anti-MRSA Agents Research Articles

Medicinal Remedies for the Treatment of Methicillin Resistant Staphylococcus Aureus

Antimicrobial resistance has led to the rise of formidable microbes like methicillin-resistant Staphylococcus aureus (MRSA). This infection can be acquired at the hospital and in a community, making the search for efficient treatment critical, given the rise in inefficacy of conventional treatments such as vancomycin. Phytocompounds can offer protection against these threats. They not only have the ability to kill MRSA but also enhance its susceptibility to previously ineffective antimicrobial agents. Plant-derived anti-MRSA agents can produce therapeutic effects comparable to some conventional treatments, and in some cases, they may even outperform an antibiotic. This article provided many examples of botanical compounds that have proven potent agents against MRSA in both in vitro and in vivo studies. These compounds achieve these effects by inhibiting the resistance mechanisms in MRSA, breaking down its defenses, making it vulnerable, and eventually killing it. Many of these compounds are inherently bactericidal; however, they may produce a synergistic response when combined with allopathic antibiotics. For example, plumbagin, from Plumbago zeylanica, not only disrupts MRSA cell wall morphology, eliciting cytoplasmic changes but also produces a synergistic effect with ciprofloxacin and piperacillin. Moreover, honokiol and magnolol glycosides, from Magnolia officinalis, reversed the quintessential resistance of MRSA by repressing genes, responsible for resistance development. The possibilities are indeed endless, but further research and financial investments are required for proper drug development.

Correlation between oxacillin MIC values with those of linezolid against clinical isolates of MRSA

Infection by methicillin-resistant (MRSA) is a great threat to medical care facilities and also in communities, due to its multidrug resistance to commonly used antimicrobial agents. The overuse of glycopeptide antibiotics, such as vancomycin and linezolid, has led to the emergence of reduced susceptibility to these anti-MRSA agents, which in turn may lead to therapeutic failure. This study has been conducted to explore the correlation if any, of MIC of oxacillin to the MIC of linezolid in clinically significant isolates of MRSA in a tertiary care hospital.: The study was carried out over the period of two months after obtaining a waiver of consent from the Institute Ethics Committee. Seventy-five clinically significant MRSA isolates were included in the study. All MRSA isolates were subjected to cefoxitin and linezolid antibiotic disk susceptibility testing. Minimum inhibitory concentration (MIC) to oxacillin and linezolid was performed by the agar dilution method. The MIC and MIC were also recorded both for oxacillin and linezolid MIC among these MRSA isolates. Correlation between oxacillin MIC and linezolid MIC was estimated using the Pearson correlation coefficient, r.Themajority of MRSA isolates (41%) were isolated from skin and soft tissue infections (SSTIs) (40%). MIC values for oxacillin ranged from 4 μg/mL to >32μg/mL and MIC values for linezolid ranged from ≤ 0.25µg/mL to 4 µg/mL. The majority of these isolates (40%) had linezolid MIC of ≤ 0.25µg/mL. All the isolates were uniformly susceptible to linezolid. Pearson correlation coefficient, r was 0.41, between oxacillin MICs and linezolid MICs, which indicated poor correlation. Although we did not observe any resistance to linezolid among the MRSA isolates, we should monitor carefully the antibiotic selection pressure and creeping MIC, to aid in the early detection of the emergence of resistance.

Discovery of new quaternized norharmane dimers as potential anti-MRSA agents

IntroductionMethicillin-resistant Staphylococcus aureus (MRSA)-caused infections greatly threaten public health. The discovery of natural-product-based anti-MRSA agents for treating infectious diseases has become one of the current research focuses. ObjectivesThis study aims to identify promising anti-MRSA agents with a clear mechanism based on natural norharmane modified by quaternization or dimerization. MethodsA total of 32 norharmane analogues were prepared and characterized. Their antibacterial activities and resistance development propensity were tested by the broth double-dilution method. Cell counting kit-8 and hemolysis experiments were used to assess their biosafety. The plasma stability, bactericidal mode, and biofilm disruption effects were examined by colony counting and crystal violet staining assays. Fluorescence microscopy, metabolomic analysis, docking simulation and spectra titration revealed its anti-MRSA mechanisms. The mouse skin infection model was used to investigate the in vivo efficacy. ResultsCompound 5a was selected as a potential anti-MRSA agent, which exhibited potent anti-MRSA activity in vitro and in vivo, low cytotoxicity and hemolysis under an effective dose. Moreover, compound 5a showed good stability in 50% plasma, a low tendency of resistance development and capabilities to disrupt bacterial biofilms. The mechanism studies revealed that compound 5a could inhibit the biosynthesis of bacteria cell walls, damage the membrane, disturb energy metabolism and amino acid metabolism pathways, and interfere with protein synthesis and nucleic acid function. ConclusionsThese results suggested that compound 5a is a promising candidate for combating MRSA infections, providing valuable information for further exploiting a new generation of therapeutic antibiotics.

