Co-trimoxazole

 
2.9 (3)
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More about Co-trimoxazole

What is/are Co-trimoxazole?

Trimethoprim/sulfamethoxazole or co-trimoxazole (abbreviated SXT, TMP-SMX, TMP-SMZ or TMP-sulfa) is a sulfonamide antibiotic combination of trimethoprim and sulfamethoxazole, in the ratio of 1 to 5, used in the treatment of a variety of bacterial infections.

The name co-trimoxazole is the British Approved Name and has been marketed worldwide under many trade names including Septra (GSK), Bactrim (Roche), and generic preparations. Opinions differ as to whether co-trimoxazole is a bactericidal or a bacteriostatic agent.

Medical uses

Co-trimoxazole was claimed to be more effective than either of its components individually in treating bacterial infections, although this was later disputed. Along with its associated greater incidence of adverse effects including allergic responses (see below), its widespread use has been restricted in many countries to very specific circumstances where its improved efficacy is demonstrated. It may be effective in a variety of upper and lower respiratory tract infections, renal and urinary tract infections, gastrointestinal tract infections, skin and wound infections, septicaemias, and other infections caused by sensitive organisms. The global problem of advancing antimicrobial resistance has led to a renewed interest in the use of co-trimoxazole more recently.

The British Commission on Human Medicines of the Medicines and Healthcare products Regulatory Agency (MHRA) recommends it can be used to treat or prevent these conditions caused by susceptible organisms:

  •     Lung infections, including pneumonia, caused by Pneumocystis jiroveci (previously known as Pneumocystis carinii)
  •     Infections caused by Toxoplasma (toxoplasmosis) organisms.

It can be used to treat:

  •     Bladder or urinary tract infections;
  •     Lung infections, such as bronchitis;
  •     Ear infections, such as otitis media;
  •     Nocardiosis, an infection that can affect the lungs, skin and brain; and
  •     Skin and soft tissue infections.

The following infections have been treated with co-trimoxazole

Viral infections

Co-trimoxazole does not have any activity against viruses such as HIV, but it is often prescribed to immunocompromised patients as Pneumocystis jirovecii pneumonia prophylaxis.

Bacterial infections

  •     Infections caused by Listeria monocytogenes, Nocardia spp., Stenotrophomonas maltophilia (Xanthomonas maltophilia)
  •     Staphylococcus saprophyticus infections presenting as urinary tract infection or cystitis
  •     Staphylococcus aureus, including some methicillin-resistant strains.
  •     Susceptible strains of Escherichia coli
  •     Shigellosis
  •     Whipple's disease
  •     Traveler's diarrhea
  •     Acne vulgaris

 

Protozoal infections

  •     Isosporiasis
  •     Prophylaxis of cerebral toxoplasmosis in HIV patients
  •     Cyclospora cayetanensis

 

Fungal infections

    Treatment and prophylaxis of pneumonia caused by the yeast-like fungus Pneumocystis jirovecii (formerly identified as P. carinii and commonly seen in immunocompromised patients including those suffering from cancer or HIV/AIDS).

Adverse effects

There has been some concern about Trimethoprim/sulfamethoxazole's use, however, since it has been associated with frequent mild allergic reactions and serious adverse effects, including Stevens–Johnson syndrome, myelosuppression, mydriasis, agranulocytosis, and severe liver damage (cholestatic hepatosis, hepatitis, necrosis, and fulminant liver failure). Due to displacement of bilirubin from albumin, there is an increased risk of kernicterus in the fetus during the last six weeks of pregnancy. Also, renal impairment up to acute renal failure and anuria have been reported. These side effects are seen especially in the elderly and may be fatal. However, TMP-SMX may elevate creatinine without causing renal damage. This elevation occurs through the inhibition of the tubular secretion of creatinine by the trimethoprim component. Folic acid and folinic acid were found equally effective in reducing the adverse effects of TMP-SMX, so unless new evidence is found for folinic acid that shows it is more effective than the cheaper folic acid, the latter will continue to be the preferred treatment method.

