Table 1.  MIC50 of Sulfamethoxazole (SMX) and Trimethoprim (TMP) Against Various Gram-Positive Bacterial Pathogensa

 

Bacteria

SMX

TMP

Streptococcus pyogenes

12

0.5

Streptococcus agalactiae

28

5

Streptococcus pneumoniae

28

1.5

Enterococcus faecalis

>1000

0.5

Enterococcus faecium

>1000

1

Staphylococcus aureus

0.2

3

Staphylococcus epidermidis

1

4

Corynebacterium diphtheriae

>100

0.5

Erysipelothrix rhusiopathiae

>100

5

Listeria monocytogenes

2

0.12

Nocardia asteroids

3

15

Mycobacterium tuberculosis

1000

150

Mycobacterium fortuitum

16

64

Clostridium perfringens

28

50

aMIC50S represent activity against strains without acquired resistance

 

 

 

Table 2MIC50 of Sulfamethoxazole (SMX) and Trimethoprim (TMP) Against Various Gram-Negative Bacterial Pathogensa

 

Bacteria

SMX

TMP

Escherichia coli

8

0.1

Shigella dysenteriae

4

0.2

Salmonella typhi

2

0.2

Salmonella enteritidis

2

0.2

Klebsiella pneumoniae

16

1

Enterobacter cloacae

16

2

Serratia marcescens

16

2

Proteus mirabilis

8

4

Pseudomonas aeruginosa

32

128

Stenotrophomonas maltophilia

4

32

Burkholderia pseudomallei

4

32

Acinetobacter baumanii

4

16

Haemophilus influenzae

8

0.5

Pasteurella multocida

1

0.1

Bordetella pertussis

50

3

Brucella melitensis

2

16

Neisseria gonorrhoeae

1

16

Neisseria meningitides

1

16

Bacteroides fragilis

4

32

aMIC50S represent activity against strains without acquired resistance

 

 

 

Table 3.  FIC Index of the Combination Trimethoprim (TMP)-Sulfadiazine (SDZ)

P. vulgaris MICs: TMP 0.1 ug/mL; SDZ 2

 

Ratio TMP:SDZ

FIC Index

1:1.24

0.53

1:5

0.31

1:20

0.25

1:83

0.31

1:333

0.53

 

 

Table 4. Synergistic Effect of SMX-TMP against Selected Pathogens (MICs in ug/mL at the ratio 20:1)

 

Organism

SMX Alone

SMX + TMP

TMP Alone

TMP + SMX

Streptococcus pyogenes

64

1

1

0.05

Streptococcus pneumoniae

32

2

2

0.1

Staphylococcus aureus

2

0.2

1

0.01

Klebsiella pneumonia

16

0.3

1

0.01

Escherichia coli

4

1

0.3

0.05

Salmonella typhimurium

8

1

0.3

0.05

Proteus vulgaris

32

2

3

0.15

 

 

Table 5.  Bacteria Naturally Resistant to Trimethoprim (TMP) (MIC 16-256)

 

Neisseria sp.

Actinomyces

Acinetobacter

Bacteroides

Moraxella

Clostridium

Branhamella

Brucella sp.

Pseudomonas

Mycobacterium

Stenotrophomonas

Legionella

Burkholderia

Campylobacter

Achromobacter

Mycoplasma

Nocardia

Chlamydia

Treponema

 

 

 

 

Table 6.  Prevalence of Resistance to TMP-SMX

 

Streptococci

<10%

S. pneumoniae

10-40%, linked to penicillin resistance

S. aureus

<5% in Europe, U.S.

>40% in Australia

E. coli

10-20 in Europe, U.S.

Proteus  sp.

30-50 in Asia

Klebsiella pneumoniae

Enterobacter sp.

 

10-60%, highly dependent on local epidemics

Serratia

Salmonella

Shigella

 

0-50% depending on local epidemics



 

 

Table 7.  Concentration of TMP and SMX in Body Tissues and Fluids

 

Tissue or Fluid

TMP Level in Tissue/

TMP Level in Serum

SMX Level in Tissue/

SMX Level in Serum

Approximate Ratio TMP-SMX

Saliva

2.0

0.03

3:1

Middle ear fluid

0.75

0.2

1:6

Human breast milk

1.25

0.1

1:2

Prostatic tissue

2.0

0.35

1:3

Seminal fluid

0.5

0.3

1:10

Epididymis

2.0

0.51

1:5

Sputum

1.5

0.2

1:3

Lung parenchyma

3.5

0.3a (?)

1:2a (?)

Vaginal secretions

1.5

0.01

8:1

Fetal blood

0.6

0.8

1:30

Amniotic fluid

0.8

0.5

1:10

Aqueous humor

0.4

0.25

1:10

Cerebrospinal fluid

0.5

0.4

1:15

Bile

1.0

0.4

1:8

Bone (spongy)

0.67

--

--

Bone (compact)

  Synovial fluid

0.1

1.0

--

1.0

--

1:20

 

 

 

Table 8.  Approved Indications of TMP-SMX

 

Diseasaes

Comments

UTI

No indications concerning complicated UT or prostatitis

Acute otitis media

Acute exacerbation of  chronic bronchitis

Shigellosis

 

Due to S. pneumoniae or H. influenzae

Only S. flexneri and S. sonnei are specified

Pneumocystis carinii pneumonia

Travelerís diarrhea in adults

 

Due to enterotoxinogenic E. coli

 

 

Figure 1. Sulfonamides, p-aminobenzoic acid, and trimethoprim

 

 

 

Figure 2. Mechanism of action of sulfonamides and trimethoprim.

 

 

 
 

Figure 3.  Synergistic effect between sulfonamides and trimethoprim against a sulfonamide-resistant (MIC > 1000 μg/mL) S. aureus.