya did not exhibit inhibitory effects against MRSA; hence, Cannabis was selected for further experimental study. The minimal inhibitory concentration (MIC) of Cannabis sativa L. extract was 0.25mgml-1 with 86% mortality. At a sub-MIC dosage of 0.125mgml-1, the biofilm formation was reduced by 71%. The two major cannabinoids detected were cannabidiol and delta-9-tetrahydrocannabinol (Δ9-THC), which were majorly attributed to substantial inhibitory action against MRSA. The time-kill kinetics demonstrated a bactericidal action at 4 MIC over an 8-20-h time window with a 90% reduction in growth rate. The results from SEM, and light microscopy Giemsa staining revealed a reduction in cells in the treated group with increased AKP activity, indicating bacterial cell membrane breakdown. These findings suggested cannabinoids may be a promising alternative to antibiotic therapy for bovine biofilm-associated MRSA.

Poly-l-lysine modified MOF nanoparticles with pH/ROS sensitive CIP release and CUR triggered photodynamic therapy against drug-resistant bacterial infection

The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly-l-lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen (1O2) and superoxide anion radical (O2−) for efficient inhibition towards methicillin-resistant Staphylococcus aureus (MRSA). The charge conversion from negative charge (−4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of H2O2, which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.

Comparison of broth microdilution and E-test for susceptibility of MRSA to vancomycin

Introduction: Healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) developed soon after the introduction of methicillin. These bacteria have shown resistance to multiple drugs and therefore vancomycin became the antibiotic of choice for treatment of MRSA infections. Vancomycin is a bactericidal antibiotic that acts by inhibiting bacterial cell wall synthesis. This study aimed to compare broth microdilution (BMD) and E-test in determining vancomycin minimum inhibitory concentration (MIC) against MRSA.Methods: A total of 30 clinical isolates of MRSA were acquired from Colombo South Teaching Hospital, Sri Lanka. These MRSA strains were identified by cefoxitin disk diffusion and the vancomycin MIC was determined through BMD and E-test. The Kruskal-Wallis test was applied to test if the samples originated from the same distribution with post hoc determination of the correlation between methods using the Mann-Whitney U test.Results: All 30 MRSA isolates were 100% vancomycin susceptible (≤2 μg/mL) irrespective of methodology, according to the Clinical and Laboratory Standards Institute (CLSI) established breakpoints. However, the E-test MIC values were 1 to 2 dilutions higher than those of BMD. A statistically significant difference between vancomycin MICs of BMD and E-test (p = <0.00001) was calculated which indicated a difference in accuracy.Conclusion: Due to cost, convenience, and the ability to detect vancomycin intermediate Staphylococcus aureus (VISA), exploring the possibility of using E-test as an alternative to BMD is worthwhile.

Effects of Phomopsidione on the Viability, Virulence, and Metabolites Profile of Methicillin-Resistant Staphylococcus aureus (MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) infections have become one of the most threatening multidrug-resistant pathogens. Thus, an ongoing search for anti-MRSA compounds remains an urgent need to effectively treating MRSA infections. Phomopsidione, a novel antibiotic isolated from Diaporthe fraxini, has previously demonstrated potent anti-candidal activity. The present study aimed to investigate the effects of phomopsidione on the viability, virulence, and metabolites profile of MRSA. MRSA was sensitive to phomopsidione in a concentration-dependent manner. Phomopsidione exhibited minimum inhibitory concentration and minimum bactericidal concentration of 62.5 and 500.00µg/mL against MRSA on broth microdilution assay. The compound showed significant reduction in virulence factors production including extracellular polymeric substances quantification, catalase, and lipase. An untargeted metabolomics analysis using liquid chromatography-high resolution mass spectrometry revealed a significant difference in the metabolites profile of MRSA with 13 putatively identified discriminant metabolites. The present study suggested the potential of phomopsidione as a promising anti-MRSA agent.

Antimicrobial activity of a natural compound and analogs against multi-drug-resistant Gram-positive pathogens.

