DESCRIPTION
Rx only To reduce the development of drug-resistant bacteria and maintain the effectiveness of sulfamethoxazole and trimethoprim tablets and other antibacterial drugs, sulfamethoxazole and trimethoprim tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
DESCRIPTION
Chemical Structure
Chemical Structure
INACTIVE INGREDIENT
Inactive ingredients
Magnesium stearate, povidone, pregelatinized starch and sodium starch glycolate.
MICROBIOLOGY
Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA). Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the required enzyme, dihydrofolate reductase. Thus, sulfamethoxazole and trimethoprim blocks two consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria. In vitro studies have shown that bacterial resistance develops more slowly with both sulfamethoxazole and trimethoprim in combination than with either sulfamethoxazole or trimethoprim alone. Sulfamethoxazole and trimethoprim have been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section. Aerobic gram-positive microorganisms: Streptococcus pneumoniae Aerobic gram-negative microorganisms: Escherichia coli (including susceptible enterotoxigenic strains implicated in traveler's diarrhea) Klebsiella species Enterobacter species Haemophilus influenzae Morganella morganii Proteus mirabilis Proteus vulgaris Shigella flexneri Shigella sonnei Other Organisms: Pneumocystis carinii
Susceptibility Testing Methods
Dilution Techniques
Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method4 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of sulfamethoxazole/trimethoprim powder. The MIC values should be interpreted according to the following criteria:
For testing Enterobacteriaceae:MIC (Interpretation2/38Susceptible (S)4/76Resistant (R)
When testing either Haemophilus influenzae * or Streptococcus pneumoniae:MIC (Interpretation*These interpretative standards are applicable only to broth microdilution susceptibility tests with Haemophilus influenzae using Haemophilus Test Medium (HTM)4.These interpretative standards are applicable only to broth microdilution susceptibility tests using cation-adjusted Mueller-Hinton broth with 2% to 5% lysed horse blood4.0.5/9.5Susceptible (S)1/192/38Intermediate (I)4/7Resistant (R)
Quality Control
Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard sulfamethoxazole/trimethoprim powder should provide the following range of values:
MicroorganismMIC (*This quality control range is applicable only to Haemophilus influenzae ATCC 49247 tested by broth microdilution procedure using Haemophilus Test Medium (HTM)4.This quality control range is applicable to tests performed by the broth microdilution method only using cation-adjusted Mueller-Hinton broth with 2% to 5% lysed horse blood4.Escherichia coliATCC 259220.5/9.5Haemophilus influenzae * ATCC 492470.03/0.590.25/4.75Streptococcus pneumoniaeATCC 496190.12/2.41/19 Diffusion Techniques
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure5 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 1.25/23.75of sulfamethoxazole/trimethoprim to test the susceptibility of microorganisms to sulfamethoxazole/trimethoprim. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 1.25/23.75of sulfamethoxazole/trimethoprim disk should be interpreted according to the following criteria:
For testing either Enterobacteriaceae or Haemophilus influenzae *:Zone Diameter (mm)Interpretation*These zone diameter standards are applicable only for disk diffusion testing with Haemophilus influenzae and Haemophilus Test Medium (HTM)5.16Susceptible (S)1115Intermediate (I)10Resistant (R) When testing Streptococcus pneumoniae *:Zone Diameter (mm)Interpretation*These zone diameter interpretative standards are applicable only to tests performed using Mueller-Hinton agar supplemented with 5% defibrinated sheep blood when incubated in 5% CO25.19Susceptible (S)1618Intermediate (I)15Resistant (R)Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for sulfamethoxazole/trimethoprim.
Quality Control
As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 1.25/23.75sulfamethoxazole/trimethoprim disk 1 should provide the following zone diameters in these laboratory test quality control strains:
MicroorganismZone Diameter Ranges (mm)*This quality control range is applicable only to Haemophilus influenzae ATCC 49247 tested by a disk diffusion procedure using Haemophilus Test Medium (HTM)5.This quality control range is applicable only to tests performed by disk diffusion using Mueller-Hinton agar supplemented with 5% defibrinated sheep blood when incubated in 5% CO25.Escherichia coliATCC 259222432Haemophilus influenzae * ATCC 492472432Streptococcus pneumoniaeATCC 496192028
1
Mueller-Hinton agar should be checked for excessive levels of thymidine or thymine. To determine whether Mueller-Hinton medium has sufficiently low levels of thymidine and thymine, an Enterococcus faecalis (ATCC 29212 or ATCC 33186) may be tested with sulfamethoxazole/trimethoprim disks. A zone of inhibitionmm that is essentially free of fine colonies indicates a sufficiently low level of thymidine and thymine.
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