Table 2. Open in new tab Studies...

Strain

Year and country

Number of isolates

Resistance (%)

In vitro (methods)/in vivo (animal and site of infection)

Partner drug

Synergistic effect (%)

Additive effect (%)

Indifferent effect (%)

Antagonistic effect (%)

Comments

Reference

2004, USA

MRSA (100)

in vitro (ET, TK)

Oxacillin

ET: 6 (33.3); TK: 11 (61)

ET: 12 (66.6); TK: 7 (39)

—

¹²

E. faecium

2004, USA

VRE (100)

in vitro (ET)

Ampicillin

13 (68.4)

1 (5.3)

5 (26.3)

—

¹³

2005, USA

MRSA (50)

in vitro (ET) (TK on 1 MSSA)

Ampicillin

ET: 4 (10)

—

ET: 35 (87.5); TK: 1 (100)

ET: 1 (2.5)

No distinction between additive and indifferent effect. TK was performed on the isolate showing antagonistic effect with ET.

¹⁴

in vitro (ET, 37 isolates tested)

Oxacillin

ET: 4 (11)

—

ET: 33 (89)

—

E. faecalis, E. faecium

VRE (50)

in vitro (ET) (TK on 1 VSE)

Ampicillin

ET: 3 (7.5)

—

ET: 37 (92.5); TK: 1 (100)

—

2006, USA

GISA (100)

in vitro (ET, TK)

Ampicillin/sulbactam

—

ET: 2 (100); TK: 2 (100)

—

¹⁵

E. faecium

2006, Turkey

VRE (100)

in vitro (ET)

Ampicillin

27 (64.2)

—

15 (35.8)

—

No distinction between additive and indifferent effect.

¹⁶

MRSA (100)

Ampicillin/sulbactam

28 (93.3)

—

2 (6.7)

—

Piperacillin/tazobactam

22 (73.3)

—

8 (26.7)

—

Ticarcillin/clavulanate

24 (80)

—

6 (20)

—

MRSE (100)

Ampicillin/sulbactam

14 (38.8)

—

22 (61.2)

—

Piperacillin/tazobactam

18 (50)

—

18 (50)

—

Ticarcillin/clavulanate

12 (33.3)

—

24 (66.7)

—

2008, Taiwan

VISA (100)

in vitro (TK)

Oxacillin

—

1 (100)

—

¹⁷

2010, USA

MRSA (100)

in vitro (TK); in vivo (rabbit, catheter-induced IE with kidney and spleen dissemination)

Oxacillin

TK: 2 (100)

in vivo: 2 (100)

—

DNS isolates. In the in vivo study, equivalent human dosage of DAP 12 mg/kg was administered.

¹⁸

2010, USA

MRSA (100)

in vitro (PK/PD model)

Nafcillin

—

2 (100)

—

DNS isolates. High inoculum tested.

¹⁹

E. faecium

2012, USA

VRE (100)

in vitro (TK, PD model)

Ampicillin

—

1 (100)

—

High inoculum tested.

²⁰

2012, Spain

MRSA (100)

in vitro (TK), in vivo (rat, tissue cage infection model)

Cloxacillin

TK: 1 (100); in vivo: 1 (100)

—

Standard and high inoculum tested.
In the in vivo study, equivalent human dosage of DAP 6 and 10 mg/kg was administered (synergism observed with both dosages).

²¹

2012, USA

MRSA (100)

in vitro (TK)

Oxacillin, Amoxicillin/clavulanate

2 (100)

—

In the in vivo study, equivalent human dosage of DAP 10 mg/kg was administered.

²²

in vivo (G. mellonella infection model)

Nafcillin

2 (100)

—

2013, USA

VISA (100)

in vitro (TK, PK/PD model)

Nafcillin

11 (55)

—

9 (45)

—

In the PK/PD model, the superiority of the combination compared with monotherapy was not as marked as in TK analysis.

