Methicillin-resistant Staphylococcus Aureus Strains Research Articles

Prevalence of Methicillin-Resistant Staphylococcus aureus in Saudi Arabia: A Systematic Review and Meta-Analysis.

Methicillin-resistant Staphylococcus aureus (MRSA) is a public health concern due to its capacity to build biofilms and acquire drug resistance. The purpose of this systematic review and meta-analysis is to analyze the prevalence of MRSA in Saudi Arabia and look into its resistance to various antibiotics. A comprehensive systematic search for key scientific databases from 1990 to June 2024 was carried out using predetermined keywords. MRSA prevalence rates were examined in studies that met the inclusion criteria, with an emphasis on clinical and community settings. The MedCalc software was used to conduct statistical analysis. The meta-analysis includes 24 trials with 16,646 samples. The overall prevalence of MRSA was discovered to be 8.601% (fixed effects) and 17.027% (random effects), with confidence ranges of 8.179-9.037 and 12.503-22.091, respectively. The research showed substantial antibiotic resistance, notably to β-lactams, whereas vancomycin remained effective against most MRSA strains. The data show an alarming incidence of MRSA in hospital settings, as well as significant resistance to numerous antibiotic classes, emphasizing the importance of improved infection control strategies and sensible antibiotic usage. Geographic differences in resistance patterns point to regional factors impacting MRSA spread and resistance. This analysis highlights the significant prevalence of MRSA in Saudi clinical settings, as well as the complexities of its resistance profiles. Continued observation and study into the genetic mechanisms that contribute to resistance are critical for successful MRSA infection management and prevention.

The prevalence and risk factors of methicillin-resistant Staphylococcus aureus among pediatric populations: a systematic review and meta-analysis.

Future research should build on these findings by emphasizing ongoing efforts to combat MRSA in pediatric settings and implementing targeted interventions. • Methicillin-resistant Staphylococcus aureus (MRSA) is considered a threat to public health. It is noteworthy to mention that the prevalence of MRSA strains has not been adequately quantified in many countries, especially in the pediatric population. The pediatric population is a pivotal source of MRSA and may play a central role in its distribution in both community and healthcare settings. A notable study underscores the gravity of the situation, estimating a tenfold increase in the incidence of MRSA infection among children in the USA between 1999 and 2008. • Here we present the first global systematic review and meta-analysis to investigate the prevalence and risk factors of MRSA among the pediatric population. A total of 124 studies encompassing 44 million participants were included in this analysis. The overall pooled estimated global prevalence of MRSA colonization in the pediatric population was 5% [95% CI 4-5%]. The prevalence was the highest in Asia and lowest in Europe. Female sex, recent surgery, recent hospitalization, and antibiotic use were significantly associated with higher odds of MRSA colonization.

Prevalence and Antibiotic Resistance Patterns of Methicillin-Resistant Staphylococcus aureus (MRSA) in a Hospital Setting: A Retrospective Study from 2018 to 2022.

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly infectious pathogen that poses a serious threat to human life and health. This study aimed to provide a scientific basis for the rational clinical use of antimicrobial drugs for treating MRSA infections and inform the development of preventive and control measures by analyzing the clinical distribution and resistance characteristics of MRSA in a hospital in Hebei China. To accomplish this, bacterial identification and drug sensitivity experiments were performed with 1858 Staphylococcus aureus (S. aureus) strains collected from a hospital from January 2018 to December 2022 using a phoenixTM-100 bacterial identification drug sensitivity analyzer. The experimental data were analyzed using WHONET 5.6 software, and the MRSA strains detected were analyzed for their clinical distribution and drug resistance. Of the 1858 S. aureus strains isolated, 429 were MRSA. Sputum samples had the highest MRSA detection rates (52.45%). Critical care medicine had the highest rate of MRSA (12.59%), followed by dermatology (9.79%). MRSA resistance to tetracycline increased by 13.9% over 5years; resistance to quinupristin/dalfopristin also increased but remained low (1.9%). Resistance decreased to gentamicin, rifampicin, ciprofloxacin, and cotrimoxazole, though most significantly to erythromycin and clindamycin, exceeding 77% and 83%, respectively. No strains were resistant to vancomycin, teicoplanin, or linezolid, and drug resistance was most prevalent in patients ≥ 60years old. This study will aid in improving the diagnosis and treatment of MRSA infections.

