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What-is-thiamphenicol

Methyl-sulfonyl analog of chloramphenicol: Thiamphenicol

Posted on  February 11, 2021, Edited by Jason, Category  

What is thiamphenicol?

1. Definition

Thiamphenicol is a broad-spectrum antibiotic of chloramphenicol, which has a stronger effect on Gram-negative bacteria than positive bacteria. It is white to off-white crystalline powder or crystals at room temperature. It can be absorbed quickly and completely after oral administration. It is mainly excreted from urine in its original form.

Clinically, it is mainly used to treat respiratory, urinary, hepatobiliary, typhoid and other diseases such as intestinal surgery, obstetrics and gynecology and ENT infections, especially for mild to moderate infections. The chemical structure is similar to that of chloramphenicol. Its methyl-sulfone group replaces the nitro group of chloramphenicol, which reduces its toxicity. While its antibacterial effect is 2.5-5 times stronger than that of chloramphenicol.

2. Pharmacological effects

Its antibacterial spectrum and antibacterial effect are basically similar to those of chloramphenicol. It mainly diffuses into bacterial cells and reversibly binds to the 50S subunit of the bacterial ribosome, blocking the growth of the peptide chain (may inhibit the effect of transpeptidase), preventing the synthesis of proteins, thereby playing an antibacterial effect.

Its antibacterial activity is inferior to chloramphenicol except for Streptococcus pyogenes, pneumococcus, Bacillus pertussis and Shigella sungii. It has a strong effect on Gram-positive bacteria such as pneumococcus and hemolytic streptococcus; it has a weaker effect on Staphylococcus aureus, Salmonella or Escherichia coli, Pneumoniae bacillus, etc. than chloramphenicol. It also has a certain effect on anaerobic bacteria, spirochetes, rickettsia, amoeba, etc.

Thiamphenicol does not easily penetrate the bacterial cell wall, which makes the antibacterial effect in vitro slightly weaker than chloramphenicol. On the contrary, thiamphenicol does not bind to glucuronic acid in the liver, and the content of free active thiamphenicol in the blood is high, so it has strong antibacterial activity, and the development of bacterial resistance to thiamphenicol is slow. And it has complete cross-resistance with chloramphenicol. Thiamphenicol still has a strong immunosuppressive effect (about 6 times stronger than chloramphenicol), which can inhibit immunoglobulin synthesis and antibody production.

3. Pharmacokinetics

Thiamphenicol is well absorbed after oral or injection administration, and the absorption is rapid and complete. The peak plasma drug concentration is reached within 2 hours after oral administration and within 1 hour after intramuscular injection.

After administration every 6 to 8 hours, it can be quickly and widely distributed in various tissues of the body. Among them, the content in kidney, spleen, liver, and lung is higher, and the content in kidney and liver is about 3 to 4 times that of the same dose of chloramphenicol. It can reach a certain concentration in brain tissue. Due to the presence of enterohepatic circulation, the concentration in bile is also high. It is easy to penetrate the blood-cerebrospinal fluid barrier and enter the cerebrospinal fluid, and can also penetrate into milk and purulent mucus in a small amount.

The plasma half-life is 1.5h, and it is little bound to plasma proteins. Thiamphenicol does not combine with glucuronic acid in the liver, and is excreted from the bile in its original form, and part of it is secreted by the renal tubules. 70% to 90% of the dose is excreted in the urine within 24 hours. Adults take 0.5g orally, and the urine concentration after 12 hours is up to 400μg/ml. Urine excretion is significantly reduced when renal function declines, and there may be a tendency for accumulation in the body.

The uses of Thiamphenicol

The-uses-of-Thiamphenicol
The-uses-of-Thiamphenicol

1. Indications

Thiamphenicol is used for infections of the respiratory system, hepatobiliary system, urinary system and digestive system caused by influenza bacillus, E. coli, and Salmonella that are sensitive to thiamphenicol. It also has a certain effect on typhoid fever, paratyphoid fever and brucellosis; it is also used for gonorrhea and gonococcal urethritis.

Clinically, it is mainly used to treat respiratory system, urinary system, liver and gallbladder, typhoid fever and other symptoms of intestinal surgery, obstetrics and gynecology, and ENT infections, especially for mild to moderate infections.