²³

2014, Spain

MRSA (100)

in vitro (TK); in vivo (rat, foreign body infection model)

Cloxacillin

in vitro: 1 (100); in vivo: 1 (100)

—

Resistance developed with monotherapies, but not with combinations. Standard and high inoculum tested. In the in vivo study, equivalent human dosage of DAP 8–10 mg/kg was administered.

²⁴

E. faecalis

2015, USA

VRE (100)

in vitro (CB, TK)

Ampicillin

2 (100)

—

²⁵

E. faecium

2 (100)

—

E. faecium

2015, USA

VRE (100)

in vitro (TK)

Ampicillin

2 (50)

—

2 (50)

—

DNS isolates.

²⁶

E. faecalis

2 (100)

—

E. faecalis

2015, USA

VRE (100)

in vitro (PK/PD model)

Ampicillin

1 (100)

—

²⁷

E. faecium

2 (100)

—

2016, USA

MRSA (100)

in vitro (CB, TK)

Piperacillin/tazobactam

7 (87.5)

1 (12.5)

—

4 DNS isolates.

²⁸

Ampicillin/sulbactam

7 (87.5)

—

1 (12.5)

—

E. faecalis

2017, Spain

—

in vitro (TK); in vivo (rabbit, IE, 2 strains)

Ampicillin

TK: 8 (100); in vivo: 2 (100)

—

When testing high inoculum, 2 isolates showed synergism and 6 isolates showed additive effect. In the in vivo study, equivalent human dosage of DAP 10 mg/kg was administered.

³¹

2018, Spain

MRSA (100)

in vitro (TK); in vivo (rabbit, IE, 1 isolate)

Cloxacillin

TK: 5 (100)

—

in vivo: 1 (100)

—

Synergism was confirmed also when high inoculum was tested. In the in vivo study, equivalent human dosage of DAP 6 and 10 mg/kg was administered (synergism observed with DAP 6 mg/kg, indifferent effect with DAP 10 mg/kg).

²⁹

2019, Taiwan

100

MRSA (100)

in vitro (CB)

Oxacillin

11 (11)

2 (2)

87 (87)

—

No distinction between indifferent and antagonistic effect.

³⁰

2020, Spain

—

in vitro (TK), in vivo (rabbit, IE, 1 isolate)

Cloxacillin

TK: 5 (100); in vivo: 1 (100)

—

Standard and high inoculum tested. In the in vivo study, equivalent human dosage of DAP 6 mg/kg was administered.

³²

E. faecalis

2021, USA

VRE (100)

in vitro (TK)

Ampicillin

2 (100)

—

³³

E. faecium

1 (50)

—

Strain

Year and country

Number of isolates

Resistance (%)

In vitro (methods)/in vivo (animal and site of infection)

Partner drug

Synergistic effect (%)

Additive effect (%)

Indifferent effect (%)

Antagonistic effect (%)

Comments

Reference

2004, USA

MRSA (100)

in vitro (ET, TK)

Oxacillin

ET: 6 (33.3); TK: 11 (61)

ET: 12 (66.6); TK: 7 (39)

—

¹²

E. faecium

2004, USA

VRE (100)

in vitro (ET)

Ampicillin

13 (68.4)

1 (5.3)

5 (26.3)

—

¹³

2005, USA

MRSA (50)

in vitro (ET) (TK on 1 MSSA)

Ampicillin

ET: 4 (10)

—

ET: 35 (87.5); TK: 1 (100)

ET: 1 (2.5)

No distinction between additive and indifferent effect. TK was performed on the isolate showing antagonistic effect with ET.

¹⁴

in vitro (ET, 37 isolates tested)

Oxacillin

ET: 4 (11)

—

ET: 33 (89)

—

E. faecalis, E. faecium

VRE (50)

in vitro (ET) (TK on 1 VSE)

Ampicillin

ET: 3 (7.5)

—

ET: 37 (92.5); TK: 1 (100)

—

2006, USA

GISA (100)

in vitro (ET, TK)

Ampicillin/sulbactam

—

ET: 2 (100); TK: 2 (100)

—

¹⁵

E. faecium

2006, Turkey

VRE (100)

in vitro (ET)

Ampicillin

27 (64.2)

—

15 (35.8)

—

No distinction between additive and indifferent effect.