Unveiling the impact of selected essential oils on MRSA strain ATCC 33591: antibacterial efficiency, biofilm disruption, and staphyloxanthin inhibition.

This work aimed to evaluate the effects of 4 selected essential oils on planktonic cells and microbial biofilms of the Staphylococcus aureus strain (MRSA ATCC 33591). The antibacterial activities of the four essential oils Geranium (Pelargonium graveolens), PgEO, Tea Tree (Melaleuca alternifolia) MaEO, Lemon peel (Citrus limon) ClEO and Peppermint (Mentha piperita) MpEO had MICs ranging from 1.56 to 12.5µl/ml. The evaluation of the antibiofilm activities of the 4 EOs revealed that they had antiadhesive activities against S. aureus MRSA biofilms; the activity reached 60% (the EO of MpEO peppermint at a concentration of 3.12µl/ml), and the eradication activity was 80% (the EO of PgEO and MpEO at 3.12µl/ml). The antibiofilm activity of S. aureus has been explained by the binding of several essential oil bioactive molecules to the SarA protein, the main target protein involved in biofilm formation. The synthesis of the virulence factor staphyloxanthin by S. aureus MRSA ATCC 33591 was significantly inhibited in the presence of PgEO at a concentration of MIC/2. This inhibition was explained by the binding of the main PgEO molecules (β-citronellol and geraniol) to the CrTM protein involved in the staphyloxanthin synthesis pathway. There is evidence that these essential oils could be used as potential anti-virulents to control Staphylococcus biofilm formation.

Gallic acid synergistically enhances the antibacterial activity of azithromycin in MRSA.

The rise of antibiotic resistance in existing pathogens has been identified as a major threat to global healthcare in the twenty-first century. This resistance has consequences such as increased cost and prolonged hospital stays, treatment failure, and ultimately increased risk of patient mortality. It is therefore imperative to develop strategies to combat drug resistance. Combined treatment of common antibiotics and natural compounds is one of the most effective methods against resistant bacterial infections. Gallic acid (GA) is a natural secondary metabolite abundantly found in plants and has significant medicinal effects in various aspects of health. In this research, the antibacterial effects of azithromycin (AZM) and GA alone and in combination with each other were investigated on planktonic and biofilm forms of methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa (P. aeruginosa). The results showed that the combination of AZM/GA had an additive effect against MSSA and P. aeruginosa and a synergistic effect against MRSA. In addition, combining these two agents significantly reduced the minimum biofilm inhibitory concentration (MBIC) of AZM and GA in the MRSA strain. Finally, the level of ROS generation in the effect of AZM plus GA was evaluated in the bacteria. Among the studied strains, ROS production was significantly increased in combination treatment compared to AZM alone in MRSA. The results show that the combination of AZM and GA has a significant effect against MRSA and can be considered as an effective treatment option.

Pathogenomic profile and clonal diversity of potential zoonotic MRSA-CC7-ST789-t091-SCCmecV from human skin and soft tissue infections

