Nitrofurantoin vs Trimethoprim for UTI treatment

Nitrofurantoin vs Trimethoprim for UTI treatment

Nitrofurantoin and Trimethoprim are two common antibiotics used for the treatment of urinary tract infections (UTIs). Nitrofurantoin vs Trimethoprim compares and contrasts key facts about both antibiotics in relation to UTI treatment.

What is UTI?

UTI stands for urinary tract infection, which is an infection that occurs in any part of the urinary system, including the kidneys, bladder, ureters, and urethra. UTIs are a common type of bacterial infection that can affect both men and women, but they are more common in women.

UTIs typically occur when bacteria from the digestive tract, such as Escherichia coli (E. coli), enter the urinary tract through the urethra and begin to multiply in the bladder.

UTIs are typically diagnosed through a urine culture, which involves testing a sample of urine for the presence of bacteria. Treatment for UTIs usually involves antibiotics, such as nitrofurantoin or trimethoprim, which can help to kill the bacteria causing the infection.

A urine sample is recommended in women with suspected UTI who (NICE, 2023):
• Are pregnant — a repeat sample following treatment should be sent to confirm bacterial culture.
• Are older than 65 years.
• Have persistent symptoms or if treatment fails.
• Have recurrent UTI.
• Are catheterized or who have recently been catheterised.
• Have risk factors for resistant or complicated UTIs.
• Have visible or non-visible haematuria (blood in the urine).

Drinking plenty of water and urinating frequently can also help to flush out the bacteria and relieve symptoms.

Symptoms of UTI

Symptoms of UTIs can include:
• pain or a burning sensation during urination,
• frequent or urgent need to urinate,
• cloudy or strong-smelling urine,
• and pain or pressure in the lower abdomen or back.

What is nitrofurantoin?

Nitrofurantoin is an antibiotic medication that is commonly used to treat urinary tract infections (UTIs). It works by killing or slowing the growth of bacteria that cause infections. Nitrofurantoin is not effective against all types of bacteria, and it is not used to treat infections outside of the urinary tract.
Nitrofurantoin is typically taken orally in the form of capsules or tablets or rarely as liquid (for children), and it is usually prescribed for a course of three to seven days. The dosage and duration of treatment will depend on the severity of the infection and other factors, such as the patient’s age and medical history.

What is trimethoprim?

Trimethoprim is an antibiotic medication that is used to treat a variety of bacterial infections, including urinary tract infections, respiratory infections, and ear infections. It works by blocking the production of folic acid in bacteria, which is essential for their growth and reproduction.

Trimethoprim is typically taken orally in the form of tablets or capsules or in form of liquid (children).

Nitrofurantoin vs trimethoprim: what is the mechanism of action?

Nitrofurantoin works by inhibiting bacterial cell wall synthesis (production) and disrupting bacterial metabolism. Specifically, it interferes with the bacterial enzymes that are involved in the production of DNA, RNA, and proteins, which are essential for bacterial growth and survival. Nitrofurantoin is active against a wide range of gram-positive and gram-negative bacteria, including Escherichia coli (E. coli), Staphylococcus aureus, and Streptococcus pyogenes, which are commonly associated with urinary tract infections.

Trimethoprim works by inhibiting the bacterial enzyme dihydrofolate reductase (DHFR), which is involved in the production of folic acid. Folic acid is essential for the synthesis of DNA, RNA, and proteins, which are necessary for bacterial growth and reproduction. By blocking the production of folic acid, trimethoprim disrupts bacterial metabolism and inhibits bacterial growth.

Trimethoprim has a selective action against bacterial dihydrofolate reductase, meaning that it does not affect human dihydrofolate reductase. This makes it effective against a wide range of gram-positive and gram-negative bacteria, including Escherichia coli (E. coli), Klebsiella pneumoniae, and Staphylococcus aureus, which are commonly associated with urinary tract infections, respiratory infections, and skin infections.

Nitrofurantoin vs trimethoprim: common side effects

BNF and other resources list a variety of side effects, most of which are classified with unknown frequency. Please refer to the product information leaflet for more information.

Nitrofurantoin: possible side effects

People taking nitrofurantoin may experience the following side effects:
• Nausea and vomiting
• Loss of appetite
• Diarrhea
• Abdominal pain
• Headache
• Dizziness
• Skin rash or itching
• Darkening of urine colour
• Shortness of breath
• Fatigue
It is important to note that not everyone who takes nitrofurantoin will experience side effects and that some people may experience different side effects than those listed above. Additionally, some side effects may be more serious and require immediate medical attention, such as severe allergic reactions, chest pain, or difficulty breathing.

