anti-MRSA Agents Research Articles

Molecular Details of Actinomycin D-Treated MRSA Revealed via High-Dimensional Data.

Methicillin-resistant Staphylococcus aureus (MRSA) is highly concerning as a principal infection pathogen. The investigation of higher effective natural anti-MRSA agents from marine Streptomyces parvulus has led to the isolation of actinomycin D, that showed potential anti-MRSA activity with MIC and MBC values of 1 and 8 μg/mL, respectively. Proteomics-metabolomics analysis further demonstrated a total of 261 differential proteins and 144 differential metabolites induced by actinomycin D in MRSA, and the co-mapped correlation network of omics, indicated that actinomycin D induced the metabolism pathway of producing the antibiotic sensitivity in MRSA. Furthermore, the mRNA expression levels of the genes acnA, ebpS, clfA, icd, and gpmA related to the key differential proteins were down-regulated measured by qRT-PCR. Molecular docking predicted that actinomycin D was bound to the targets of the two key differential proteins AcnA and Icd by hydrogen bonds and interacted with multiple amino acid residues of the proteins. Thus, these findings will provide a basic understanding to further investigation of actinomycin D as a potential anti-MRSA agent.

The antibacterial activity of plantaricin GZ1–27 against MRSA and its bio-preservative effect on chilled pork in combination with chitosan

Methicillin-resistant Staphylococcus aureus (MRSA) poses great threats to human health. In this research, we found that the newly discovered bacteriocin plantaricin GZ1–27 could efficiently inhibit the MRSA, with a MIC of 32 μg/mL. Comprehensive investigations were carried out by analysis of K+ leakage, propidium iodide assay, and cell ultra-structure analysis with scanning electron microscopy and transmission electron microscopy. The results consistently showed that plantaricin GZ1–27 could increase the permeability of the membrane and impair its integrity, which induced the collapse of the cell structure and thus led to cell death. Furthermore, by sensory evaluation and biochemical analysis, it was found that plantaricin GZ1–27 combined with chitosan could significantly improve the preservation of pork when applied to the surface of meat slices. Overall, our research clearly showed the anti-MRSA bactericidal mechanism of plantaricin GZ1–27, which, together with its preliminary application trials in pork, suggested plantaricin GZ1–27 could be a potential anti-MRSA agent and is promising to be applied in pork preservation to extend the shelf life.

New tunable pyridinium benzenesulfonate amphiphiles as anti-MRSA quaternary ammonium compounds (QACs)

A new class of quaternary ammonium compounds (QACs) with two different spacer lengths was developed and tested for antibacterial activity. The results of the experiments revealed that compounds with a longer cinnamoyl spacer had a broad bactericidal effect against both Gram-negative and Gram-positive bacteria with substantial anti-Methicillin-Resistant Staphylococcus aureus (anti-MRSA) activity. The MICMRSA values of the compounds with the long spacer ranged from 4.65 to 9.37 mg/L, showing that they are 16-times more effective anti-MRSA agents than the derivatives with the short spacer. Micrographs clearly show MRSA cellular breakdown induced by the synthesized QAC. The novel cinnamoyl pyridinium derivatives were discovered to be potentially excellent disinfectants, and their anti-MRSA impact might be increased by varying the length of their spacers.

Novel FabI inhibitor disrupts the biofilm formation of MRSA through down-regulating the expression of quorum-sensing regulatory genes

ObjectivesThe aim of this study was to explore the antibiofilm and antivirulence efficacy of benzylaniline 4k against MRSA. MethodsThe clinical MRSA strains were identified and used to evaluate their potential to form biofilm using crystal violet assay. The minimal inhibitory concentration (MIC) was determined using broth microdilution method. The expression of genes was detected using quantitative real-time PCR (qRT-PCR). Rabbit blood hemolytic assay was used to observe the inhibitory ability of alpha-hemolysin (Hla). ResultsCompound 4k showed potent antibacterial activity against 16 clinical MRSA with an MIC50 of 1.25 mg/L and MIC90 of 2.25 mg/L. The value of minimum biofilm eradication concentration (MBEC) against MRSA2858 biofilm was of 1.5 mg/L, close to its MIC, superior to those of vancomycin and erythromycin. Compound 4k eradicated the formation of biofilm through inhibiting the gene expression of branched-chain fatty acid synthesis, down-regulating the expression of quorum-sensing (QS) regulatory genes (norA, agrA, icaA, hla), decreasing the level of hemolysis in a dose-dependent manner, and inhibiting rabbit blood hemolysis by 86.9% at a concentration of 1.25 mg/L. In a mouse model of abdominal infection, compound 4k was more effective than vancomycin in reducing bacterial load. ConclusionsThese results suggested that compound 4k could be developed as promising an anti-MRSA agent through affecting quorum-sensing system.