The whole genome sequence (WGS) of prevalent MRSA strains harboring mecA gene obtained from skin and soft tissue infections (SSTIs) in Nigerian hospitals were profiled for pathogenomic structure and evaluated for clonal diversity. The two MRSA strains identified among 66 isolated multi-drug resistant S. aureus from a collection of 256 clinical samples were phenotyped for antibiotic resistance and genotyped for mecA, SCCmec, and spa types. The mecA positive MRSA was analysed using whole-genome sequencing for resistomes, virulomes, phylogenomic profiles and clonal diversity. The identified MRSA-CC7-ST789-t091-SCCmecV strains from a female child (aged 1 year) with severe otorrhea and an adult male (aged 23) with purulent wound abscess showed high-level resistance to streptomycin, vancomycin, kanamycin, sulfamethoxazole and ciprofloxacin. Both strains harbored abundant resistomes, inherent plasmids, chromosomal replicons and typical seven housekeeping genes (arc3, aroE4, glpF1, gmk4, pta4, tpi6, yqiL3). The most abundant putative virulomes were pathogenesis-associated proteins (included hemolysin gamma, leucocidins, proteases, staphylococcal superantigen/enterotoxin-like genes (Set/Ssl), capsule- and biofilm-associated genes, and hyaluronate lyase). Comparative phylogenomic analysis revealed the relatedness of the two clonal strains with prevalent MRSA-CC7 pathotypes observed in Italy (2013 and 2014), Denmark (2014), Thailand (2015 and 2016), USA (2018), and Nigeria (2016 and 2020); and share high genetic similarities with livestock strains from cow milk and cattle. Identified MRSA-CC7-ST789-t091-SCCmecV pathotypes implicated in SSTIs from Nigeria harboring repertoires of antibiotic resistance and virulence genes, and genetic relatedness with livestock strains; show the possibility of gene transfer between animal and human. Adequate hospital MRSA infection control and geno-epidemiological surveillance for animal and human transfer is required.

Phenotypic and genotypic characterization of methicillin resistant Staphylococcus aureus associated with pyogenic infections.

Staphylococcal infections are one of the major infectious diseases affecting globally in spite of advances in development of antimicrobial agents. Knowledge and awareness about the local pattern and prevalence of MRSA infections plays a key role in treatment. The aim of this study was to identify MRSA strains by phenotypic and genotypic methods and to analyze the antibiotic susceptibility pattern of MRSA strains from patients attending a tertiary care hospital. This study was conducted over a period of 1 year, where 296 isolates of Staphylococcus aureus were isolated from various clinical specimens. The isolated strains were examined for antibiotic susceptibility by the modified Kirby Bauer disc diffusion method. Methicillin resistance was detected by cefoxitin disk diffusion test. A total of 104 isolates were found to be MRSA and 192 were found to be MSSA. Among the 104 MRSA isolates, 10 strains that were multidrug resistant were subjected to 16S rRNA gene sequencing analysis. All the 10 strains had a 99% match with S. aureus strains that were responsible for causing some serious biofilm mediated clinical manifestations like cystic fibrosis and device mediated infections. The biofilms were quantified using crystal violet staining and their ability to produce biofilms was analyzed using scanning electron microscopy and matched with the Genbank. Hence these phylogenetic analysis aid in treating the patients and combating resistance to antibiotics.

PLGA Nanoparticles Formulations Loaded With Antibiotics Induce Sustained and Controlled Antibiotics Release for Prolonged Antibacterial Action Against MRSA, and Pseudomonas aeruginosa FRD1.