Anti-methicillin-resistant Staphylococcus aureus and antibiofilm activity of new peptides produced by a Brevibacillus strain.

Methicillin-resistant Staphylococcus aureus (MRSA) is listed as a highly prioritized pathogen by the World Health Organization (WHO) to search for effective antimicrobial agents. Previously, we isolated a soil Brevibacillus sp. strain SPR19 from a botanical garden, which showed anti-MRSA activity. However, the active substances were still unknown. The cell-free supernatant of this bacterium was subjected to salt precipitation, cation exchange, and reversed-phase chromatography. The antimicrobial activity of pure substances was determined by broth microdilution assay. The peptide sequences and secondary structures were characterized by tandem mass spectroscopy and circular dichroism (CD), respectively. The most active anti-MRSA peptide underwent a stability study, and its mechanism was determined through scanning electron microscopy, cell permeability assay, time-killing kinetics, and biofilm inhibition and eradication. Hemolysis was used to evaluate the peptide toxicity. The pure substances (BrSPR19-P1 to BrSPR19-P5) were identified as new peptides. Their minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) against S. aureus and MRSA isolates ranged from 2.00 to 32.00 and 2.00 to 64.00 µg/mL, respectively. The sequence analysis of anti-MRSA peptides revealed a length ranging from 12 to 16 residues accompanied by an amphipathic structure. The physicochemical properties of peptides were predicted such as pI (4.25 to 10.18), net charge at pH 7.4 (-3 to +4), and hydrophobicity (0.12 to 0.96). The CD spectra revealed that all peptides in the water mainly contained random coil structures. The increased proportion of α-helix structure was observed in P2-P5 when incubated with SDS. P2 (NH2-MFLVVKVLKYVV-COOH) showed the highest antimicrobial activity and high stability under stressed conditions such as temperatures up to 100 °C, solution of pH 3 to 10, and proteolytic enzymes. P2 disrupted the cell membrane and caused bacteriolysis, in which its action was dependent on the incubation time and peptide concentration. Antibiofilm activity of P2 was determined by which the half-maximal inhibition of biofilm formation was observed at 2.92 and 4.84 µg/mL for S. aureus TISTR 517 and MRSA isolate 2468, respectively. Biofilm eradication of tested pathogens was found at the P2 concentration of 128 µg/mL. Furthermore, P2 hemolytic activity was less than 10% at concentrations up to 64 µg/mL, which reflected the hemolysis index thresholds of 32. Five novel anti-MRSA peptides were identified from SPR19. P2 was the most active peptide and was demonstrated to cause membrane disruption and cell lysis. The P2 activity was dependent on the peptide concentration and exposure time. This peptide had antibiofilm activity against tested pathogens and was compatible with human erythrocytes, supporting its potential use as an anti-MRSA agent in this post-antibiotic era.

Molecular Docking Studies of an Isolated Angucycline of Stereospermum fimbriatum, a Novel Anti-MRSA Agent

A novel angucycline, C1 isolated from Stereospermum fimbriatum stem bark was subjected to molecular docking studies on five main targets of penicillin-binding protein 2a (PBP2a), β-lactamase, DNA topoisomerase IV, dehydrosqualene synthase (CrtM) and sortase A (SrtA) for anti-MRSA activity. The binding sites and docking scores of known inhibitors (positive control) were compared with C1. Docking analysis was carried out by AutoDock 4.0 package. The binding site of C1 closely resembled the positive control in all screened receptors. Inhibition constant of C1 was lower than the positive control tested for PBP2a, β-lactamase, dehydrosqualene synthase and sortase A except against DNA Topoisomerase IV. Structure-activity relationship (SAR) analysis of C1 showed that 7-CO was the most significant contributor to its activity since it formed hydrogen bonds with four of the five screened receptors. Molecular docking of C1 indicated that C1 can be a good candidate for new anti-MRSA drug development.

