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Clinical Microbiology Reviews Dec 2023Methicillin-resistant (MRSA) is a leading cause of severe and often fatal infections. MRSA epidemics have occurred in waves, whereby a previously successful lineage has... (Review)
Review
Methicillin-resistant (MRSA) is a leading cause of severe and often fatal infections. MRSA epidemics have occurred in waves, whereby a previously successful lineage has been replaced by a more fit and better adapted lineage. Selection pressures in both hospital and community settings are not uniform across the globe, which has resulted in geographically distinct epidemiology. This review focuses on the mechanisms that trigger the establishment and maintenance of current, dominant MRSA lineages across the globe. While the important role of antibiotic resistance will be mentioned throughout, factors which influence the capacity of to colonize and cause disease within a host will be the primary focus of this review. We show that while MRSA possesses a diverse arsenal of toxins including alpha-toxin, the success of a lineage involves more than just producing toxins that damage the host. Success is often attributed to the acquisition or loss of genetic elements involved in colonization and niche adaptation such as the arginine catabolic mobile element, as well as the activity of regulatory systems, and shift metabolism accordingly (e.g., the accessory genome regulator, ). Understanding exactly how specific MRSA clones cause prolonged epidemics may reveal targets for therapies, whereby both core (e.g., the alpha toxin) and acquired virulence factors (e.g., the Panton-Valentine leukocidin) may be nullified using anti-virulence strategies.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcus aureus; Virulence; Anti-Bacterial Agents; Community-Acquired Infections; Exotoxins; Staphylococcal Infections; Virulence Factors
PubMed: 37982596
DOI: 10.1128/cmr.00148-22 -
The Annals of Pharmacotherapy Nov 2023To compare the efficacy of antimicrobial therapies used in the management of persistent methicillin-susceptible (MSSA) bacteremia. (Review)
Review
OBJECTIVE
To compare the efficacy of antimicrobial therapies used in the management of persistent methicillin-susceptible (MSSA) bacteremia.
DATA SOURCES
A literature search using the PubMed database (inception to December 2022) was conducted using the search terms " bacteremia," "methicillin-susceptible bacteremia," "persistent methicillin-susceptible bacteremia," and "refractory methicillin-susceptible bacteremia ." In addition, therapeutic agents which could be used as treatment for MSSA including "nafcillin," "oxacillin," "cefazolin," "ceftaroline," "gentamicin," "rifampin," and "daptomycin" were also combined with the aforementioned search terms to capture data using these agents.
STUDY SELECTION/DATA EXTRACTION
Clinical data were limited to those published in the English language. Articles and abstracts were considered for inclusion in addition to ongoing trials identified through ClinicalTrials.gov.
DATA SYNTHESIS
A total of 78 articles were reviewed including 17 in vitro or animal model studies and 39 studies including patient data. The remaining 22 articles included guidelines, review articles, and editorials. Recent data evaluating use of dual β-lactam regimens for persistent MSSA bacteremia were limited to 8 case reports or case series.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
At present, there is little guidance on how to best manage patients with persistent MSSA bacteremia. This narrative review collates the available data to assist clinicians in selecting the best possible antimicrobial regimen when facing this clinical conundrum.
CONCLUSIONS
Modification of antimicrobial therapy, in conjunction with source control and infectious diseases consultation, may all be necessary to sterilize blood cultures in patients with persistent MSSA bacteremia.
Topics: Animals; Humans; Adult; Anti-Bacterial Agents; Staphylococcus aureus; Methicillin; Cefazolin; Bacteremia; Staphylococcal Infections
PubMed: 36946576
DOI: 10.1177/10600280231158809 -
Nature Medicine Oct 2023Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin... (Randomized Controlled Trial)
Randomized Controlled Trial
Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .
Topics: Adult; Humans; Anti-Bacterial Agents; Bacteremia; Cloxacillin; Fosfomycin; Methicillin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Drug Therapy, Combination
PubMed: 37783969
DOI: 10.1038/s41591-023-02569-0 -
Deutsches Arzteblatt International Jun 2023
Topics: Humans; Methicillin-Resistant Staphylococcus aureus
PubMed: 37594462
DOI: 10.3238/arztebl.m2023.0131 -
Diseases (Basel, Switzerland) Nov 2023() is a common pathogen involved in community- and hospital-acquired infections. Its biofilm formation ability predisposes it to device-related infections.... (Review)
Review
() is a common pathogen involved in community- and hospital-acquired infections. Its biofilm formation ability predisposes it to device-related infections. Methicillin-resistant (MRSA) strains are associated with more serious infections and higher mortality rates and are more complex in terms of antibiotic resistance. It is still controversial whether MRSA are indeed more virulent than methicillin-susceptible (MSSA) strains. A difference in biofilm formation by both types of bacteria has been suggested, but how only the presence of the SCC cassette or influences this phenotype remains unclear. In this review, we have searched for literature studying the difference in biofilm formation by MRSA and MSSA. We highlighted the relevance of the operon in the PIA-dependent biofilms generated by MSSA under osmotic stress conditions, and the role of extracellular DNA and surface proteins in the PIA-independent biofilms generated by MRSA. We described the prominent role of surface proteins with the LPXTG motif and hydrolases for the release of extracellular DNA in the MRSA biofilm formation. Finally, we explained the main regulatory systems in involved in virulence and biofilm formation, such as the SarA and Agr systems. As most of the studies were in vitro using inert surfaces, it will be necessary in the future to focus on biofilm formation on extracellular matrix components and its relevance in the pathogenesis of infection by both types of strains using in vivo animal models.