The purpose of the present study was to create resorbable nanoparticles (NPs) using poly(lactic-co-glycolic acid) (PLGA) to develop novel antibacterial therapeutics for the treatment of chronic wound infections that are susceptible to recurrent infections. By first performing a release study, it was possible to predict the behavior of the different PLGA NP formulations and assess the efficacy of the nanocomposite drug delivery system. These PLGA NP formulations consisted of varying ratios of PLGA without polyvinyl alcohol (PVA) and PLGA with PVA (PLGA-PVA) (i.e., 25:75[PLGA25], 50:50[PLGA50], and 75:25[PLGA75]). Then, different antibiotics (i.e., ciprofloxacin and gentamicin) were incorporated into the PLGA NP formulations to test the antibacterial efficacy of these antimicrobial NPs against different pathogens (i.e., methicillin-resistant Staphylococcus aureus USA300 [MRSA], Pseudomonas aeruginosa FRD1, and Acinetobacter baumannii BAA1605). Of particular interest was testing against the MRSA strain USA300 and the P. aeruginosa strain FRD1. This was possible by measuring the zone of inhibition. A 3-day period was used to monitor the antibacterial efficacy of the different PLGA NP formulations (i.e., PLGA25, PLGA50, and a 1:1 combination of PLGA25:PLGA50) against A. baumannii BAA1605, MRSA, and P aeruginosa FRD1. Throughout the study, A. baumannii was a negative control and was resistant to all the PLGA NP formulations loaded with ciprofloxacin and gentamicin. At the end of the 3-day period, the PLGA and PLGA50 ciprofloxacin-loaded formulations produced zones of inhibition of 27 mm and 23 mm, respectively, against P. aeruginosa FRD1. This indicated that P. aeruginosa FRD1 was susceptible to both formulations. The mixed formulations with equal parts PLGA25:PLGA50 loaded with ciprofloxacin produced a zone of inhibition (i.e., 25 mm). This again indicated that P. aeruginosa FRD1 was susceptible to ciprofloxacin. The formulations tested against MRSA showed that only gentamicin-loaded formulations produced intermediate results, and that ciprofloxacin-loaded formulations were ineffective. The PLGA25 and the PLGA50 NP formulations loaded with gentamicin both produced zones of inhibition of 13 mm. This indicated that MRSA was intermediate to both the formulations. The PLGA25:PLGA50 loaded with gentamicin produced a zone of inhibition of 14 mm, which again showed that MRSA was intermediate to this formulation. Overall, these PLGA NP formulations showed the sustained antibacterial potential of a burst release, followed by a sustained release of antibiotics from antibiotics loaded PLGA NPs in a controlled manner. In the future, this can help prevent the emergence of recurrent infections in the treatment of chronic wounds and reduce the number of medical dressing changes.

Novel Insights into the Antimicrobial and Antibiofilm Activity of Pyrroloquinoline Quinone (PQQ); In Vitro, In Silico, and Shotgun Proteomic Studies.

Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a natural medicinal drug involved in various cellular processes, holds promise as a potential antimicrobial agent. In the present study, our aim was, for the first time, to explore the antimicrobial activity of PQQ against 29 pathogenic microbes, including 13 fungal strains, 8 Gram-positive bacteria, and 8 Gram-negative bacteria. Our findings revealed potent antifungal properties of PQQ, particularly against Syncephalastrum racemosum, Talaromyces marneffei, Candida lipolytica, and Trichophyton rubrum. The MIC values varied between fungal strains, and T. marneffei exhibited a lower MIC, indicating a greater susceptibility to PQQ. In addition, PQQ exhibited notable antibacterial activity against Gram-positive and -negative bacteria, with a prominent inhibition observed against Staphylococcus epidermidis, Proteus vulgaris, and MRSA strains. Remarkably, PQQ demonstrated considerable biofilm inhibition against the MRSA, S. epidermidis, and P. vulgaris strains. Transmission electron microscopy (TEM) studies revealed that PQQ caused structural damage and disrupted cell metabolism in bacterial cells, leading to aberrant morphology, compromised cell membrane integrity, and leakage of cytoplasmic contents. These findings were further affirmed by shotgun proteomic analysis, which revealed that PQQ targets several important cellular processes in bacteria, including membrane proteins, ATP metabolic processes, DNA repair processes, metal-binding proteins, and stress response. Finally, detailed molecular modeling investigations indicated that PQQ exhibits a substantial binding affinity score for key microbial targets, including the mannoprotein Mp1P, the transcriptional regulator TcaR, and the endonuclease PvuRTs1I. Taken together, our study underscores the effectiveness of PQQ as a broad-spectrum antimicrobial agent capable of combating pathogenic fungi and bacteria, while also inhibiting biofilm formation and targeting several critical biological processes, making it a promising therapeutic option for biofilm-related infections.

Genomic characterization of methicillin-resistant Staphylococcus aureus isolated from patients attending regional referral hospitals in Tanzania