¹⁶

MRSA (100)

Ampicillin/sulbactam

28 (93.3)

—

2 (6.7)

—

Piperacillin/tazobactam

22 (73.3)

—

8 (26.7)

—

Ticarcillin/clavulanate

24 (80)

—

6 (20)

—

MRSE (100)

Ampicillin/sulbactam

14 (38.8)

—

22 (61.2)

—

Piperacillin/tazobactam

18 (50)

—

18 (50)

—

Ticarcillin/clavulanate

12 (33.3)

—

24 (66.7)

—

2008, Taiwan

VISA (100)

in vitro (TK)

Oxacillin

—

1 (100)

—

¹⁷

2010, USA

MRSA (100)

in vitro (TK); in vivo (rabbit, catheter-induced IE with kidney and spleen dissemination)

Oxacillin

TK: 2 (100)

in vivo: 2 (100)

—

DNS isolates. In the in vivo study, equivalent human dosage of DAP 12 mg/kg was administered.

¹⁸

2010, USA

MRSA (100)

in vitro (PK/PD model)

Nafcillin

—

2 (100)

—

DNS isolates. High inoculum tested.

¹⁹

E. faecium

2012, USA

VRE (100)

in vitro (TK, PD model)

Ampicillin

—

1 (100)

—

High inoculum tested.

²⁰

2012, Spain

MRSA (100)

in vitro (TK), in vivo (rat, tissue cage infection model)

Cloxacillin

TK: 1 (100); in vivo: 1 (100)

—

Standard and high inoculum tested.
In the in vivo study, equivalent human dosage of DAP 6 and 10 mg/kg was administered (synergism observed with both dosages).

²¹

2012, USA

MRSA (100)

in vitro (TK)

Oxacillin, Amoxicillin/clavulanate

2 (100)

—

In the in vivo study, equivalent human dosage of DAP 10 mg/kg was administered.

²²

in vivo (G. mellonella infection model)

Nafcillin

2 (100)

—

2013, USA

VISA (100)

in vitro (TK, PK/PD model)

Nafcillin

11 (55)

—

9 (45)

—

In the PK/PD model, the superiority of the combination compared with monotherapy was not as marked as in TK analysis.

²³

2014, Spain

MRSA (100)

in vitro (TK); in vivo (rat, foreign body infection model)

Cloxacillin

in vitro: 1 (100); in vivo: 1 (100)

—

Resistance developed with monotherapies, but not with combinations. Standard and high inoculum tested. In the in vivo study, equivalent human dosage of DAP 8–10 mg/kg was administered.

²⁴

E. faecalis

2015, USA

VRE (100)

in vitro (CB, TK)

Ampicillin

2 (100)

—

²⁵

E. faecium

2 (100)

—

E. faecium

2015, USA

VRE (100)

in vitro (TK)

Ampicillin

2 (50)

—

2 (50)

—

DNS isolates.

²⁶

E. faecalis

2 (100)

—

E. faecalis

2015, USA

VRE (100)

in vitro (PK/PD model)

Ampicillin

1 (100)

—

²⁷

E. faecium

2 (100)

—

2016, USA

MRSA (100)

in vitro (CB, TK)

Piperacillin/tazobactam

7 (87.5)

1 (12.5)

—

4 DNS isolates.

²⁸

Ampicillin/sulbactam

7 (87.5)

—

1 (12.5)

—

E. faecalis

2017, Spain

—

in vitro (TK); in vivo (rabbit, IE, 2 strains)

Ampicillin

TK: 8 (100); in vivo: 2 (100)

—

When testing high inoculum, 2 isolates showed synergism and 6 isolates showed additive effect. In the in vivo study, equivalent human dosage of DAP 10 mg/kg was administered.