Beta Lactams Plus Daptomycin Combination Therapy for Infective Endocarditis: An Italian National Survey (BADAS).

Background: infective endocarditis (IE) remains a severe disease frequently encountered in clinical practice and often requiring interdisciplinary medical and surgical management. This national survey aims to describe the clinical prescribing habits of the use of daptomycin in the setting of IE and the possible role for combination therapy with beta-lactams. Methods: The study was a cross-sectional internet-based questionnaire survey on therapy with daptomycin. The questionnaire was designed with closed-ended questions and distributed using the SurveyMonkey® platform between October 2019 to December 2020. Results: 55 clinicians from twelve Italians regions joined the questionnaire. The survey reported use of daptomycin as first-line choice in 31.48% of cases and as the first-line anti-MRSA agent in 44.44%. The empiric use of daptomycin was stated in the high suspicion of MRSA rather than MSSA, enterococcal or streptococcal IE. The rationale of daptomycin for the empirical treatment of native and prosthetic valve IE was mostly the possibility of administering an aminoglycoside-sparing combination regimen, high bacterial killing rate and high clinical efficacy. Conclusions: In conclusion, in selected patients, daptomycin could be a feasible option for the treatment of infective endocarditis in line with data from the European registry of daptomycin.

Methicillin resistant Staphylococcus aureus - importance of appropriate empirical therapy in serious infections

India has been titled the capital of antimicrobial resistance in the world with the centre for disease dynamics, economics and policy (CDDEP) predicting two million deaths in India by 2050. As per the World Health Organisation’s global priority pathogen list of 2017, methicillin resistant Staphylococcus aureus (MRSA) has been classified as a ‘high priority’ pathogen due to its association with increased mortality rate, rising prevalence of resistance and increased burden on healthcare settings. A recent report by Indian Council of Medical Research signifies the exponential rise in the prevalence of MRSA in India, from 29% in 2009 to 39% in 2018. Serious MRSA infections are commonly associated with poor clinical outcomes coupled with increased hospitalisation stay and cost. Therefore, early identification and appropriate empiric treatment of MRSA plays a crucial role in healthcare settings. However, the constant rise in multi-drug resistance to the currently available anti-MRSA agents as well as their compromised safety profile limits its clinical use to manage severe MRSA infections. This review article explores the implications of severe MRSA infections and inappropriate empirical therapy on the clinical as well as economic outcomes. In addition, it also highlights limitations of the currently available anti-MRSA agents and the need for newer agents to manage multi drug resistant (MDR) gram positive infections.

An unanticipated discovery towards novel naphthalimide corbelled aminothiazoximes as potential anti-MRSA agents and allosteric modulators for PBP2a

Available therapeutic strategies are urgently needed to conquer multidrug resistance of MRSA. A visible effort was guided towards the advancement of novel antibacterial framework of naphthalimide corbelled aminothiazoximes, and desired to assert some insight on the conjunction of individual pharmacophore with distinct biological activities and unique action mechanism. Preliminary assessment displayed that dimethylenediamine derivative 13d presented a wonderful inhibition on MRSA (MIC = 0.5 μg/mL), and showed excellent membrane selectivity (HC50 > 200 μg/mL) from an electrostatic distinction of the electronegative bacterial membranes and the electroneutral mammalian membranes. Moreover, 13d could effectually relieve the development of MRSA resistance. Investigations into explaining the mechanism of anti-MRSA disclosed that 13d displayed strong lipase affinity, which facilitated its permeation into cell membrane, causing membrane depolarization, leakage of cytoplasmic contents and lactate dehydrogenase (LDH) inhibition. Meanwhile, 13d could exert interaction with DNA to hinder biological function of DNA, and disrupt the antioxidant defense system of MRSA through up-regulation of ROS subjected the strain to oxidative stress. In particular, the unanticipated mechanism for naphthalimide corbelled aminothiazoximes that 13d could suppress the expression of PBP2a by inducing allosteric modulation of PBP2a and triggering the open of the active site, was discovered for the first time. These findings of naphthalimide corbelled aminothiazoximes as a small-molecule class of anti-MRSA agents held promise in strategies for treatment of MRSA infections.

