Methicillin-resistant Staphylococcus Aureus Research Articles

Molecular epidemiology and clinical characteristics of Staphylococcus aureus bacteremia in Japanese adults

IntroductionStaphylococcus aureus bacteremia (SAB), especially when caused by methicillin-resistant S. aureus (MRSA), is of considerable clinical importance. In recent years, the proportion of MRSA among S. aureus has decreased, and a relative increase in the proportion of methicillin-susceptible S. aureus (MSSA) has been observed. It is therefore necessary to consider both MRSA and MSSA when assessing the microbiological and clinical significance of SAB. Materials and MethodsWe included SAB cases from the Nara Medical University Hospital between January 2015 and February 2017. We performed drug susceptibility testing, toxicity gene analysis, multilocus sequence typing (MLST), and polymerase chain reaction-based open reading frame typing (POT) of stored strains to integrate clinical and bacteriological characteristics. ResultsThere were 90 cases during the experimental period (42 MRSA and 48 MSSA), with 30-day mortality rates of 19% for MRSA and 10.4% for MSSA. Deaths were more frequently complicated by septic shock and disseminated intravascular coagulation. MLST studies showed that ST8, ST764, ST1, and ST15 were prevalent in the MRSA group, whereas ST5, ST188, and ST12 were prevalent in MSSA. Infective endocarditis cases had a long time from onset to the initiation of effective antimicrobials and were all MSSA. MLST and POT results correlated well, and POT appeared to have better discriminatory power. ConclusionsThe severity and mortality of SAB, along with the microbiological characteristics of causative isolates, vary by location and time. Continued studies integrating clinical and microbiological investigations are thus needed.

Generation and characterization of a monoclonal antibody fab fragment targeting PBP2a in methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main pathogens associated with nosocomial and community infections that are difficult to treat owing to its resistance to all β-lactams and other classes of antibiotics. Reports of MRSA demonstrate the pathogen relevance and urgency for developing innovative diagnostic and treatment strategies against this microorganism. In this context, monoclonal antibodies (mAbs) represent a powerful tool for such purposes. Beta-lactam resistance in MRSA is caused by penicillin-binding protein 2a (PBP2a). The characteristics of PBP2a make this protein a potential target for immunobiologicals to combat this pathogen. This study describes the development of a recombinant Fab fragment from a mAb directed against the PBP2a protein, designed to identify and treat MRSA infections. The Fd and light chain coding sequences for Fab expression were amplified and ligated into the mammalian cell expression vector. Recombinant DNA constructs were used to transfect Expi293F cells expressing anti-PBP2a Fab. A purification based on ion-exchange chromatography was used for Fab separation, followed by analysis of antigen target recognition and interaction, either with the isolated antigen or with the antigen on the MRSA cell surface. The experimental approach allowed us to obtain significant Fab expression levels in the Expi293F system when transfecting the cells with the genetic constructs developed in pCDNA3.4 vector. Antigen target interaction assays revealed the capacity of Fab to recognize and interact with the PBP2a protein. Biodistribution analysis indicated serum Fab presence, in the serum, kidneys, lungs, and spleen, and a plasma half-life averaging 6–8 h.

Cross-sectional Hospital-based Investigation on Clinical Characteristics of Pediatric Staphylococcus aureus Isolates in a Beijing Hospital from 2013 to 2022.