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) colonization increases the risk of subsequent infection by MRSA strain complex interlinking between hospital and community-acquired MRSA which increases the chance of drug resistance and severity of the disease.ObjectiveGenomic characterization of Staphylococcus aures strains isolated from patients attending regional referral hospitals in Tanzania.MethodologyA laboratory-based cross-sectional study using short read-based sequencing technology, (Nextseq550,Illumina, Inc. San diego, California, USA). The samples used were collected from patients attending selected regional referral hospitals in Tanzania under the SeqAfrica project. Sequences were analyzed using tools available in the center for genomic and epidemiology server, and visualization of the phylogenetic tree was performed in ITOL 6.0. SPSS 28.0 was used for statistical analysis.ResultsAmong 103 sequences of S. aureus, 48.5% (50/103) carry the mecA gene for MRSA. High proportions of MRSA were observed among participants aged between 18 and 34 years (52.4%), in females (54.3%), and among outpatients (60.5%). The majority of observed MRSA carried plasmids rep5a (92.0%), rep16 (90.0%), rep7c (90.0%), rep15 (82.0%), rep19 (80.0%) and rep10 (72.0%). Among all plasmids observed rep5a, rep16, rep20, and repUS70 carried the blaZ gene, rep10 carried the erm(C) gene and rep7a carried the tet(K) gene. MLST and phylogeny analysis reveal high diversity among MRSA. Six different clones were observed circulating at selected regional hospitals and MRSA with ST8 was dominant.ConclusionThe study reveals a significant presence of MRSA in Staphylococcus aureus strains from Tanzanian regional hospitals, with nearly half carrying the mecA gene. MRSA is notably prevalent among young adults, females, and outpatients, showing high genetic diversity and dominance of ST8. Various plasmids carrying resistance genes indicate a complex resistance profile, highlighting the need for targeted interventions to manage MRSA infections in Tanzania.

Effects of geographical variation on the phytochemicals gallic acid, corilagin, and ellagic acid, as well as medicinal properties of Emblica officinalis Gaertn (Fruit)

Geographical variation can significantly influence the abundance and distribution of phytochemicals within the raw drug, which in turn may affect its medicinal efficacy and potential health benefits. Understanding these variations is crucial for optimizing cultivation practices and harnessing the full therapeutic potential of herbal raw drug. Owing to the lack of availability of the comprehensive study on the effects of geographical variation on phytochemicals & micronutrient content and antioxidant & antibacterial potential of Emblica officinalis (EO), in the current study, EO fruit samples from different terrestrial regions of India were analyzed to identify variations in certain phytochemicals and nutrients content. A broad study including the identification, substantiation and phytochemical analysis of EO has been performed via a validated HPLC method. The complete profiling of various volatile metabolites present in the sample has been done by GC-MS/MS technique. The observed range of phytochemicals present in different EO samples using validated HPLC-DAD method are 4.38 to 69.41 mg/g for Gallic acid, 0.50 to 5.54 mg/g for Corilagin and 3.92 to 15.34 mg/g for ellagic acid. The total phenolic content (TPC) and total flavonoid content (TFC) for different samples of EO ranged from 52.86–175.47 mg GAE/g of wt. and 1.28–13.88 mg QCE/g of wt. respectively. ICP-OES analysis depicts substantial amount of various essential micronutrients such as Fe, Cu, Mn and Zn. In antibacterial assay, methanolic extracts of EO obtained from Pune zone exhibited promising activity against S. aureus, S. typhi and MRSA strains with inhibition zones of 28, 23 and 28 mm, respectively. Further, the antioxidant, antidiabetic and anti-inflammatory activities of EO on the basis of analyzed phytochemicals have also been evaluated through molecular docking study.

In Vitro and In Vivo Studies on a Mononuclear Ruthenium Complex Reveals It is a Highly Effective, Fast-Acting, Broad-Spectrum Antimicrobial in Physiologically Relevant Conditions.

The crystal structure of a previously reported antimicrobial RuII complex that targets bacterial DNA is presented. Studies utilizing clinical isolates of Gram-negative bacteria that cause catheter-associated urinary tract infection, (CA)UTI, in media that model urine and plasma reveal that good antimicrobial activity is maintained in all conditions tested. Experiments with a series of Staphylococcus aureus clinical isolates show that, unlike the majority of previously reported RuII-based antimicrobial leads, the compound retains its potent activity even in MRSA strains. Furthermore, experiments using bacteria in early exponential growth and at different pHs reveal that the compound also retains its activity across a range of conditions that are relevant to those encountered in clinical settings. Combinatorial studies involving cotreatment with conventional antibiotics or a previously reported analogous dinuclear RuII complex showed no antagonistic effects. In fact, although all combinations show distinct additive antibacterial activity, in one case, this effect approaches synergy. It was found that the Galleria Mellonella model organism infected with a multidrug resistant strain of the ESKAPE pathogen Acinetobacter baumannii could be successfully treated and totally cleared within 48 h after a single dose of the lead complex with no detectable deleterious effect to the host.

