Fluoroquinolones are the best studied antibiotic group for bone infections, both for Gram- negative and Gram-positive bacteria, with reported infec­tion curation rates of 60–80% [22]. They have patient-friendly posology, often only requiring administration once or twice a day, and high oral bioavailability. Rifampicin, though somewhat less-studied, can target intracellular bacterial res­ervoirs (as well as biolm) and has been observed to improve outcomes when used against chronic Staphylococcus aureus bone infections in combi­nation with either uoroquinolones or other active agents (daptomycin, linezolid, cefazolin, cloxacillin, vancomycin, gentamicin) [22]. Drawbacks to rifampicin use include its numer­ous drug interactions, which must be reviewed before its administration to a particular patient, and the rapid development of resistance to it, which forbids monotherapy with rifampicin, especially when the bacterial load is high. Rifampicin should always be administered with another anti-staphylococcal drug and started a few days after surgery, once the bacterial burden has been reduced [5, 15]. In addition, rifampicin therapy can produce severe adverse effects, such as allergic reactions or acute renal failure, which cause treatment discontinuation in almost 20% of patients [23], as well as the more common gas­trointestinal symptoms. The occurrence of these adverse events is known to increase with increas­ing dose of rifampicin, without an apparent improvement in outcomes, but there is contro­versy as to the optimal posology of rifampicin.