Staphylococcus aureus (S. aureus) was a prevalent pathogenic bacterium among children. Due to the extensive use of antibiotics, the sensitivity of S. aureus to these drugs has gradually declined. Since the 1960s, methicillin-resistant Staphylococcus aureus (MRSA) has emerged and spread worldwide, becoming a primary cause of both healthcare-associated (HA) and community-acquired (CA) infections. This retrospective study aimed to highlight the significance of S. aureus among bacteria isolated from children in Beijing, China, and to elucidate its antimicrobial resistance patterns. Data on all S. aureus infections from 2013 to 2022 were collected from the microbiology department of Beijing Children's Hospital. Only the first isolate from the same kind of specimen was analyzed. Antimicrobial susceptibility tests were carried out by Vitek 2 automated system (bio Mérieux, France) or Kirby-Bauer disc diffusion method, according to the guidelines recommended by the Clinical and Laboratory Standards Institute (CLSI). During the decade-long research period, a total of 47,062 bacterial isolates were isolated from 433,081 submitted specimens, with 6477 of these isolates identified as S. aureus. The majority of patients with S. aureus infections belonged to the age group of infants under one-year-old, accounting for 37.9% of cases. S. aureus isolates were predominantly found in the Pneumology Department, and the most common source of these isolates was lower respiratory tract specimens, comprising 34.3% of the total. The resistance rates of S. aureus to penicillin and erythromycin were notably high, at 89.5% and 73.8%, respectively. In contrast, the resistance rates to linezolid, vancomycin, rifampicin, and moxifloxacin were remarkably low, at 0.0%, 0.0%, 1.3%, and 3.9%, respectively. The detection rate of MRSA was 27.8%. MRSA isolates were predominantly found in the newborn group, ICU, and sterile body fluids. In our study, the most prevalent specimen type was derived from the lower respiratory tract, whereas the highest positive rate was observed in ear secretions. These findings underscored the pressing necessity for ongoing antimicrobial resistance (AMR) surveillance and the revision of treatment guidelines, particularly given the elevated detection of MRSA in ICU wards, sterile body fluids, and the neonatal age group. MRSA exhibited significant resistance to all β-lactam antibiotics, erythromycin, and ciprofloxacin. Therefore, future research endeavors should prioritize examining specific antimicrobial resistance populations and potential intervention strategies, as these were vital in mitigating the dissemination of antimicrobial-resistant isolates.

Methicillin- and vancomycin-resistant Staphylococcus aureus in chicken carcasses, ready-to-eat chicken meat sandwiches, and buffalo milk

Methicillin-resistant Staphylococcus aureus (MRSA) is a growing public health concern; however, there is limited information about MRSA and VRSA (Vancomycin-resistant S. aureus) among animal-origin food. Therefore, this study intended to elucidate the prevalence, enterotoxin existence, antimicrobial resistance profiles, and antimicrobial resistance genes of S. aureus strains isolated from chicken carcasses, ready-to-eat (RTE) chicken meat sandwiches, and buffalo milk samples marketed in Mansoura City, Egypt. Of the 240 samples examined, 52.1 % were contaminated with S. aureus, with a mean count of 4.11 log10 CFU/g. A total of 250 isolates were verified as S. aureus by PCR targeting nuc gene, of which 39.2 % (98/250) harbored at least one S. aureus enterotoxin (SE) gene. The predominant SE genes were sea (61.2 %, 60/98), followed by sed (58.2 %, 57/98), sec (38.8 %, 38/98), and seb (27.6 %, 27/98). All isolates were resistant to at least one antimicrobial, with an average MAR (multiple antibiotic resistance) index of 0.530. Four isolates exhibited resistance to all antimicrobial agents tested. Interestingly, 100 %, 76.4 %, 35.6 %, 30.8, 10.4 %, 6 %, and 1.6 % of isolates were resistant to penicillin, azithromycin, oxacillin, ceftaroline, vancomycin, linezolid, and daptomycin, respectively. Of the 250 S. aureus strains tested, 38 % were confirmed as MRSA by mecA gene, while 10.4 % were identified as VRSA by vanA gene. The high prevalence of MRSA and VRSA isolates among samples tested is worrisome. Hence, monitoring antimicrobial usage in veterinary medicine and applying strict hygienic measures during food handling and processing is imperative to prevent the spread of such resistant bacteria and protect public health.

Two codependent routes lead to high-level MRSA.

Methicillin-resistant Staphylococcus aureus (MRSA), in which acquisition of mecA [which encodes the cell wall peptidoglycan biosynthesis component penicillin-binding protein 2a (PBP2a)] confers resistance to β-lactam antibiotics, is of major clinical concern. We show that, in the presence of antibiotics, MRSA adopts an alternative mode of cell division and shows an altered peptidoglycan architecture at the division septum. PBP2a can replace the transpeptidase activity of the endogenous and essential PBP2 but not that of PBP1, which is responsible for the distinctive native septal peptidoglycan architecture. Successful division without PBP1 activity requires the alternative division mode and is enabled by several possible chromosomal potentiator (pot) mutations. MRSA resensitizing agents differentially interfere with the two codependent mechanisms required for high-level antibiotic resistance, which provides opportunities for new interventions.

