Clinical outcome of combination of vancomycin and ceftaroline versus vancomycin monotherapy for treatment of methicillin resistant Staphylococcus aureus bloodstream infection.

Background: The role of combination therapies for serious methicillin-resistant Staphylococcus aureus (MRSA) infections is widely debated.

Methods: This retrospective cohort study included adults with MRSA bacteraemia treated between January 1, 2013, to December 31, 2022. Patients receiving combination therapy with vancomycin and ceftaroline were matched in a 2:1 ratio with those on vancomycin monotherapy based on bacteraemia source and illness severity.

Virulence Potential of Biofilm-Producing , and Causing Skin Infections in Companion Animals.

Coagulase-positive staphylococci (CoPS) account for most bacteria-related pyoderma in companion animals. Emergence of methicillin-resistant strains of (MRSP), (MRSA) or (MRSC), often with multidrug-resistant (MDR) phenotypes, is a public health concern. The study collection comprised 237 staphylococci ( ( = 155), ( = 55) and ( = 27)) collected from companion animals, previously characterized regarding resistance patterns and clonal lineages.

Carbapenemase-Producing Extraintestinal Pathogenic From Argentina: Clonal Diversity and Predominance of Hyperepidemic Clones CC10 and CC131.

Extraintestinal pathogenic (ExPEC) causes infections outside the intestine. Particular ExPEC clones, such as clonal complex (CC)/sequence type (ST)131, have been known to sequentially accumulate antimicrobial resistance that starts with chromosomal mutations against fluoroquinolones, followed with the acquisition of and, more recently, carbapenemases. Here we aimed to investigate the distribution of global epidemic clones of carbapenemase-producing ExPEC from Argentina in representative clinical isolates recovered between July 2008 and March 2017.

Rapid detection of the widely circulating B.1.617.2 (Delta) SARS-CoV-2 variant.

The emergence of the B.1.617.

's PBP4 Is Directly Associated with the Dissociated Oxacillin and Cefoxitin Phenotype.

is an important pathogen responsible for infections in dogs and in humans. The emergence and dissemination of methicillin-resistant (MRSP) and the multidrug resistance frequently seen in this species make difficult the treatment of these pathogens. The cefoxitin disk is widely used as a marker of methicillin resistance mediated by the gene in and other staphylococcal species; however, it is not useful to detect β-lactam resistance of MRSP in clinical microbiology laboratories.

Impact of PrsA on membrane lipid composition during daptomycin-resistance-mediated β-lactam sensitization in clinical MRSA strains.

Background: The cyclic anionic lipopeptide daptomycin is used in the treatment of severe infections caused by Gram-positive pathogens, including MRSA. Daptomycin resistance, although rare, often results in treatment failure. Paradoxically, in MRSA, daptomycin resistance is usually accompanied by a concomitant decrease in β-lactam resistance in what is known as the 'see-saw effect'.

Carotenogenesis of Staphylococcus aureus: New insights and impact on membrane biophysical properties.

Staphyloxanthin (STX) is a saccharolipid derived from a carotenoid in Staphylococcus aureus involved in oxidative-stress tolerance and antimicrobial peptide resistance. STX influences the biophysical properties of the bacterial membrane and has been associated to the formation of lipid domains in the regulation of methicillin-resistance. In this work, a targeted metabolomics and biophysical characterization study was carried out to investigate the biosynthetic pathways of carotenoids, and their impact on the membrane biophysical properties.

Impact of Bicarbonate on PBP2a Production, Maturation, and Functionality in Methicillin-Resistant (MRSA).

Certain methicillin-resistant (MRSA) strains exhibit β-lactam-susceptibility , and in the presence of NaHCO (NaHCO-responsive MRSA). Herein, we investigate the impact of NaHCO on factors required for PBP2a functionality. Prototype NaHCO-responsive and -nonresponsive MRSA strains (as defined ) were assessed for the impact of NaHCO on: expression of genes involved in PBP2a production-maturation pathways (, , , , , , and ); membrane PBP2a and PrsA protein content; and membrane carotenoid content.

Carbapenems drive the collateral resistance to ceftaroline in cystic fibrosis patients with MRSA.