Oxazolidinone-containing Hybrids with Antibacterial Activity against Methicillin-resistant Staphylococcus aureus (MRSA): A Mini-review.

The increasing danger of methicillin-resistant Staphylococcus aureus (MRSA) and the limited therapeutic options for invasive MRSA infections make an urgent demand for the development of novel anti-MRSA agents. Oxazolidinone derivatives could inhibit protein synthesis by acting on the ribosomal 50S subunit of the bacteria and prevent the formation of a functional 70S initiation complex, so oxazolidinones are a novel class of antimicrobial agents with potential activity against a wide range of clinically significant multidrug-resistant Gram-positive pathogens. However, oxazolidinones such as linezolid are associated with significant adverse events, and myelosuppression represents the main unfavorable side effects. Moreover, MRSA isolates that are resistant to oxazolidinones have already emerged. Hybridization of oxazolidinone with other antibacterial pharmacophores has the potential to interact with multiple targets or to counterbalance the known side effects associated with each pharmacophore. Thus, oxazolidinone-containing hybrids are useful scaffolds for the development of novel anti-MRSA agents. This review covers the recent advances of oxazolidinonecontaining hybrids with anti-MRSA activity developed in the last decade to set up the direction for the design and development of oxazolidinone-containing hybrids with high efficiency and low toxicity.

Aminoglycosides with Anti-MRSA Activity: A Concise Review.

Methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of infections in human being and is usually associated with a multidrug-resistant profile, represents a significant health threat and public burden globally. The limited options of effective antibiotics motivate the search for novel anti-MRSA agents. Aminoglycoside antibiotics have been extensively applied in the medical field due to their desirable broad-spectrum antibacterial activity, especially for systemic infections caused by Gram-negative organisms. Recent studies demonstrated that aminoglycosides also possessed potential activity against MRSA, so aminoglycosides may be useful weapons to fight against MRSA. The present work aims to summarize the current scenario of aminoglycosides with anti- MRSA potential, covering articles published between 2010 and 2020. The structure-activity relationship and the mechanism of action are also discussed for the further rational design of novel potential drug candidates.

592. Antimicrobial Utilization in Solid Organ Transplant Recipients 12-Months Post-Transplantation

BackgroundAntimicrobials are widely used in solid organ transplant recipients (SOTr). Yet, antimicrobial utilization in the transplant (TP) population is not well characterized. National Healthcare Safety Network antimicrobial use (NHSN-AU) does not provide data specific to SOTr. This study sought to describe inpatient antibiotic use among SOTr up to 1-year post-TP.MethodsA cross-sectional study was performed of all SOTr who received a TP between January 2015 to December 2016. Demographics, TP type, antibiotic use variables, hospital days, and Clostridioides difficile infection (CDI) are described. Inpatient antibiotic administration was measured for 365 days starting from date of TP surgery. Automated data generated for NHSN-AU reporting was utilized, and SOTr data was abstracted by cross-matching with the transplant database. Transplant-patient days was used as the denominator for metrics. Variables included duration of therapy (DOT), DOT/1000 patient days, antimicrobial free days (inpatient days no antimicrobials were administered), and NHSN-AU reporting targets of anti-methicillin resistant S. aureus (MRSA), broad spectrum, and high-risk CDI agents. Data was analyzed using descriptive statistics via Microsoft Excel®. ResultsA total of 530 SOTr were analyzed. Baseline characteristics are shown in Table 1. Median age was 61, male gender 64%, median Charlson Comorbidity Index was 5. Kidney TP (43%), liver TP (32%), lung (9%) and heart (8%) were most common TP types. Among these four TP types: Lung TP had the highest median DOT (13 days), DOT/1000 patient days (6.6) and ratio of DOT/total patient (1.9) (Table 2). Liver TP had the most antimicrobial free days (34%). Proportionally, anti-MRSA agents use was highest in thoracic TP (lung/heart), broad-spectrum agent use was common in all but kidney TPs, and high-risk CDI agents use was highest among kidney TP (Table 3). A total of 34 SOTr had CDI, 76% in kidney/liver TPs. Table 1. Antimicrobial usage and SOT - ID Week 2021 Table 2. Antimicrobial usage and SOT - ID Week 2021 Table 3. Antimicrobial usage and SOT - ID Week 2021ConclusionOur study provides preliminary and important data of inpatient antibiotic utilization specifically in SOTr, generated using automated NHSN-AU data cross-matched to transplant database. These metrics can be utilized to promote antimicrobial stewardship efforts directed to specific TP types. Disclosures Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)