Biofilm formation, agr typing and antibiotic resistance pattern in methicillin-resistant Staphylococcus aureus isolated from hospital environments.

Biofilm development significantly enhances the virulence of methicillin-resistant Staphylococcus aureus (MRSA), leading to severe infections and decreased susceptibility to antibiotics, especially in strains associated with hospital environments. This study examined the occurrence of MRSA, their ability to form biofilms, agr typing, and the antibiotic resistance profiles of biofilm-forming MRSA strains isolated from environmental surfaces at Mymensingh Medical College Hospital (MMCH). From 120 swab samples, 86 (71.67%) tested positive for S. aureus. MRSA was identified in 86 isolates using the disk diffusion technique, and by polymerase chain reaction (PCR), 56 (65.1%) isolates were confirmed to carry the mecA gene. The Crystal Violet Microtiter Plate (CVMP) test revealed that 80.35% (45 isolates) were biofilm-forming and 19.6% (11 isolates) were non-biofilm-forming. Out of 45 biofilm producer isolates 37.5% and 42.9% isolates exhibited strong and intermediate biofilm-forming characteristics, respectively. Molecular analysis revealed that 17.78% of MRSA isolates carried at least one gene related to biofilm formation, specifically icaA, icaB, and icaD genes were discovered in 13.33%, 8.89%, 6.67% of the MRSA isolates, respectively. In agr typing, the most prevalent group was agr I (71.11%), followed by group III (17.78%) and group II (11.11%). Group IV was not detected. The distribution of agr gene groups showed a significant difference among biofilm-forming isolates (p < 0.05). In agr group I, 18.75% of isolates carried the icaA gene, 12.5% carried the icaB gene, and 9.37% carried the icaD gene. Biofilm-forming genes were not detected in any of the isolates from agr groups II or III. There are no statistically significant differences between agr groups and the presence of these genes (p > 0.05). Antibiotic resistance varied significantly among agr groups, with agr group I displaying the highest resistance, agr group II, and agr group III exhibiting the least resistance (p < 0.05). Seventy-three (73.3%) of the isolates were multi-drug resistant, with agr group I displaying nineteen MDR patterns. The occurrence of MRSA in hospital environments and their capacity to form biofilm raises concerns for public health. These findings support the importance of further research focused on agr quorum sensing systems as a basis for developing novel antibacterial agents.

The Study of Genetic Affinity of Methicillin Resistance Staphylococcus Aureus Strains Isolated from Cream Pastries and Nasal Isolates at Shiraz Confectionaries

Background: Staphylococcus aureus (S. aureus) is responsible for most cases of food poisoning all around the world. These carriers and manipulated foodstuffs are the main sources of bacteria transmission to ready-to-eat food. This study aims to determine the genetic affinity of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from cream pastries and workers, nasal of Shiraz city confectioneries. Methods: 30 MRSA strains (7 nasal carriers, 23 food isolates) were selected from the bank of bacteria at Shiraz medical faculty. To determine the genetic affinity of the isolates, RAPD-PCR technique was performed using OLP6, OLP11, and OLP13 primers. RAPD-PCR patterns were analyzed using the software GelJ. Results: By using primer OLP6 only 5 RAPD-PCR patterns were produced from DNA ampliqons of creamy pastry isolates and were not enough to compare the genetic affinity of all the isolates. Based on 100% similarity, OLP13 primer produced 20 different patterns with some bands in the range of 1 to 11, and the OLP11 primer produced 22 patterns with some bands from 3 to 11 bands. At closely and possibly genetically related levels, the isolates are categorized into (13-15) and (1-5) clusters. In general, all the isolates are classified into human and food isolates. Conclusions: There was no genetic affinity of MDSA isolates regarding human and food samples; but, a high percentage of close genetic relationship between the isolates increases the possibility of bacteria transfer from humans to pastries and food poisoning.