Synthesis and Biological Activities of Oxazolidinone Pleuromutilin Derivatives as a Potent Anti-MRSA Agent.

A series of pleuromutilin derivatives containing an oxazolidinone skeleton were synthesized and evaluated in vitro and in vivo as antibacterial agents. Most of the synthesized derivatives exhibited potent antibacterial activities against three strains of Staphylococcus aureus (including MRSA ATCC 33591, MRSA ATCC 43300, and MSSA ATCC 29213) and two strains of Staphylococcus epidermidis (including MRSE ATCC 51625 and MSSE ATCC 12228). Compound 28 was the most active antibacterial agent in vitro (MIC = 0.008-0.125 μg·mL-1) and exhibited a significant bactericidal effect, low cytotoxicity, and weak inhibition (IC50 = 20.66 μmol·L-1) for CYP3A4, as well as exhibited less possibility to cause bacterial resistance. Furthermore, in vivo activities indicated that the compound was effective in reducing MRSA load in a murine thigh infection model. Moreover, it clearly facilitated the healing of MRSA skin infection and inhibited the secretion of the TNF-α, IL-6, and MCP-1 inflammatory factors in serum. These results suggest that oxazolidinone pleuromutilin is a promising therapeutic candidate for drug-resistant bacterial infections.

The depsidones from marine sponge-derived fungus Aspergillus unguis IB151 as an anti-MRSA agent: Molecular docking, pharmacokinetics analysis, and molecular dynamic simulation studies

Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging nosocomial pathogen among hospitalized patients, with high morbidity and mortality rates. The discovery of a novel antibacterial is urgently needed to address this resistance problem. The present study aims to explore the antibacterial potential of three depsidone compounds: 2-clorounguinol (1), unguinol (2), and nidulin (3), isolated from the marine sponge-derived fungus Aspergillus unguis IB1, both in vitro and in silico. The antibacterial activity of all compounds was evaluated by calculating the Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) against MRSA using agar diffusion and total plate count methods, respectively. Bacterial cell morphology changes were studied for the first time using scanning electron microscopy (SEM). Molecular docking, pharmacokinetics analysis, and molecular dynamics simulation were performed to determine possible protein–ligand interactions and the stability of the targeting penicillin-binding protein 2a (PBP2a) against 2-clorounguinol (1). The research findings indicated that compounds 1 to 3 exhibited MIC and MBC values of 2 µg/mL and 16 µg/mL against MRSA, respectively. MRSA cells displayed a distinct shape after the addition of the depsidone compound, as observed in SEM. According to the in silico study, 2-chlorounguinol exhibited the highest binding-free energy (BFE) with PBP2a (-6.7 kcal/mol). For comparison, (E)-3-(2-(4-cyanostyryl)-4-oxoquinazolin-3(4H)-yl) benzoic acid inhibits PBP2a with a BFE less than −6.6 kcal/mol. Based on the Lipinski's rule of 5, depsidone compounds constitute a class of compounds with good pharmacokinetic properties, being easily absorbed and permeable. These findings suggest that 2-chlorounguinol possesses potential antibacterial activity and could be developed as an antibiotic adjuvant to reduce antimicrobial resistance.

Design, synthesis, and biological evaluation of novel pleuromutilin derivatives containing benzimidazoles as effective anti-MRSA agents.

A series of pleuromutilin derivatives containing benzimidazole were designed, synthesized, and evaluated for their antibacterial activities against Methicillin-resistant Staphylococcus aureus (MRSA) in this study. The in vitro antibacterial activities of the synthesized derivatives against four strains of S. aureus (MRSA ATCC 43300, S. aureus ATCC 29213, S. aureus 144, and S. aureus AD3) were determined by the broth dilution method. Among these derivatives, compound 58 exhibited superior in vitro antibacterial effect against MRSA (minimal inhibitory concentration [MIC] = 0.0625 μg/mL) than tiamulin (MIC = 0.5 μg/mL). Compound 58 possessed a faster bactericidal kinetic and a longer post-antibiotic effect time against MRSA than tiamulin. Meanwhile, at 8 μg/mL concentration, compound 58 did not display obviously cytotoxic effect on the RAW 264.7 cells. In addition, compound 58 (-2.04 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (-1.02 log10 CFU/mL) in reducing MRSA load in mice thigh infection model. In molecular docking study, compound 58 can successfully attach to the 50S ribosomal active site (the binding free energy is -8.11 kcal/mol). Therefore, compound 58 was a potential antibacterial candidate for combating MRSA infections.