Chronic airways infection with methicillin-resistant Staphylococcus aureus (MRSA) is associated with worse respiratory disease cystic fibrosis (CF) patients. Ceftaroline is a cephalosporin that inhibits the penicillin-binding protein (PBP2a) uniquely produced by MRSA. We analyzed 335 S.

Characterization of the First A-Positive Multidrug-Resistant Isolated from an Argentinian Patient.

is commonly associated with colonization or infection in dogs, and was identified as a novel species within the genus in 2006. Methicillin resistance emerged in during the last decade. We describe here a genomic characterization of the first methicillin-resistant (MRSP) recovered from a human patient in Argentina.

Efficacy of newly generated short antimicrobial cationic lipopeptides against methicillin-resistant Staphylococcus aureus (MRSA).

Introduction: Infection caused by methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) is a serious clinical challenge and research to develop new antimicrobials is imperative.

Methods: This study investigated the in vitro and in vivo efficacy of the short cationic dialkyl lipopeptides (C)-KKKK-NH and (C)-KKKK-NH.

Tedizolid is a promising antimicrobial option for the treatment of Staphylococcus aureus infections in cystic fibrosis patients.

Background: Tedizolid is a protein synthesis inhibitor in clinical use for the treatment of Gram-positive infections. Pulmonary MRSA infections are a growing problem in patients with cystic fibrosis (CF) and the efficacy of tedizolid-based therapy in CF pulmonary infections is unknown.

Objectives: To evaluate the in vitro and in vivo activity of tedizolid and predict the likelihood of tedizolid resistance selection in CF-background Staphylococcus aureus strains.

Identification and molecular epidemiology of methicillin resistant Staphylococcus pseudintermedius strains isolated from canine clinical samples in Argentina.

Background: Staphylococcus pseudintermedius is the leading cause of pyoderma in dogs and the frequent use of antimicrobial treatment is associated to the development of resistance to nearly all classes of antibiotics. Despite S. pseudintermedius significance, our understanding of the molecular mechanism of β-lactam resistance and its genetic diversity remains limited.

VraSR and Virulence Trait Modulation during Daptomycin Resistance in Methicillin-Resistant Infection.

Methicillin-resistant (MRSA) threatens human health in hospital and community settings. The lipopeptide antibiotic daptomycin (DAP) is a frequently used treatment option for MRSA infection. DAP exposure can cause bacterial resistance because mutations are induced in genes implicated in cell membrane and cell wall metabolism.

Activity of Telavancin against Staphylococcus aureus Isolates, Including Those with Decreased Susceptibility to Ceftaroline, from Cystic Fibrosis Patients.

Methicillin-resistant (MRSA) acquisition in cystic fibrosis (CF) patients confers a clinical outcome worse than that in non-CF patients with an increased rate of declined lung function. Telavancin, an approved lipoglycopeptide used to treat infections due to , has a dual mode of action causing inhibition of peptidoglycan synthesis and membrane depolarization. MRSA infections in CF patients remain an important problem with no foreseeable decline in prevalence rates.

Daptomycin Resistance in Clinical MRSA Strains Is Associated with a High Biological Fitness Cost.

Daptomycin remains as one of the main treatment options for Methicillin-Resistant Staphylococcus aureus (MRSA). Sporadic resistance cases reported in patients treated with either daptomycin or glycopeptides are a growing concern. In a previous study, we described a clinical case of a patient with a community-acquired MRSA infection resistant to daptomycin and with intermediate resistance to vancomycin who developed a recurrent infection with a susceptible isogenic strain.

Genetic Diversity of KPC-Producing Escherichia coli, Klebsiella oxytoca, Serratia marcescens, and Citrobacter freundii Isolates from Argentina.

The predominance of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae was caused by the spread of ST258 clone. In Latin America, KPC was reported in 2006, with the isolation of genetically unrelated K.

Combination Antibiotic Exposure Selectively Alters the Development of Vancomycin Intermediate Resistance in Staphylococcus aureus.

Invasive methicillin-resistant (MRSA) treated with vancomycin (VAN) is associated with reduced VAN susceptibility and treatment failure. VAN combination therapy is one strategy to improve response, but comprehensive assessments of combinations to prevent resistance are limited. This study identifies optimal combinations to prevent the emergence of VAN-intermediate (VISA).

