What is the preferred antibiotic for treating urinary tract infections (UTIs), cephalosporins (e.g. ceftriaxone or cefixime) or nitrofurantoin?

Antibiotic Selection for Urinary Tract Infections

Direct Answer

For uncomplicated lower urinary tract infections (cystitis), nitrofurantoin is the preferred choice over cephalosporins, while cephalosporins (specifically ceftriaxone or cefotaxime) are reserved for upper urinary tract infections like pyelonephritis. 1, 2

Lower Urinary Tract Infections (Uncomplicated Cystitis)

Nitrofurantoin is recommended as a first-choice agent for lower UTIs, alongside amoxicillin-clavulanic acid and sulfamethoxazole-trimethoprim, according to the 2024 WHO Essential Medicines guidelines. 1

Why Nitrofurantoin for Lower UTIs:

• Maintains excellent susceptibility rates of 95-96% against E. coli urinary isolates, with only 2.3% resistance rates, compared to 24% resistance to fluoroquinolones and 29% to trimethoprim-sulfamethoxazole. 3, 4

• Classified as an "Access" antibiotic in the WHO AWaRe framework, meaning it has lower resistance potential and should be prioritized to preserve broader-spectrum agents. 1

• Cephalosporins are NOT recommended for uncomplicated lower UTIs because oral antibiotics with narrower spectrum are preferred to minimize antimicrobial resistance development. 2

Critical Caveat:

Nitrofurantoin is contraindicated in patients with any degree of renal impairment and in the last trimester of pregnancy, and should be avoided in elderly patients for long-term use due to risk of pulmonary reactions and polyneuropathy. 5

Upper Urinary Tract Infections (Pyelonephritis)

Ceftriaxone becomes the appropriate choice for upper UTIs, with its role determined by severity:

Mild-to-Moderate Pyelonephritis:

• Ciprofloxacin is first-choice (if local resistance patterns allow), with ceftriaxone or cefotaxime as second-choice. 1, 2

Severe Pyelonephritis:

• Ceftriaxone or cefotaxime are first-choice agents for severe upper UTIs requiring hospitalization. 1, 2
• Initial IV therapy with ceftriaxone 1g is recommended before transitioning to oral therapy based on culture results. 2

Important Considerations:

• Ceftriaxone is classified as a "Watch" antibiotic, indicating higher resistance potential and should be reserved for more serious infections. 2
• When fluoroquinolone resistance exceeds 10% locally, an initial dose of ceftriaxone is recommended before oral transition. 2
• Always obtain urine culture and susceptibility testing in suspected pyelonephritis to guide definitive therapy. 2

Clinical Algorithm

Step 1: Determine infection location (lower vs. upper UTI)

Step 2: For lower UTI (cystitis):

• Use nitrofurantoin (5-day course) as first-line 1, 4, 6
• Alternative: amoxicillin-clavulanic acid or sulfamethoxazole-trimethoprim 1
• Avoid cephalosporins to preserve broader-spectrum agents 2

Step 3: For upper UTI (pyelonephritis):

• Mild-moderate: Ciprofloxacin first, ceftriaxone second 1
• Severe: Ceftriaxone or cefotaxime first-line 1, 2

Step 4: Check local resistance patterns—if fluoroquinolone resistance >10%, favor ceftriaxone earlier. 2

Resistance Considerations

The WHO Expert Committee removed amoxicillin from recommendations in 2021 after GLASS data showed 75% median resistance rates in E. coli urinary isolates globally. 1 This underscores the importance of checking local antibiograms before empiric selection, particularly for fluoroquinolones which now exceed acceptable resistance thresholds in many regions. 1

For patients with risk factors for ESBL-producing organisms, ceftriaxone may be preferred over fluoroquinolones even for moderate pyelonephritis. 2, 6