Imipenem/Cilastatin: Recommended Use and Dosage for Bacterial Infections
Imipenem/cilastatin is recommended for treating severe bacterial infections, particularly for carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa (DTR-PA) at a standard dosage of 500 mg IV every 6 hours or 1000 mg IV every 8 hours, with adjustments based on renal function. 1, 2
Indications and Clinical Uses
Imipenem/cilastatin is indicated for:
Carbapenem-resistant Enterobacterales (CRE) infections:
Difficult-to-treat Pseudomonas aeruginosa (DTR-PA) infections:
- When combined with relebactam (imipenem/cilastatin/relebactam 1.25g IV q6h) 1
Mixed infections in necrotizing skin, fascia, and muscle infections 1
Standard Dosing Regimen
For patients with normal renal function (CrCl ≥90 mL/min):
For susceptible bacterial species:
- 500 mg IV every 6 hours OR
- 1000 mg IV every 8 hours 2
For bacterial species with intermediate susceptibility:
- 1000 mg IV every 6 hours 2
Administration:
- 500 mg doses: Infuse over 20-30 minutes
- 1000 mg doses: Infuse over 40-60 minutes 2
- May slow infusion rate if nausea develops
Dosage Adjustment for Renal Impairment
Renal adjustment is crucial as imipenem is primarily excreted unchanged in urine:
| Creatinine Clearance (mL/min) | Susceptible Pathogens | Intermediate Susceptibility |
|---|---|---|
| ≥90 | 500 mg q6h or 1000 mg q8h | 1000 mg q6h |
| <90 to ≥60 | 400 mg q6h or 500 mg q6h | 750 mg q8h |
| <60 to ≥30 | 300 mg q6h or 500 mg q8h | 500 mg q6h |
| <30 to ≥15 | 200 mg q6h or 500 mg q12h | 500 mg q12h |
| <15 | Not recommended unless hemodialysis is instituted within 48 hours |
Important caution: Patients with CrCl <30 mL/min have increased risk of seizures 2
Treatment Duration
Duration varies by infection type:
- Complicated UTI: 5-7 days
- Complicated intra-abdominal infections: 5-7 days
- Hospital-acquired/ventilator-associated pneumonia: 10-14 days
- Bloodstream infections: 10-14 days 1, 3
Duration should be individualized based on:
- Infection site
- Source control
- Underlying comorbidities
- Initial response to therapy 1
Special Considerations
Combination Therapy
- For carbapenem-resistant Acinetobacter baumannii (CRAB):
- Consider combination with colistin 1
- For CRE infections:
- May be combined with polymyxins or tigecycline 1
- For DTR-PA:
- Imipenem/cilastatin/relebactam is preferred 1
Hemodialysis Patients
- Use dosage for CrCl <30 to ≥15 mL/min
- Administer after hemodialysis session
- Monitor carefully, especially those with CNS disease 2
Pediatric Use
- Not recommended for CNS infections due to seizure risk
- Not recommended in patients <30 kg with renal impairment
- Maximum daily dose should not exceed 4 g/day 2
Efficacy and Safety
Imipenem/cilastatin has demonstrated high efficacy in treating severe bacterial infections with response rates of 94-96% in clinical studies 4, 5. Common adverse effects include:
- Phlebitis/thrombophlebitis (most common)
- Mild liver function abnormalities
- Gastrointestinal effects (nausea, diarrhea)
- Skin rash 6, 7
Monitoring
- Monitor renal function regularly
- Watch for signs of CNS effects (seizures), particularly in patients with renal impairment
- Assess clinical response within 5 days to determine if treatment extension is needed 3
Imipenem/cilastatin remains a valuable broad-spectrum antibiotic for severe infections, particularly when dealing with resistant organisms. Its appropriate use with proper dosing adjustments based on renal function is essential to maximize efficacy while minimizing adverse effects.