What Is the First-Line Antibiotic for UTI?

first-line antibiotic for UTI
First-line antibiotics for UTIs include fosfomycin, nitrofurantoin and trimethoprim

First-line antibiotics for acute, uncomplicated urinary tract infections (UTIs) typically include:

Drug (Brand) Dosage Cost of generic (Cost of brand)
First Fosfomycin (Monurol) 3 grams single dose NA ($51)
Nitrofurantoin macrocrystals (Macrodantin) 100 mg twice daily for 5 days $55 ($64)
Pivmecillinam 400 mg orally 2-3 times daily for 3-7 days NA in the U.S.
Trimethoprim/sulfamethoxazole (Bactrim DS, Septra DS) 160/800 mg twice daily for 3 days $17 ($34)
Second Ciprofloxacin (Cipro) 250 mg twice daily for 3 days $26 ($30)
Ciprofloxacin, extended release (Cipro XR) 500 mg daily for 3 days $57 ($76)
Levofloxacin (Levaquin) 250 mg daily for 3 days NA ($86)

200 mg daily for 3 days or
400 mg single dose

$14 (NA)
$10 (NA)
Third Amoxicillin/clavulanate (Augmentin) 500/125 mg twice daily for 7 days $32 ($98)
Cefdinir (Omnicef) 300 mg twice daily for 10 days $40 ($119)
Cefpodoxime 100 mg twice daily for 7 days $71 (NA)

Since there is a lower chance of antibiotic resistance with nitrofurantoin and fosfomycin as compared to other classes of antibiotics, they are often used as first-line antibiotics for the treatment of UTI.

However, for severe UTI with complications, fosfomycin or nitrofurantoin may not be effective.

How do doctors choose which antibiotics to treat UTI?

Your doctor chooses which antibiotic to use for treating UTI based on the:

  • Effectiveness of the antibiotic on the bacteria causing the infection
  • Severity of the infection
  • Age group of the infected person
  • Potential for antibiotic resistance

What other antibiotics are used to treat UTI?

Other antibiotics used to treat UTI include:

  • Beta-lactams, including penicillins and cephalosporins (amoxicillin, Augmentin, Keflex, Duricef, Ceftin, Lorabid, Rocephin, Cephalexin, Suprax and others). Many organisms have shown resistance to some of these drugs.
  • Trimethoprim-sulfamethoxazole combination antibiotic (Bactrim DS and Septra DS).  Many organisms have shown resistance to some of these drugs.
  • Fluoroquinolones (Cipro, Levaquin and Floxin). The risk of antibiotic resistance to this is developing. These should not be given to pregnant women or children. 
  • Tetracyclines (Sumycin, Vibramycin or Minocin) are used for Mycoplasma or Chlamydia infections. These should not be given to pregnant women or children. 
  • Aminoglycosides (gentamicin, amikacin and tobramycin) are usually used in combination with other antibiotics to treat severe UTIs.
  • Macrolides (clarithromycin, azithromycin and erythromycin) are often used to treat urinary problems caused by sexually transmitted diseases.
  • Fosfomycin (Monurol) is a synthetic phosphonic acid derivative and used for acute cystitis but not for more complicated UTIs.
Severe UTI (high fever, chills, hypotension, etc.)
Agent What to consider
First Ceftriaxone Can be used safely in patients with a mild penicillin allergy (i.e., rash); cross-reactivity is very low
Second Gentamicin Use with caution if there is a concern of kidney toxicity or ear toxicity
Cystitis/lower UTI (complicated or uncomplicated)
Agent What to consider
First Nitrofurantoin Most active agent against E coli
Trimethoprim/sulfamethoxazole Potassium levels need to be monitored if using alongside spironolactone, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs)
Second Cephalexin Active against E coli, Proteus and Klebsiella pneumoniae
Pyelonephritis/upper UTI
Agents What to consider
First Trimethoprim/sulfamethoxazole One dose of intravenous/intramuscular injection ceftriaxone should be administered before starting oral therapy
Second Ciprofloxacin If patients are unable to tolerate trimethoprim/sulfamethoxazole


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Health Solutions From Our Sponsors

Colgan G, Williams M. Diagnosis and Treatment of Acute Uncomplicated Cystitis. Am Fam Physician. Oct 1, 2011;84(7):771-776. https://www.aafp.org/afp/2011/1001/p771.html

Rochester Nursing Home Collaborative. Guidelines for the Diagnosis and Management of Urinary Tract Infections. https://www.rochesterpatientsafety.com/Images_Content/Site1/Files/Pages/UTI_Treatment_Guidelines.pdf