The treatment of Methicillin-sensitive Staphylococcus aureus bacteremia is based on the first-line use of cefazolin or M penicillins (oxacillin and cloxacillin). The use of the latter is recommended at high doses (150-200 mg/kg/24h). In a study on infectious endocarditis, 52 of 56 patients with staphylococcal endocarditis treated with (cl)oxacillin were overdosed with the recommended doses. Although the main mechanism of renal toxicity described for M penicillins is immunoallergic, a frequent overdose is observed in cases of acute renal failure with M penicillins. There is also a significant association between overdose and risk of neurological toxicity. The currently recommended treatment duration is a minimum of 14 days of IV treatment from the first negative blood culture, which leaves room for carrying out a plasma assay and possible dosage adjustment subsequently. Overdose is a risk factor for nephrotoxicity and neurotoxicity. Plasma level could be predictive of clinical success. Systematic plasma dosing would reduce the risk of toxicity and improve the clinical cure rate.