As indicated, the FDA-approved dose of daptomycin for S aureus bacteremia and right-sided IE is currently 6 mg/kg IV once daily. Some experts recommend higher doses of daptomycin at 8 to 10 mg/ kg for complicated infections, including left-sided IE (these doses are not approved by the FDA).109 This recommenda- tion is based in part on evidence suggesting that higher-dose daptomycin may reduce the likelihood of treatment-emergent resistance, is generally well tolerated, and is not associated with excess toxicities. Whether this higher dosing strategy prevents treatment-emergent resistance of daptomycin is still not answered. Daptomycin is inhibited by pulmonary surfactant160 and thus is contraindicated in the treatment of S aureus pneu- monia acquired via the aspiration route. In the registrational however, this agent performed as well as vancomycin or -lactams in treating septic pulmonary emboli caused by S aureus, reflecting the distinct pathogenesis of this syndrome as opposed to traditional pneumonia. Recommendations 1. Cefazolin is reasonable in patients with a well- defined history of nonanaphylactoid reactions to penicillins (Class IIa; Level of Evidence B). 2. Allergy evaluation for tolerance to -lactam therapy should be done in every case in which vancomycin is considered for treatment of MSSA IE (Class I; Level of Evidence B). 3. Clindamycin is not recommended as a result of an increased IE relapse rate (Class III; Level of Evidence B). 4. Daptomycin is a reasonable alternative to vancomy- cin for NVE caused by MSSA (Class IIa; Level of Evidence B). Additional or Adjunctive Therapies As discussed above, combination therapy with gentamicin therapy in S aureus NVE is discouraged because of the rela- tively high rates of intrinsic gentamicin resistance, a lack of clear-cut efficacy, and documented toxicity issues.149,153,161 Although most staphylococci are highly susceptible to rifampin, resistance develops rapidly when this agent is used alone. 