First-Line Antibiotic for Uncomplicated UTI

Nitrofurantoin 100 mg twice daily for 5 days is the preferred first-line antibiotic for uncomplicated urinary tract infections in adults. 1, 2

Primary Recommendation

Nitrofurantoin 100 mg PO BID for 5 days is recommended by both the Infectious Diseases Society of America (IDSA) and American Urological Association (AUA) as first-line therapy for uncomplicated cystitis 1
This agent offers superior clinical and microbiologic cure rates compared to other first-line options 2
Nitrofurantoin produces minimal "collateral damage" to normal flora and helps preserve broader-spectrum antibiotics like fluoroquinolones 1

Fosfomycin trometamol 3 g single oral dose is a convenient alternative, though it has slightly inferior efficacy compared to nitrofurantoin 1, 2
Pivmecillinam 400 mg TID for 3-5 days is recommended by European guidelines as first-line for uncomplicated lower UTIs 2
Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg BID for 3 days should only be used if local E. coli resistance rates are below 20% 1, 2, 3

Do not use for pyelonephritis or upper UTIs - nitrofurantoin does not achieve adequate tissue concentrations 1, 2
Avoid if creatinine clearance <60 mL/min - consider TMP-SMX or amoxicillin-clavulanate instead 1
Contraindicated in infants under 4 months due to risk of hemolytic anemia 1
Do not use if patient has fever, flank pain, or systemic symptoms suggesting upper tract infection - choose a fluoroquinolone or other agent with good tissue penetration 1, 2

Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved as alternative agents only, not first-line, due to FDA warnings about serious safety issues affecting tendons, muscles, joints, nerves, and the central nervous system, plus significant collateral damage to normal flora 1, 2
β-lactams (amoxicillin-clavulanate, cephalosporins) can be used when first-line agents cannot be used, but generally have inferior efficacy and more adverse effects 1
Amoxicillin or ampicillin alone should not be used empirically due to poor efficacy and high prevalence of resistance 1

Urine culture is not necessary before starting empiric therapy in straightforward uncomplicated UTI 1, 2
Obtain culture if symptoms persist or recur within 2-4 weeks after treatment 1, 2
For recurrent UTIs, obtain urinalysis, culture, and sensitivity with each symptomatic episode prior to initiating treatment 1, 2
Do not treat asymptomatic bacteriuria - it does not improve outcomes and promotes antimicrobial resistance 1, 2

The risk of serious pulmonary toxicity is 0.001% and hepatic toxicity is 0.0003%, which should not deter short-term use 1
Treatment duration should generally not exceed 7 days for acute cystitis 1

Rising resistance rates to TMP-SMX among uropathogens have made nitrofurantoin preferable as first-line, with studies showing lower treatment failure rates 1
Local resistance rates for fluoroquinolones now exceed the recommended threshold of <10% for empiric use in many countries 1
If local E. coli resistance to nitrofurantoin exceeds 10%, consider alternative treatments 1