What are the first-line medications for treating urinary tract infections (UTIs)?

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Last updated: June 18, 2025View editorial policy

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From the Guidelines

The first-line medications for treating uncomplicated urinary tract infections (UTIs) are typically oral antibiotics, with nitrofurantoin, trimethoprim-sulfamethoxazole, and fosfomycin being the preferred options, as recommended by the most recent guidelines 1. When considering treatment options, it's essential to take into account the patient's medical history, allergies, and local resistance patterns.

  • Nitrofurantoin (Macrobid) 100mg twice daily for 5 days is often recommended as first-line therapy due to its effectiveness against common UTI pathogens and low resistance rates.
  • Trimethoprim-sulfamethoxazole (Bactrim, Septra) DS tablet twice daily for 3 days is another first-line option, though it should be avoided if local resistance rates exceed 20% 1.
  • Fosfomycin (Monurol) as a single 3-gram dose is convenient and effective, and can be used as an alternative to the above options. For patients who cannot take these medications, fluoroquinolones like ciprofloxacin 250mg twice daily for 3 days may be used, though they're generally reserved as second-line due to resistance concerns and side effects 1. The choice of antibiotic should consider patient allergies, pregnancy status, kidney function, and local resistance patterns. Patients should complete the full course of antibiotics even if symptoms improve, drink plenty of fluids, and seek medical attention if symptoms worsen or don't improve within 48 hours. These medications work by either preventing bacterial cell wall formation, inhibiting bacterial DNA synthesis, or interfering with bacterial metabolism, thereby eliminating the infection-causing bacteria from the urinary tract. It's worth noting that the American College of Physicians recommends short-course antibiotics for uncomplicated UTIs, with the goal of minimizing antibiotic resistance and side effects 1.

From the FDA Drug Label

Levofloxacin tablets are indicated for the treatment of uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus. Levofloxacin tablets are indicated for the treatment of complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis The first-line medications for treating urinary tract infections (UTIs) include levofloxacin for:

  • Uncomplicated UTIs: due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus.
  • Complicated UTIs: due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis 2

From the Research

First-Line Medications for Urinary Tract Infections (UTIs)

The first-line medications for treating urinary tract infections (UTIs) include:

  • Nitrofurantoin: a 5-day course 3, 4, 5, 6, 7
  • Fosfomycin tromethamine: a 3-g single dose 3, 4, 7
  • Pivmecillinam: a 5-day course 3

Second-Line Options

Second-line options for UTIs include:

  • Oral cephalosporins such as cephalexin or cefixime 3
  • Fluoroquinolones 3
  • β-lactams, such as amoxicillin-clavulanate 3

Treatment Options for Specific Types of UTIs

Treatment options for UTIs due to specific types of bacteria include:

  • AmpC- β-lactamase-producing Enterobacteriales: nitrofurantoin, fosfomycin, pivmecillinam, fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems 3
  • ESBLs-E coli: nitrofurantoin, fosfomycin, pivmecillinam, amoxicillin-clavulanate, finafloxacin, and sitafloxacin 3
  • ESBLs-Klebsiella pneumoniae: pivmecillinam, fosfomycin, finafloxacin, and sitafloxacin 3
  • Carbapenem-resistant Enterobacteriales (CRE): ceftazidime-avibactam, meropenem/vaborbactam, imipenem/cilastatin-relebactam, colistin, fosfomycin, aztreonam, and cefiderocol 3
  • Multidrug-resistant (MDR)-Pseudomonas spp.: fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, ceftolozane-tazobactam, ceftazidime-avibactam, aminoglycosides, and cefiderocol 3

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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