What is the recommended use and dosage of ertapenem for patients with severe or complicated infections, particularly those with impaired renal function or at risk of Clostridioides difficile infection?

Ertapenem: Clinical Use and Dosing Guidelines

Standard Dosing and Administration

Ertapenem is administered as 1 gram intravenously once daily for adults and pediatric patients ≥13 years of age, with a maximum treatment duration of 14 days for intravenous administration. 1

• For pediatric patients 3 months to 12 years of age, the dose is 15 mg/kg twice daily, not to exceed 1 gram per day 1
• Intravenous infusion should be administered over 30 minutes 1
• Do not mix or co-infuse with other medications, and do not use diluents containing dextrose 1

Specific Indications and Treatment Duration

Complicated Intra-Abdominal Infections

Ertapenem 1 gram once daily is specifically recommended for patients with inadequate/delayed source control or those at high risk of infection with community-acquired ESBL-producing Enterobacterales. 2

• Treatment duration: 5-14 days for adults 1
• For immunocompetent, non-critically ill patients with adequate source control: 4 days of therapy 2
• For immunocompromised or critically ill patients: extend therapy up to 7 days based on clinical condition and inflammatory markers 2
• Ertapenem is appropriate for non-critically ill patients with community-acquired infections 3

Complicated Skin and Soft Tissue Infections

• Treatment duration: 7-14 days, with adult patients receiving up to 28 days in diabetic foot infections 1
• Ertapenem has not been studied in diabetic foot infections with concomitant osteomyelitis 1

Community-Acquired Pneumonia

• Treatment duration: 10-14 days, with possible switch to oral therapy after at least 3 days of parenteral therapy once clinical improvement is demonstrated 1
• For patients at risk of gram-negative enteric bacteria, particularly ESBL-producing strains without risk of Pseudomonas aeruginosa, ertapenem may be used 3

Complicated Urinary Tract Infections

• Treatment duration: 10-14 days 1
• For cUTI in patients without septic shock, ertapenem is a first-line option 3

Acute Pelvic Infections

• Treatment duration: 3-10 days 1

Surgical Prophylaxis

• Single 1 gram intravenous dose given 1 hour prior to surgical incision for elective colorectal surgery 1

Dosing in Renal Impairment

For patients with creatinine clearance >30 mL/min/1.73 m², no dosage adjustment is necessary. 1

• For severe renal impairment (CrCl ≤30 mL/min/1.73 m²) and end-stage renal disease (CrCl ≤10 mL/min/1.73 m²): reduce dose to 500 mg daily 1
• If ertapenem is administered within 6 hours prior to hemodialysis, give a supplementary dose of 150 mg following the hemodialysis session 1
• If administered at least 6 hours prior to hemodialysis, no supplementary dose is needed 1
• No data available for pediatric patients with renal impairment or on hemodialysis 1

Critical Limitations and When NOT to Use Ertapenem

Ertapenem lacks activity against Pseudomonas aeruginosa, Acinetobacter species, methicillin-resistant staphylococci, and enterococci. 4

When to Choose Alternative Carbapenems

For patients in septic shock, consider alternative carbapenems with more frequent dosing rather than ertapenem: 2

• Meropenem 1 gram every 6 hours by extended infusion or continuous infusion 2
• Doripenem 500 mg every 8 hours by extended infusion or continuous infusion 2
• Imipenem/cilastatin 500 mg every 6 hours by extended infusion 2

Healthcare-Associated and Nosocomial Infections

For critically ill patients with healthcare-associated intra-abdominal infections requiring coverage against P. aeruginosa, Enterobacter spp., or MRSA, use broader-spectrum carbapenems (meropenem, imipenem-cilastatin, doripenem) rather than ertapenem. 3

• Ertapenem is appropriate only for non-critically ill patients with healthcare-associated infections when ESBL-producing organisms are suspected but Pseudomonas is not a concern 3

Microbiological Activity

Ertapenem demonstrates potent activity against Enterobacteriaceae (including ESBL-producers), Streptococcus pneumoniae, methicillin-susceptible Staphylococcus aureus, and most anaerobic bacteria. 4, 5

• MIC₉₀ values for most Enterobacteriaceae species were <1 mg/L, significantly lower than imipenem 4
• All tested isolates of Enterobacteriaceae (n=1088), S. pyogenes, S. agalactiae, MSSA, H. influenzae, and M. catarrhalis were susceptible to ertapenem 5
• MIC₉₀ for most Bacteroides fragilis group isolates ranged from 1-4 mg/L 4
• Ertapenem was equivalent to or better than piperacillin-tazobactam against most anaerobic species 4

Clinical Efficacy Data

Ertapenem demonstrated equivalent efficacy to piperacillin-tazobactam and ceftriaxone in multiple randomized controlled trials. 6, 7

• Combined microbiological and clinical response rates: 84-87% for complicated intra-abdominal infections 7
• Clinical response rate: 82% for complicated skin and soft tissue infections 7
• Microbiological cure rates: 86-92% for complicated urinary tract infections 7
• Clinical cure rate: 92% for community-acquired pneumonia 7
• For infections caused by Enterobacteriaceae specifically, cure rates were 84.8% with ertapenem versus 82.9% with piperacillin-tazobactam 8

Important Safety Considerations

Carbapenems, including ertapenem, are particularly unstable after reconstitution and should not be stored for extended periods. 2

• Complete infusion within 6 hours of reconstitution for intravenous administration 1
• For intramuscular administration, use reconstituted solution within 1 hour 1

Risk of Clostridioides difficile Infection

While not specifically addressed in the provided evidence for ertapenem, all broad-spectrum antibiotics including carbapenems carry risk of C. difficile infection. 3 The once-daily dosing and shorter treatment durations possible with ertapenem (4 days for non-critically ill patients with adequate source control) may theoretically reduce this risk compared to longer courses. 2

Limit treatment duration to the minimum necessary based on clinical response and source control adequacy to minimize risk of secondary infections including C. difficile. 2, 1