1071. Efficacy of Anti-Staphylococcal Lysin, LSVT-1701, in Combination with Daptomycin in Experimental Left-Sided Infective Endocarditis (IE) Due to Methicillin-Resistant Staphylococcus aureus (MRSA)

BackgroundAnti-staphylococcal phage lysins, such as LSVT-1701, represent important candidate adjunctive agents against invasive MRSA infections because of both their microbicidal and anti-biofilm properties. We, thus, sought to examine the in vivo efficacy of LSVT-1701 combination with daptomycin, a standard-of-care anti-MRSA agent with proven efficacy against bacteremia and IE in humans.MethodsWe utilized the rabbit model of aortic valve infective endocarditis (using the prototype MRSA strain, MW2) to examine the combined efficacy of LSVT-1701 plus daptomycin. We examined microbiologic outcomes in distinct target tissues (cardiac vegetations, spleen and kidney) in this model, as well as the pharmacokinetic and pharmacodynamic drivers and target attainment values most predictive of treatment outcomes. LSVT-1701 was given at two dose-regimens (32.5 mg/kg and 50 mg/kg) with different dose-durations (single dose vs daily dose for 2 d vs daily dose for 4 d); daptomycin was administered in combination with daptomycin at a sub-lethal daily dose of 4 mg/kg for 4 d to maximize potential synergistic interaction outcomes.ResultsThe Table below shows all LSVT-1701 regimens in combination with daptomycin significantly reduced MRSA burdens in all target tissue as compared to untreated controls. The reduction in MRSA counts was statistically significant in instances of both increasing LSVT-1701 dose level (i.e., single doses of 50 mg/kg vs 32.5 mg/kg iv), as well as increased numbers of lysin doses (i.e., four daily doses vs a single-dose or two daily-doses) in combination with daptomycin. Of note, both the LSVT-1701 50 mg/kg and 32.5 mg/kg daily dose-strategies given for four days in combination with daptomycin sterilized all target tissues (i.e., quantitative cultures ≤ the lower limit of detection of 1 log10 CFU/g. tissue). MRSA bio-burdens in blood, vegetations, kidneys and spleen in rabbit IE modelConclusionLSVT-1701 administered at 32.5 or 50 mg/kg in a 4 d daily-dose regimen in combination with daptomycin resulted in microbiologic sterilization of all target organs in this MRSA IE model. These data support further clinical development of LSVT-1701 for the treatment of MRSA endovascular infections including IE.Disclosures David Huang, MD, PhD, Lysovant (Consultant) Eric Gaukel, BS, Lysovant (Employee) Katyna Borroto-Esoda, PhD, Lysovant (Consultant) Arnold Bayer, MD, PhD, Lysovant (Grant/Research Support)

Design, synthesis and biological evaluation of pleuromutilin-Schiff base hybrids as potent anti-MRSA agents invitro and invivo.

