What is the use of Bactrim (Trimethoprim/Sulfamethoxazole) for treating Gram-negative bacteria?

From the Guidelines

Bactrim (trimethoprim-sulfamethoxazole) is a suitable option for treating gram-negative bacterial infections, particularly when the uropathogen is known to be susceptible, as recommended by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases 1.

Key Considerations

• The standard adult dosage is typically one double-strength tablet (160mg trimethoprim/800mg sulfamethoxazole) twice daily for 3-14 days, depending on the infection type.
• For urinary tract infections, a 3-day course is often sufficient, while more complicated infections may require 7-14 days of treatment.
• Bactrim works by inhibiting two consecutive steps in bacterial folate synthesis, with sulfamethoxazole blocking dihydropteroate synthetase and trimethoprim inhibiting dihydrofolate reductase.
• However, Bactrim is not effective against Pseudomonas aeruginosa, and increasing resistance has been observed in some Enterobacteriaceae.

Recent Guidelines

• A 2024 consensus statement published in JAMA Network Open recommends 7 days of treatment for gram-negative bacteremia from a urinary source when source control has been addressed, with no specific class of medications recommended, but emphasizing the importance of optimizing drug choice and doses for the patient and the urinary focus of infection 1.

Important Factors

• Local antimicrobial susceptibility patterns, particularly for Escherichia coli, should be considered in empirical antimicrobial selection for uncomplicated UTIs.
• Predictors of resistance, such as recent use of trimethoprim-sulfamethoxazole or travel outside the United States, can inform empirical antimicrobial choice.
• Patients should be advised to take Bactrim with plenty of fluids to prevent crystalluria and to complete the full prescribed course even if symptoms improve.

From the FDA Drug Label

To reduce the development of drug-resistant bacteria and maintain the effectiveness of sulfamethoxazole and trimethoprim tablets USP and other antibacterial drugs, sulfamethoxazole and trimethoprim tablets USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria Urinary Tract Infections: For the treatment of urinary tract infections due to susceptible strains of the following organisms: Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis and Proteus vulgaris Traveler’s Diarrhea in Adults: For the treatment of traveler's diarrhea due to susceptible strains of enterotoxigenic E. coli.

Bactrim use for gram negative bacteria is supported for the treatment of:

• Urinary tract infections due to Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis, and Proteus vulgaris
• Traveler’s diarrhea due to enterotoxigenic E. coli
• Shigellosis due to Shigella flexneri and Shigella sonnei 2 3

From the Research

Bactrim Use for Gram-Negative Infections

• Bactrim, also known as trimethoprim-sulfamethoxazole, is an antibiotic used to treat various infections, including those caused by gram-negative bacteria 4.
• However, the use of Bactrim for gram-negative infections is limited due to increasing resistance rates 5, 6, 7, 8.
• Studies have shown that the resistance rate for trimethoprim-sulfamethoxazole (TMP/SMX) can be as high as 34% for certain gram-negative bacteria, such as Escherichia coli 7.
• The resistance mechanisms for TMP/SMX are different between Enterobacteriaceae and glucose non-fermenting gram-negative bacilli, with class 1 integron being widely disseminated in uropathogenic gram-negative bacilli 8.

Alternative Treatment Options

• For urinary tract infections (UTIs) caused by gram-negative bacteria, alternative treatment options include nitrofurantoin, fosfomycin, fluoroquinolones, and beta-lactams such as amoxicillin-clavulanate 5, 6.
• For UTIs caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, treatment options include carbapenems, ceftazidime-avibactam, and ceftolozane-tazobactam 5, 6.
• For UTIs caused by carbapenem-resistant Enterobacteriaceae (CRE), treatment options include ceftazidime-avibactam, meropenem/vaborbactam, and colistin 6.

Considerations for Bactrim Use

• The use of Bactrim for gram-negative infections should be guided by local susceptibility patterns and the severity of the infection 5, 6.
• The dosage of Bactrim should be adjusted in patients with decreased renal function, as the drug is primarily excreted in the urine 4.
• The emergence of resistance to Bactrim and other antibiotics highlights the need for prudent use of antimicrobial agents and the establishment of a surveillance system to monitor resistance rates 8.