Molecular Bases Determining Daptomycin Resistance-Mediated Resensitization to β-Lactams (Seesaw Effect) in Methicillin-Resistant Staphylococcus aureus.

Antimicrobial resistance is recognized as one of the principal threats to public health worldwide, yet the problem is increasing. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains are among the most difficult to treat in clinical settings due to the resistance of MRSA to nearly all available antibiotics. The cyclic anionic lipopeptide antibiotic daptomycin (DAP) is the clinical mainstay of anti-MRSA therapy.

The Staphylococcus aureus Chaperone PrsA Is a New Auxiliary Factor of Oxacillin Resistance Affecting Penicillin-Binding Protein 2A.

Expression of the methicillin-resistant S. aureus (MRSA) phenotype results from the expression of the extra penicillin-binding protein 2A (PBP2A), which is encoded by mecA and acquired horizontally on part of the SCCmec cassette. PBP2A can catalyze dd-transpeptidation of peptidoglycan (PG) because of its low affinity for β-lactam antibiotics and can functionally cooperate with the PBP2 transglycosylase in the biosynthesis of PG.

Impact of efflux in the development of multidrug resistance phenotypes in Staphylococcus aureus.

Background: Efflux has been recognized as a resistance mechanism to antimicrobials in Staphylococcus aureus; however its role on the development of clinically relevant resistance is still poorly characterized. This study aimed to examine the impact of efflux on development of resistance to fluoroquinolones and other antimicrobials in S. aureus strains representing relevant phenotypes in terms of antibiotic susceptibility and efflux activity.

PBP2a mutations causing high-level Ceftaroline resistance in clinical methicillin-resistant Staphylococcus aureus isolates.

Ceftaroline is the first member of a novel class of cephalosporins approved for use in the United States. Although prior studies have identified eight ceftaroline-resistant methicillin-resistant Staphylococcus aureus (MRSA) isolates in Europe and Asia with MICs ranging from 4 to 8 mg/liter, high-level resistance to ceftaroline (>32 mg/liter) has not been described in MRSA strains isolated in the United States. We isolated a ceftaroline-resistant (MIC > 32 mg/liter) MRSA strain from the blood of a cystic fibrosis patient and five MRSA strains from the respiratory tract of this patient.

Ceftaroline is active against heteroresistant methicillin-resistant Staphylococcus aureus clinical strains despite associated mutational mechanisms and intermediate levels of resistance.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important infectious human pathogen responsible for diseases ranging from skin and soft tissue infections to life-threatening endocarditis. β-Lactam resistance in MRSA involves acquisition of penicillin-binding protein 2a (PBP2a), a protein with low affinity for β-lactams that mediates cell wall assembly when the normal staphylococcal PBPs (PBP1 to -4) are blocked by these agents. Many MRSA strains display heterogeneous expression of resistance (HeR) against β-lactam antibiotics.

TCA cycle-mediated generation of ROS is a key mediator for HeR-MRSA survival under β-lactam antibiotic exposure.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug resistant pathogen responsible for several difficult-to-treat infections in humans. Clinical Hetero-resistant (HeR) MRSA strains, mostly associated with persistent infections, are composed of mixed cell populations that contain organisms with low levels of resistance (hetero-resistant HeR) and those that display high levels of drug resistance (homo-resistant HoR). However, the full understanding of β-lactam-mediated HeR/HoR selection remains to be completed.

Staphylococcal phenotypes induced by naturally occurring and synthetic membrane-interactive polyphenolic β-lactam resistance modifiers.

Galloyl catechins, in particular (-)-epicatechin gallate (ECg), have the capacity to abrogate β-lactam resistance in methicillin-resistant strains of Staphylococcus aureus (MRSA); they also prevent biofilm formation, reduce the secretion of a large proportion of the exoproteome and induce profound changes to cell morphology. Current evidence suggests that these reversible phenotypic traits result from their intercalation into the bacterial cytoplasmic membrane. We have endeavoured to potentiate the capacity of ECg to modify the MRSA phenotype by stepwise removal of hydroxyl groups from the B-ring pharmacophore and the A:C fused ring system of the naturally occurring molecule.