A series of pleuromutilin derivatives with 1,2,4-triazole-3-substituted Schiff base structure were designed and synthesized under mild conditions. The invitro antibacterial activities of the synthesized derivatives against 4 strains of Staphylococcus aureus (MRSA ATCC 43300, S.aureus ATCC 29213, S.aureus 144 and S.aureus AD3) and 1 strain of E.coli (ATCC 25922) were evaluated by the broth dilution method. Among these derivatives, compound 60 exhibited superior invitro antibacterial effect against MRSA (MIC=0.25μg/mL) than tiamulin (MIC=0.5μg/mL), and compound 60 (-2.28 log10CFU/mL) also displayed superior invivo antibacterial efficacy than tiamulin (-1.40 log10CFU/mL) in reducing MRSA load in the mouse thigh infection model. The time-kill study and the post-antibiotic effect study indicated that compound 60 showed a faster bactericidal kinetic and longer PAE time (exposure to 2×MIC and 4×MIC for 2h, the PAE was 4.06 and 4.27h) against MRSA compared with tiamulin (exposure to 2×MIC and 4×MIC for 2h, the PAE was 1.72 and 2.14h). Meanwhile, most of these compounds had no significant inhibitory effect on RAW 264.7cells and HepG2 cells at the concentration of 4μg/mL. Additionally, the development of resistance study showed that MRSA did not easily develop resistance against compound 60 compared with tiamulin after induction for 8 passages.

Preliminary Insight of Pyrrolylated-Chalcones as New Anti-Methicillin-Resistant Staphylococcus aureus (Anti-MRSA) Agents.

Bacterial infections are regarded as one of the leading causes of fatal morbidity and death in patients infected with diseases. The ability of microorganisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), to develop resistance to current drugs has evoked the need for a continuous search for new drugs with better efficacies. Hence, a series of non-PAINS associated pyrrolylated-chalcones (1–15) were synthesized and evaluated for their potency against MRSA. The hydroxyl-containing compounds (8, 9, and 10) showed the most significant anti-MRSA efficiency, with the MIC and MBC values ranging from 0.08 to 0.70 mg/mL and 0.16 to 1.88 mg/mL, respectively. The time-kill curve and SEM analyses exhibited bacterial cell death within four hours after exposure to 9, suggesting its bactericidal properties. Furthermore, the docking simulation between 9 and penicillin-binding protein 2a (PBP2a, PDB ID: 6Q9N) suggests a relatively similar bonding interaction to the standard drug with a binding affinity score of −7.0 kcal/mol. Moreover, the zebrafish model showed no toxic effects in the normal embryonic development, blood vessel formation, and apoptosis when exposed to up to 40 µM of compound 9. The overall results suggest that the pyrrolylated-chalcones may be considered as a potential inhibitor in the design of new anti-MRSA agents.

Streptomyces sp.-A Treasure Trove of Weapons to Combat Methicillin-Resistant Staphylococcus aureus Biofilm Associated with Biomedical Devices.

Biofilms formed by methicillin-resistant S. aureus (MRSA) are among the most frequent causes of biomedical device-related infection, which are difficult to treat and are often persistent and recurrent. Thus, new and effective antibiofilm agents are urgently needed. In this article, we review the most relevant literature of the recent years reporting on promising anti-MRSA biofilm agents derived from the genus Streptomyces bacteria, and discuss the potential contribution of these newly reported antibiofilm compounds to the current strategies in preventing biofilm formation and eradicating pre-existing biofilms of the clinically important pathogen MRSA. Many efforts are evidenced to address biofilm-related infections, and some novel strategies have been developed and demonstrated encouraging results in preclinical studies. Nevertheless, more in vivo studies with appropriate biofilm models and well-designed multicenter clinical trials are needed to assess the prospects of these strategies.

Design, synthesis of pyridine coupled pyrimidinone/pyrimidinthione as anti-MRSA agent: Validation by molecular docking and dynamics simulation

Methicillin Resistant Staphylococcus aureus (MRSA) is a major cause of severe hospital and infections acquired by the population and related morbidity and mortality. In this unique situation, there is a need of dynamic strong drug candidates to control MRSA diseases. Thus, the present work focuses on the synthesis and characterization of pyrimidinones and pyrimidinthiones coupled pyridine derivatives as anti-MRSA agent. The synthesized compounds were characterized by different spectroscopic techniques and evaluated against MRSA strain. Among them, 4e and 4 g possessed better antibacterial activity with MIC values of 10 μg and 8 μg respectively. The key determinant of the wide range beta-lactam resistance in MRSA strains is the Penicillin-Binding Protein 2a (PBP2a) but the gene encodes PBP2a which has a low affinity towards β-lactam antibiotics. Because of this, the present investigation focused on the mechanism of PBP2a protein binding studies by in-silico studies. The synthesized compounds showed very good interactions with PBP2A compared with standard drug Vancomycin, among them compound 4 g showed better interaction with the binding score of −9.8 kcal/mol. Antibacterial activity was validated with molecular docking and molecular dynamic simulation. Simulation results revealed that protein-ligand interactions of 4 g compound stably sustained up to 20,000ps. Communicated by Ramaswamy H. Sarma

Evaluation of A-azepano-triterpenoids and related derivatives as antimicrobial and antiviral agents.