Pharmacovigilance Study on Eosinophilic Pneumonia Induced by Anti-MRSA Agents: Analysis Based on the FDA Adverse Event Reporting System.

Eosinophilic pneumonia (EP) is a rare adverse event caused by several types of drugs, such as antibiotics; however, its characteristics remain poorly described. This study aimed to analyze the disproportionality between the occurrence of EP and anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) agents and to characterize anti-MRSA agent-induced EP events using the Food and Drug Administration Adverse Event Reporting System (FAERS). Disproportionality linking EP and anti-MRSA agents was analyzed through bayesian confidence propagation neural networks of information components and reporting odds ratio methodologies. The FAERS data set for the fourth quarter of 2012 to the fourth quarter of 2022 was used. We also analyzed the characteristics of EP induced by anti-MRSA agents. A total of 14 805 795 reports were obtained from FAERS. Disproportionality analysis revealed that the EP signal was detected only in cases with the administration of daptomycin (DAP). This disproportionality signal was consistently detected in the sensitivity analysis. When compared with other reports of DAP-related adverse events, the reports of DAP-related EP were characterized by male sex (odds ratio [OR], 1.94; 95% CI, 1.12-3.37), older age (>70 years; OR, 2.70; 95% CI, 1.68-4.33), and longer duration of treatment (>21 days; OR, 5.08; 95% CI, 3.21-8.05). This study revealed that among the anti-MRSA agents, disproportionality in the occurrence of EP was observed only with DAP. Our results suggest that sex, age, and treatment duration may affect the occurrence of DAP-induced EP. Clinicians should exercise caution regarding EP during DAP administration.

Evaluation of the Effectiveness and Use of Anti-Methicillin-Resistant Staphylococcus aureus Agents for Aspiration Pneumonia in Older Patients Using a Nationwide Japanese Administrative Database.

Studies indicated potential harm from empirical broad-spectrum therapy. A recent study of hospitalizations for community-acquired pneumonia suggested that empirical anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy was associated with an increased risk of death and other complications. However, limited evidence supports empirical anti-MRSA therapy for older patients with aspiration pneumonia. In a nationwide Japanese database, patients aged ≥65 years on admission with aspiration pneumonia were analyzed. Patients were divided based on presence of respiratory failure and further sub-categorized based on their condition within 3 days of hospital admission, either receiving a combination of anti-MRSA agents and other antibiotics, or not using MRSA agents. An inverse probability weighting method with estimated propensity scores was used. Out of 81,306 eligible patients, 55,098 had respiratory failure, and 26,208 did not. In the group with and without respiratory failure, 0.93% and 0.42% of the patients, respectively, received anti-MRSA agents. In patients with respiratory failure, in-hospital mortality (31.38% vs. 19.03%, p < 0.001), 30-day mortality, and 90-day mortality were significantly higher, and oxygen administration length was significantly longer in the anti-MRSA agent combination group. Anti-MRSA agent combination use did not improve the outcomes in older patients with aspiration pneumonia and respiratory failure, and should be carefully and comprehensively considered.

Implementation of a Rapid Multiplex Polymerase Chain Reaction Pneumonia Panel and Subsequent Antibiotic De-escalation.

Net effects of implementation of a multiplex polymerase chain reaction (PCR) pneumonia panel (PNP) on antimicrobial stewardship are thus far unknown. This retrospective study evaluated the real-world impact of the PNP on time to antibiotic de-escalation in critically ill patients treated for pneumonia at an academic medical center. This retrospective, quasi-experimental study included adult intensive care unit (ICU) patients with respiratory culture results from 1 May to 15 August 2019 (pre-PNP group) and adult ICU patients with PNP results from 1 May to 15 August 2020 (PNP group) at Nebraska Medical Center. Patients were excluded for the following reasons: any preceding positive coronavirus disease 2019 PCR test, lack of antibiotic receipt, or non-respiratory tract infection indications for antibiotics. The primary outcome was time to discontinuation of anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy. Secondary outcomes included time to discontinuation of antipseudomonal therapy, frequency of early discontinuation for atypical coverage, and overall duration (in days) of antibiotic therapy for pneumonia. Sixty-six patients in the pre-PNP group and 58 in the PNP group were included. There were significant differences in patient characteristics between groups. The median time to anti-MRSA agent discontinuation was 49.1 hours in the pre-PNP and 41.8 hours in the PNP group (P = .28). The median time to discontinuation of antipseudomonal agents was 134.4 hours in the pre-PNP versus 98.1 hours in the PNP group (P = .47). Other outcomes were numerically but not significantly improved in our sample. This early look at implementation of a multiplex PNP did not demonstrate a statistically significant difference in antibiotic use but lays the groundwork to further evaluate a significant real-world impact on antibiotic de-escalation in ICU patients treated for pneumonia.

