Bactrim is a sulfa drug, which is a compound preparation of sulfamethoxazole (SMZ) and trimethoprim(TMP). It has good antibacterial effects for enterobacteriaceae such as Helicobacter, Klebsiella, Salmonella, Proteus, Morganella, Shigella, Neisseria meningitidis and Haemophilus influenzae. In particular, its antibacterial effect on Escherichia coli, Haemophilus influenzae, and Staphylococcus aureus is significantly stronger than that of SMZ.
This product is a compound preparation, each containing active ingredients sulfamethoxazole 0.4g and trimethoprim 0.08g.
A. Sulfamethoxazole
a. Definition
Sulfamethoxazole is a white crystalline powder; it is odorless with a slightly bitter taste. It is almost insoluble in water; soluble in dilute hydrochloric acid, sodium hydroxide test solution or ammonia test solution. It is mainly used for urinary tract infections, respiratory infections, intestinal infections, biliary tract infections and local soft tissue or wound infections caused by sensitive bacteria.
On October 27, 2017, the list of carcinogens published by the International Agency for Research on Cancer of the World Health Organization was initially compiled for reference. Sulfamethoxazole was included in the list of three types of carcinogens.
Sulfamethoxazole, is a broad-spectrum antibacterial drug that has a particularly strong effect on Staphylococcus and Escherichia coli. It is used to treat urinary tract infections and avian cholera. Sulfamethoxazole is a moderately effective sulfa drug for systemic application. It can compete with PABA to act on the dihydrofolate synthase in bacteria to prevent the synthesis of bacterial dihydrofolate, thereby inhibiting the growth and reproduction of bacteria. Three sulfa drugs, sulfadiazine, sulfisoxazole, and trisulfadiazine, are currently the best drugs for the treatment of nocardiac disease.
With a half-life of 10-12 hours, it can be partially acetylated. Although the number of medications required for this product is less than that of sulfisoxazole (2 times a day instead of 4 times), its acetylated metabolites have lower solubility in urine, so the possibility of crystaluria is slightly higher. So patients should maintain adequate hydration (adult daily urine output is not less than 1,500ml). When combined with the synergist trimethoprim, the antibacterial effect is significantly enhanced.
The bactrim (sulfamethoxazole/trimethoprim SMZ/TMP) is often better than monotherapy (see dihydrofolate reductase). It is often used clinically to treat urinary tract infections, respiratory tract infections, typhoid fever, Salmonella infections, pneumocystis carinii disease, nocardiasis, etc., and can also be used to prevent epidemic meningitis. Some clinicians advocate the combination of minocycline, ampicillin or erythromycin and sulfamethoxazole for the treatment of such infections, but there is no clinical data to prove that the combination therapy is better than sulfa drugs alone. Bactrim (TMP/SMZ), minocycline (minocy-cline; Minocin) and amikacin (amikacin) can also be used for the treatment of Nocardia stellaria infection.
Because this product prevents the metabolism of folic acid and aggravates the folate deficiency in patients with megaloblastic anemia, this product is forbidden for patients with this disease.
Pregnant and lactating women should not use this product.
Babies younger than 2 months of age should not use this product.
People with severe liver and kidney damage should not use this product.
Trimethoprim, TMP for short, is white or almost white crystalline powder; odorless, bitter taste. This product is slightly soluble in chloroform, slightly soluble in ethanol or acetone, and almost insoluble in water; it is easily soluble in glacial acetic acid. The melting point of this product is 199～203℃, molecular formula: C14H18N4O3, molecular weight: 290.31800, absorption coefficient 198～210. Trimethoprim is a synthetic broad-spectrum antibacterial agent, used alone for respiratory tract infections, urinary tract infections, intestinal infections and other diseases. It can be used to treat sepsis, meningitis, otitis media, typhoid fever, and Shigellosis caused by sensitive bacteria (Bacillary dysentery), etc. The combination of trimethoprim and sulfa-2,6-dimethoxine can also be used to treat malaria resistant to chloroquine.
b. Pharmacological effects
Trimethoprim is an inhibitor of bacterial dihydrofolate reductase and is a sulfonamide synergist. The principle of its antibacterial action is to interfere with the folate metabolism of bacteria. The main purpose is to selectively inhibit the activity of bacterial dihydrofolate reductase, so that dihydrofolate cannot be reduced to tetrahydrofolate, thereby inhibiting the growth and reproduction of bacteria.
Trimethoprim has antibacterial activity against most gram-positive and gram-negative bacteria; in addition, trimethoprim also has a certain effect on malaria parasites and certain fungi, such as Nocardia, histoplasma, and yeast. Among gram-positive bacteria, Streptococcus pneumoniae is sensitive to trimethoprim. Among gram-negative bacteria, Escherichia coli, Salmonella, Proteus mirabilis, Bacillus pneumoniae, Bacillus dysentery, Bacillus typhi, Bacillus pertussis, etc. are sensitive to trimethoprim. Trimethoprim has no antibacterial effect on Pseudomonas aeruginosa, Meningococcus and Alcaligenes.
c. Contraindication
Premature infants and newborns should not use trimethoprim.
People with liver damage, kidney damage, megaloblastic anemia caused by folate deficiency or other blood system diseases need to use this medicine with caution.
The effect of drugs on breastfeeding: Trimethoprim can be secreted into breast milk at a high concentration, and the drug may interfere with the metabolism of folate in nursing babies. Therefore, mothers must weigh the pros and cons before deciding whether to take the drug.
The peripheral blood should be checked regularly during medication.
3. Bactrim Uses
Since many common clinical pathogens are often resistant to this product, the treatment of bacterial infections needs to refer to the drug sensitivity results. The main indications of this product are the following infections caused by sensitive strains.