A series of semisynthetic triterpenoids with A-ring azepano- and A-seco-fragments as well as hydrazido/hydrazono-substituents at C3 and C28 has been synthesized and evaluated for antimicrobial activity against key ESKAPE pathogens and DNA viruses (HSV-1, HCMV, HPV-11). It was found that azepanouvaol 8, 3-amino-3,4-seco-4(23)-en derivatives of uvaol 21 and glycyrrhetol-dien 22 as well as azepano-glycyrrhetol-tosylate 32 showed strong antimicrobial activities against MRSA with MIC ≤ 0.15 μM that exceeds the effect of antibiotic vancomycin. Azepanobetulinic acid cyclohexyl amide 4 exhibited significant bacteriostatic effect against MRSA (MIC ≤ 0.15 μM) with low cytotoxicity to HEK-293 even at a maximum tested concentration of >20 μM (selectivity index SI 133) and may be considered a noncytotoxic anti-MRSA agent. Azepanobetulin 1, azepanouvaol 8, and azepano-glycyrrhetol 15 showed high potency towards HCMV (EC50 0.15; 0.11; 0.11 µM) with selectivity indexes SI50 115; 136; 172, respectively. The docking studies suggest the possible interactions of the leading compounds with the molecular targets.

The Prevalence and Antimicrobial Susceptibility Pattern of Gram-Positive Pathogens: Three-Year Study at a Tertiary Care Hospital in Mumbai, India

Introduction The growing resistance pattern of the gram-positive pathogens along with a steady increase in minimum inhibitory concentration of the currently available antibiotics have led to an increase in morbidity and mortality rates in India. This study aims to access the shifting antibiotic susceptibility paradigm of the gram-positive pathogens in various infections at a tertiary care center. Methods This is a 3-year retrospective observational study which was performed from January 2016 to December 2018 at a tertiary care hospital in Mumbai. All clinically significant gram-positive cocci isolated from a variety of clinical specimens were studied for their prevalence and antimicrobial susceptibility. Results Out of 4,428 gram-positive isolates, Staphylococcus aureus (35.3%) was the commonly encountered pathogen, followed by Enterococcus spp. (32.1%) and coagulase-negative Staphylococcus (CoNS) (25.7%). S. aureus was majorly isolated from skin and soft tissue infections (60.3%), followed by patients with respiratory tract infections (18.2%) and blood stream infections (13%). Among S. aureus , particularly methicillin-resistant S. aureus (MRSA), prevalence increased from 29.5% in 2016 to 35.1% in 2018, with an overall prevalence of 33.6%. All S. aureus isolates were 100% sensitive toward vancomycin, linezolid, tigecycline, and teicoplanin. However, the CoNS isolates showed a higher resistance rate with reduced susceptibility toward linezolid and teicoplanin. High prevalence of resistance was observed across gram-positive isolates with commonly used antibiotics such as ciprofloxacin, levofloxacin, and erythromycin. While the prevalence of linezolid-resistant enterococcus (LRE) was 3.6%, vancomycin (VRE) and teicoplanin resistance among the enterococcus species was as high as 7.7% and 7.5%, respectively. Conclusion Rising methicillin resistance among the Staphylococcal species (MRSA and MR-CoNS) along with reduced susceptibility toward currently available anti-MRSA agents is a matter of serious concern as it limits the therapeutic options for treating multidrug resistant (MDR) gram-positive infections.

Use of Ceftaroline in Hospitalized Patients with and without COVID-19: A Descriptive Cross-Sectional Study.