The rapid emergence of methicillin-resistant Staphylococcus aureus (MRSA) isolates has precipitated a critical need for novel antibiotics. We have developed a one-pot synthesis method for naturally occurring compounds such as MC21-A (C58) and its chloro-analog, C59. Our findings demonstrate that these compounds kill MRSA isolates at lower or comparable concentrations to standard-of-care (SoC) antimicrobials. C59 eradicates MRSA cells in biofilms, which are notoriously difficult to treat with SoC antibiotics. Additionally, the lack of resistance development observed with C59 treatment is a significant advantage when compared to currently available antibiotics. Furthermore, these compounds are non-toxic to mammalian cell lines at effective concentrations. Our findings indicate the potential of these compounds to treat MRSA infections and underscore the importance of exploring natural products for novel antibiotics. Further investigation will be essential to fully realize the therapeutic potential of these next-generation antimicrobials to address the critical issue of antimicrobial resistance.

Efficacy and clinical potential of phage therapy in treating methicillin-resistant Staphylococcus aureus (MRSA) infections: A review.

Staphylococcus aureus infections have already presented a substantial public health challenge, encompassing different clinical manifestations, ranging from bacteremia to sepsis and multi-organ failures. Among these infections, methicillin-resistant S. aureus (MRSA) is particularly alarming due to its well-documented resistance to multiple classes of antibiotics, contributing significantly to global mortality rates. Consequently, the urgent need for effective treatment options has prompted a growing interest in exploring phage therapy as a potential non-antibiotic treatment against MRSA infections. Phages represent a class of highly specific bacterial viruses known for their ability to infect certain bacterial strains. This review paper explores the clinical potential of phages as a treatment for MRSA infections due to their low toxicity and auto-dosing capabilities. The paper also discusses the synergistic effect of phage-antibiotic combination (PAC) and the promising results from in vitro and animal model studies, which could lead to extensive human clinical trials. However, clinicians need to establish and adhere tostandard protocols governing phage administration and implementation. Prominent clinical trials areneeded to develop and advance phage therapy as a non-antibiotic therapy intervention, meeting regulatory guidelines, logistical requirements, and ethical considerations, potentially revolutionizing the treatment of MRSA infections.

In Vitro and Ex Vivo Investigation of the Antibacterial Effects of Methylene Blue against Methicillin-Resistant Staphylococcus aureus.

Methylene blue (MB) is a water-soluble dye that has a number of medical applications. Methicillin-resistant Staphylococcus aureus (MRSA) was selected as a subject for research due to the numerous serious clinical diseases it might cause and because there is a significant global resistance challenge. Our main goal was to determine and analyze the antibacterial effects of MB against S. aureus both in vitro and ex vivo to enhance treatment options. A total of 104 MRSA isolates recovered from various clinical specimens were included in this study. Minimum inhibitory concentration (MIC) values of MB against MRSA isolates were determined by the agar dilution method. One randomly selected MRSA isolate and a methicillin-susceptible S. aureus strain (S. aureus ATCC 25923) were employed for further evaluation of the antibacterial effects of MB in in vitro and ex vivo time-kill assays. A disc diffusion method-based MB + antibiotic synergy assay was performed to analyze the subinhibitory effects of MB on ten isolates. MICs of MB against 104 MRSA isolates, detected by the agar dilution method, ranged between 16 and 64 µg/mL. MB concentrations of 4 and 16 µg/mL showed a bactericidal effect at 24 h in the ex vivo time-kill assays and in vitro time-kill assays, respectively. We observed a significant synergy between cefoxitin and methylene blue at a concentration of 1-2 μg/mL in two (20%) test isolates. Employing MB, which has well-defined pharmacokinetics, bioavailability, and safety profiles, for the treatment of MRSA infections and nasal decolonization could be a good strategy.

Treatment of MRSA Infection: Where are We?

Staphylococcus aureus is a leading cause of septicemia, endocarditis, pneumonia, skin and soft tissue infections, bone and joint infections, and hospital-acquired infections. In particular, methicillin-resistant Staphylococcus aureus (MRSA) is associated with high morbidity and mortality, and continues to be a major public health problem. The emergence of multidrug-resistant MRSA strains along with the wide consumption of antibiotics has made anti-MRSA treatment a huge challenge. Novel treatment strategies (e.g., novel antimicrobials and new administrations) against MRSA are urgently needed. In the past decade, pharmaceutical companies have invested more in the research and development (R&D) of new antimicrobials and strategies, spurred by favorable policies. All research articles were collected from authentic online databases, including Google Scholar, PubMed, Scopus, and Web of Science, by using different combinations of keywords, including 'anti-MRSA', 'antibiotic', 'antimicrobial', 'clinical trial', 'clinical phase', clinical studies', and 'pipeline'. The information extracted from articles was compared to information provided on the drug manufacturer's website and Clinical- Trials.gov (https://clinicaltrials.gov/) to confirm the latest development phase of anti- MRSA agents. The present review focuses on the current development status of new anti-MRSA strategies concerning chemistry, pharmacological target(s), indications, route of administration, efficacy and safety, pharmacokinetics, and pharmacodynamics, and aims to discuss the challenges and opportunities in developing drugs for anti-MRSA infections.