CRO infection and the Use of MRSA-active Medication for Prophylaxis affect the Prognosis of Patients with Hematological Malignancies after CAR-T Infusion

Carbapenem-resistant organisms (CRO) are a high priority issue because there are limited medications available to treat CRO infections, and these pathogens replicate rapidly in immunosuppressed patients, including those with hematological malignancy. Risk factors and prognosis of CRO infections after chimeric antigen receptor-modified T cells (CAR-T) therapy are unclear. This study was conducted to analyse the risk factors for CRO infection in patients with hematological malignancies following CAR-T therapy, and prognosis 1 year after CAR-T infusion. Patients who were diagnosed with hematological malignancies and treated with CAR-T therapy between June 2018 and December 2020 at our center were included. The case group consisted of 35 patients who developed CRO infections within 1 year of CAR-T infusion, and the control group comprised 280 patients who did not develop CRO infections. Shockingly, therapy failure occurred in 62.82% of CRO patients vs. 13.21% of the control group (P=0.000). Patients with CRO colonization (odds ratio [OR]=15.48, confidence interval [CI] (6.43-37.25), P=0.000) and hypoproteinemia (OR=2.84, CI (1.20-6.73), P=0.018) were susceptible to CRO infections. CRO infections (hazard ratio [HR]=4.40, CI (2.32-8.37), P=0.000), prophylaxis with combination regimens containing methicillin-resistant Staphylococcus aureus (MRSA)-active agents (HR=5.42, CI (2.65-11.11), P=0.000), and bacterial infections occurring within 30 days of CAR-T infusion (HR=1.97, CI (1.08-3.59), P=0.028) were risk factors for poor outcomes within 1 year. This study shows that prophylaxis of CRO infection should be a top priority in CAR-T therapy, the serum albumin level of patients should be dynamically monitored and interventions put in place if necessary, and caution is required in prophylaxis with anti-MRSA activity agents.

Change to hospitalist providers had a minimal influence on overall antibiotic use in a VA long-term care setting

Background: In long-term care settings, practice patterns among practitioners are stronger determinants of antibiotic use than resident characteristics. In July 2021, hospitalists from the acute medicine service replaced geriatricians and assumed the care of residents in a 110-bed community living center (CLC) at a large academic Veterans Affairs (VA) medical center. We assessed changes in antibiotic use associated with that change of practitioners to guide stewardship efforts. We hypothesized that antibiotic use in the CLC would shift, reflecting the practice pattern of practitioners accustomed to treating patients in acute-care settings. Methods: We conducted a retrospective cohort study from July 1, 2020, through June 30, 2022, 1 year before and after the change of practitioners on July 1, 2021. We assessed resident characteristics and the following metrics of antibiotic use at monthly intervals: days of therapy (DOT) per 1,000 bed days of care (BDOC), antibiotic starts per 1,000 BDOC, and mean length of therapy (LOT) in days. We also compared the DOT per 1,000 BDOC for various antibiotics, in groups and individually. Results: In the years before and after the change of practitioners on July 1, 2021, the characteristics of CLC residents were comparable. Before and after July 1, 2021, monthly DOT per 1,000 BDOC (Fig. 1A), antibiotic starts per 1,000 BDOC, and mean LOT (Fig. 1B) were similar. After July 1, 2021, the use of fluoroquinolones decreased (14.31 vs 5.83 DOT per 1,000 BDOC; P &lt; .01), and variations in anti-MRSA, narrow-spectrum, and broad-spectrum hospital agents were small, whereas the use of broad-spectrum community agents increased (29.42 vs 47.81 DOT per 1,000 BDOC; P &lt; .01) (Fig. 2A). Within this group, there was increased use of doxycycline (7.42 vs 19.13 DOT per 1,000 BDOC; P &lt; .01), ertapenem (2.03 vs 4.58 DOT per 1,000 BDOC; P &lt; .01), and, modestly, azithromycin (0.40 vs 1.80 DOT per 1,000 BDOC) (Fig. 2B). Conclusions: The overall use of antibiotics, as measured by DOT, antibiotic starts, and LOT did not change after hospitalists assumed care of CLC residents. However, a notable decrease was observed in the use of fluoroquinolones, and an increase was observed in the use of doxycycline and ertapenem. Stewardship that is tailored to the type of provider and incorporates their practice patterns is needed to reinforce the prudent use of antibiotics.Disclosures: None

