Can I start ceftriaxone (a cephalosporin antibiotic) instead for a patient with a complicated urinary tract infection (UTI) and possible sepsis or significant comorbidities?

Can You Start Ceftriaxone for Complicated UTI with Sepsis?

Yes, intravenous ceftriaxone (1-2g once daily) is explicitly recommended as first-line empiric therapy for complicated urinary tract infections with systemic symptoms, including sepsis. 1

Guideline-Based Recommendation

The 2024 European Association of Urology guidelines provide a strong recommendation for using an intravenous third-generation cephalosporin (which includes ceftriaxone) as empirical treatment for complicated UTI with systemic symptoms. 1 This positions ceftriaxone alongside combination regimens (amoxicillin plus aminoglycoside, or second-generation cephalosporin plus aminoglycoside) as acceptable first-line options. 1

Ceftriaxone offers several advantages in this clinical scenario:

• Once-daily dosing (1-2g IV/IM every 24 hours) provides convenience and reduces nursing burden, particularly important in septic patients requiring multiple interventions 2, 3, 4
• Broad-spectrum coverage against common uropathogens including E. coli, Proteus spp., and Klebsiella spp. that cause complicated UTIs 2, 3
• Excellent tissue penetration with therapeutic urinary concentrations despite lower urinary excretion rates compared to other β-lactams 5
• No renal dose adjustment required in isolated renal impairment, making it ideal when renal function is unknown or impaired 3, 4

Clinical Evidence Supporting Ceftriaxone

Recent 2025 data specifically addressed concerns about ceftriaxone's lower urinary excretion rate, demonstrating that ceftriaxone achieved identical 30-day mortality (3.8%) compared to other β-lactams in patients with Enterobacterales bacteremia and pyelonephritis, with no reinfections or rehospitalizations. 5 Historical studies from the 1980s-1990s showed 86-91% clinical efficacy rates in complicated UTIs, including catheter-associated infections. 6, 7, 8

Treatment Algorithm

Step 1: Immediate empiric therapy

• Start ceftriaxone 2g IV once daily for severe infection/sepsis 2, 3
• Use 1g IV once daily for less severe complicated UTI 2, 3
• Obtain blood and urine cultures before first dose 1, 3

Step 2: Address complicating factors

• Replace or remove indwelling catheters that have been in place ≥2 weeks 1, 3
• Identify and manage urological obstruction, incomplete voiding, or anatomical abnormalities 1

Step 3: Duration of therapy

• 7 days total if patient becomes afebrile within 48 hours and shows prompt clinical improvement 2, 3
• 14 days total if delayed response, male patient (cannot exclude prostatitis), or persistent fever beyond 48 hours 2, 9, 3

Step 4: Oral step-down therapy (when clinically stable)

• Switch to oral antibiotics once afebrile for 48 hours and hemodynamically stable 3
• Options based on susceptibility: ciprofloxacin 500-750mg twice daily (if local resistance <10%), levofloxacin 750mg daily, or trimethoprim-sulfamethoxazole 160/800mg twice daily 2, 3

When to Choose Alternative Agents

Do NOT use ceftriaxone monotherapy if:

• Multidrug-resistant organisms suspected (prior ESBL, CRE, or recent carbapenem exposure) - use ceftazidime/avibactam, meropenem/vaborbactam, or carbapenem instead 2, 3
• Pseudomonas aeruginosa suspected - add aminoglycoside or use antipseudomonal β-lactam like piperacillin/tazobactam or cefepime 2, 3
• Patient from urology department with recent fluoroquinolone use (higher resistance rates) - consider combination therapy with aminoglycoside 1

Critical Monitoring Parameters

Monitor for ceftriaxone-specific adverse effects:

• Gallbladder pseudolithiasis - appears as sonographic sludge, reversible upon discontinuation 4
• Urolithiasis - ceftriaxone-calcium precipitates may cause ureteral obstruction; ensure adequate hydration 4
• Prothrombin time alterations - monitor in patients with hepatic disease or malnutrition; may require vitamin K supplementation 4
• Pancreatitis - rare, possibly secondary to biliary obstruction 4

Reassess at 72 hours if no clinical improvement (defervescence, hemodynamic stability) - consider culture-directed therapy adjustment or extended urologic evaluation. 3

Common Pitfalls to Avoid

• Failing to obtain pre-treatment cultures - complicated UTIs have broader microbial spectrum and increased resistance; culture guidance is mandatory 1, 3
• Inadequate treatment duration - stopping at 5 days increases recurrence risk, particularly in males where prostatitis cannot be excluded 2, 9
• Not replacing long-term catheters - catheters in place ≥2 weeks should be replaced at treatment initiation to hasten resolution and reduce recurrence 3
• Using ceftriaxone for ESBL or CRE without susceptibility data - these organisms require newer β-lactam/β-lactamase inhibitor combinations or carbapenems 2, 3
• Ignoring local resistance patterns - if local fluoroquinolone resistance exceeds 10%, avoid empiric fluoroquinolone use even for step-down therapy 1, 3