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 2. MIC50 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 Traveler’s 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.