Reducing the rate of guideline-discordant therapy for inpatients with community-acquired pneumonia

Background: Despite guidelines recommending shorter durations of therapy and empiric coverage of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) only for patients with certain risk factors, optimizing therapy for community-acquired pneumonia (CAP) remains a challenge for antimicrobial stewardship (AMS) teams. We investigated the impact of a multimodal AMS initiative on the rate of guideline-discordant empiric antibiotic selection and total duration of therapy for CAP. Methods: A quality improvement initiative was implemented at 9 community hospitals in 2022 to optimize CAP therapy. Education was provided to pharmacists and providers. Alerts were implemented within the electronic medical record to prompt the AMS team to review fluoroquinolones, antipseudomonal β-lactams, and anti-MRSA agents ordered for CAP. Clinical pharmacists reviewed antibiotic orders for CAP at hospital discharge and encouraged providers to prescribe a total antibiotic duration of 5–7 days. For the preintervention period (July– September 2021) and the postintervention period (July to September 2022), a random sample of 320 patients with an antibiotic order for CAP were evaluated retrospectively via chart review. Patients treated for an indication other than CAP were excluded. The primary outcome was the proportion of patients with a total duration of therapy &gt;7 days. Secondary outcomes included average duration of therapy, rate of guideline-discordant empiric therapy, and type of guideline discordance. Results: In total, 317 patients were included. The proportion of patients with a total duration of therapy &gt;7 days decreased from 29% to 14% (P &lt; .01). Average duration of therapy and guideline-discordant empiric therapy also decreased significantly (Table 1). Conclusions: This multifaceted AMS initiative was associated with decreased guideline-discordant empiric therapy and decreased total duration of therapy for CAP.Disclosures: None

An observational study for evaluation of antibiotic utilization and growing resistance against antibiotics in pediatric patients suffering from meningitis in a tertiary care hospital

Background: Meningitis, inflammation of the meninges with systemic septicemia, from the bacterial, viral, or fungal origin, is a fatal disease in all age groups, particularly infants and children. The present study was done to evaluate the usage of antibiotics in pediatric patients with meningitis in a tertiary care hospital. Aims and Objectives: The study was conducted to evaluate the prescription pattern of antibiotics for pediatric patients suffering from meningitis. The efficacy of antibiotics, combination of antibiotics, and the resistance developed against them were reevaluated. Materials and Methods: An observational, noninterventional study with 34 pediatric patients (The mean age of the patients were 6.17 year. ±4.84 SD) admitted in Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar from September 2012 to February 2014 were evaluated. Data were collected after the approval of the research protocol by the Institutional Ethics committee, KIMS from case sheets of patients from the ward as well as the Medical Record and Data section. Comparative statistical analysis was done by using student’s t-test in respect of data measured on a continuous scale. All differences with P&lt;0.05 were labeled as statistically significant. Results: Ceftriaxone±ß lactamase inhibitor (βLI) (77.4%), and Cefoperazone±βLI (12.9%) were the most frequently used cephalosporin. In 55.8% of patients, three or more antibiotics in combination were given. Two drugs regimen like β lacatam+aminoglycoside in 23.5% of patients and β lactam+anti-Methicillin-resistant Staphylococcus aureus (MRSA) in 20.6% were given. Emerging resistance pattern against both Gram-positive cocci and Gram-negative bacilli to penicillins, cephalosporins, and aminoglycosides which are the primary first-line drugs has been observed. Conclusion: Very severe meningitis patients were treated with multiple antibiotics including anti-MRSA agents. High resistance (≥60%) was observed against β lactams.

