Background Methicillin-resistant Staphylococcus aureus (MRSA) continues to pose a major global public health concern due to its resistance to commonly used antibiotics. Ceftaroline has emerged as a promising therapeutic agent against MRSA; however, local susceptibility data remain limited. This study evaluated the in vitro susceptibility of clinical MRSA isolates to ceftaroline using the E-test strip method and described antimicrobial susceptibility patterns and clinical characteristics of affected patients in a tertiary care setting. Methods This prospective, observational, cross-sectional study included non-repetitive MRSA-positive clinical samples obtained from patients aged ≥1 year over a two-year period. Identification and baseline antimicrobial susceptibility testing were performed using the VITEK 2 automated microbiological identification system. Ceftaroline susceptibility was determined using E-test minimum inhibitory concentration (MIC) strips. Results Out of 180 patients assessed, 167 MRSA isolates were included in the final analysis. The mean patient age was 34.51 ± 21.35 years, with 103 (61.7%) males. Surgical departments accounted for 99 (59.3%) of isolates, while most patients were admitted to wards (134; 80.2%). Surgical site infections (61; 36.5%) and skin and soft tissue infections (30; 18.0%) were the most frequent diagnoses. Pus samples constituted 90 (53.9%) of the isolates. Ceftaroline demonstrated high in vitro activity against MRSA, with 166 (99.4%) of isolates being susceptible and only one (0.6%) resistant. Most MIC values ranged from 0.1 to 0.4 µg/mL. Tetracycline, vancomycin, linezolid, and daptomycin also demonstrated sensitivity rates above 80%. Conclusions These findings demonstrate excellent in vitro susceptibility of MRSA isolates to ceftaroline and support further multicenter studies incorporating clinical outcome data to evaluate its therapeutic role in tertiary care settings. Its clinical use should, however, be reserved for MRSA infections resistant to other antimicrobials.

Our retrospective observational cohort study investigated the effect of the timing of escalation to dual salvage therapy utilizing ceftaroline with vancomycin or daptomycin for the treatment of persistent methicillin-resistant Staphylococcus aureus bacteremia on patient outcomes. Eligibility criteria included age ≥18 years old, at least one positive blood culture for methicillin-resistant Staphylococcus aureus, and receipt of salvage therapy consisting of ceftaroline in combination with either vancomycin or daptomycin for any duration during their bloodstream infection within our health system over a 10-year period. This resulted in the inclusion of 189 adult patients. Patients were stratified by the timing of ceftaroline initiation: ≤5 days (early initiation) versus >5 days (late initiation) from index positive culture. The study populations were similar, although there was a higher prevalence of persons who inject drugs started on early salvage therapy (36.0% versus 18.0%, P = 0.005) and fewer patients with type II diabetes (25.8% versus 41.0%, P = 0.028). Analysis revealed no statistically significant differences between 90-day all-cause mortality or readmission rates in either group; however, there was less 90-day microbiologic recurrence in the early initiation group (3.4% versus 11.0%, P = 0.046). Patients started on early salvage therapy also had fewer total days of bacteremia (7.0 versus 10.5 days, P < 0.001), fewer metastatic foci of infection (61.8% versus 82.0%, P = 0.002), and a shorter duration of treatment (46.0 versus 50.0 days, P = 0.013).IMPORTANCETreatment of methicillin-resistant Staphylococcus aureus bacteremia remains a challenge due to its high morbidity and mortality. Ceftaroline has been studied for off-label utilization in dual salvage therapy with daptomycin or vancomycin in these patients, although current data regarding the optimal timing for its addition are limited. We sought to address this knowledge gap with our retrospective review of patient outcomes at our hospital system who received ceftaroline for this indication. Overall, earlier initiation of ceftaroline-based dual therapy was beneficial, as evidenced by reduced microbiologic recurrence, shorter duration of bacteremia, reduced metastatic disease, and subsequent shorter duration of therapy if patients were escalated to dual salvage therapy with ceftaroline within 5 days of the index culture.

