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daptomycin binding by decreasing the positive surface charge) for NVE, and with gentamicin and rifampin for PVE.326–328 However, in a randomized trial including 352 patients with MRSA bacteraemia, daptomycin or vancomycin combined with i.v. flucloxacillin, cloxacillin, or cefazolin did not result in a significant reduction of the primary composite endpoint of mortality, persistent bacteraemia, relapse, or treatment failure as compared with daptomycin or vancomycin alone.328 The study was stopped prematurely before recruiting the target number of patients (n = 440) due to increased incidence of acute kidney injury in the combination therapy arm and, therefore, the results should be interpreted with caution.

Other alternatives include fosfomycin plus imipenem,336 ceftaroline,337 quinupristin–dalfopristin with or without beta-lactams,338,339 beta-lactams plus oxazolidinones (linezolid),340 beta-lactams plus vancomycin,341 and high doses of trimethoprim/sulfamethoxazole and clindamycin.342,343 These clinical and therapeutic scenarios warrant collaborative management with the Endocarditis Team including an infectious disease specialist, since the evidence is based on very small populations.

Recommendation Table 8 — Recommendations for antibiotic treatment of infective endocarditis due to Staphylococcus spp.

Recommendations Classa Levelb

IE caused by methicillin-susceptible staphylococci In patients with NVE due to methicillin-susceptible staphylococci, (flu)cloxacillin or cefazolin is recommended for 4–6 weeks using the following doses:264,314,316–318

I B

Adult antibiotic dosage and route (Flu)cloxacillinc 12 g/day i.v. in 4–6 doses Cefazoline 6 g/day i.v. in 3 doses Paediatric antibiotic dosage and route (Flu)cloxacillinc 200–300 mg/kg/day i.v. in 4–6 equally divided doses Cefazoline 100 mg/kg/day i.v. in 3–4 doses, up to maximum of 6 g/day In patients with PVE due to methicillin-susceptible staphylococci, (flu)cloxacillin or cefazolin with rifampin for at least 6 weeks and gentamicin for 2 weeks is recommended using the following doses:264,314,316–318,320

I B

Adult antibiotic dosage and route (Flu)cloxacillinc 12 g/day i.v. in 4–6 doses Cefazolin 6 g/day i.v. in 3 doses Rifampin 900 mg/day i.v. or orally in 3 equally divided doses Gentamicind 3 mg/kg/day i.v. or i.m. in 1 (preferred) or 2 doses Paediatric antibiotic dosage and route (Flu)cloxacillinc 200–300 mg/kg/day i.v. in 4–6 equally divided doses Cefazolin 100 mg/kg/day i.v. in 3–4 doses, up to maximum of 6 g/day Rifampin 20 mg/kg/day i.v. or orally in 3 equally divided doses up to maximum of 900 mg/day Gentamicind 3 mg/kg/day i.v. or i.m. in 1 (preferred) or 2 doses Allergy to beta-lactams In patients with NVE due to methicillin-susceptible staphylococci who are allergic to penicillin, cefazolin for 4–6 weeks is recommended using the following doses:322–327 I B Adult antibiotic dosage and route Cefazoline 6 g/day i.v. in 3 doses Paediatric antibiotic dosage and route Cefazoline 100 mg/kg/day i.v. in 3–4 doses, up to maximum of 6 g/day In patients with PVE due to methicillin-susceptible staphylococci who are allergic to penicillin, cefazolin combined with rifampin for at least 6 weeks and gentamicin for 2 weeks is recommended using the following doses:344

I B

Adult antibiotic dosage and route Cefazoline 6 g/day i.v. in 3 doses Rifampin 900 mg/day i.v. or orally in 3 equally divided doses Gentamicind 3 mg/kg/day i.v. or i.m. in 1 (preferred) or 2 doses Paediatric antibiotic dosage and route Cefazoline 100 mg/kg/day i.v. in 3–4 doses, up to maximum of 6 g/day Rifampin 20 mg/kg/day i.v. or orally in 3 equally divided doses up to maximum of 900 mg/day Gentamicind 3 mg/kg/day i.v. or i.m. in 1 (preferred) or 2 doses

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