Trimethoprim: possible side effects

Common side effects of trimethoprim may include (emc, 2019):
• Nausea and vomiting
• Diarrhoea
• Headache
• Skin rashes, urticaria (itching)
• Hyperkalaemia (A higher than normal level of potassium)

Which antibiotic is better nitrofurantoin or trimethoprim?

The above question is wrongly formulated. In the past, trimethoprim was recommended as the first-line treatment of UTIs. In 2014 national guidelines for the management of UTIs changed, with nitrofurantoin becoming a first-line treatment for UTIs. This recommendation was based on the increasing bacterial resistance to trimethoprim. Resistance to nitrofurantoin is also possible and happening, which can make the treatment unsuccessful.

Antibiotic resistance is the ability of bacteria to resist the effects of antibiotics. Antibiotic resistance occurs when bacteria evolve mechanisms to counteract or avoid the effects of antibiotics, making these drugs less effective or completely ineffective.

Does antibiotic resistance matter?

Antibiotic resistance is a major public health concern, as it can lead to longer and more severe infections, increased healthcare costs, and higher mortality rates. Preventing antibiotic resistance requires:
• responsible use of antibiotics, including avoiding their unnecessary use
• following prescribed dosages, and
• completing the full course of treatment.

Nitrofurantoin vs trimethoprim: recommended dosage

A NICE guide on the management of urinary tract infection in women recommends the use of antibiotics according to urine culture test results (if available), otherwise, the first choice is based on antimicrobial resistance patterns. Usually, the first choice for the treatment is (NICE, 2023):
• Nitrofurantoin 100mg modified-release capsules (Macrobid) twice a day for 3 days or
• Trimethoprim 200mg twice a day for 3 days (if the low risk of resistance)
For the second choice with no improvement in symptoms (fail to improve within 48 hours of starting antibiotics):
• Nitrofurantoin 100mg modified-release twice a day for 3 days
• Pivmecillinam (penicillin) 400mg initial dose, then 200mg three times a day for a total of 3 days or
• Fosfomycin 3g single dose sachet.

Which antibiotic is recommended in pregnancy?

Trimethoprim should be avoided in pregnancy due to teratogenic risk, especially in the first trimester. Trimethoprim can cause birth defects or abnormalities in a developing foetus.
A first choice antibiotic for UTI treatment in pregnancy is nitrofurantoin (NICE, 2023):
• Nitrofurantoin (avoid at term) 100mg modified-release twice a day for 7 days


Nitrofurantoin and trimethoprim are both antibiotics used to treat urinary tract infections (UTIs), but they have some differences in their effectiveness and potential side effects. The choice of which antibiotic to use will depend on various factors, including the type of infection, the individual patient’s medical history and health status, and any other medications they may be taking.

In general, both nitrofurantoin and trimethoprim are effective in treating uncomplicated UTIs, although some studies suggest that nitrofurantoin may have slightly better efficacy in treating lower UTIs. Nitrofurantoin is also recommended as a first-line treatment for UTIs during pregnancy, as it has a low risk of teratogenic effects on the developing fetus.

However, both nitrofurantoin and trimethoprim have some potential side effects that should be considered. Nitrofurantoin may cause gastrointestinal upset, headaches, and lung reactions in rare cases. Trimethoprim may cause allergic reactions, anaemia, and a rare but potentially serious skin condition called Stevens-Johnson syndrome.

Ultimately, the choice of antibiotic will depend on the specific circumstances of the patient and local antibiotic prescribing guidelines. In some cases, nitrofurantoin may be preferred over trimethoprim, while in other cases the opposite may be true.

Emc (2019). SmPC: Trimethoprim 50 mg/5 ml Suspension. Available at: Accessed on 06/03/2023
NICE (2023). Urinary tract infection (lower) – women. Available at: Accessed on 07/03/2023
NICE (2023). Scenario: UTI — (no visible haematuria, not pregnant or catheterized). Available at: Accessed on 07/03/2023.
NICE (2023). Scenario: Suspected urinary tract infection without visible haematuria during pregnancy. Available at: Accessed on 07/03/2023.


I am a qualified pharmacist working in an independent pharmacy in the UK.
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