Trimethoprim/sulfamethoxazole may have the following adverse reactions:

  •     Allergic – Stevens–Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angiodema, drug fever, chills, Henoch–Schönlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria and rash. In addition, periarteritis nodosa and systemic lupus erythematosis have been reported.
  •     Endocrine – The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides), and oral hypoglycemic agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides.
  •     Gastrointestinal – Hepatitis, including cholestatic jaundice and hepatic necrosis, elevation of serum transaminase and bilirubin, pseudo-membranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhea, constipation, anorexia.
  •     Genitourinary – Renal failure, interstitial nephritis, BUN and serum creatinine elevation NOT associated with renal damage, toxic nephrosis with oliguria and anuria, and crystalluria.
  •     Hematologic – Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrominemia, methemoglobinemia, eosinophilia.
  •     Metabolic – Hyperkalemia, hyponatremia.
  •     Musculoskeletal – Arthralgia and myalgia.
  •     Neurologic – Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, permanent tinnitus, headache.
  •     Psychiatric – Hallucinations, depression, apathy, nervousness.
  •     Respiratory System – Cough, shortness of breath, and pulmonary infiltrates.
  •     Miscellaneous – Weakness, fatigue, insomnia.

Mechanism of action

The synergy between trimethoprim and sulfamethoxazole was first described in a series of in vitro and in vivo experiments published in the late 1960s. Trimethoprim and sulfamethoxazole have a greater effect when given together than when given separately; the reason is because they inhibit successive steps in the folate synthesis pathway.

It is unclear whether this synergy occurs at doses used in humans, because, at the concentrations seen in blood and tissues, the ratio of trimethoprim to sulfamethoxazole is 1:20, which is less than the 1:5 ratio needed in vitro for synergy to occur.

Sulfamethoxazole acts as a false-substrate inhibitor of dihydropteroate synthetase. Sulfonamides such as sulfamethoxazole are analogues of p-aminobenzoic acid (PABA) and, thus, are competitive inhibitors of the enzyme, inhibiting the production of dihydropteroic acid.

Trimethoprim acts by interfering with the action of bacterial dihydrofolate reductase, inhibiting synthesis of tetrahydrofolic acid.

Folic acid is an essential precursor in the de novo synthesis of the DNA/RNA nucleosides thymidine and uridine. Bacteria are unable to take up folic acid from the environment (i.e., the infection host) and, thus, are dependent on their own de novo synthesis – inhibition of the enzyme starves the bacteria of two bases necessary for DNA replication and transcription.

This article uses material from the Wikipedia article Co-trimoxazole, which is released under the Creative Commons Attribution-Share-Alike License 3.0.

Reviews for Co-trimoxazole

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3 reviews

Overall rating
 
2.9
Overall satisfaction
 
2.8(3)
Efficacy
 
3.5(3)
Lack of side effects
 
2.3(3)
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Overall rating
 
1.8
Overall satisfaction
 
2.0
Efficacy
 
2.0
Lack of side effects
 
1.5
Side affects are difficult

I had an upset stomach, chills and sweats at night, constipation, and slight headache. Also felt wired with it. If it worked it was worth it but the side affects are difficult.

Relevant Brand Name and Medical Condition

Brand Name
Bactrim ds
Medical Condition
Urinary Tract Infection

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0-1 months
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Overall rating
 
5.0
Overall satisfaction
 
5.0
Efficacy
 
5.0
Lack of side effects
 
5.0
Relieved all my problems

The doctor said I actually had a kidney infection; I felt faint, weak, and nauseated. The medicine and some bed rest relieved all of these problems and caused me no discomfort/adverse side effects.

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Brand Name
Bactrim ds
Medical Condition
Urinary Tract Infection

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0-1 months
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Overall rating
 
1.8
Overall satisfaction
 
1.5
Efficacy
 
3.5
Lack of side effects
 
0.5
Bactrim's Side Effects Too Much For Me

I was prescribed Bactrim for a Urinary Tract Infection. It worked for my bladder infection, but I had a painful side effect: open sores developed in my mouth.

The second time I was prescribed this same "sulfa antibiotic" was for a sinus infection that moved to my inner ear. This time I believe the Bactrim could probably have resolved my infection, but I had an even worse reaction to the medication. As well as multiple mouth ulcers, there was also swelling in my face after taking the med.
I was advised to avoid "Sulfa Drugs" because it appeared I was having worse reactions each time I took one. Thankfully, I am able to take penicillin and other antibiotics without severe reactions like I did with Bactrim.

For people able to take this medicine without severe side effects, I've seen it work well for infections and it seems to be a good med for them. Just be sure to tell your doctor without delay if you begin to have problems with side effects from it.

Hope this helps.

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Brand Name
Bactrim
Medical Condition
Urinary Tract Infection

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1 month - 6 months
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