Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of healthcare-associated infections in Europe. It has become increasingly prevalent in community settings, causing skin and soft tissue infections (SSTIs). Managing community-acquired (CA) MRSA infections is challenging due to its high virulence and resistance to common antibiotics, and prevention outside the hospital setting is complex. Combination therapy has demonstrated efficacy in the treatment of severe MRSA infections. Furthermore, surgical source control is critical in treating CA-MRSA infections, involving removing the primary infection site to interrupt bacterial replication. Timeliness and a correct surgical approach are essential for successful treatment outcomes and improved quality of life. Methods: This report details the case of a 15-year-old athlete who was admitted to the intensive care unit with septic shock caused by CA-MRSA. Results: Despite initial treatment, his condition rapidly worsened. A computed tomography (CT) scan identified multiple abscesses (in the lungs, limbs, thyroid, and subscapular region) along with other complications. To achieve adequate tissue concentrations at all affected sites, a triple-targeted antimicrobial therapy was initiated and adjusted based on therapeutic drug monitoring (TDM). At the same time, daily surgical debridement was performed. The patient responded significantly to this treatment, and blood cultures eventually returned negative. Conclusions: A multidisciplinary approach involving early source control, tailored antimicrobial therapy, and, if monotherapy fails to control infection, combination therapy is advisable to treat life-threatening CA-MRSA infections.

Background: Linezolid standard dosing is typically applied in ICU without adjustments, even in renal impairment. This study examines serum concentration variability by renal function or CRRT administration in patients receiving 1200 mg/day of linezolid. Methods: This retrospective, single-center, non-randomized observational study was conducted at Niguarda Hospital (Milan, Italy) on data from the two-year period 2023–2024. ICU patients receiving linezolid, with a renal function determination and trough TDM performed at steady-state were included and stratified by renal function or CRRT status. Results: 54 patients were included, with 18 (33%) undergoing CRRT (CVVH). CRRT patients presented higher median linezolid concentrations (4.6 mg/L) than non-CRRT patients (3.2 mg/L), and a lower risk of underdosing (17% vs. 39%). CRRT patients showed significantly lower concentrations (4.6 mg/L vs. 10 mg/L, p = 0.007) than non-CRRT patients with renal function ≤ 30 mL/min, with fewer out-of-range levels (39% vs. 91%, p = 0.008) and overdosing (22% vs. 73%, p = 0.018). A significant inverse correlation was found between renal function and linezolid levels (Spearman’s rho = −0.61, p < 0.001), with CRRT patients exhibiting concentrations comparable to those of individuals with moderately impaired renal function. Continuous infusion resulted in significantly higher median concentrations (7.2 mg/L) than extended infusion (2.7 mg/L), with an increased risk of overdosing (47% vs. 17%; p = 0.018). Conclusions: After standard-dosing administration, linezolid levels vary widely in critically ill patients. Renal function significantly affects pharmacokinetics: severe impairment increases overdose risk, while ARC may cause underdosing. Standard-dosing appears adequate in CRRT patients, with levels similar to moderate-impairment. Continuous infusion aids target attainment in normal or ARC patients but raises overdose risk in severe impairment. TDM-based personalized dosing seems crucial to optimize therapy and reduce toxicity or failure.