Storage stability of lysostaphin solution and its pulmonary delivery.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a leading causative pathogen of nosocomial pneumonia with an alarming in-hospital mortality rate of 30%. Last resort antibiotic, vancomycin, has been increasingly used to treat MRSA infections, but the rapid emergence of vancomycin-resistant strains urges the development of alternative treatment strategies against MRSA-associated pneumonia. The bacteriolytic enzyme, lysostaphin, targeting the cell wall peptidoglycan of S. aureus, has been considered as a promising alternative for MRSA infections. Its proteinaceous nature is likely benefit from direct delivery to the lungs, but the challenges for successful pulmonary delivery of lysostaphin lying on a suitable inhalation device and a formulation with sufficient storage stability. In this study, the applicability of a vibrating mesh nebulizer (Aerogen Solo®) and a soft mist inhaler (Respimat®) was investigated. Both devices were capable of aerosolizing lysostaphin solution into inhalable droplets and caused minimum antibacterial activity loss. In addition, lysostaphin stabilized with phosphate-buffered saline and 0.1% Tween 80 was proved to have acceptable stability for at least 12 months when stored at 4 °C. These promising data encourage further clinical development of lysostaphin for management of MRSA-associated lung infections.

Computational Study of Antimicrobial Peptides for Promising Therapeutic Applications Against Methicillin-resistant Staphylococcus Aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a causative agent for multiple drug-resistant diseases and is a prime health concern. Currently, antibiotics like vancomycin, daptomycin, fluoroquinolones, linezolid, fifth-generation cephalosporin and others are available in the market for the treatment of MRSA infection. With the increasing prevalence of drug-resistant cases, researchers are actively investigating alternative strategies to combat MRSA, including the exploration of peptide therapeutics. This study employed computational methods to prospect for potential Antimicrobial Peptides (AMPs). A total of One hundred and fifty antimicrobial peptides were explored based on physicochemical properties. The results showed that Clavanin B was the most appropriate candidate. Molecular Docking and Molecular Dynamics Simulation results showed the protein-peptide interaction of the MRSA target proteins, Penicillin Binding Protein 2a and Panton-Valentine Leukocidin Toxin, with the Antimicrobial Peptide Clavanin B. Currently, the antimicrobial peptide database highlights Clavanin B's role as an anti-HIV peptide. Moreover, this investigation proposes Clavanin B as a viable repurposed drug for treating MRSA, underscoring its potential deployment in the management of MRSA infections.

Assessment of carvacrol-antibiotic combinations' antimicrobial activity against methicillin-resistant Staphylococcus aureus.

This study aimed to assess the antimicrobial activity of carvacrol in combination with approved antibiotics against methicillin-resistant Staphylococcus aureus (MRSA). Carvacrol, a phenolic monoterpenoid component of essential oils, has demonstrated antimicrobial properties against gram positive and gram negative bacteria. The study evaluated the antimicrobial effects of carvacrol combined with sulfamethoxazole, linezolid, minocycline, and trimethoprim. The MRSA strain (ATCC-33591) was used, and various assays, including MIC determination, checkerboard assay, and microdilution assay were conducted. The results showed that the combination of carvacrol with antibiotics yielded better outcomes compared to monotherapy, leading to reduced bacterial colonization. Carvacrol, sulfamethoxazole, and trimethoprim exhibited weak anti-staphylococcal effects, while linezolid and minocycline demonstrated stronger effects. This suggests that conventional antibiotic therapy may not be sufficient to effectively treat MRSA infections, potentially causing delays in healing or an exacerbation of the condition. Carvacrol combinations with two antibiotics displayed superior results compared to other pairs, indicating synergistic or additive effects of carvacrol with linezolid, minocycline, and sulfamethoxazole. These findings propose a new approach for developing drug molecules for MRSA treatment which combine volatile oils with available regimens. Further studies are recommended to evaluate the efficacy and biosafety of these combinations using in vivo or ex vivo models, aiming to minimize side effects and facilitate human trials. This study provides valuable insights into the potential use of carvacrol-antibiotic combinations as a novel therapeutic approach against MRSA.

