Table 1. In Vitro Activity of Fusidic Acid.   

 

Organism

N

Country

(year of report)

MIC50

MIC90

MIC range

ref

Gram positive aerobes

 

 

 

 

 

 

Staphylococcus aureus

  Methicillin susceptible

 

162

72

20

 

 

USA (1987)

Japan (1987)

Belgium (1990)

 

0.03

0.2

0.06

 

0.06

1.56

0.06

 

0.008-0.25

0.1 – 3.13

0.06 – 0.12

  

(39)

(40)

(92)

Staphylococcus aureus

  Methicillin  resistant

 

 

185

111

108

100

 

 

Ireland (1985)

USA (1987)

Belgium (1990)

Germany (1992)

 

 

>32

0.03

0.06

0.125

 

 

>32

0.12

0.06

4

 

 

0.03 – 64

0.008 – 4

0.03 – 8

0.03 - 8

 

 

(50) (39)

(92)

(32)

Staphylococcus spp

  Coagulase negative

  

100

197

  

Germany (1992)

Canada (1995)

 

0.25

0.25

  

0.25

0.5

  

0.03 – 8

0.12 - 32

 

(32)

(87)

Streptococcus pyogenes

102

France (2000)

4

8

1 - 32

(43)

Group G streptococci

69

France (2000)

8

8

0.25 – 128

(43)

Streptococcus agalactiae

50

France (2000)

16

32

1 - 64

(43)

Group C streptococci

10

France (2000)

4

16

4 - 32

(43)

Enterococcus faecalis

152

Canada (1995

4

8

1.0 - 32

(87)

Corynebacterium spp

118

Germany (1977)

0.04

2

0.04 – 12.5

(30)

 

 

 

 

 

 

 

Gram negative aerobes

 

 

 

 

 

 

Bordetella pertussis

100

Canada (1960-81)

0.1

0.2

0.03 – 0.5

(4)

Moraxella catarrhalis

9

UK (1962)

0.12

0.12

0.06 – 0.12

(5)

Neisseria gonorrhoeae

96

Denmark (1968)

0.6

2

0.25 - 2

(70)

Neisseria meningitidis

100

UK (1978)

0.03

0.12

0.015 – 0.5

(48)

 

 

 

 

 

 

 

Mycobacterium spp

 

 

 

 

 

 

M. tuberculosis

170

Turkey (2001)

16

16

16 - 256

(18)

M. tuberculosis

64

Belgium (1990)

8

16

4 - 32

(91)

M. avium

22

Belgium (1990)

32

64

1 - > 128

(91)

M. chelonei

17

Belgium (1990)

64

128

32 - >128

(91)

M. fortuitum

19

Belgium (1990)

64

>128

16 - >128

(91)

M. kansasii

19

USA (1992)

32

32

2.0 - 64

(101)

 

 

 

 

 

 

 

Anaerobic bacteria

 

 

 

 

 

 

Clostridium difficile

80

Australia (2002)

0.75

2

0.125 - 4

(45)

Clostridium perfringens

39

USA (1979)

0.12

0.5

£0.06 - 1

(79)

Peptostreptococcus anaerobius

 

34

 

USA (1979)

 

0.25

 

0.5

 

£0.06 - 2

 

(79)

Propionibacterium acnes

 

25

 

USA(1979)

 

0.25

 

1

 

£0.06 - 2

 

(79)

Bacteroides fragilis

100

UK (1987)

2

2

0.5 - 4

(74)

Prevotella intermedia

31

USA (1979)

0.25

1

£0.06 - 1

(79)

Porphyromonas asaccharolytica

 

31

 

USA (1979)

 

0.25

 

1

 

£0.06 - 1

 

(79)

Fusobacterium spp

15

UK (1987)

1

64

£0.25 - >128

(74)

·         Susceptibility breakpoints have not been determined by NCCLS

·         The Comite de l’Antibiogramme de la Societe Francaise de Microbiologie (68)give MIC breakpoints £ 2mg/L = susceptible and >16 mg/L = resistant for non fastidious organisms

·         The BSAC (1) MIC breakpoints for staphylococci are £ 1mg/L = susceptible, ³ 2mg/L = resistant

 

Table 2. Pharmacokinetics of Fusidic Acid/Sodium Fusidate After Oral or IV Administration in Adults.

Route

Number subjects

Cmax

mg/L

Tmax

h

C 8 h

mg/L

C12 h

mg/L

AUC range

AUC

mg.h/l

b

h

Cl

ml/min

Vd

l/kg

oral (100)

6

31.4

3

~12

 

0-8h

162

 

 

 

oral (46

  fasting 

  after food

12

30.6

 

22.7

2.2

 

3.2

 

 

0 - ¥

 

0 - ¥

329

 

276

8.9

 

9.5

 

 

oral (84)

8

33.3

2.1

~12.5

~10

0 - ¥

368

16.0

 

 

oral (52)

10

30

~2

 

8.5

0 - ¥

315

11.0

33

0.52 (b)

IV (2h infusion) (76)

8

52.4

2

~15

~10

 

411

9.8

21

0.3

IV (2h infusion) (75)

 

12

23.6

2

~11

~8

 

204

14.5

42

0.46

Cmax = peak concentration, Tmax = time to peak concentration, C8h = concentration 8 hours after dosing, C12h = concentration 12 hours after dosing, AUC = area-under-the-curve, t½ß = elimination half-life, Cl = clearance, Vd = volume of distribution, ß = elimination half-life volume of distribution

 

 

Figure 1. Chemical Structure