What is the best oral antibiotic for Escherichia coli (E. coli) infections?

From the Guidelines

For the treatment of E. coli infections, particularly in cases of uncomplicated cystitis, nitrofurantoin for 5 days is recommended as the best oral antibiotic option, as suggested by the American College of Physicians in 2021 1. This recommendation is based on the most recent and highest quality evidence available, which prioritizes the use of nitrofurantoin due to its efficacy and lower propensity for adverse effects compared to other options like fluoroquinolones. The choice of antibiotic should always consider the site of infection, local antibiotic resistance patterns, and patient-specific factors.

• Key considerations in the management of E. coli infections include:
  • The infection site: Different infections (e.g., cystitis vs. pyelonephritis) may require different treatment durations and antibiotic choices.
  • Antibiotic resistance patterns: Local resistance rates, especially for E. coli, should guide empirical antibiotic selection, as resistance patterns can vary significantly by region and over time 1.
  • Patient factors: Including previous antibiotic use, travel history, and the presence of any underlying health conditions that could affect treatment choice or duration.
• Alternatives to nitrofurantoin may include trimethoprim-sulfamethoxazole (TMP-SMX) for 3 days or fosfomycin as a single dose for uncomplicated cystitis, and fluoroquinolones or TMP-SMX for longer durations in the case of pyelonephritis, depending on susceptibility patterns and patient factors 1.
• It is crucial to complete the full course of antibiotics as prescribed, even if symptoms improve quickly, to ensure the infection is fully cleared and to minimize the development of antibiotic resistance.
• Given the increasing concern of antibiotic resistance in E. coli, treatment should ideally be guided by susceptibility testing when available, and patients should be advised to stay well-hydrated during treatment and to report any worsening symptoms or lack of improvement after 48-72 hours.

From the FDA Drug Label

Fosfomycin tromethamine granules for oral solution is indicated only for the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis. Fosfomycin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section: Aerobic gram-negative microorganisms Escherichia coli

The best oral antibiotic for E. coli is fosfomycin (PO), as it is specifically indicated for the treatment of uncomplicated urinary tract infections due to susceptible strains of Escherichia coli 2 2.

• Key points:
  • Fosfomycin is bactericidal in urine at therapeutic doses.
  • It has in vitro activity against a broad range of gram-positive and gram-negative aerobic microorganisms.
  • There is generally no cross-resistance between fosfomycin and other classes of antibacterial agents.

From the Research

Oral Antibiotic Options for E. coli

• The recommended first-line empiric antibiotic therapy for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females includes a 5-day course of nitrofurantoin, a 3-g single dose of fosfomycin tromethamine, or a 5-day course of pivmecillinam 3.
• Second-line options include oral cephalosporins such as cephalexin or cefixime, fluoroquinolones, and β-lactams, such as amoxicillin-clavulanate 3.
• Treatment oral options for UTIs due to ESBLs-E coli include nitrofurantoin, fosfomycin, pivmecillinam, amoxicillin-clavulanate, finafloxacin, and sitafloxacin 3.

Resistance Rates

• High rates of resistance for trimethoprim-sulfamethoxazole and ciprofloxacin preclude their use as empiric treatment of UTIs in several communities, particularly if patients who were recently exposed to them or in patients who are at risk of infections with extended-spectrum β-lactamases (ESBLs)-producing Enterobacteriales 3.
• The E. coli species detected in one study were least resistant to fosfomycin (2.4%) 4.
• Resistance rates to ampicillin (63%), trimethoprim-sulfamethoxazole (44%), ciprofloxacin (31%), and cefazolin (30%) were detected in another study, while no or low resistance against amikacin (0%), fosfomycin (0%), and nitrofurantoin (2.7%) was detected 5.

Predictors of Resistance

• Having a prior UTI caused by a trimethoprim-sulfamethoxazole resistant gram-negative organism and being born outside the U.S increased the odds of trimethoprim-sulfamethoxazole resistance 5.
• Having a complicated UTI, prior fluoroquinolone use, and a prior UTI with ciprofloxacin resistance increased the odds of having a ciprofloxacin resistance 5.
• Recurrent UTI, genitourinary abnormalities, and trimethoprim-sulfamethoxazole use within 90 days were identified as predictors of trimethoprim-sulfamethoxazole resistance in another study 6.