In a multi-center clinical trial organized by 15 hospitals in Shanghai, a total of 344 patients were enrolled, including 176 patients with respiratory, urinary, biliary, and digestive system infections, 121 bronchial infections, and 47 skin infections. The effective rates were 88%, 86%, and 53%, respectively. Among them, the treatment for pustular psoriasis had the best effect, and the condition was controlled quickly after medication. According to foreign reports, thiamphenicol has been successfully used to treat gonococcal urethritis in Japan and Europe. A single oral dose of 2.5g has the same effect as spectinomycin and cefuroxime.

From 1960 to 1974, France alone had treated more than 6 million cases with thiamphenicol. Among the 15,796 cases announced by the hospital, including gonorrhea, liver and gallbladder, urinary tract, intestinal, respiratory, gynecological and otolaryngology infections, as well as pertussis and salmonella infections, more than 90% achieved "good" curative effects.

It has also been used for pustular psoriasis, 1 to 1.5g per day, administered in divided doses, the course of treatment is 10 days to 4 weeks, 5 cases are treated, 4 cases cured. After the medication, the high fever subsided quickly, the pustules were controlled, the joint pain was significantly reduced, the rashes disappeared or the erythema diminished.

2. Usage and dosage

  • Adults: Oral administration: 1.5~3.0g per day, divided into 3~4 doses. Air-soluble inhalation: 5% to 10% thiamphenicol solution can be used for air-soluble inhalation. Intra-thoracic, abdominal cavity, and bladder administration: 0.5~1g each time.
  • Oral administration for children: 25-50 mg/kg per day in 4 divided doses.
  • For typhoid fever: 3g orally every day for the first to 3 days, 1.5g a day for the 4th to 6th days, and 1g every day thereafter;
  • For gonorrhea: a single dose of 2.5g.
  • Intramuscular injection, intravenous injection: the dose is the same as oral.

3. Thiamphenicol veterinary

Thiamphenicol is a medicine that can be used by humans and animals. It is used for the respiratory tract, urinary tract and intestinal infections caused by sensitive bacteria such as Haemophilus influenzae, Escherichia coli, Salmonella, etc.

Veterinary Thiamphenicol is an alternative product of chloramphenicol. It has strong antibacterial effect by inhibiting the combination of bacterial TRAN and ribosomes. It is a veterinary drug with broad spectrum, low toxicity and no residue and stronger antibacterial activity than chloramphenicol. It is effective in one dose. The blood concentration can be maintained for more than 17 hours, and the effect is strong and lasting.

It is mainly used to treat intestinal and respiratory tract infections caused by Salmonella, E. coli and Pasteurella, such as paratyphoid fever in young animals, pullorum in calves, dysentery in lambs, pullorum, chicken typhoid, salmonella enteritis in dogs and cats, chronic sinusitis, Pneumonia, avian cholera, etc., and brain abscesses in dogs and cats caused by anaerobic bacteria and prostatitis in dogs and cats caused by gram-negative bacteria, and eye infections and endometritis.

As a feed additive, it is effective in preventing intestinal infections of pigs and chickens caused by Salmonella.

Thiamphenicol can also treat red limb disease, larval bacteremia, crustacean ulcer disease, black gills caused by Vibrio, Streptococcus, Pseudomonas, Edwards, and Aeromonas in fish and shrimp, and gill rot disease, filamentous bacterial disease, crab limb rot disease, water mold disease, tremor disease, fish vibriosis, pseudomonas disease, ascites disease, Edwards disease, Chinese crab gill disease, Herpes disease, white eye disease.