A single-center cross-sectional study was conducted to describe the use of ceftaroline in a large teaching hospital in Northern Italy, during a period also including the first months of the coronavirus disease 2019 (COVID-19) pandemic. The primary objective was to describe the use of ceftaroline in terms of indications and characteristics of patients. A secondary objective was to describe the rate of favorable clinical response in patients with bloodstream infections (BSI) due to methicillin-resistant Staphylococcus aureus (MRSA-BSI) receiving ceftaroline. Overall, 200 patients were included in the study. Most of them had COVID-19 (83%, 165/200) and were hospitalized in medical wards (78%, 155/200). Included patients with COVID-19 pneumonia were given empirical ceftaroline in the suspicion of bacterial co-infection or superinfection. Among patients with MRSA-BSI, ceftaroline was used as a first-line therapy and salvage therapy in 25% (3/12) and 75% (9/12) of cases, respectively, and as a monotherapy or in combination with daptomycin in 58% (7/12) and 42% (5/12) of patients, respectively. A favorable response was registered in 67% (8/12) of patients. Improving etiological diagnosis of bacterial infections is essential to optimize the use of ceftaroline in COVID-19 patients. The use of ceftaroline for MRSA-BSI, either as a monotherapy or in combination with other anti-MRSA agents, showed promising rates of favorable response.

Chemistry and Pharmacology of Natural Catechins from Camellia sinensis as Anti-MRSA Agents.

Tea, a worldwide popular beverage rich in polyphenols, contributes to the prevention of many diseases and thus is beneficial to human health. Tea is a product through processing the fresh leaves picked from the plant Camellia sinensis (C. sinensis, genus Camellia section Thea). To date, systematic studies have been conducted on the phytochemicals from more than 20 tea varieties and related tea products, resulting in the structural determination of over 400 constituents viz. different types of polyphenols, purines, and their derivatives, mono to tetra-terpenoids, and minor other phytomolecules. These various tea phytochemicals contribute to the anti-oxidative effects, anti-diabetes, anti-inflammation, anti-cancer, blood lipid reduction, neuroprotection, anti-Alzheimer's disease, hepatoprotection, and anti-microbial activities, etc. Staphylococcus aureus (S. aureus), the significant human pathogens, could cause nosocomial and community-acquired infections, which is also responsible for various infectious diseases from mild to severe life-threatening conditions, such as bacteremia (bloodstream infection), endocarditis (heart valves infection), pneumonia, and meningitis (brain infection), leading to 2% clinical disease in of all patient admissions. The multidrug resistance (MDR) and antibiotics losing efficacy, esp. in methicillin resistance Staphylococcus aureus (MRSA) urge for novel antimicrobial agents. The MRSA strains are resistant to the entire class of β-lactam antibiotics and limit effective treatment, leading to still spread of staphylococcal infections. MRSA also exhibits resistance to cephalosporins, macrolides, fluoroquinolones, aminoglycosides, and glycopeptides (teicoplanine and vancomycin), leading to resistant strains-glycopeptide resistant strain (GRSA) and glycopeptide intermediate (GISA) S. aureus. In this review, chemical constituents responsible for the anti-MRSA activity of tea are explored.

Screening of Anti-MRSA metabolites in bacteria symbiotic with Batissa violaceae celebensis marten 1897

Currently, infectious diseases are still a serious problem in Indonesia, especially with thewidespread resistance of microbes to antibiotics. Staphylococcus aureus as one of the commonpathogens causing infection has experienced resistance to various classes of beta-lactam antibiotics known as Methicillin-resistant Staphylococcus aureus (MRSA). Therefore antibiotic alternatives sourced from nature are needed to treat the MRSA pathogenic infection. This study aims to explore the potential of bacteria in symbiosis with Pokea Shells (Batissaviolaceacelebensis Martens 1897) from Konawe Regency, Southeast Sulawesi Province to be used as the newest anti-MRSA. In this research, Pokea Shell’s symbiont bacteria were isolated from Konawe Regency to obtain pure isolates. Pure isolates that have been produced from secondary metabolites to be tested for their potential in inhibiting the growth of pathogenic bacteria MRSA. The inhibition test was done qualitatively by using a paper disk. Based on the results five bacterial isolates were obtained with different abilities to inhibit MRSA bacteria. Based on the qualitative test obtained that the Bvc1 and Bvc3 bacterial isolates had the potency to be used as anti-MRSA agents. These isolates have an inhibition zone of 25 mm and 22 mm with a sensitive category according to CLSI standards (Sensitive ≥17 mm). Determination of the gram of these 2 isolates found as gram-positive bacteria in the form of bacilli so it can be concluded that the 2 isolates can be used as anti-MRSA agents.