Dhvar5- and MSI78-coated titanium are bactericidal against methicillin-resistant Staphylococcus aureus, immunomodulatory and osteogenic

Infection is one of the major issues associated with the failure of orthopedic devices, mainly due to implant bacterial colonization, biofilm formation, and associated antibiotic resistance. Antimicrobial peptides (AMP) are a promising alternative to conventional antibiotics given their broad-spectrum of activity, low propensity to induce bacterial resistance, and ability to modulate host immune responses. Dhvar5 (LLLFLLKKRKKRKY) and MSI78 (GIGKFLKKAKKFGKAFVKILKK) are two AMP with broad-spectrum activity against bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), one of the most problematic etiologic agents in Orthopedic Devices-Related Infections (ODRI). This work aims to evaluate the bactericidal, immunomodulatory and osteogenic potential of Dhvar5- and MSI78-coated titanium surfaces (AMP-Ti). Two AMP-Ti surfaces were successfully obtained by grafting Dhvar5 (0.8 ± 0.1 µM/mm2) or MSI78 (0.5 ± 0.3 µM/mm2) onto titanium substrates through a polydopamine layer. Both AMP-Ti were bactericidal against MRSA, eradicating bacteria upon contact for 6 h in a culture medium supplemented with human plasma proteins. The AMP-Ti immunomodulatory potential was evaluated using human primary macrophages, by assessing surfaces capacity to induce pro-/anti-inflammatory (M1/M2) markers and cytokines. While in naïve conditions both AMP-Ti surfaces slightly promoted the M2 marker CD163, in response to LPS and IFN-γ (simulating a bacterial infection), both AMP increased the M1 marker CCR7 and enhanced macrophage secretion of pro-inflammatory IL-6 and TNF-α cytokines, particularly for Ti-MSI78 surfaces. Additionally, both AMP-Ti surfaces were cytocompatible and promoted osteoblastic cell differentiation. This proof-of-concept study demonstrated the high potential of Dhvar5- and MSI78-Ti as antimicrobial coatings for ODRI prevention. STATEMENT OF SIGNIFICANCE: This study investigates the bactericidal effects of the antimicrobial peptides Dhvar5 and MSI78, immobilized on titanium (Ti) surfaces through a polydopamine coating, aiming at the prevention of Orthopedic-Device Related Infections (ODRIs). The developed coatings displayed MRSA-sterilizing activity, while revealing an immunomodulatory potential towards macrophages and promoting osteoblastic cell differentiation. This strategy allows a quick and easy immobilization of high quantities of AMP, unlike most other approaches, thus favoring its clinical translation.

“On-demand” nanosystem-integrated microneedles for amplified triple therapy against recalcitrant bacteria and biofilm growth

Phototherapy has emerged to eradicate recalcitrant bacteria without causing drug resistance, but it is often accompanied by considerable limitations owing to a high tolerance of recalcitrant bacteria to heat and oxidative damage, leading to low efficiency of monotherapy and unwanted side effects. Assuming that employing antimicrobial peptides (AMPs) to disrupt bacterial membranes can reduce bacterial tolerance, a multifunctional “on-demand” nanosystem based on zeolitic imidazolate framework-8 (ZIF-8) with metal ions for intrinsic antibacterial activity was constructed to potently kill methicillin-resistant Staphylococcus aureus (MRSA). Then, microneedles (MNs) were used to transdermally deliver the ZIF-8-based nanosystem for localized skin infection. After MNs insertion, the nanoplatform could specifically deliver the loaded therapeutic components to bacterial infection sites through employing hyaluronic acid (HA) as a capping agent, thus realizing the “on-demand” payload release triggered by excess hyaluronidase secreted by MRSA. The prepared nanosystem and MNs were confirmed to exert an amplified triple therapy originating from membranolytic effect, phototherapy, and ion therapy, thus displaying a powerful bactericidal and MRSA biofilm destruction ability. This intelligent antimicrobial strategy may bring a dawn of hope for eradicating multidrug-resistant bacteria and biofilms.

Distribution of Pathogenic Bacteria and Drug Resistance in ICU of a Newly Built Hospital.