Thiamphenicol side effects

Thiamphenicol-side-effects
Thiamphenicol-side-effects

1. Adverse reactions

  • Bone marrow suppression: Reversible bone marrow suppression is the most serious adverse reaction of this drug. This reaction is related to the dosage and course of treatment, and it is common in patients with a blood concentration of more than 25μg/ml. The clinical manifestations are anemia, and may be accompanied by leukopenia and thrombocytopenia.
  • Aplastic anemia: Aplastic anemia is rare after medication. The clinical manifestations include bleeding tendency caused by thrombocytopenia, accompanied by petechiae, ecchymosis, and nose bleeding, as well as signs of infection caused by neutropenia, such as high fever, sore throat, and jaundice.
  • Gray baby syndrome: There are no reports of "gray baby syndrome" caused by the drug in premature infants and newborns. Only cases of transient pale complexion have been reported.
  • Hepatotoxicity: Patients with pre-existing liver disease may cause jaundice, liver fatty infiltration, and even acute severe hepatitis after medication.
  • Allergic reactions: skin rash, solar dermatitis, angioedema, drug fever and other allergic reactions are rare after medication, and the general symptoms are mild, and they can get better after stopping the medication.
  • Nervous system: Peripheral neuritis and optic neuritis can occur after long-term medication, manifested as hearing loss, insomnia, visual hallucinations, delirium and other neurological symptoms, mostly reversible. There are also reports of blindness caused by optic atrophy after long-term medication.
  • Gastrointestinal reactions: Gastrointestinal symptoms such as loss of appetite, nausea, vomiting, upper abdominal discomfort and diarrhea are common after medication, and the incidence is about 10% or less.
  • Double infection: After long-term medication, the normal flora in the body reduce, causing double infection.
  • Others: Some patients with congenital glucose-6-phosphate dehydrogenase deficiency can develop hemolytic anemia after medication; long-term oral administration may inhibit the intestinal flora and hinder the synthesis of vitamin K and induce bleeding tendency.

2. Thiamphenicol toxicity

Thiamphenicol antibacterial spectrum is similar to chloramphenicol, but the antibacterial effect is not as good as chloramphenicol. Oral absorption is complete, and the plasma half-life is 1.5h. The usual dose for adults is 1 to 2g/d, divided into 3 to 4 times. The adverse reactions in the application of this drug are less than those of chloramphenicol, mainly gastrointestinal reactions, and less toxic to the hematopoietic system, which can cause peripheral neuritis. There is no report of gray baby syndrome. Patients with renal insufficiency may suffer from total head baldness.

Nausea, vomiting, lack of appetite, glossitis, and stomatitis may occur during oral administration. Patients with existing liver disease may have jaundice, liver fatty infiltration, and even acute severe hepatitis.

3. Matters needing attention

  • Blood routine should be checked regularly during the course of treatment. For long-term treatment, the reticulocyte count should be checked to find adverse effects of the blood system in time.
  • If the white blood cell count tends to decrease, the drug should be stopped immediately.
  • The excretion of thiamphenicol is reduced in patients with renal insufficiency, and there may be an accumulation in the body and should use a reduced amount.
  • The copper sulfate method can cause false positive result when measuring urine sugar.
  • During medication, the surrounding whole blood should be checked regularly; for long-term treatment, the reticulocyte count should be checked; if necessary, bone marrow examination should be performed to detect adverse blood system reactions in time.
  • During pregnancy, especially in late pregnancy or childbirth, women should try to avoid using it. Breastfeeding should be suspended for breastfeeding women.
  • Due to the immature liver enzyme system and poor renal excretion in neonates, the drug is excreted from the kidneys more slowly than adults, so the application of thiamphenicol to neonates can easily lead to excessive blood drug concentration and toxic reactions (gray baby syndrome).

Thiamphenicol prospects

Thiamphenicol hydrochloride glycinate is clinically mainly used for respiratory tract infections, typhoid fever, urinary tract, biliary tract, intestinal infections, and chronic bronchitis and other secondary lung bacterial infections.

Thiamphenicol hydrochloride glycinate can rapidly hydrolyze in the body to release thiamphenicol and exert antibacterial activity. In the treatment of secondary bacterial infections in the lungs such as bronchitis, thiamphenicol glycinate hydrochloride can be administered by inhalation and intra-respiratory injection, and thiamphenicol can be administered orally or intramuscularly or intravenously.

Thiamphenicol hydrochloride glycinate has clinically shown its high curative effect and safety, which can treat infections of various pathogens for clinical selection. The thiamphenicol hydrochloride glycinate for injection is the exclusive domestic one, so the market prospect is very optimistic.

Conclusion

Thiamphenicol is a broad-spectrum antibiotic of chloramphenicol. Compared with chloramphenicol, the toxicity of thiamphenicol is much lower. At the same time, thiamphenicol is complementary to chloramphenicol. Thiamphenicol has a good effect on urinary system, intestinal and respiratory tract infections.

BALLYA provides a thiamphenicol test to tell you if there are thiamphenicol residues in dairy products you eat every day.

References

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