PubMed: 37987271
DOI: 10.3390/diseases11040160 -
Clinical & Experimental Ophthalmology Apr 2024Antimicrobial resistance (AMR) is a global public health threat with significant impact on treatment outcomes. The World Health Organization's Global Action Plan on AMR... (Review)
Review
Antimicrobial resistance (AMR) is a global public health threat with significant impact on treatment outcomes. The World Health Organization's Global Action Plan on AMR recommended strengthening the evidence base through surveillance programs and research. Comprehensive, timely data on AMR for organisms isolated from ocular infections are needed to guide treatment decisions and inform researchers and microbiologists of emerging trends. This article aims to provide an update on the development of AMR in ocular organisms, AMR in bacterial ocular infections and on AMR stewardship programs globally. The most common ocular pathogens are Pseudomonas aeruginosa, Staphylococcus spp., Streptococcus pneumoniae, and Haemophilus influenzae in ocular infections. A variety of studies and a few surveillance programs worldwide have reported on AMR in these infections over time. Fluoroquinolone resistance has increased particularly in Asia and North America. For conjunctivitis, the ARMOR cumulative study in the USA reported a slight decrease in resistance to ciprofloxacin. For keratitis, resistance to methicillin has remained stable for S. aureus and CoNS, while resistance to ciprofloxacin has decreased for MRSA globally. Methicillin-resistance and multidrug resistance are also emerging, requiring ongoing monitoring. Antimicrobial stewardship (AMS) programmes have a critical role in reducing the threat of AMR and improving treatment outcomes. To be successful AMS must be informed by up-to-date AMR surveillance data. As a profession it is timely for ophthalmology to act to prevent AMR leading to greater visual loss through supporting surveillance programmes and establishing AMS.
Topics: Humans; Anti-Bacterial Agents; Methicillin; Staphylococcus aureus; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Eye Infections, Bacterial; Ciprofloxacin
PubMed: 38494451
DOI: 10.1111/ceo.14377 -
Expert Opinion on Drug Metabolism &... Sep 2023Omadacycline is a new analog of the tetracycline class active against atypical bacteria, as well as against staphylococci, including methicillin-resistant strains, and . (Review)
Review
INTRODUCTION
Omadacycline is a new analog of the tetracycline class active against atypical bacteria, as well as against staphylococci, including methicillin-resistant strains, and .
AREAS COVERED
This review has summarized the available clinical evidence on the use of oral omadacycline in the treatment of community-acquired pneumonia (CAP) and described the mechanism of action, pharmacokinetic/pharmacodynamic (PK/PD) parameters in healthy and special populations and the latest research on omadacycline.
EXPERT OPINION
The available clinical evidence on oral omadacycline for the treatment of CAP shows that its properties provide reliable empirical coverage for pathogens such as , , and species of , , and . Omadacycline is also active against methicillin-resistant (MRSA); penicillin-resistant and multidrug-resistant , , and ; and vancomycin-resistant spp. A dose of 450 mg orally once daily is recommended, followed by a maintenance dose of 300 mg orally once daily. Importantly, omadacycline does not require dose adjustment for patients based on BMI, age, gender, or renal or hepatic impairment.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Bacteria; Tetracyclines; Anti-Bacterial Agents; Streptococcus pneumoniae; Pneumonia, Bacterial; Community-Acquired Infections; Microbial Sensitivity Tests
PubMed: 37728376
DOI: 10.1080/17425255.2023.2261376 -
Antibiotics (Basel, Switzerland) Aug 2023Antimicrobial resistance (AMR) has emerged as an urgent global public health issue that requires immediate attention. Methicillin-resistant staphylococci (MRS) is a...
Antimicrobial resistance (AMR) has emerged as an urgent global public health issue that requires immediate attention. Methicillin-resistant staphylococci (MRS) is a major problem, as it may cause serious human and animal infections, eventually resulting in death. This study determined the proportional distribution, genetic characteristics, and antimicrobial susceptibility of A- or C-carrying staphylococci isolated from food chain products. A total of 230 samples were taken from meat, food, fermented food, and food containers. Overall, 13.9% (32/230) of the samples were identified to have isolates; of those, 3.9% (9/230) were MRS, with eight mecA-positive and one mecC-positive samples, and 1.3% (3/230) methicillin-resistant (MRSA). MRSA strains belonging to three sequence types (ST9, ST22, and a newly identified ST), three different types (T005, t526, and a newly identified type), and three different SCC types (IV, V, and an unidentified SCC) were detected. Additionally, eight A-positive staphylococcal isolates were identified as , , , and , while the C-harboring isolate was . The enterotoxin gene, , was detected at 1.56% in , whereas was detected at 0.31%, and was also found in MRSA. Our study emphasizes the importance of enhanced hygiene standards in reducing the risk of occupational and foodborne MRSA infections associated with the handling or consumption of meat, food, and preserved food products.
PubMed: 37627707
DOI: 10.3390/antibiotics12081287