This study investigated the distribution and resistance patterns of pathogens in the intensive care unit of a newly established hospital in Guizhou Province to promote the rational use of antibiotics to reduce multidrug resistance. A retrospective analysis was conducted on the distribution of pathogens and changes in drug resistance in the ICU of a newly built hospital in Guizhou Province from March 2019 to December 2023. WHONET 5.6 was used to analyze the results. A total of 2444 culture samples were received, predominantly sputum (34.66%) and blood (23.36%) samples, with a steady annual increase in specimen types. A total of 572 pathogenic strains were isolated, predominantly from respiratory specimens (54.02%), including 345 Gram-negative bacteria (60.31%), 135 Gram-positive cocci (23.60%), and 92 fungi (16.08%). The most frequent pathogens included Acinetobacter baumannii (30.77%), Candida albicans (11.71%), and Klebsiella pneumoniae (9.97%). Drug sensitivity tests indicated a fluctuating resistance rate of Acinetobacter baumannii over the past five years. Staphylococcus aureus displayed strong in vitro activity against vancomycin, tigecycline, and linezolid, with no resistant strains identified. The detection rates of carbapenem-resistant Acinetobacter baumannii (CR-AB), carbapenem-resistant Pseudomonas aeruginosa (CR-PA), methicillin-resistant Staphylococcus aureus (MRSA), and strains producing extended-spectrum beta-lactamases (ESBL) were 86.78%, 26.79%, 32.45%, 70.27%, and 23.54%, respectively. Compared with other countries in the world, China has increased its data on the prevalence of MDR pathogens and antibiotic resistance.The high resistance rate of Acinetobacter baumannii in the ICU underscores the need for effective infection control measures. Enhanced monitoring of CR-AB, ESBL-producing bacteria, and MRSA is essential, along with improved management of antibacterial drugs and the pursuit of new therapeutic options.

Molecular insights into antimicrobial resistant Staphylococcus aureus strains: A potential zoonosis of goat origin

Antimicrobial-resistant (AMR) Staphylococcus aureus (S. aureus) strains have attained global attention due to their life-threatening zoonotic nature. Being a member of ESKAPE group, S. aureus has an ability to escape the biocidal action of antimicrobial drugs. The current study investigated the prevalence and molecular characterization of methicillin-resistant S. aureus (MRSA), β-lactam-resistant S. aureus (BRSA), aminoglycoside-resistant S. aureus (ARSA), tetracycline-resistant S. aureus (TRSA), and fluoroquinolones-resistant S. aureus (FRSA) associated with goat subclinical mastitis (SCM). Furthermore, the antimicrobial resistance and susceptibility profile of various antibiotics and non-antibiotics (NSAIDs, nisin, N-acetylcysteine, vitamin-C) along with their possible role in modulating the antibiotic resistance of MDR isolates was also investigated. A total of 768 goat milk samples were subjected to California mastitis test for SCM followed by bacteriological and molecular characterization of S. aureus. Moreover, in-vitro susceptibility of resistant antibiotics, non-antibiotics, and their combination against MDR S. aureus were conducted through well diffusion and broth microdilution assays. The results depicted that 55.47% and 26.82% of milk samples were positive for SCM and S. aureus, respectively. The molecular assay confirmed 35.92% of isolates as MRSA, 45.63% as BRSA, 50.49% as ARSA, and 32.52% but no isolate was confirmed as FRSA on molecular basis. The multidrug resistance was observed in 62.13% and 47.09% isolates, respectively. Molecular characterized MDR S. aureus revealed high homology of study isolates with the isolates of neighboring countries like India, Korea, Iran, and China. Antimicrobial susceptibility trials on well diffusion assay showed higher efficacy of different non-antibiotics with resistant antibiotics as penicillin with ketoprofen and gentamicin with flunixin meglumine while oxytetracycline with N-acetylcystiene. The synergy testing by checkerboard assay revealed synergistic activity of penicillin with ketoprofen, gentamicin with flunixin meglumine, and oxytetracycline with N-acetylcysteine. The current study highlighted the emergence and spread of AMR S. aureus strains from goat SCM and provided insights into possible drug repurposing of various non-antibiotics to modulate the multidrug resistance of S. aureus which will be helpful in devising the therapeutic options and control measures for this pathogen.

Evaluating omadacycline dosing regimens against drug-resistant pathogens including Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in adults: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

The objective of this study was to evaluate the efficacy of various dosing regimens of omadacycline against main drug-resistant pathogens in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to calculate cumulative fractions of response (CFRs) in terms of drug area under the concentration curve/minimum inhibition concentration targets.CFR ≥ 90% was considered optimal for a dosage regimen. CFR of any approved oral/intravenous regimen with loading-dose was ≥ 90% against methicillin-resistant Staphylococcus aureus (MRSA) for ABSSSI and penicillin-resistant Streptococcus pneumonia, tetracycline-resistant Streptococcus pneumonia, MRSA and β-lactamase positive Haemophilus influenzae for CABP. In conclusion, approved oral/intravenous loading and maintenance doses of omadacycline showed enough efficacy in the treatment of ABSSI and CABP caused by the main drug-resistant pathogens.

