Reference Number

Combinations

Pathogen

Test Method

Interaction

Definition

Tsuji, 2006

Dapto+Vanco

hGISA

E-test

Additive

FIC index > 0.5 <

Credito, 2007

Dapto + Gent

MSSA

MRSA(CA, HA, PVL+/-)

VISA

VRSA

Time kill

Synergistic

>2 log₁₀ decrease in CFU/ml

Tsuji, 2006

hGISA

E-test

Time kill

Additive

Additive

FIC index >0.5 to ≤1

1to 2-log₁₀ CFU/ml at 24h

Snydman, 2005

MRSA

Checkerboard

Time-kill

Synergistic

FIC index ≤ 0.5

Reduction >2 log₁₀ CFU/ml

Tsuji, 2005

GISA

MSSA

MRSA

E-test

Time-kill

Time-kill

Additive

Enhance 24h

Enhance 4-24h

FIC index >0.5 to ≤1
> 20-log2- log₁₀ CFU/ml

> 20-log2- log₁₀ CFU/ml

LaPlante, 2004

MSSA/MRSA

Time-kill

Increased bacteriocidal activity

The time to 99% bacteriocidal kill by 3.8h to 5.2h (statistically not significant)

Sakoulas, 2003

Dapto+Rif

MRSA

Animal study (vegetation bacterial density)

Superior to monotherapy

The difference of mean bacterial densities between dapto + rif and dapto monotherapy was statistically significant (p=0.006)

Baltch, 2007

Dapto+Gent+Rif

MRSA

Time-kill using Monocyte-derived Macrophages (MDM),

Superior to monotherapy

Greater activitiy than double or single (p<0.01)

Tsuji, 2006

Linez + Vanco

hGISA

E-test

Additive

FIC index > 0.5 to < 1

Grohs, 2003

MSSA/MRSA

Time-kill

Antagonistic

Decrease 100-hold at 24/48h

Chiang, 2003

MRSA

Checkerboard

Indifferent

Jacqueline, 2003

MRSA

Time-kill

Indifferent

Allen, 2002

MSSA/MRSA/MRSE

In vitro pharmaco-dynamic model

Improvement

Increase in kill <2- log₁₀ CFU/ml

Grohs, 2003

Linez+Gent

MSSA/MRSA

Time-kill

Indifferent

Jacqueline, 2003

MRSA

Time-kill

Antagonistic

Increase C.C >2- log₁₀ CFU/ml

LaPlante, 2004

MSSA/MRSA

Time-kill

Indifferent

Grohs, 2003

Linez + Rif

MSSA/MRSA

Time-kill

Indifferent

Jacqueline, 2003

MRSA

Time-kill

Synergistic

Decrease C.C >2- log₁₀ CFU/ml

Dailey, 2003

MSSA

Experimental endocarditis model

Indifferent

Allen, 2002

Linez + QD

MRSA

In vitro pharmacodynamic model

Enhance

Increase in kill >2- log₁₀ CFU/ml

Sahuquillo Arce, 2006

Linez + fosfomycin

MSSA

Time-kill Checkerboard

Synergistic

Decrease  >2- log₁₀ CFU/ml

FIC index < 0.5

Jacqueline, 2006

Linez + Ertapenem

MRSA

Time-kill, Dynamic checkerboard

(in vivo IE model)

Synergistic

Decrease  >2- log₁₀ CFU/ml

Jacqueline, 2005

Linez + Imipenem

hGISA

Time-kill, Dynamic checkerboard

Synergistic

Decrease C.C. >2- log₁₀ CFU/ml

Tsuji, 2006

Q/D+Vanco

hGISA

GISA

Time-kill

E-test

Synergistic

Additive

>2- log₁₀ CFU/ml at 24h

FIC index > 0.5 to < 1

Kang, 1995

MRSA/MSSA

Time-kill

Additive

TR:>5-log₁₀ CFU/ml

Allen, 2002

MRSA

In vitro pharmacodynamic model

Enhance

Increase in kill >2- log₁₀ CFU/ml

Kang ,  1997

MSSA/MRSA

Time-kill

Synergistic

Reduction >2- log₁₀ CFU/ml at 24 h

Tsuji, 2006

Q/D + Gent

hGISA

GISA

E-test

Time-kill

E-test

Time-kill

Indifferent

Indifferent

Indifferent

Indifferent

FIC index >0.5 to < 1

1 to 2- log₁₀ CFU/ml at 24h

Zarrouk, 2001

Q/D+Rif

S. aureus

(HM1054, RP13, HM1054R)

Time kill

Animal study

(IE model)

Bactericidal

Bactericidal

Decrease 3-log₁₀ CFU/ml

Decrease 3-log₁₀ CFU/ml

Hamel, 2008

Q/D+Rif

MRSA

In vivo, rabbit arthritis model

Synergistic

No definition

log₁₀ CFU/ml reduction: -3.4 ±0.5  (p=0.0005 vs control)

Sambatakou, 1998

MRSA

Time-kill

Synergistic

Decrease >2- log₁₀ CFU/ml

Petersen, 2006

Tige+Vanco

MRSA

Checkerboard

Time-kill

Indifferent

Indifferent

Mercier, 2002

Tige+Gent

MRSA

GISA

Time-kill

Time-kill

Enhance

Improve

> 100-hold or > in kill at 24h

< 100-hold

Petersen, 2006

Tige+Rif

MRSA

Checkerboard

Time-kill

Indifferent

Indifferent

Palmer, 1996

Levo+Rif

MSSA

MRRA

Time-kill

Time-kill

Indifferent

Indifferent

Mean CFU at 72h was ind.

Mean CFU at 72h was ind.

Kang,  1994

MSSA

MRSA

Checkerboard

Checkerboard

Synergistic

Synergistic

FIC index < 0.5

FIX index < 0.5