Persistent Staphylococcus aureus infections treated with prolonged daptomycin (DAP) can select for DAP resistance (DAP-R), reinforcing the need for combination strategies that both improve killing and constrain resistance evolution. Prior work suggests the DAP+ceftaroline (CPT) combination can deliver synergistic killing, prevent emergence of DAP-R, and resensitize DAP-R subpopulations toward a DAP-susceptible (DAP-S) phenotype. Here, using a clinically derived, MSSA isogenic DAP-S (616)/DAP-R (703) strain pair, we evaluated DAP+CPT activity across in vitro assays, ex vivo models, and an in vivo experimental infective endocarditis (IE) model, and integrated ultra-deep targeted sequencing to link phenotypic responses to genomic adaptation. DAP+CPT produced enhanced killing of both strains in vitro and ex vivo, improved target-tissue clearance of the DAP-R strain in vivo, prevented emergence of DAP-R in the DAP-S parental strain in vitro and ex vivo, and resensitized the DAP-R strain toward a DAP-S phenotype ex vivo. Genomically, ultra-deep sequencing of resistance loci (thousands-fold coverage) identified fixed background divergence versus the N315 reference and revealed regimen-dependent selection in membrane-stress pathways, including a high-frequency mixed mprF subpopulation consistent with DAP-driven heterogeneity under monotherapy, contrasted by distinct locus-level changes under combination exposure. In addition, coverage profiling detected a large, combination-associated mobile-element/prophage gene-content event in the 703 background affecting an immune-evasion/β-hemolysin-converting region, highlighting that antibiotic pressure can couple resistance dynamics with pathogenesis-relevant genome remodeling. Together, these data show that DAP+CPT provides potent activity beyond synergistic killing-improving clearance while constraining or reshaping resistance evolution-and they define genomic signatures that help explain divergent evolutionary trajectories under DAP alone versus DAP+CPT.

Cheese, a widely consumed dairy product, can be contaminated with Staphylococcus aureus (S. aureus), a pathogen capable of producing toxins harmful to humans. Of particular concern is Methicillin-Resistant S. aureus (MRSA), which harbors antimicrobial resistance genes and secretes super-antigenic toxins. Present investigation aimed at determining the occurrence and characterizing MRSA in commercial cheese, to evaluate its potential public health risks. 120 cheese samples representing twelve commercial brands were collected in ten different batches over a six-month period in Sylhet, Bangladesh. The quality of the cheeses was evaluated and compared against the standards of Bangladesh Food Safety Authority (BFSA), European Union (EU), and Food Safety and Standards Authority of India (FSSAI). The occurrence of MRSA and its virulence factors were determined using standard microbiological and molecular techniques. Results revealed that 65% samples were positive for S. aureus, with staphylococcal load surpassing safety thresholds according to the above-mentioned standards. MRSA was detected in 30% of the samples, exhibiting resistance to multiple antibiotics. All the isolates showed resistance against penicillin, tetracycline, doxycycline, trimethoprim-sulfamethoxazole and azithromycin, whereas ceftaroline, norfloxacin, and levofloxacin exhibited intermediate level of sensitivity. Enterotoxin genes SEa and SEc were prevalent in 16.67% and 8.97% of isolates, respectively, while TSST-1 gene was identified in 25.64% among the exfoliative toxin genes. Notably, 85.90% and 80.77% of the isolates exhibited biofilm formation based on the Congo Red and microtiter plate techniques, respectively, with significant percentages of biofilm associated regulatory genes icaA (73.08%), icaD (53.85%), clfA (78.21%), clfB (61.54%), and fnbA (69.23%). The substantial prevalence of blaCTX-M-2a (88.46%) and blaTEM (25.64%) highlights the significant public health risks associated with MRSA contamination in cheese. The high occurrence of S. aureus and the detection of multiple toxin-encoding genes further emphasize the need for strengthened monitoring and stricter control measures across the production and distribution chain to reduce contamination and ensure product safety.