Low molecular weight Fucoidan induces M2 macrophage polarization to attenuate inflammation through activation of the AMPK/mTOR autophagy pathway.

Fucoidan, a sulfated polysaccharide with a complex structure, has gradually become the focus of biomedical research due to its remarkable biological activity and low toxicity. In this research, it was noted that low molecular weight fucoidan (LMWF) exhibited significant antimicrobial effects on Methicillin-resistant Staphylococcus aureus (MRSA) and promoted polarization towards M2 macrophages, leading to a substantial reduction in inflammatory responses within the lipopolysaccharide (LPS)-activated macrophages. We further explored the mechanism underlying the anti-inflammation activity. Our findings indicated that LMWF significantly enhanced the phosphorylation level of AMP-activated protein kinase (AMPK), inhibited the phosphorylation of the mammalian target of rapamycin (mTOR), and enhanced the expression of LC3II. Meanwhile, Compound C (CC) substantially reversed the anti-inflammation effect of LMWF, indicating that the AMPK pathway plays a pivotal role in this effect. In in vivo research, LMWF revealed impressive anti-inflammatory potential. LMWF treatment significantly eliminated MRSA and ameliorated inflammatory symptoms in mice's MRSA-infected skin wound model. Further analysis using Western Blot (WB) indicated significant AMPK/mTOR signaling pathway activation in mice treated with LMWF, which led to accelerated polarization of macrophages from the M1 to the M2 phenotype. In summary, we systematically explored the mechanism by which LMWF exerts anti-inflammatory effects through in vitro and in vivo experiments. It was confirmed that LMWF effectively induced the conversion of macrophages to an anti-inflammatory M2 phenotype by activating the AMPK/mTOR pathway. Simultaneously, LMWF effectively eradicated MRSA and accelerated wound healing in mice. This finding provides an important theoretical basis for further research on fucoidan.

Biofilm formation and antibiogram profile of bacteria from infected wounds in a general hospital in southern Ethiopia

Biofilm-producing bacteria associated with wound infections exhibit exceptional drug resistance, leading to an escalation in morbidity, worse clinical outcomes (including delay in the healing process), and an increase in health care cost, burdening the whole system. This study is an attempt to estimate the prevalence and the relationship between the biofilm-forming capacity and multi-drug resistance of wound bacterial isolates. The findings intended to help clinicians, healthcare providers and program planners and to formulate an evidence-based decision-making process, especially in resource-limited healthcare settings. This study was done to assess the prevalence of bacterial infections in wounds and the antibiogram and biofilm-forming capacity of those bacteria in patients with clinical signs and symptoms, attending a General Hospital in southern Ethiopia. A cross-sectional study was performed in Arba Minch General Hospital from June to November 2021. The study participants comprised 201 patients with clinically infected wounds. Demographic and clinical data were gathered via a structured questionnaire. Specimens from wounds were taken from each participant and inoculated onto a series of culture media, namely MacConkey agar, mannitol salt agar, and blood agar, and different species were identified using a number of biochemical tests. Antimicrobial susceptibility tests were performed by means of the Kirby-Bauer disc diffusion technique following the guidelines of the Clinical and Laboratory Standards Institute. A micro-titer plate method was employed to detect the extent of biofilm formation. Bivariable and multivariable logistic regression models were applied to analyse the association between dependent and independent variables, and P values ≤ 0.05 were considered as statistically significant. Data analyses were done with Statistical Package for the Social Sciences version 25. Out of the 201 clinically infected wounds, 165 were found culture-positive with an overall prevalence of 82% (95% CI: 75.9–86.9). In total, 188 bacteria were recovered; 53.1% of them were Gram-positive cocci. The often-isolated bacterial species were Staphylococcus aureus, 38.3% (n = 72), and Pseudomonas aeruginosa, 16.4% (n = 31). The Gram-positive isolates showed considerable resistance against penicillin, 70%, and somewhat strong resistance against tetracycline, 57.7%. Gram-negative isolates showed severe resistance to ampicillin, 80.68%. The overall multi-drug resistance (MDR) among isolates was 48.4%. Extended beta-lactamase (ESBL)-producing Gram-negatives and methicillin-resistant Staphylococcus aureus (MRSA) accounted for 49 and 41.67%, respectively; 62.2% of the isolates were biofilm formers and were correlated statistically with MDR, ESBL producers, and MRSA (P < 0.005). The extent of biofilm formation and the prevalence of MDR bacteria associated with infected wounds hint at a public health threat that needs immediate attention. Thus, a more balanced and comprehensive wound management approach and antimicrobial stewardship program are essential in the study setting.

