What is the Difference Between Nitrofurantoin and Trimethoprim

The key difference between Nitrofurantoin and Trimethoprim is that Nitrofurantoin elicits a bactericidal effect by interfering with bacterial DNA, RNA, and protein synthesis, while Trimethoprim elicits a bactericidal activity by inhibiting the dihydrofolate synthesis to disrupt folate synthesis.

Nitrofurantoin and Trimethoprim are the nitrofuran class of antibiotics commonly used to treat urinary tract infections (UTIs). They primarily work by disrupting bacterial DNA. Nitrofurantoin is a broad-spectrum antibiotic, while Trimethoprim is a narrow-spectrum antibiotic that causes UTIs. Nitrofurantoin and Trimethoprim are often used together to treat UTIs since they work in different ways and can be more effective than drugs alone. Nitrofurantoin and Trimethoprim can cause side effects, such as nausea, vomiting, and diarrhea. More serious side effects, such as liver damage and bone marrow suppression, are rare. Ultimately, the choice of antibiotic will depend on the specific bacteria causing the UTI, the patient’s medical history, and any other medications that the patient is taking.

CONTENTS

1. Overview and Key Difference
2. What is Nitrofurantoin 
3. What is Trimethoprim
4. Similarities – Nitrofurantoin and Trimethoprim
5. Nitrofurantoin vs. Trimethoprim in Tabular Form
6. Summary – Nitrofurantoin vs. Trimethoprim

What is Nitrofurantoin?

Nitrofurantoin is an antibiotic used as a first-line therapy to treat uncomplicated urinary tract infections. It is effective against most gram-positive and gram-negative bacterial strains. Several studies have found that due to the low serum concentration, Nitrofurantoin primarily cures lower urinary tract infections without harming bowel microbiota. Bacterial nitroreductases convert Nitrofurantoin into electrophilic intermediates that hinder the citric acid cycle and the production of DNA, RNA, and protein. This leads to bacterial death by disrupting their essential processes. Since Nitrofurantoin targets multiple sites in bacteria, the drug is more resistant to the development of bacterial resistance. The FDA approval for Nitrofurantoin was obtained in 1953.

Oral administration of Nitrofurantoin results in 80% bioavailability in healthy adults and is mainly distributed through the body by binding with plasma proteins. Studies have demonstrated that foods positively influence absorption. After metabolism in the liver, most of the metabolized and unmetabolized drugs are eliminated in the urine with an elimination half-life of 0.7 hours. Major over-dose symptoms include vomiting, while excessive Nitrofurantoin is removed by dialysis in extreme cases. Brand names of Nitrofurantoin include Furadantin, Macrobid, and Macrodantin.

What is Trimethoprim?

Trimethoprim is another antibiotic used to treat urinary tract infections. It is also used against respiratory tract and gastrointestinal tract infections. Trimethoprim is an antifolate that inhibits bacterial dihydrofolate reductase (DHFR), preventing bacterial nucleic acid and protein synthesis and thereby bacterial survival. Trimethoprim is structurally and chemically related to Pyrimethamine while often combined with Sulfamethoxazole due to complementary and synergistic mechanisms. Furthermore, it is available as an ophthalmic solution combined with Polymyxin B for treating diseases such as conjunctivitis caused by susceptible bacteria. Trimethoprim displays a higher affinity towards the bacterial DHFR than its mammalian counterpart, allowing it to possess selective interference with the bacterial biosynthesis process.

After oral administration, Trimethoprim reaches peak plasma concentrations within 1-4 hours and is extensively distributed in various tissues. It has been estimated that 44% of the absorbed drug remained bound with plasma proteins during the distribution. Approximately 10-20% of ingested Trimethoprim is metabolized in the liver by CYP2C9 and CYP3A4 enzymes. Most of the drug is excreted in the urine, and approximately 80% is included as the parent drug with an elimination half-life of 8-10 hours. Overdose symptoms of Trimethoprim include nausea, vomiting, mental depression, and dizziness. Bactrim, Polytrim, Primsol, Septra, and Sulfatrim are the commonly found brand names of Trimethoprim.

What are the Similarities Between Nitrofurantoin and Trimethoprim?

• Nitrofurantoin and Trimethoprim are effective against gram-negative bacteria, such as coli.
• They can be used to treat both acute and chronic UTIs.
• They both have similar side effects, such as nausea, vomiting, and diarrhea.
• Nitrofurantoin and Trimethoprim should be avoided by people who are allergic to them or have kidney or liver problems.

What is the Difference Between Nitrofurantoin and Trimethoprim?

Nitrofurantoin and Trimethoprim are the nitrofuran class of antibiotics commonly used to treat urinary tract infections. Nitrofurantoin exhibits the bactericidal effect by interfering with bacterial DNA, RNA, and protein synthesis. In contrast, Trimethoprim exhibits bactericidal activity by inhibiting the dihydrofolate synthesis to disrupt the folate synthesis. Thus, this is the key difference between Nitrofurantoin and Trimethoprim. Unlike Trimethoprim, Nitrofurantoin is more effective in having a broad spectrum of gram-negative bacteria, such as E. coli. Nitrofurantoin is available as oral capsules and suspensions and is generally considered safe during pregnancy. In contrast, Trimethoprim is available as oral tablets and is not considered safe during pregnancy.

Below is a summary of the difference between Nitrofurantoin and Trimethoprim in tabular form for side-by-side comparison.

Summary – Nitrofurantoin vs. Trimethoprim

Nitrofurantoin and Trimethoprim are antibiotics primarily used to treat UTIs. Nitrofurantoin works by inhibiting bacterial DNA, RNA, and protein synthesis. It is more effective against gram-negative bacteria like E. coli. It has a short half-life of 0.7 hours and is available as oral capsules and suspensions. Nitrofurantoin is pregnancy category B, generally considered safe during pregnancy. In contrast, Trimethoprim disrupts bacterial folate synthesis by inhibiting dihydrofolate synthesis. It has a broader spectrum of activity but is less effective against gram-negative bacteria. Trimethoprim has a longer half-life of 8-10 hours and is available as oral tablets. Its pregnancy category is C, meaning the risks during pregnancy are not fully known. This is the summary of the difference between Nitrofurantoin and Trimethoprim. Ultimately, the choice between these antibiotics depends on the specific infection, the causative bacteria, and individual factors.

Reference:

1. Crellin, Elizabeth, et al. “Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: Cohort study.” BMJ, 2018.
2. Ten Doesschate, T., et al. “The effectiveness of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in relation to renal function.” Clinical Microbiology and Infection, vol. 26, no. 10, 2020, pp. 1355–1360.

Image Courtesy:

1. “Nitrofurantoin” By Vaccinationist – PubChem (Public Domain) via Commons Wikimedia
2. “Trimethoprim” By Fvasconcellos (talk · contribs) – Own work (Public Domain) via Commons Wikimedia