Clindamycin Resistance Detection among MRSA at a Tertiary Care Hospital: A Cross-sectional Study

Introduction: Antimicrobial resistance is on the rise, posing a global threat to the success of modern surgical procedures. A common and notorious superbug causing community and hospital-acquired infections is Methicillin-resistant Staphylococcus aureus (MRSA). Its potential for easy and rapid spread leads to increased mortality in hospitals. Clindamycin, a relatively inexpensive and effective drug, is empirically prescribed for the treatment of MRSA infections. Due to the risk of misidentifying clindamycin resistance as susceptibility, leading to treatment failure, its judicious use after D-test is advocated. Aim: To isolate Staphylococcus aureus (S.aureus) from various clinical specimens and to identify MRSA using cefoxitin disc (30 μg), further determining the incidence of inducible clindamycin resistance among MRSA by the disc diffusion method (D-test). Materials and Methods: The present cross-sectional study was conducted in the Department of Microbiology, Government Mohan Kumaramangalam Medical College Hospital (GMKMCH), Salem, Tamil Nadu, India, from June 2023 to August 2023. Study was conducted using 185 S.aureus isolates collected from samples received from patients of all genders treated at the present study hospital. Various clinical samples such as pus, sputum, blood, urine and fluids collected from patients treated at the study Institute Salem during the study period were included. A cefoxitin disc (30 μg) was used to detect MRSA among the 185 S.aureus isolates by disc diffusion method as per Clinical and Laboratory Standards Institute (CLSI) guidelines, which were further tested for clindamycin resistance using clindamycin (2 μg) with erythromycin (15 μg) discs by the D-test. The data of the study were analysed using Statistical Package for the Social Sciences (SPSS) software version 21.0. Further descriptive statistics and a chi-square test with a level of significance, p-value ≤0.005 (statistically significant), were used. Results: Among 185 S.aureus isolates, 130 (70.27%) were Methicillin-sensitive S.aureus (MSSA) and 55 (29.7%) were MRSA. Inducible clindamycin resistance was observed in 22 (40%) isolates, while 17 (30.9%) isolates showed constitutive resistance, 9 (16.36%) showed the MS phenotype, and the remaining 7 (12.72%) showed the susceptible phenotype. Among the clindamycin resistance patterns in MRSA, inducible clindamycin resistance was reported predominantly. Conclusion: The majority of S.aureus was isolated from pus samples, highlighting its importance as a pyogenic microorganism. The current study records a high rate of MRSA resistance among S.aureus isolates. The present study reports a higher rate of inducible clindamycin resistance among MRSA isolates when compared to other phenotypes of clindamycin resistance. Therefore, routine D-testing must be implemented to identify inducible resistance to clindamycin in MRSA to avoid treatment failure.

High and Low Level Mupirocin Resistance among Clinical Isolates of Methicillin Resistant Staphylococcus aureus (MRSA)

Background: Staphylococcus aureus is a significant source of nosocomial infections, causing illnesses ranging from minor to life-threatening septic shock. Routine culturing and specific testing can confirm the presence of the bacteria. Antibiotic resistance is a major concern, and methicillin-resistant Staphylococcus aureus (MRSA) is particularly dangerous as it has mutations in the mecA gene, making it resistant to beta-lactam antibiotics. Mupirocin is an effective antibiotic against MRSA, binding to isoleucyl transfer-RNA synthetase to inhibit protein and RNA synthesis.
 Objective: In this study, two different concentrations of mupirocin were tested against MRSA.
 Material & Method: This study aimed to determine the antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) against two different doses of mupirocin. Clinical samples were collected in the duration of one year from different wards of Jinnah Hospital Lahore and processed in microbiology laboratory of Allama Iqbal medical college and after confirmation of Staphylococcus aureus, the modified Kirby Bauer method was used to test antimicrobial susceptibility. MRSA was confirmed by resistance to cefoxitin. High and low-level doses of mupirocin were applied, and zone sizes were measured.
 Results: Total 172 isolated methicillin resistant Staphylocuccus aureus (MRSA) from all age and genders were tested against two doses of mupirocin. Both (mupriocin 5 µg and 200µg) were highly effective and MRSA were around 97% sensitive to mupirocin.
 Conclusion: After the resistance of all beta lactam drugs, mupirocin can be very helpful in the treatment of MRSA infections.
 Key Words:MRSA, Mupriocin