³¹

2018, Spain

MRSA (100)

in vitro (TK); in vivo (rabbit, IE, 1 isolate)

Cloxacillin

TK: 5 (100)

—

in vivo: 1 (100)

—

²⁹

2019, Taiwan

100

MRSA (100)

in vitro (CB)

Oxacillin

11 (11)

2 (2)

87 (87)

—

No distinction between indifferent and antagonistic effect.

³⁰

2020, Spain

—

in vitro (TK), in vivo (rabbit, IE, 1 isolate)

Cloxacillin

TK: 5 (100); in vivo: 1 (100)

—

Standard and high inoculum tested. In the in vivo study, equivalent human dosage of DAP 6 mg/kg was administered.

³²

E. faecalis

2021, USA

VRE (100)

in vitro (TK)

Ampicillin

2 (100)

—

³³

E. faecium

1 (50)

—

Table 2.

Open in new tab

Studies evaluating daptomycin in combination with penicillins and penicillins + BLIs

Strain	Year and country	Number of isolates	Resistance (%)	In vitro (methods)/in vivo (animal and site of infection)	Partner drug	Synergistic effect (%)	Additive effect (%)	Indifferent effect (%)	Antagonistic effect (%)	Comments	Reference
SA	2004, USA	18	MRSA (100)	in vitro (ET, TK)	Oxacillin	ET: 6 (33.3); TK: 11 (61)	ET: 12 (66.6); TK: 7 (39)	—	—	—	¹²
E. faecium	2004, USA	19	VRE (100)	in vitro (ET)	Ampicillin	13 (68.4)	1 (5.3)	5 (26.3)	—	—	¹³
SA	2005, USA	40	MRSA (50)	in vitro (ET) (TK on 1 MSSA)	Ampicillin	ET: 4 (10)	—	ET: 35 (87.5); TK: 1 (100)	ET: 1 (2.5)	No distinction between additive and indifferent effect. TK was performed on the isolate showing antagonistic effect with ET.	¹⁴
SA		40	MRSA (50)	in vitro (ET, 37 isolates tested)	Oxacillin	ET: 4 (11)	—	ET: 33 (89)	—
E. faecalis, E. faecium		40	VRE (50)	in vitro (ET) (TK on 1 VSE)	Ampicillin	ET: 3 (7.5)	—	ET: 37 (92.5); TK: 1 (100)	—
SA	2006, USA	2	GISA (100)	in vitro (ET, TK)	Ampicillin/sulbactam	—	—	ET: 2 (100); TK: 2 (100)	—		¹⁵
E. faecium	2006, Turkey	42	VRE (100)	in vitro (ET)	Ampicillin	27 (64.2)	—	15 (35.8)	—	No distinction between additive and indifferent effect.	¹⁶
SA		30	MRSA (100)		Ampicillin/sulbactam	28 (93.3)	—	2 (6.7)	—
					Piperacillin/tazobactam	22 (73.3)	—	8 (26.7)	—
					Ticarcillin/clavulanate	24 (80)	—	6 (20)	—
SE		36	MRSE (100)		Ampicillin/sulbactam	14 (38.8)	—	22 (61.2)	—
					Piperacillin/tazobactam	18 (50)	—	18 (50)	—
					Ticarcillin/clavulanate	12 (33.3)	—	24 (66.7)	—
SA	2008, Taiwan	1	VISA (100)	in vitro (TK)	Oxacillin	—	1 (100)	—	—		¹⁷
SA	2010, USA	2	MRSA (100)	in vitro (TK); in vivo (rabbit, catheter-induced IE with kidney and spleen dissemination)	Oxacillin	TK: 2 (100)	in vivo: 2 (100)	—	—	DNS isolates. In the in vivo study, equivalent human dosage of DAP 12 mg/kg was administered.	¹⁸
SA	2010, USA	2	MRSA (100)	in vitro (PK/PD model)	Nafcillin	—	—	2 (100)	—	DNS isolates. High inoculum tested.	¹⁹
E. faecium	2012, USA	1	VRE (100)	in vitro (TK, PD model)	Ampicillin	—	1 (100)	—	—	High inoculum tested.	²⁰