Urinary tract infections caused by sensitive strains of Escherichia coli, Klebsiella, Enterobacter, Proteus mirabilis, Proteus vulgaris and Morgenella.
Acute otitis media in children over 2 years old caused by Streptococcus pneumoniae or Haemophilus influenzae.
Acute attack of adult chronic bronchitis caused by Streptococcus pneumoniae or Haemophilus influenzae.
Intestinal infections and Shigella infections caused by sensitive strains of Shigella flexneri or Shigella sungii.
Treatment of Pneumocystis carinii pneumonia.
It can prevent Pneumocystis carinii pneumonia for patients with at least one episode of pneumocystis carinii disease, or those with HIV adult infection, whose CD4 lymphocyte count is ≤200/mm3 or less than 20% the total lymphocyte count.
Tourists' diarrhea caused by enterotoxigenic Escherichia coli (ETEC).
Bactrim side effects
Allergic reaction to Bactrim is more common, which can be manifested as drug eruptions. In severe cases, exudative erythema multiforme, exfoliative dermatitis, and epidermolysis bullosa atrophic dermatitis may occur; it may also be manifested as photosensitivity, drug fever, joint and muscle pain, fever and other serum sickness-like reactions, and occasionally anaphylactic shock.
Neutropenia or deficiency, thrombocytopenia and aplastic anemia. Patients may present with sore throat, fever, paleness, and bleeding tendency.
Hemolytic anemia and hemoglobinuria. They are prone to occur after the application of sulfa drugs in patients lacking glucose-6-phosphate dehydrogenase, and it is more common in newborns and children than in adults.
Hyperbilirubinemia and neonatal kernicterus. Because this product competes with bilirubin for protein binding sites, it can increase free bilirubin. Newborns with imperfect liver function and poor treatment of bilirubin are prone to hyperbilirubinemia and neonatal jaundice, and kernicterus may occasionally occur.
Liver damage. Jaundice, decreased liver function can occur, and acute liver necrosis can occur in severe cases.
Kidney damage. Crystaluria, hematuria, and tubular urine may occur; occasionally, severe adverse reactions such as interstitial nephritis or renal tubular necrosis may occur in patients.
Nausea, vomiting, decreased appetite, diarrhea, headache, fatigue, etc. The general symptoms are mild. Occasionally, patients get C. difficile enteritis, and the drug needs to be stopped at this time.
Goiter enlargement and hypofunction occasionally occur.
Central nervous system toxic reactions can occur occasionally, manifested as confusion, disorientation, hallucinations, euphoria or depression.
Occasionally, aseptic meningitis may occur, with headache, stiff neck, nausea, etc.
Although serious adverse reactions caused by the product are rare, they often involve various organs and can be fatal, such as exudative erythema multiforme, exfoliative dermatitis, epidermolysis bullosa, atrophic dermatitis, fulminant hepatic necrosis, agranulocytosis, and abnormalities in the blood system such as deficiency and aplastic anemia. The above-mentioned adverse reactions of AIDS patients are more common than those of non-AIDS patients.
Bactrim Pecautions
People using this medicine are prone to crystaluria, hematuria, proteinuria, oliguria, low back pain, etc. Patients with hepatic insufficiency should not use bactrim tablets.
Because it is not easy to remove bacteria, this product should not be used as a treatment or preventive medicine for the following diseases
Prevention or long-term treatment of otitis media.
Group A hemolytic streptococcal tonsils and pharyngitis.
Cross allergic reaction. Patients who are allergic to one sulfa drug may also be allergic to other sulfa drugs.
Liver damage. Jaundice, decreased liver function can occur, and acute liver necrosis can occur in severe cases, so patients with liver damage should avoid application.
Kidney damage. Crystaluria, hematuria and tubular urine can occur easily, so you should drink more water during the period of taking the product to maintain a high urine flow. If the product is used for a long treatment course and large doses, in addition to drinking more water, it is advisable to take sodium bicarbonate together to prevent this adverse reaction.
The use of this product in patients with dehydration or shock is likely to cause kidney damage, and the product should be used with caution or avoided. Patients with impaired renal function should not use this product.
Patients who are allergic to furosemide, sulfones, thiazide diuretics, sulfonylureas, and carbonic anhydrase inhibitors may also be allergic to sulfa drugs.
The following conditions should be used with caution: patients lack of glucose-6-phosphate dehydrogenase, hematoporphyria, have folic acid deficiency blood system diseases, dehydration, AIDS, or shock.
Severely infected patients should measure the blood drug concentration, which is effective for most infected patients with free sulfonamide concentrations of 50-150g/ml (for severe infections, 120-150g/ml). The total sulfa blood concentration should not exceed 200g/ml, otherwise the incidence of adverse reactions will increase.
Do not arbitrarily increase the dose, increase the frequency of medication or extend the course of treatment to prevent accumulated poisoning.
Since this product can inhibit the growth of Escherichia coli and hinder the synthesis of B vitamins in the intestine, people who use this product for more than a week should also be given vitamin B to prevent deficiency in vitamin B.
If folic acid deficiency is caused by taking this product, folic acid preparations can be taken at the same time, the latter does not interfere with the antibacterial activity of TMP, because the bacteria cannot use the synthesized folic acid. If signs of bone marrow suppression occur, the product should be stopped immediately, and 3-6 mg of folic acid should be given intramuscularly once a day for 2 days or as needed until hematopoietic function returns to normal. For those who use the product for a long time and overdosed, give them high doses of folic acid and extend the course of treatment.
Conclusion
Bactrim is a relatively common drug among sulfa drugs, which has good antibacterial effect on many kinds of bacteria, but it must be mentioned that many bacteria are also resistant to it. In addition, there are many side effects of Bactrim that need our attention.