Genetic characteristics and antimicrobial resistance of Staphylococcus aureus isolates from pig farms in Korea: emergence of cfr-positive CC398 lineage

BackgroundLivestock-associated Staphylococcus aureus (LA-SA) has gained global attention because of its ability to colonize farm animals and transmit to the environment and humans, leading to symptomatic infections and the spread of antimicrobial resistance (AMR). In the last decade, numerous studies have reported a high prevalence of S. aureus clonal complex (CC) 398 in pig farms.ResultsIn this study, 163 S. aureus isolates were collected from healthy pigs (n = 110), farm environments (n = 42), and farm workers (n = 11), and their AMR profiles and epidemiological characteristics were analyzed. We identified 51 (31.3%) methicillin-resistant S. aureus (MRSA) and 112 (68.7%) methicillin-susceptible S. aureus (MSSA), with 161 (98.8%) isolates belonging to the CC398 lineage. The highest prevalence of spa type t571 was observed among the CC398 isolates. All 47 sequence type (ST) 398 MRSA isolates carried staphylococcal cassette chromosome mec (SCCmec) V, while four ST541 isolates carried SCCmec IV. High levels of resistance to commonly used antibiotics, including phenicols, quinolones, lincosamides, macrolides, aminoglycosides, and tetracyclines, have been observed on Korean pig farms. Notably, 21 cfr-positive CC398 isolates (four ST541-SCCmec IV MRSA and 17 ST398 MSSA) displaying increased resistance to linezolid were identified in healthy pigs.ConclusionsIn summary, these findings suggest that the multidrug-resistant CC398 S. aureus lineage predominantly colonizes healthy pigs and farm environments in Korea. The emergence of cfr-positive S. aureus at human-animal interfaces presents a significant threat to food safety and public health.

Rapidly in situ forming antibiotic-free injectable hydrogel wound dressing for eradicating drug-resistant bacterial infections in human skin organoids

The rising prevalence of global antibiotic resistance evokes the urgent requirement to explore the alternative antimicrobial candidates. It is of great significance to overcome these serious threats of multidrug-resistant bacterial infections and difficult-to-heal cutaneous wounds to human health. Herein, we proposed a rapidly in situ forming innovative antibiotic-free hydrogel dressing with excellent biocompatibility, easy injectability, strong tissue adhesion and superior antibacterial activity against drug-resistant bacteria. An octa-armed poly(ethylene glycol) amine (Octa-PEG-NH2) was quickly crosslinked with a green industrial microbicide tetrakis (hydroxymethyl) phosphonium chloride (THPC) to form an antibacterial hydrogel (OPTH) by simple mixing without any other initiators or crosslinkers. A significant broad-spectrum antibacterial efficacy was demonstrated against Gram-positive Staphylococcus aureus (S. aureus), Gram-negative Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). Significantly, benefiting from its flexible injectability and reliable tissue adhesion, the excellent antibacterial performances were further evidenced by employing human-induced pluripotent stem cell (iPSC)-derived skin organoids in a 3D culture system and rat animal wound models in vivo with MRSA infection, thus allowing for reepithelization promotion and wound healing. Collectively, the findings not only propose a facile gelatinization strategy for readily accessible antibiotic-free hydrogel dressings for effective MRSA therapy but also hold great clinical translation potential in obliterating multi-pathogenic bacteria and accelerating wound healing.

Selenium nanoparticles: effect of autoclave treatment on size, shape, phase and antimicrobial properties

Amorphous selenium nanoparticles have been synthesized by pulsed laser ablation in liquids. After undergoing a thermal treatment at 121°C for 60 minutes, the amorphous nanoparticles crystallized into trigonal ones. The antimicrobial properties of both amorphous and trigonal nanoparticles have been compared; and the amorphous ones displayed better antibacterial and antifungal properties compared to the trigonal ones. Specifically, Methicillin-resistant Staphylococcus aureus (MRSA), Ampicillin-resistant Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Candida albicans were almost completely inhibited in the presence of amorphous selenium nanoparticles at 0.025 microgram/ml concentrations after 24 hours of in vitro culture, compared to controls (no nanoparticles). In summary, such a high sensitivity of these bacterial and fungal strains to low concentrations of amorphous selenium nanoparticles warrants further investigation to develop efficient anti-bacterial and anti-fungal treatments.

