What is the significance of elevated liver function tests in a female patient with a urinary tract infection (UTI) admitted for 3 days and treated with Bactrim (trimethoprim/sulfamethoxazole)?

From the Guidelines

Discontinuing Bactrim immediately and switching to an alternative antibiotic such as nitrofurantoin (Macrobid) 100mg twice daily for 5 days is recommended for a female patient with a urinary tract infection (UTI) who was hospitalized for 3 days due to elevated liver function tests while on Bactrim. This recommendation is based on the guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women, which suggest considering alternate diagnoses and treating accordingly 1. Given the patient's allergy history and tolerance, nitrofurantoin is a suitable alternative, as it has low resistance rates and is effective for treating UTIs 1.

Key Considerations

• The patient's elevated liver function tests while on Bactrim suggest hepatotoxicity, which can be caused by hypersensitivity reactions or direct toxicity 1.
• Nitrofurantoin is a recommended antimicrobial for the treatment of acute uncomplicated cystitis, with a suggested dosage of 100mg twice daily for 5 days 1.
• The choice of antibiotic should be individualized based on patient allergy and compliance history, local practice patterns, local community resistance prevalence, availability, cost, and patient and provider threshold for failure 1.
• A more recent study suggests that nitrofurantoin can be used as a first-line agent for re-treatment of UTIs, as resistance is low and decays quickly 1.

Treatment Approach

• Discontinue Bactrim immediately to prevent further liver injury.
• Initiate nitrofurantoin 100mg twice daily for 5 days, as it is a recommended alternative antibiotic for treating UTIs.
• Monitor liver function tests until normalization.
• Document Bactrim as an allergy or adverse reaction in the patient's medical record to avoid future use.

From the FDA Drug Label

If a patient develops skin rash, fever, leukopenia or any sign of adverse reaction, re-evaluate benefit-risk of continuing therapy or re-challenge with sulfamethoxazole and trimethoprim Laboratory Tests Complete blood counts and clinical chemistry testing should be done frequently in patients receiving sulfamethoxazole and trimethoprim. Discontinue sulfamethoxazole and trimethoprim if a significant electrolyte abnormality, renal insufficiency or reduction in the count of any formed blood element is noted.

The patient was admitted for high liver function test while on Bactrim (sulfamethoxazole and trimethoprim) for a UTI.

• The drug label recommends frequent laboratory tests, including complete blood counts and clinical chemistry testing.
• It also advises to discontinue sulfamethoxazole and trimethoprim if a significant electrolyte abnormality or renal insufficiency is noted.
• Given the patient's high liver function test, it is likely an adverse reaction to the medication.
• The best course of action would be to discontinue Bactrim and re-evaluate the benefit-risk of continuing therapy 2.

From the Research

Bactrim-Induced Hepatotoxicity in UTI Treatment

• Bactrim (sulfamethoxazole/trimethoprim) is a commonly used antimicrobial agent for treating urinary tract infections (UTIs) 3.
• Hepatotoxicity is a recognized but rare adverse reaction to Bactrim, which may lead to liver failure in adults and is even rarer in children 3.
• A case study reported a 43-year-old male patient who developed jaundice and highly elevated liver enzymes one week after taking Bactrim for UTI treatment, and made a good recovery after discontinuing the medication 3.

Drug-Induced Liver Disorders

• The International Consensus Meeting Criteria can be used to screen and diagnose drug-induced liver disorders, as seen in a case report of an 88-year-old man who developed reversible drug-induced liver disorders after taking trimethoprim/sulfamethoxazole for a UTI 4.
• The criteria can help establish the diagnosis and causality assessment of drug-induced liver injuries, and can also be used to show that a patient has had separate liver injuries 4.

Prediction of Trimethoprim/Sulfamethoxazole Resistance

• A study aimed to predict trimethoprim/sulfamethoxazole (SXT) resistance in patients with community-onset UTIs due to Enterobacteriaceae based on patient-specific risk factors 5.
• The study found that prior urinary infection/colonization with SXT-resistant Enterobacteriaceae and SXT use within the past 12 months were predictors of SXT resistance among urinary isolates 5.

Evaluation of Elevated Liver Enzymes

• A study compared extensive testing and focused testing strategies for evaluating patients with elevated liver enzymes, and found that extensive testing required the lowest monetary cost and yielded diagnoses for 54% of patients 6.
• However, focused testing generated fewer false-positives and more biopsies, and became the most cost-effective strategy when accounting for pre-test probabilities and prior evaluations performed 6.

Biological Significance of Cytochrome Methylation

• A study investigated the biological significance of cytochrome methylation and found that methylation did not have a stabilizing effect on the tridimensional structure of ferricytochrome c 7.
• The study suggested that other possible physiological roles of methylation should be considered, taking into account the relative instability of ascomycetes' cytochromes compared to mammalian ones 7.