What is the role of ertapenem in treating urinary tract infections (UTIs)?

Ertapenem for UTI

Ertapenem is an effective and FDA-approved carbapenem for treating complicated urinary tract infections (cUTIs) including pyelonephritis, with particular utility in ESBL-producing Enterobacterales infections, administered as 1g IV once daily for adults. 1

FDA-Approved Indications

Ertapenem is specifically indicated for treating complicated UTIs including pyelonephritis in adults and pediatric patients (≥3 months) caused by susceptible organisms, particularly E. coli (including bacteremic cases) and Klebsiella pneumoniae. 1

• Adult dosing: 1g IV once daily 1
• Pediatric dosing (3 months-12 years): 15 mg/kg twice daily (maximum 1g/day) 1
• Adolescents (≥13 years): 1g once daily 1
• Treatment duration: Typically 10-14 days, with option to switch to oral therapy after ≥3 days of parenteral treatment once clinical improvement demonstrated 1

Role in Multidrug-Resistant Infections

ESBL-Producing Enterobacterales

For bloodstream infections (BSI) due to 3rd-generation cephalosporin-resistant Enterobacterales (3GCephRE) without septic shock, ertapenem may be used instead of imipenem or meropenem. 2

• ESCMID guidelines provide a conditional recommendation for ertapenem in BSI due to 3GCephRE without septic shock (moderate certainty of evidence) 2
• For severe infections with septic shock, broader-spectrum carbapenems (imipenem/meropenem) are recommended over ertapenem 2
• One observational study comparing oral fosfomycin to ertapenem for stepdown therapy in ESBL-producing Enterobacterales cUTI showed no significant difference, though the study had high risk of bias 2

Carbapenem-Resistant Enterobacterales (CRE)

For CRE-associated cUTIs, ertapenem is not the preferred agent. Newer beta-lactam/beta-lactamase inhibitor combinations are recommended: 2

• First-line options: Ceftazidime-avibactam, meropenem-vaborbactam, or imipenem-cilastatin-relebactam (weak recommendations, low-to-very-low quality evidence) 2
• Ertapenem lacks activity against CRE and should not be used for these infections

Clinical Efficacy Data

Comparative Effectiveness

Ertapenem demonstrates equivalent efficacy to ceftriaxone for complicated UTIs: 3, 4, 5

• Combined analysis (850 patients): 89.5% favorable microbiological response with ertapenem vs 91.1% with ceftriaxone (equivalent outcomes) 3
• Single trial (592 patients): 91.8% success with ertapenem vs 93.0% with ceftriaxone 4
• Korean trial (271 patients): 87.9% success with ertapenem vs 88.7% with ceftriaxone 5
• Most patients (95-96%) switched to oral therapy after median 4 days of parenteral treatment 3, 4

Microbiological Activity

Ertapenem demonstrates excellent in vitro activity against antibiotic-resistant uropathogens: 6

• 100% susceptibility against 482 tested Enterobacteriaceae strains, including ESBL-producers and AmpC-producers 6
• MIC₉₀ ranges from 0.03 mg/L (Proteus vulgaris) to 1 mg/L (Enterobacter spp.) 6
• Most active agent tested compared to 12 other antibiotics 6
• Minimal MIC increase for ESBL-producers (MIC₅₀ 0.015 mg/L for non-ESBL vs 0.03 mg/L for ESBL-producers) 6

Administration Considerations

Route of Administration

• Intravenous: 30-minute infusion, approved for up to 14 days 1
• Intramuscular: Alternative route, approved for up to 7 days 1
• Subcutaneous: Off-label but effective route demonstrated in French study of 25 patients with ESBL-E UTIs, with 100% cure rate and suitability for outpatient parenteral antibiotic therapy (OPAT) 7

Important Contraindications and Warnings

• Do NOT mix with dextrose-containing solutions 1
• Do NOT co-infuse with other medications 1
• Valproic acid interaction: Ertapenem significantly reduces valproic acid levels; alternative anticonvulsants may be needed 1
• Patients should report previous beta-lactam hypersensitivity reactions 1

Antimicrobial Stewardship Context

Ertapenem serves as a carbapenem-sparing option for ESBL infections while preserving broader-spectrum carbapenems (meropenem/imipenem) for more resistant organisms. 2

• Appropriate for low-risk, non-severe 3GCephRE infections 2
• Suitable for stepdown therapy or outpatient parenteral treatment 2, 7
• Lacks activity against Pseudomonas aeruginosa and Acinetobacter species, making it a narrower-spectrum carbapenem choice 2
• New beta-lactam/beta-lactamase inhibitors should be reserved for extensively resistant bacteria, not routine 3GCephRE infections 2

Clinical Algorithm for Ertapenem Use in UTI

For complicated UTI/pyelonephritis:

1. Identify organism and resistance pattern:

   • Susceptible organisms or ESBL-producers → Ertapenem appropriate 1
   • CRE → Use newer agents (ceftazidime-avibactam, meropenem-vaborbactam) 2

2. Assess severity:

   • Septic shock → Use meropenem/imipenem over ertapenem 2
   • No septic shock → Ertapenem acceptable 2

3. Duration strategy:

   • Start ertapenem 1g IV daily 1
   • After ≥3 days and clinical improvement, switch to oral agent based on susceptibilities 1, 3
   • Total treatment duration: 10-14 days 1

4. Consider outpatient therapy:

   • Ertapenem's once-daily dosing facilitates OPAT 7
   • Subcutaneous administration possible if IV access challenging 7