Impact of antimicrobial stewardship with the Xpert MRSA/SA BC assay at a tertiary hospital in Japan

IntroductionGenetic testing is gaining increasing importance as a part of antimicrobial stewardship (AS). Rapid identification and determination of methicillin susceptibility using the Xpert MRSA/SA BC assay can improve the management of Staphylococcus aureus bacteremia (SAB) and reduce inappropriate antibiotic use. However, few reports have described the effectiveness of this approach. MethodsThe present study aimed to assess the influence of AS using the Xpert MRSA/SA BC assay. Cases were classified into the pre-intervention group (n = 98 patients), in which SAB was identified by traditional culture (November 2017 to November 2019), and the post-intervention group (n = 97 patients), in which the Xpert MRSA/SA BC assay was performed when necessary (December 2019 to December 2021). ResultsPatient characteristics, prognosis, duration of antimicrobial use, and length of hospital stay were compared between the groups. The Xpert assay was performed in 66 patients in the post-intervention group (68.0%). The two groups showed no significant differences in severity and mortality. The rate of cases treated with anti-MRSA agents reduced following the intervention (65.3% vs. 40.4%, p = 0.008). The number of cases involving definitive therapy within 24 h was higher in the post-intervention group (9.2% vs. 24.7%, p = 0.007). The hospitalization rate at >60 days was lower in Xpert implementation cases among MRSA bacteremia cases (28.6% vs. 0%, p = 0.01). ConclusionsThus, the Xpert MRSA/SA BC assay has potential as an AS tool, especially for early definitive treatment to SAB and reduction of long-term hospitalization in MRSA bacteremia cases.

A Review of Pyridine and Pyrimidine Derivatives as Anti-MRSA Agents

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a gram-positive strain whose resistance against existing antibiotics is a major concern for the researchers across the globe. Gram-positive infections, particularly methicillin-resistant Staphylococcus aureus spreading among S. aureus isolates, observed to increase exponentially from 29% in 2009 to 47% in 2014. Literature reviews revealed about 13-74% of worldwide S. aureus strains are Methicillin-resistant. Objective: In this article, we have summarized the mechanism of bacterium resistance, molecular targets to treat MRSA, and the activity of reported pyridine and pyrimidine derivatives against methicillin-resistant Staphylococcus aureus. Results: The data collected for this study from online peer reviewed research articles and Molecular-docking study of reported anti-MRSA agents performed by using Maestro Module of Schrodinger software. Results of in silico studies showed that some pyridine derivatives having better binding interactions than standard anti-MRSA agents. Conclusion: Molecular docking studies of reported pyridine derivatives resulted in excellent hits for the development of novel anti- MRSA agents. Overall, this study will be immense importance for researchers working in design and development of target based anti-MRSA agents.

In vitro Antibacterial and in silico Evaluation of Ficus benghalensis Methanolic Bark Extract, as Potential Anti-MRSA Agent

Abstract: Background: Methicillin-resistant Staphylococcus aureus (MRSA), known to be highly resistant bacterium, leading to dreadful infections with limited treatment options. Objectives: The current study mainly focused to investigate the anti-staphylococcal activity of Ficus benghalensis methanolic bark (FBMB) extract against Methicillin-resistant Staphylococcus aureus (MRSA). Materials and Methods: The assessment of Ficus benghalensis methanolic bark (FBMB) extract was performed by agar well diffusion method and broth dilution method. Further, the pathogenic factors such as formation of biofilm, hemolysis, adhesion and staphyloxanthin production were evaluated to confirm antibiofilm and anti-adhesion activity. Cytoplasmic leakage analysis was also carried out to confirm the antibacterial activity of the extract. Results: From agar well diffusion method, it was observed that even at low dosage (1.6 mg/ml) showed the zone of inhibition which is significantly as dose dependent manner. 50 mg/ml extract showed Minimum inhibitory concentration (MIC) and 100 mg/ml extract showed minimum bactericidal concentration (MBC). The inhibitory activity of extracts was observed information of biofilm, hemolytic activity and production of staphyloxanthin. Oxidative survival resulted in decreased colonies of Methicillin-resistant Staphylococcus aureus (MRSA) and cytoplasmic leakage elevation was observed with the treatment. Further, in silico analysis also confirms the binding and interaction of the active molecules of FBMB extract, such as Beta-sitosterol, Lupeol Acetate and Alpha-amyrin against the MSCRAMMs family of MRSA using AutoDock Vina, Accelrys BIOVIA and pyMol tools and furthermore these molecules have better pharmacokinetic profile as based on Lipinski's rule of five violation. Conclusion: Ficus benghalensis methanolic bark extract, can be used as an drug candidate for antibiotic-resistant infection caused by Methicillin-resistant Staphylococcus aureus (MRSA). Keywords: MRSA, Ficus benghalensis, Bark extract, Anti-biofilm, Anti-virulence, Anti-bacterial, Membrane stability, in silico.