Clioquinol derivatives as potent inhibitors of Methicillin-Resistant Staphylococcus aureus and their mechanistic study

AimsMethicillin-Resistant Staphylococcus aureus cause many nosocomial, and community-acquired infections, burdening healthcare systems globally. The aim of the current study was to identify the potent inhibitors of MRSA strains as first step towards drug discovery against MRSA related infections. Methods and ResultsClioquinol derivatives 1–10 were evaluated against MRSA strains, using microplate alamar blue assay (MABA). Among them compounds 1–3, and 6–8 were found to be active with MIC values within the range of 61.08–213.58 µM. Compounds 1, and 7 were found highly potent with MIC values of 64.04 and 61.08 µM, respectively. Both these compounds also showed non-covalent interactions with active site key residues of topoisomerase IV enzyme in molecular docking studies. Mechanisms of action of the most active compounds 1, and 7 were further studied through AFM, and fluorescence microscopy. It was observed that compounds 1, and 7 caused a massive destruction in shape, and greatly reduced the size and number of viable cells. Flow cytometry analysis showed a significant rise in DiBAC4(3) fluorescence, and a non-significant rise in PI fluorescence indicating increased bacterial membrane depolarization of treated cells. Most importantly the clioquinol derivatives 1, and 7 did not cause any hemolytic effect. Moreover, all the compounds were found to be non-cytotoxic to BJ (Human fibroblast) normal cell line. ConclusionOur findings suggest that clioquinol derivatives 1, and 7 possess highly potent antibacterial activity against three MDR, and one sensitive strains of S. aureus. Significance and impact of the studyClioquinol derivatives 1, and 7 could be further studied as potential antibacterial agents.

Analysis of Pathogen Distribution and Antimicrobial Resistance in Bone and Joint Infections Among Young Children.

This study aimed to analyze the distribution of pathogens and antimicrobial resistance in bone and joint infections (BJIs) among children under four years old. A retrospective analysis was conducted on the clinical data of children under four years old who received inpatient treatment for BJIs at the Children's Hospital of Soochow University between January 2016 and December 2022. Results of bacterial culture and antimicrobial resistance were analyzed. Among the 131 patients, 52 (39.7%) showed positive bacterial culture results. There were Gram-positive (G+) bacteria detected in 38 strains (73.07%), Gram-negative (G-) bacteria in 12 strains (23.08%), and fungi in 2 strains (3.85%). Thirty-one strains of Staphylococcus aureus (S. aureus) were detected (59.62%), including 7 MRSA strains (22.58%). The resistance rate of G+ bacteria to penicillin was 72.97%, while resistance to erythromycin and clindamycin was approximately 50%. No resistance was found against linezolid, vancomycin, and teicoplanin. G- bacteria showed a sensitivity of 100% to carbapenems, including meropenem, ertapenem, and imipenem, a resistance rate of 91.67% to ampicillin-sulbactam, and relatively high resistance rates to compound sulfamethoxazole, ampicillin/sulbactam, and piperacillin. Regional variations existed in the distribution of pathogens and antimicrobial resistance in children under four years old with BJIs. In our hospital, the most common pathogen is S. aureus, with MRSA accounting for approximately one-fourth of all S. aureus patients. Additionally, extended-spectrum β-lactamase (ESBL)-producing G- bacteria have been identified, underscoring the importance of careful consideration during empirical antibiotic therapy.

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.