SA	2012, Spain	1	MRSA (100)	in vitro (TK), in vivo (rat, tissue cage infection model)	Cloxacillin	TK: 1 (100); in vivo: 1 (100)	—	—	—	Standard and high inoculum tested. In the in vivo study, equivalent human dosage of DAP 6 and 10 mg/kg was administered (synergism observed with both dosages).	²¹
SA	2012, USA	2	MRSA (100)	in vitro (TK)	Oxacillin, Amoxicillin/clavulanate	2 (100)	—	—	—	In the in vivo study, equivalent human dosage of DAP 10 mg/kg was administered.	²²
SA	2012, USA	2	MRSA (100)	in vivo (G. mellonella infection model)	Nafcillin	2 (100)	—	—	—		²²
SA	2013, USA	20	VISA (100)	in vitro (TK, PK/PD model)	Nafcillin	11 (55)	—	9 (45)	—	In the PK/PD model, the superiority of the combination compared with monotherapy was not as marked as in TK analysis.	²³
SA	2014, Spain	1	MRSA (100)	in vitro (TK); in vivo (rat, foreign body infection model)	Cloxacillin	in vitro: 1 (100); in vivo: 1 (100)	—	—	—	Resistance developed with monotherapies, but not with combinations. Standard and high inoculum tested. In the in vivo study, equivalent human dosage of DAP 8–10 mg/kg was administered.	²⁴
E. faecalis	2015, USA	2	VRE (100)	in vitro (CB, TK)	Ampicillin	2 (100)	—	—	—		²⁵
E. faecium	2015, USA	2	VRE (100)	in vitro (CB, TK)	Ampicillin	2 (100)	—	—	—		²⁵
E. faecium	2015, USA	4	VRE (100)	in vitro (TK)	Ampicillin	2 (50)	—	2 (50)	—	DNS isolates.	²⁶
E. faecalis	2015, USA	2	VRE (100)	in vitro (TK)	Ampicillin	2 (100)	—	—	—	DNS isolates.	²⁶
E. faecalis	2015, USA	1	VRE (100)	in vitro (PK/PD model)	Ampicillin	1 (100)	—	—	—		²⁷
E. faecium	2015, USA	2	VRE (100)	in vitro (PK/PD model)	Ampicillin	2 (100)	—	—	—		²⁷
SA	2016, USA	8	MRSA (100)	in vitro (CB, TK)	Piperacillin/tazobactam	7 (87.5)	1 (12.5)	—	—	4 DNS isolates.	²⁸
SA	2016, USA	8	MRSA (100)	in vitro (CB, TK)	Ampicillin/sulbactam	7 (87.5)	—	1 (12.5)	—	4 DNS isolates.	²⁸
E. faecalis	2017, Spain	8	—	in vitro (TK); in vivo (rabbit, IE, 2 strains)	Ampicillin	TK: 8 (100); in vivo: 2 (100)	—	—	—	When testing high inoculum, 2 isolates showed synergism and 6 isolates showed additive effect. In the in vivo study, equivalent human dosage of DAP 10 mg/kg was administered.	³¹
SA	2018, Spain	5	MRSA (100)	in vitro (TK); in vivo (rabbit, IE, 1 isolate)	Cloxacillin	TK: 5 (100)	—	in vivo: 1 (100)	—	Synergism was confirmed also when high inoculum was tested. In the in vivo study, equivalent human dosage of DAP 6 and 10 mg/kg was administered (synergism observed with DAP 6 mg/kg, indifferent effect with DAP 10 mg/kg).	²⁹
SA	2019, Taiwan	100	MRSA (100)	in vitro (CB)	Oxacillin	11 (11)	2 (2)	87 (87)	—	No distinction between indifferent and antagonistic effect.	³⁰
SA	2020, Spain	5	—	in vitro (TK), in vivo (rabbit, IE, 1 isolate)	Cloxacillin	TK: 5 (100); in vivo: 1 (100)	—	—	—	Standard and high inoculum tested. In the in vivo study, equivalent human dosage of DAP 6 mg/kg was administered.	³²
E. faecalis	2021, USA	2	VRE (100)	in vitro (TK)	Ampicillin	2 (100)	—	—	—		³³
E. faecium	2021, USA	2	VRE (100)	in vitro (TK)	Ampicillin	1 (50)	1 (50)	—	—		³³