Background/Objectives: Ceftaroline fosamil (CFT) is a fifth-generation cephalosporin approved in Spain for skin and soft tissue infections and community-acquired pneumonia. CFT may also be useful against endovascular infections. This real-world study aimed to evaluate its effectiveness and safety in patients with Gram-positive (GP) infective endocarditis (IE). Methods: This observational, retrospective multicenter study enrolled adults with GP-IE treated with CFT for ≥48 h. Recruitment extended from CFT incorporation in participating hospitals through May 2024. Data were gathered on demographic, clinical, and microbiological variables, adverse effects, overall and IE-related mortality, relapses, and a composite unfavorable outcome. Results: Seventy-six patients (65.8% male) were enrolled, with a mean age of 68.9 ± 12.8 years and an age-adjusted Charlson index of 4; 55.3% had previous moderate/severe valvular heart disease, 35.5% had atrial fibrillation, 34.2% chronic heart failure, 17.1% chronic kidney disease, and 22.4% septic shock. IE was native valve-related in 53.9%, involving the aortic valve in 38.2% and the mitral in 30.3%. Staphylococcus aureus was isolated in 48.7%, being methicillin-resistant in 40.5% of cases. CFT was salvage therapy in 65.8% and combined with other antibiotics in 94.7%. Valve replacement was indicated in 64.5% but performed in only 67.3% of these. At six months, the adverse effect rate was 9.2%, overall crude mortality 38.2%, infection-related mortality 28.9%, and composite unfavorable outcome 40.1%. In multivariate analysis, mortality-related factors were age-adjusted Charlson index, septic shock, and methicillin-sensitive S. aureus. Conclusions: CFT showed favorable outcomes and acceptable safety in the real-life treatment of GP-related IE in clinically complex patients with high comorbidity and previous antibiotic therapy failures.

Methicillin-resistant Staphylococcus aureus (MRSA) endovascular infections are associated with high mortality. The increasing reports of clinical failure and toxicities associated with first-line vancomycin provide a medical need for alternative therapies. In this narrative review, we analyze studies published from 2017 to 2025 on the efficacy and tolerability of ceftaroline, a β-lactam antibiotic with anti-MRSA activity, for off-label treatment of endovascular infections. Identified publications included 1 randomized controlled trial (RCT), 17 retrospective cohort studies, four case series, and one meta-analysis. Failure rates were similar between ceftaroline, vancomycin, and daptomycin when used as monotherapies. Ceftaroline, used in combination with vancomycin or daptomycin, showed efficacy and tolerability in high-risk MRSA bacteremia cases. Although higher-level evidence is needed to definitively establish ceftaroline as a mainstay treatment of MRSA endovascular infections, the current evidence positions ceftaroline as one of several antibiotic strategies in serious cases of MRSA endovascular infections.

Staphylococcus aureus is now the leading cause of infective endocarditis (IE) worldwide and is associated with high mortality and frequent complications. Combination antimicrobial therapy has long been proposed to enhance bactericidal activity, improve biofilm penetration, and limit resistance; however, its true clinical value remains uncertain. This narrative review examines the experimental and clinical evidence for combination regimens in Staphylococcus aureus infective endocarditis (S. aureus IE). We searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library through September 2025 for randomised trials, comparative observational studies, major guidelines, and key experimental reports. Evidence is synthesised across methicillin-susceptible and methicillin-resistant strains, and across native and prosthetic valve disease. We summarise the biological rationale, potential benefits, and stewardship impact of combination therapy. We also highlight the practical implications for when to consider, avoid, or de-escalate combination therapy, and outline priorities for future research. We find that evidence for combination therapy in S. aureus endocarditis remains limited and largely observational. Adjunctive rifampin and aminoglycosides have not shown consistent clinical benefit and are associated with increased toxicity. Beta-lactam combinations with vancomycin or daptomycin may reduce the bacteremia duration, but this has not translated into improved survival. Emerging regimens, particularly daptomycin combined with ceftaroline show promise in persistent bacteremia, although evidence remains observational. Overall, current data do not support routine use of combination therapy and favour a selective, case-based approach. High-quality multicentre studies integrating microbiological, pharmacodynamic, and clinical endpoints are urgently needed to define optimal combination strategies.