What is the contraindication (CI) for Bactrim (Trimethoprim/Sulfamethoxazole)?

From the Guidelines

Bactrim (sulfamethoxazole-trimethoprim) should be used with caution and only when the local resistance rates of uropathogens do not exceed 20%, as recommended by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases 1.

Key Considerations

• The use of Bactrim is recommended for the treatment of acute uncomplicated cystitis in women, with a 3-day course of trimethoprim-sulfamethoxazole (160/800 mg twice daily) being an appropriate choice for therapy, given its efficacy as assessed in numerous clinical trials 1.
• However, the threshold of 20% as the resistance prevalence at which the agent is no longer recommended for empirical treatment of acute cystitis is based on expert opinion derived from clinical, in vitro, and mathematical modeling studies 1.
• A more recent study published in 2021 by the American College of Physicians recommends short-course antibiotics with either nitrofurantoin for 5 days, trimethoprim–sulfamethoxazole (TMP–SMZ) for 3 days, or fosfomycin as a single dose for the treatment of uncomplicated bacterial cystitis in women 1.

Important Contraindications and Precautions

• Patients with known hypersensitivity to sulfonamides or trimethoprim should not receive Bactrim due to the risk of severe allergic reactions.
• Bactrim should be avoided in pregnant women at term and in nursing mothers, as it can displace bilirubin from albumin binding sites, potentially causing kernicterus in neonates.
• Patients with megaloblastic anemia due to folate deficiency should not receive Bactrim, as it may worsen folate deficiency.
• Those with severe renal impairment (creatinine clearance <15 mL/min) should avoid Bactrim unless benefits outweigh risks, as drug accumulation can occur.
• Patients with G6PD deficiency are at increased risk for hemolytic anemia with Bactrim use.
• The medication is also contraindicated in infants less than 2 months of age.
• Caution is warranted in patients taking other medications that may interact with Bactrim, such as warfarin, phenytoin, methotrexate, and ACE inhibitors.

Clinical Evidence

• Studies have demonstrated that trimethoprim-sulfamethoxazole remains a highly effective treatment for acute uncomplicated cystitis in women when the rate of resistance is known or expected to be < 20% 1.
• Early clinical and microbiological cure rates are in the 90% - 100% range, with late outcomes being harder to compare across studies but generally in the 80% - 90% range when calculated using intent to treat criteria 1.

From the FDA Drug Label

CONTRAINDICATIONS Sulfamethoxazole and trimethoprim tablets USP is contraindicated in patients with a known hypersensitivity to trimethoprim or sulfonamides, in patients with a history of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides, and in patients with documented megaloblastic anemia due to folate deficiency Sulfamethoxazole and trimethoprim tablets USP is also contraindicated in pregnant patients and nursing mothers, because sulfonamides pass the placenta and are excreted in the milk and may cause kernicterus. Sulfamethoxazole and trimethoprim tablets USP is contraindicated in pediatric patients less than 2 months of age Sulfamethoxazole and trimethoprim tablets USP is also contraindicated in patients with marked hepatic damage or with severe renal insufficiency when renal function status cannot be monitored. Contraindications Sulfamethoxazole and trimethoprim is contraindicated in the following situations: known hypersensitivity to trimethoprim or sulfonamides history of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides documented megaloblastic anemia due to folate deficiency pediatric patients less than 2 months of age marked hepatic damage severe renal insufficiency when renal function status cannot be monitored concomitant administration with dofetilide (see PRECAUTIONS).

The contraindications for Bactrim (sulfamethoxazole and trimethoprim) include:

• Known hypersensitivity to trimethoprim or sulfonamides
• History of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides
• Documented megaloblastic anemia due to folate deficiency
• Pediatric patients less than 2 months of age
• Marked hepatic damage
• Severe renal insufficiency when renal function status cannot be monitored
• Concomitant administration with dofetilide
• Pregnant patients and nursing mothers 2, 3

From the Research

Bactrim CI (Trimethoprim-Sulfamethoxazole) Information

• Bactrim CI, also known as trimethoprim-sulfamethoxazole, is an antibiotic used to treat various bacterial infections, including urinary tract infections (UTIs) 4, 5, 6, 7, 8.
• The drug has been shown to be effective in treating UTIs in patients with severe renal disease, with all patients achieving bacteriologic cure in one study 4.
• However, trimethoprim-sulfamethoxazole has also been associated with an increased risk of acute kidney injury (AKI) in some patients, particularly those with pre-existing renal impairment or other risk factors such as hypertension and diabetes mellitus 5.
• Resistance to trimethoprim-sulfamethoxazole is a growing concern, with studies showing high resistance rates among certain bacterial isolates, including Escherichia coli 6, 8.
• The use of trimethoprim-sulfamethoxazole for Pneumocystis pneumonia prophylaxis in renal transplant recipients has been associated with a lower risk of UTIs compared to pentamidine 7.
• Patient-specific risk factors, such as prior urinary infection or colonization with trimethoprim-sulfamethoxazole-resistant Enterobacteriaceae and recent use of the drug, can predict the likelihood of trimethoprim-sulfamethoxazole resistance in community-onset UTIs 8.

Key Findings

• Trimethoprim-sulfamethoxazole is effective in treating UTIs, but may be associated with an increased risk of AKI in certain patients 4, 5.
• Resistance to trimethoprim-sulfamethoxazole is a significant concern, particularly among Escherichia coli isolates 6, 8.
• Patient-specific risk factors can predict the likelihood of trimethoprim-sulfamethoxazole resistance in community-onset UTIs 8.
• The use of trimethoprim-sulfamethoxazole for Pneumocystis pneumonia prophylaxis may be associated with a lower risk of UTIs in renal transplant recipients 7.