What carbapenem (carbapenam) is recommended for treating severe infections, such as complicated intra-abdominal infections or hospital-acquired pneumonia, in patients with or without impaired renal function?

Choosing the Appropriate Carbapenem for Different Infections

Carbapenems should be used selectively based on infection type, severity, and patient factors, with meropenem being the preferred option for severe infections requiring broad coverage, while ertapenem is appropriate for community-acquired infections without Pseudomonas risk. 1

General Principles for Carbapenem Selection

• Carbapenems should not be used as empirical treatment for community-acquired bacterial infections unless specific risk factors are present 1
• Carbapenems offer a wide spectrum of antimicrobial activity against gram-positive, gram-negative, and anaerobic pathogens 1
• They are classified into two main groups:
  • Group 1: Ertapenem - active against ESBL-producing pathogens but not active against Pseudomonas aeruginosa or Enterococcus species 1
  • Group 2: Imipenem/cilastatin, meropenem, and doripenem - active against non-fermentative gram-negative bacilli including Pseudomonas 1

Indications for Carbapenem Use

Carbapenems should be considered in patients with:

• Known history of colonization/infection by ESBL-producing Enterobacteriaceae or ceftazidime-resistant P. aeruginosa within the last 3 months, plus severe sepsis or septic shock 1
• Hospital-acquired severe bacterial infections with at least two of the following:
  • Previous treatment with third-generation cephalosporin, fluoroquinolones, or piperacillin-tazobactam in the last 3 months
  • Carriage of ESBL-producing Enterobacteriaceae or ceftazidime-resistant P. aeruginosa within the last 3 months
  • Hospitalization during the last 12 months
  • Patient from nursing facility with indwelling catheter/gastrostomy tube
  • Ongoing epidemic of multidrug-resistant bacteria in the healthcare institution 1

Specific Carbapenem Selection Guide

Meropenem

• Best for: Severe infections including complicated intra-abdominal infections, nosocomial pneumonia, and infections with suspected Pseudomonas aeruginosa 2
• Dosage: 1 gram every 8 hours by intravenous infusion over 15-30 minutes for intra-abdominal infections 2
• Advantages:
  • Better CNS tolerability than imipenem (suitable for bacterial meningitis) 3
  • Slightly greater activity against gram-negative bacilli than imipenem 4
  • Can be administered as IV bolus or infusion 3
• Renal adjustment: Required for CrCl ≤50 mL/min 2

Ertapenem

• Best for: Community-acquired infections, outpatient IV therapy, once-daily dosing 5
• Advantages:
  • Once-daily dosing (4-hour half-life) 5
  • Good for ESBL-producing Enterobacteriaceae 1
• Limitations: Lacks activity against Pseudomonas aeruginosa and Enterococcus species 1, 5
• Best use case: Mild to moderately severe intra-abdominal infections without risk of Pseudomonas 1

Imipenem/Cilastatin

• Best for: Severe infections with mixed bacterial pathogens 4
• Advantages: Slightly greater activity against gram-positive cocci compared to meropenem 4
• Limitations: Higher risk of seizures compared to other carbapenems, requires co-administration with cilastatin 5
• Renal adjustment: Required for decreased renal function 5

Doripenem

• Best for: Serious infections with suspected Pseudomonas aeruginosa 6
• Advantages:
  • Better in vitro activity against P. aeruginosa compared to other carbapenems 6
  • Combines desirable activities of both imipenem and meropenem 6
  • May reduce hospital length of stay and duration of mechanical ventilation for ICU patients 6

Special Considerations

Renal Impairment

• For meropenem with CrCl 26-50 mL/min: Use recommended dose every 12 hours
• For meropenem with CrCl 10-25 mL/min: Use half recommended dose every 12 hours
• For meropenem with CrCl <10 mL/min: Use half recommended dose every 24 hours 2

Multidrug-Resistant Infections

• For carbapenem-resistant infections, consider newer combinations:
  • Ceftazidime-avibactam for KPC and OXA-48 producers 1
  • Meropenem-vaborbactam for KPC-producing Enterobacteriaceae 1
  • Imipenem-cilastatin-relebactam for certain carbapenem-resistant infections 1
• High-dose extended-infusion meropenem (6g/day, 3-hour infusion) may be effective against some carbapenem-resistant Enterobacteriaceae with MICs ≤16 mg/L 1

Practical Algorithm for Carbapenem Selection

1. For community-acquired infections:

   • First choice: Non-carbapenem options (e.g., amoxicillin-clavulanate, ceftriaxone+metronidazole) 1
   • If ESBL risk factors present: Consider ertapenem 1

2. For hospital-acquired/severe infections:

   • Without Pseudomonas risk: Ertapenem 1, 5
   • With Pseudomonas risk: Meropenem, imipenem, or doripenem 1
   • For critically ill with suspected MDR: Meropenem (preferred) or doripenem 1, 6

3. For specific infections:

   • Complicated intra-abdominal infections: Meropenem 1g every 8 hours 2, 7
   • Bacterial meningitis: Meropenem (safer CNS profile than imipenem) 3
   • Febrile neutropenia: Meropenem or doripenem 3, 6

4. After culture results:

   • De-escalate to narrower spectrum antibiotics when possible 1
   • For carbapenem-resistant organisms: Consider newer combination therapies 1

Remember that carbapenems should be used judiciously to preserve their effectiveness and minimize the development of resistance 1.