A multifunctional injectable, self-healing, and adhesive hydrogel-based wound dressing stimulated diabetic wound healing with combined reactive oxygen species scavenging, hyperglycemia reducing, and bacteria-killing abilities

The proficient handling of diabetic wounds, a rising issue coinciding with the global escalation of diabetes cases, poses significant clinical difficulties. A range of biofunctional dressings have been engineered and produced to expedite the healing process of diabetic wounds. This study proposes a multifunctional hydrogel dressing for diabetic wound healing, which is composed of Polyvinyl Alcohol (PVA) and N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1, N1, N3, N3-teramethylpropane-1, 3-diaminium (TSPBA), and a dual-drug loaded Gelatin methacryloyl (GM) microgel. The GM microgel is loaded with sodium fusidate (SF) and nanoliposomes (LP) that contain metformin hydrochloride (MH). Notably, adhesive and self-healing properties the hydrogel enhance their therapeutic potential and ease of application. In vitro assessments indicate that SF-infused hydrogel can eliminate more than 98% of bacteria within 24 h and maintain a sustained release over 15 days. Additionally, MH incorporated within the hydrogel has demonstrated effective glucose level regulation for a duration exceeding 15 days. The hydrogel demonstrates a sustained ability to neutralize ROS throughout the entire healing process, predominantly by electron donation and sequestration. This multifunctional hydrogel dressing, which integrated biological functions of efficient bactericidal activity against both MSSA and MRSA strains, blood glucose modulation, and control of active oxygen levels, has successfully promoted the healing of diabetic wounds in rats in 14 days. The hydrogel dressing exhibited significant effectiveness in facilitating the healing process of diabetic wounds, highlighting its considerable promise for clinical translation.Graphical

Prevalence and Antimicrobial Susceptibility Pattern of MRSA amongst Patients from an Indian Tertiary Care Hospital: An Eye Opener

Staphylococcus aureus (S. aureus) is a very common human pathogenic microorganism that can cause a variety of infectious diseases, including skin and soft tissue infections, endocarditis, osteomyelitis, bacteremia, and lethal pneumonia. About one-third of the common population is colonized with S. aureus. MRSA is a formidable pathogen known to cause high mortality &amp; morbidity, that poses a significant threat to public health worldwide. Presence of MRSA strains, resistant to multiple antibiotics especially in hospital stay, has complicated the management of infections caused by this bacterium. The aim of this study was to shed light on the prevalence and antimicrobial sensitivity pattern of MRSA among patients in a tertiary care center located in Faridabad, Haryana. This cross-sectional observational study was conducted in the Department of Microbiology, ESIC Medical College &amp; Hospital, a 510 bedded tertiary care teaching hospital in Faridabad, Haryana, India. All wound samples including pus, exudates, wound swab and tissue samples received for aerobic culture and antimicrobial sensitivity from various clinical departments from January 2019 to July 2019 were included in this study. A total of 747 samples were received from January 2019-July 2019. Mean age of this study population was found to be 50.7 ± 14.8 years. Out of 747 samples, 226 (30.25%) were culture positive. Among the S. aureus isolates, methicillin resistance was seen amongst 39 (58.2%). Antibiotic Susceptibility results of S. aureus showed 100% resistance to Penicillin along with 100% resistance to Fluoroquinolones in both MRSA and MSSA. High prevalence of MRSA amongst patients highlights the importance of continued surveillance and implementation of antimicrobial stewardship program to control the menace of antimicrobial resistance. Strict adherence to Infection Control practices its regular follow up to assess the effectiveness of any hospital infection control measures taken is the key.

Hla protein expression and artesunate prevented mice from further damage caused by Staphylococcus aureus pneumonia

The laboratory standard MRSA strain WHO-2 and clinical isolate S1 were used to establish a pneumonia infection model. The results showed that methicillin increased the expression of Hla and PVL protein at subminimum inhibitory concentration, while artesunate decreased the secretion of Hla and PVL protein. Artesunate alone reduced hemolysin expression and reversed methicillin-induced increases in Hla and PVL proteins. In addition, the study found that the combination of artesunate and methicillin had the best therapeutic effect, with survival rates of 70 % and 40 % at seven days, respectively (corresponding to the WHO-2 and S1 strains). The combination treatment was able to reduce cell mortality, showing a 65 % and 46 % reduction in cell mortality, respectively. The study also found that the combination therapy decreased the expression of alpha-hemolysin and pantone valentin leukin in the culture medium and significantly reduced the activation of NF-kB. This is caused by a significant decrease in the expression of inflammatory factors.