Vesicular phospholipid gels: A new strategy to improve topical antimicrobial dermatotherapy

Therapeutically effective and biocompatible dermal formulations that can ensure localization of a high level of antimicrobial drug at the site of action for an appropriate duration, while at the same time providing intrinsic reepithelization properties, are of particular importance for the treatment of infected and injured skin. The current research aimed to explore the potentials of using vesicular phospholipid gels (VPGs), semisolid formulations consisting of tightly packed liposomes (100–––200 nm), as innovative local depot drug vehicles for advanced topical dermatotherapy. Ciprofloxacin hydrocholoride (CPX) was selected as a model hydrophilic antibacterial drug and was loaded into several VPGs, differing in their composition. Various CPX-loaded VPGs (CPX-VPGs) were evaluated in vitro for the rheological and physicochemical characteristics, drug release profile, stability under in vivo mimicked conditions and during storage, skin permeability, biocompatibility with the epidermal cells, antibacterial efficacy and wound healing assay, to determine the optimal CPX-VPG for topical dermatotherapy. Viscosity and bilayers fluidity of VPGs affected the release of CPX from CPX-VPGs and its skin localization, limiting CPX percutaneous absorption. All CPX-VPGs exhibited even a 2-fold increase in anti-biofilm activity against both Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) clinical isolate compared to the free drug, while showing no toxic effects on human keratinocytes in vitro. Based on the pronounced proliferative effects on keratinocytes, superior in vitro wound healing effect and drug localization on/inside the skin, CPX-VPGs containing chitosan and hydrogenated phospholipid proved to be the most promising for topical dermatotherapy. These findings, along with increased bioadhesiveness and the slow drug release, with CPX concentrations significantly above the minimum biofilm inhibitory concentrations for bacteria typical in infected wounds, would contribute not only to the improvement of the antimicrobial dermatotherapy, but also to reduction of the frequency of the drug administration.

Nano Revolution: Harnessing Nanoparticles to Combat Antibiotic-resistant Bacterial Infections.

Nanoparticles, defined as particles ranging from 1 to 100 nanometers in size, are revolutionizing the approach to combating bacterial infections amid a backdrop of escalating antibiotic resistance. Bacterial infections remain a formidable global health challenge, causing millions of deaths annually and encompassing a spectrum from common illnesses like Strep throat to severe diseases such as tuberculosis and pneumonia. The misuse of antibiotics has precipitated the rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Mycobacterium tuberculosis (MDR-TB), and carbapenem-resistant Enterobacteriaceae (CRE), underscoring the critical need for innovative therapeutic strategies. Nanotechnology offers a promising avenue in this crisis. Nanoparticles possess unique physical and chemical properties that distinguish them from traditional antibiotics. Their high surface area to volume ratio, ability to be functionalized with various molecules, and distinctive optical, electronic, and magnetic characteristics enable them to exert potent antibacterial effects. Mechanisms include physical disruption of bacterial membranes, generation of Reactive Oxygen Species (ROS), and release of metal ions that disrupt bacterial metabolism. Moreover, nanoparticles penetrate biofilms and bacterial cell walls more effectively than conventional antibiotics and can be precisely targeted to minimize off-target effects. Crucially, nanoparticles mitigate the development of bacterial resistance by leveraging multiple simultaneous mechanisms of action, which make it challenging for bacteria to adapt through single genetic mutations. As research advances, nanotechnology holds immense promise in transforming antibacterial treatments, offering effective solutions that address current infections and combat antibiotic resistance globally. This review provides a comprehensive overview of nanoparticle applications in antibacterial therapies, highlighting their mechanisms, advantages over antibiotics, and future directions in healthcare innovation.

