Antibiotic Combinations with Daptomycin for Treatment of Staphylococcus aureus Infections

Table 2

Information on in vivo synergy of antibiotic combinations.

Model	Strain	Combination	Observation	Ref.
Experimental model of IE	MRSA	Daptomycin 6 mg/kg q24 h + rifampin 300 mg q8 h	Rifampin and gentamicin antagonized/delayed the bactericidal activity of daptomycin	[39]
		Daptomycin 6 mg/kg q24 h + gentamicin 1.3 mg/kg q12 h
Rabbit model of IE	MRSA	Daptomycin 6 mg/kg q24 h + gentamicin 1 mg/kg q8 h	60% vegetations sterilized	[41]
		Daptomycin 6 mg/kg q24 h + rifampin 300 mg q8 h	20% vegetations sterilized
Rabbit model of IE	DNS MRSA	Daptomycin 12 mg/kg q24 h + oxacillin 200 mg/kg q8 h	Enhanced bacterial clearance from tissues	[56]
Case report on IE	MRSA with progressive loss of susceptibility during treatment	Treated with vancomycin, then daptomycin 6 mg/kg q24 h, then daptomycin 12 mg/kg q24 h + rifampin 300 mg q8 h	Clinical success	[42]
Rabbit acute osteomyelitis model	MRSA	Daptomycin 6 mg/kg q24 h	Failure to eradicate bacteria	[50]
		Daptomycin 6 mg/kg q24 h + rifampin 20^a mg/kg q12 h	Eradication of bacteria: bone 100%, bone marrow 89%, and joint fluid 44%
Guinea pig foreign-body infection model	MRSA	Daptomycin 20 mg/kg q24 h + rifampin 12.5 mg/kg q12 h	25% cure	[51]
		Daptomycin 30^b mg/kg q24 h + rifampin 12.5 mg/kg q12 h	67% cure
		Vancomycin 15 mg/kg q12 h + rifampin 12.5 mg/kg q12 h	8% cure
Rat foreign-body infection model	MRSA	Daptomycin 100^c mg/kg q24 h + rifampin 25 mg/kg q12 h	94% cure	[53]
		Daptomycin 45 mg/kg q24 h + rifampin 25 mg/kg q12 h	64% cure
		Vancomycin 50 mg/kg q12 h +rifampin 25 mg/kg q12 h	25% cure
In vitro PK/PD model of SEV	DNS MRSA	Daptomycin 6 mg/kg q24 h + TMP/SMX 160/800 mg q12 h	Bactericidal activity reached at 8 hours	[59]
		Daptomycin 6 mg/kg q24 h + cefepime 2 g q8 h
In vitro PK/PD model of SEV	MSSA, MRSA	Daptomycin 6–8 mg/kg q24 h + gentamicin 5 mg/kg as a single dose; or + gentamicin 1 mg/kg q8 h, three doses only	Daptomycin 6–8 mg/kg/day combined with one 5mg/kg dose of gentamicin was bactericidal in 4 h	[66]
In vitro PK/PD model of SEV	GISA, MRSA	Daptomycin 3–6 mg/kg q24 h + arbekacin 100 mg q12 h	Synergy, but regrowth in 48 h in the regimen with daptomycin 4 mg/kg/day	[67]

Equivalent dosing to (a) rifampin 10 mg/kg q12 h oral administration (b) daptomycin 6 mg/kg q24 h (c) daptomycin 10 mg/kg q24 h in humans; PK/PD: pharmacokinetic/pharmacodynamic; SEV: simulated endocardial vegetations; TMP/SMX: trimethoprim-sulfamethoxazole; IE: infective endocarditis, DNS: daptomycin non-susceptible; MRSA: meticillin-resistant S. aureus; GISA: glycopeptide-intermediate S. aureus.