Antimicrobial Effects of Propolis Ethanol Extract Tetragonula laeviceps Against Bacteria Methicillin Resistant Staphylococcus aureus

Staphylococcus aureus bacteria, especially Methicillin Resistant Staphylococcus aureus (MRSA), is one of the main causes of antibiotic resistance. MRSA is a bacteria that is resistant to the ?-lactam class of penicillin antibiotics. MRSA infections can cause a variety of health problems, including skin infections, pneumonia, and bacteremia. This problem requires alternative resources that can be an option. Propolis from the stingless bee species Tetragonula laeviceps can be a potential alternative for treating MRSA infections. This research is classified as a true experiment with a posttest control group design. The concentration of propolis ethanol extract tested was 20%; 10%; 5%; 2.5%; 1.25%; and 0.625% in the diffusion and dilution methods. These two methods provide assessment output in the form of inhibition zone diameter, minimum inhibition concentration, and minimum bactericidal concentration. The data obtained will be tested statistically using One-way Anova and Fisher's exact tests. Test results show that the ethanol extract of Tetragonula laeviceps propolis has an antimicrobial effect against MRSA bacteria. The diffusion test showed that the average diameter of the inhibition zone formed by the ethanol extract of propolis successively from a concentration of 20% to 1,25% with six repetitions was 12.7 ± 1.23 mm; 11.36 ± 0.67 mm; 10.24 ± 0.61 mm; 7.59 ± 1.69 mm; and 6.5 ± 1.14 mm. From these averages, the One-Way Anova test revealed a statistically significant difference in the diameter of the inhibition zone (F(7,40) = [ 192.79], p = 0.000).

Pinus koraiensis Essential Oil Attenuates the Pathogenicity of Superbacteria by Suppressing Virulence Gene Expression.

In the quest to combat infections attributable to antibiotic-resistant superbacteria, an essential oil derived from the needles of Pinus koraiensis Sieb. et Zucc. (PKEO) has emerged as a promising solution. In this study, we demonstrate that PKEO can be used to inhibit the growth, glucose metabolite acidogenicity, and biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA). Quantitative PCR analysis provided direct evidence that PKEO reduces the mRNA expression of the accessory gene regulator A (agrA) and staphylococcal accessory regulator A (sarA), thereby indicating its inhibitory effect on pathogenic regulatory genes. Chromatographic analyses of PKEO identified terpene hydrocarbons as prominent essential oil constituents. These compounds, notably α-pinene, limonene, and β-caryophyllene, have been established to have antimicrobial properties. Our findings indicate that an oil derived from P. koraiensis can effectively combat antibiotic-resistant strains by disrupting the pathogenicity regulatory system, thereby establishing PKEO as a promising candidate for the treatment of MRSA infections.

Topical antimicrobial formulations using medicinal plant-derived essential oils targeting methicillin resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) causes a variety of healthcare-associated and community-acquired infections. Due to limited availability of effective antimicrobials for treating MRSA infections, there is a growing need to explore alternative therapeutic approaches. Here, the antimicrobial activities of 19 oils, popularly used for their medicinal properties, were tested against MRSA USA300. Oils obtained from cinnamon, clove, tangerine, and coriander showed the most promising activities, demonstrating bactericidal, anti-adhesive and anti-biofilm activities, and synergistic properties with common antibiotics. Given that clove and cinnamon oils showed the best activities, they were incorporated into topical formulations. Not only did the formulations with oils maintain antimicrobial and anti-adhesive activities, but their anti-biofilm property was potentiated. Tests on Galleria mellonella larvae suggested that the formulation is non-toxic. The formulations proposed here are a great alternative for the decolonisation of surfaces containing MRSA and can help circumventing antimicrobial resistance, a growing threat in the hospital environment.