Community-Associated MRSA—Not So Innocent Sibling per Se: A Case Report

Background: Methicillin-resistant S. aureus (MRSA) is a major healthcare burden and is classified as healthcare-associated (HA-MRSA) and community-associated (CA-MRSA). While HA-MRSA is clinically feared, CA-MRSA is often considered less pathogenic. This case report highlights the serious course of illness due to CA-MRSA infection and provides a treatment strategy for the management of such cases. Case description: A 41-year-old male presented with fever and breathlessness for five days. Upon admission, he was provided empirical treatment for atypical infections and vasopressor support for hypotension. His condition deteriorated, necessitating ventilator support. Although the initial tracheal Bio Fire test indicated MRSA, his clinical manifestations did not match MRSA pneumonia symptoms; however, CA-MRSA was confirmed within 12 h. Skin legions developed within 16 h and progressed gradually from ecchymosis, petechial, and palpable purpura to bullous lesions over 72 h. The antibiotic regimen was modified and optimized with the addition of Clindamycin, Vancomycin, and Meropenem–Colistin. Owing to high IL-6 levels, dual vasopressor support, and acute kidney failure, he was started on early (within 12 h) continuous renal replacement therapy (CRRT) with CytoSorb filter (for 3 days) for cytokine removal. IL-6 levels decreased after two days of CytoSorb use. Subsequently, the patient stabilized with reduced dependence on vasopressor and ventilator assistance. Discussion: Early diagnosis of CA-MRSA and management with CRRT using CytoSorb may help improve patient outcomes. To our knowledge, this is the first report of clinical management of CA-MRSA with CytoSorb therapy in India that resulted in positive outcomes.

Mussel-like polydopamine-assisted aggregation-induced emission nanodot for enhanced broad-spectrum antimicrobial activity: In vitro and in vivo validation

Emerging luminogens with aggregation-induced emission properties, namely AIEgens, demonstrated excellent anti-bacteria activity potential. However, their application still limited by the low antibacterial activity caused by the poor binding with bacteria. Polydopamine (PDA), an important biological macromolecule, possesses superior adhesion ability toward various material surface, including bacteria. In this study, the novel mussel-like PDA-assisted AIE Nanodot was proposed, achieving with robust bacterial binding ability and enhanced broad-spectrum antibacterial activity. Binding ability inherited from the PDA enables the constructed PDA-assisted AIE Nanodot to adhere efficiently to the bacterial membrane surface. Meanwhile, the AIE properties endowed them with monitoring capability, allowing for tracking their interaction with bacteria through facile fluorescence imaging in real time. More importantly, excellent killing of both Gram-positive and Gram-negative bacteria were successfully achieved in vitro antibacterial tests with excellent biocompatibility. Furthermore, in the treatment of Methicillin-resistant S. aureus (MRSA)-infected mouse-wound model, the mice exhibited accelerated wound healing with low bacterial load. This novel integrated strategy introduced a simple but effectively design to enhance the binding and antibacterial ability of AIEgens and would diversify the existing pool of antibacterial agents.

Cannabinoids as Antibacterial Agents: A Systematic and Critical Review of In Vitro Efficacy Against Streptococcus and Staphylococcus

Background: Two major bacterial pathogens, Staphylococcus aureus and Streptococcus pyogenes, are becoming increasingly antibiotic-resistant. Despite the urgency, only a few new antibiotics have been approved to address these infections. Although cannabinoids have been noted for their antibacterial properties, a comprehensive review of their effects on these bacteria has been lacking. Objective: This systematic review examines the antibacterial activity of cannabinoids against S. aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) strains, and S. pyogenes. Methods: Databases, including CINAHL, Cochrane, Medline, Scopus, Web of Science, and LILACS, were searched. Of 3510 records, 24 studies met the inclusion criteria, reporting on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration of cannabinoids. Results: Cannabidiol (CBD) emerged as the most effective cannabinoid, with MICs ranging from 0.65 to 32 mg/L against S. aureus, 0.5 to 4 mg/L for MRSA, and 1 to 2 mg/L for VRSA. Other cannabinoids, such as cannabichromene, cannabigerol (CBG), and delta-9-tetrahydrocannabinol (Δ9-THC), also exhibited significant antistaphylococcal activity. CBD, CBG, and Δ9-THC also showed efficacy against S. pyogenes, with MICs between 0.6 and 50 mg/L. Synergistic effects were observed when CBD and essential oils from Cannabis sativa when combined with other antibacterial agents. Conclusion: Cannabinoids’ antibacterial potency is closely linked to their structure–activity relationships, with features like the monoterpene region, aromatic alkyl side chain, and aromatic carboxylic groups enhancing efficacy, particularly in CBD and its cyclic forms. These results highlight the potential of cannabinoids in developing therapies for resistant strains, though further research is needed to confirm their clinical effectiveness.