Strain	Year and country	Number of isolates	Resistance (%)	In vitro (methods)/in vivo (animal and site of infection)	Partner drug	Synergistic effect (%)	Additive effect (%)	Indifferent effect (%)	Antagonistic effect (%)	Comments	Reference
SA	2004, USA	18	MRSA (100)	in vitro (ET, TK)	Oxacillin	ET: 6 (33.3); TK: 11 (61)	ET: 12 (66.6); TK: 7 (39)	—	—	—	¹²
E. faecium	2004, USA	19	VRE (100)	in vitro (ET)	Ampicillin	13 (68.4)	1 (5.3)	5 (26.3)	—	—	¹³
SA	2005, USA	40	MRSA (50)	in vitro (ET) (TK on 1 MSSA)	Ampicillin	ET: 4 (10)	—	ET: 35 (87.5); TK: 1 (100)	ET: 1 (2.5)	No distinction between additive and indifferent effect. TK was performed on the isolate showing antagonistic effect with ET.	¹⁴
SA		40	MRSA (50)	in vitro (ET, 37 isolates tested)	Oxacillin	ET: 4 (11)	—	ET: 33 (89)	—
E. faecalis, E. faecium		40	VRE (50)	in vitro (ET) (TK on 1 VSE)	Ampicillin	ET: 3 (7.5)	—	ET: 37 (92.5); TK: 1 (100)	—
SA	2006, USA	2	GISA (100)	in vitro (ET, TK)	Ampicillin/sulbactam	—	—	ET: 2 (100); TK: 2 (100)	—		¹⁵
E. faecium	2006, Turkey	42	VRE (100)	in vitro (ET)	Ampicillin	27 (64.2)	—	15 (35.8)	—	No distinction between additive and indifferent effect.	¹⁶
SA		30	MRSA (100)		Ampicillin/sulbactam	28 (93.3)	—	2 (6.7)	—
					Piperacillin/tazobactam	22 (73.3)	—	8 (26.7)	—
					Ticarcillin/clavulanate	24 (80)	—	6 (20)	—
SE		36	MRSE (100)		Ampicillin/sulbactam	14 (38.8)	—	22 (61.2)	—
					Piperacillin/tazobactam	18 (50)	—	18 (50)	—
					Ticarcillin/clavulanate	12 (33.3)	—	24 (66.7)	—
SA	2008, Taiwan	1	VISA (100)	in vitro (TK)	Oxacillin	—	1 (100)	—	—		¹⁷
SA	2010, USA	2	MRSA (100)	in vitro (TK); in vivo (rabbit, catheter-induced IE with kidney and spleen dissemination)	Oxacillin	TK: 2 (100)	in vivo: 2 (100)	—	—	DNS isolates. In the in vivo study, equivalent human dosage of DAP 12 mg/kg was administered.	¹⁸
SA	2010, USA	2	MRSA (100)	in vitro (PK/PD model)	Nafcillin	—	—	2 (100)	—	DNS isolates. High inoculum tested.	¹⁹
E. faecium	2012, USA	1	VRE (100)	in vitro (TK, PD model)	Ampicillin	—	1 (100)	—	—	High inoculum tested.	²⁰
SA	2012, Spain	1	MRSA (100)	in vitro (TK), in vivo (rat, tissue cage infection model)	Cloxacillin	TK: 1 (100); in vivo: 1 (100)	—	—	—	Standard and high inoculum tested. In the in vivo study, equivalent human dosage of DAP 6 and 10 mg/kg was administered (synergism observed with both dosages).	²¹
SA	2012, USA	2	MRSA (100)	in vitro (TK)	Oxacillin, Amoxicillin/clavulanate	2 (100)	—	—	—	In the in vivo study, equivalent human dosage of DAP 10 mg/kg was administered.	²²
SA	2012, USA	2	MRSA (100)	in vivo (G. mellonella infection model)	Nafcillin	2 (100)	—	—	—		²²