2-Hydroxypropyl Group Linked Derivatives of Indole Azoles as Potential Multifunctional Antibacterial Candidates for Effectively Inhibiting the Activity of MRSA and Responding Inflammatory Factors.

The increasing resistance of methicillin-resistant Staphylococcus aureus (MRSA) to antibiotics has led to escalating efforts to design and synthesize new structural agents with significant antimicrobial potential. A novel class of 2-hydroxypropyl group linked derivatives of indole azoles was developed as potential antibacterial agents. Bioactivity screening results demonstrated that metronidazole-modified indole derivative 4 a had excellent antibacterial capacity against MRSA (MIC=6 μM), which was about 4 times that of norfloxacin (MIC=25 μM). Highly active hybrid 4 a did not cause obvious drug-resistance in MRSA after multiple generations (15 passage operations). Compound 4 a showed low toxicity to normal mammalian cells (RAW 264.7). Molecular docking and molecular electrostatic potential (MEP) surface studies were used to map hydrogen bond interactions and the electron distribution in the highly active compounds. In addition, the preliminary exploration of the antibacterial mechanism revealed that the active molecule 4 a could infiltrate the membrane of MRSA and insert into MRSA DNA to prevent its replication, thus activating strong inhibition of the bacteria. Furthermore, highly active derivative 4 a could better respond to inflammatory factors (IL-6, IL-10, TNF-α and PGE-2), and it is less likely to cause inflammatory complications, hence diversifying the functions of antibacterial candidate molecules. These findings effectively indicate the potential of the bioactive hybrid 4 a as a multifunctional anti-MRSA agent. Further exploration of the development of antimicrobials combining these kinds of 2-hydroxypropyl group linked indole derivatives is of great value.

Community-Acquired Skin and Soft Tissue Infections: Epidemiology and Management in Patients Presenting to the Emergency Department of a Tertiary Care Hospital.

Skin and soft tissue infections are one of the most common diseases presenting to the emergency department (ED). There is no study available on the management of Community-Acquired Skin and Soft Tissue Infections (CA-SSTIs) in our population recently.This study aims to describe the frequency and distribution ofCA-SSTIs as well as their medical and surgical management among patients presenting to our ED. We conducted a descriptive cross-sectional study on patients presenting with CA-SSTIs to the EDof a tertiary care hospital in Peshawar, Pakistan. The primary objective was to estimate the frequency of common CA-SSTIs presenting to the ED and to assess the management of these infections in terms of diagnostic workup and treatment modalities used. The secondary objectives were to study the association of different baseline variables, diagnostic modalities,treatment modalities, and improvement with the surgical procedure performancefor these infections. Descriptive statistics were obtained for quantitative variables like age. Frequencies and percentages were derived for categorical variables. The chi-square test was used to compare different CA-SSTIs in terms of categorical variables like diagnostic and treatment modalities. We divided the data into two groups based on the surgical procedure. A chi-square analysis was conducted to compare these two groups in terms of categorical variables. Out of the 241 patients, 51.9% were males and the mean age was 34.2 years. The most common CA-SSTIs were abscesses, infected ulcers, and cellulitis. Antibiotics were prescribed to 84.2% of patients. Amoxicillin + Clavulanate was the most frequently prescribed antibiotic. Out of the total, 128 (53.11%) patients received some type of surgical intervention. Surgical procedures were significantly associated with diabetes mellitus, heart disease, limitation of mobility, or recent antibiotic use. There was a significantly higher rate of prescription of any antibiotic and anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) agents in the surgical procedure group. This group also saw a higher rate of oral antibiotics prescription, hospitalization, wound culture, and complete blood count. This study shows a higher frequency of purulent infections in our ED. Antibiotics were prescribed more frequently for all infections. Surgical procedures like incision and drainage were much lower even in purulent infections. Furthermore, beta-lactam antibiotics like Amoxicillin-Clavulanate were commonly prescribed. Linezolid was the only systemic anti-MRSA agent prescribed. We suggest physicians should prescribe antibiotics appropriate to the local antibiograms and the latest guidelines.