SA	2013, USA	20	VISA (100)	in vitro (TK, PK/PD model)	Nafcillin	11 (55)	—	9 (45)	—	In the PK/PD model, the superiority of the combination compared with monotherapy was not as marked as in TK analysis.	²³
SA	2014, Spain	1	MRSA (100)	in vitro (TK); in vivo (rat, foreign body infection model)	Cloxacillin	in vitro: 1 (100); in vivo: 1 (100)	—	—	—	Resistance developed with monotherapies, but not with combinations. Standard and high inoculum tested. In the in vivo study, equivalent human dosage of DAP 8–10 mg/kg was administered.	²⁴
E. faecalis	2015, USA	2	VRE (100)	in vitro (CB, TK)	Ampicillin	2 (100)	—	—	—		²⁵
E. faecium	2015, USA	2	VRE (100)	in vitro (CB, TK)	Ampicillin	2 (100)	—	—	—		²⁵
E. faecium	2015, USA	4	VRE (100)	in vitro (TK)	Ampicillin	2 (50)	—	2 (50)	—	DNS isolates.	²⁶
E. faecalis	2015, USA	2	VRE (100)	in vitro (TK)	Ampicillin	2 (100)	—	—	—	DNS isolates.	²⁶
E. faecalis	2015, USA	1	VRE (100)	in vitro (PK/PD model)	Ampicillin	1 (100)	—	—	—		²⁷
E. faecium	2015, USA	2	VRE (100)	in vitro (PK/PD model)	Ampicillin	2 (100)	—	—	—		²⁷
SA	2016, USA	8	MRSA (100)	in vitro (CB, TK)	Piperacillin/tazobactam	7 (87.5)	1 (12.5)	—	—	4 DNS isolates.	²⁸
SA	2016, USA	8	MRSA (100)	in vitro (CB, TK)	Ampicillin/sulbactam	7 (87.5)	—	1 (12.5)	—	4 DNS isolates.	²⁸
E. faecalis	2017, Spain	8	—	in vitro (TK); in vivo (rabbit, IE, 2 strains)	Ampicillin	TK: 8 (100); in vivo: 2 (100)	—	—	—	When testing high inoculum, 2 isolates showed synergism and 6 isolates showed additive effect. In the in vivo study, equivalent human dosage of DAP 10 mg/kg was administered.	³¹
SA	2018, Spain	5	MRSA (100)	in vitro (TK); in vivo (rabbit, IE, 1 isolate)	Cloxacillin	TK: 5 (100)	—	in vivo: 1 (100)	—	Synergism was confirmed also when high inoculum was tested. In the in vivo study, equivalent human dosage of DAP 6 and 10 mg/kg was administered (synergism observed with DAP 6 mg/kg, indifferent effect with DAP 10 mg/kg).	²⁹
SA	2019, Taiwan	100	MRSA (100)	in vitro (CB)	Oxacillin	11 (11)	2 (2)	87 (87)	—	No distinction between indifferent and antagonistic effect.	³⁰
SA	2020, Spain	5	—	in vitro (TK), in vivo (rabbit, IE, 1 isolate)	Cloxacillin	TK: 5 (100); in vivo: 1 (100)	—	—	—	Standard and high inoculum tested. In the in vivo study, equivalent human dosage of DAP 6 mg/kg was administered.	³²
E. faecalis	2021, USA	2	VRE (100)	in vitro (TK)	Ampicillin	2 (100)	—	—	—		³³
E. faecium	2021, USA	2	VRE (100)	in vitro (TK)	Ampicillin	1 (50)	1 (50)	—	—		³³

CB, chequerboard; ET, Etest; IE, infective endocarditis; DAP, daptomycin; DNS, daptomycin non-susceptible; SA, S. aureus; SE, S. epidermidis; TK, time–kill assay.

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