What are the guidelines for treating bacteria that require carbapenem (carbapenem) treatment, such as meropenem, imipenem/cilastatin, or doripenem?

Treatment Guidelines for Bacteria Requiring Carbapenem Treatment

For bacteria that require carbapenem treatment, the recommended approach should be based on the specific carbapenem-resistant organism, with newer β-lactam/β-lactamase inhibitor combinations as first-line options for KPC-producing organisms and combination therapy for other resistant pathogens. 1

Identifying Carbapenem-Requiring Organisms

Bacteria that typically require carbapenem treatment include:

• Carbapenem-resistant Enterobacterales (CRE)
• Carbapenem-resistant Acinetobacter baumannii (CRAB)
• Carbapenem-resistant Pseudomonas aeruginosa (CRPA)
• Difficult-to-treat resistant P. aeruginosa (DTR-PA)
• Extended-spectrum β-lactamase (ESBL) producing organisms

Treatment Recommendations by Organism Type

1. KPC-producing Carbapenem-resistant Enterobacterales (CRE)

First-line options:

• Ceftazidime-avibactam 2.5g IV q8h 1
• Meropenem-vaborbactam 4g IV q8h 1

Alternative options:

• Imipenem-cilastatin-relebactam 1.25g IV q6h 1
• Cefiderocol (for selected cases) 1

2. Metallo-β-lactamase (MBL) producing CRE (NDM, VIM, IMP)

• Polymyxin-based combination therapy 1
• Selection of companion drugs should be based on susceptibility testing 1
• Consider aztreonam plus avibactam for MBL producers 1

3. Carbapenem-resistant Acinetobacter baumannii (CRAB)

For pneumonia:

• Colistin (5 mg CBA/kg IV loading dose, then 2.5 mg CBA IV q12h) with or without carbapenem 1
• Adjunctive inhaled colistin (1.25-15 MIU/day in 2-3 divided doses) 1

For bloodstream infections:

• Colistin-carbapenem combination therapy 1
• Alternative: colistin plus tigecycline or sulbactam 1

4. Difficult-to-treat Pseudomonas aeruginosa (DTR-PA)

• Ceftolozane-tazobactam or ceftazidime-avibactam as first-line options 1
• Imipenem-cilastatin-relebactam or cefiderocol as alternatives 1

Site-Specific Treatment Recommendations

Bloodstream Infections

• For CRE: Ceftazidime-avibactam 2.5g IV q8h infused over 3h 1
• For CRAB: Colistin-carbapenem combination therapy 1
• Duration: 7-14 days 1

Complicated Urinary Tract Infections

• Ceftazidime-avibactam 2.5g IV q8h 1
• Meropenem-vaborbactam 4g IV q8h or imipenem-cilastatin-relebactam 1.25g IV q6h 1
• Plazomicin 15 mg/kg IV q12h (alternative) 1
• Single-dose aminoglycoside for simple cystitis due to CRE 1
• Duration: 5-7 days 1

Complicated Intra-abdominal Infections

• Ceftazidime-avibactam 2.5g IV q8h plus metronidazole 500mg IV q6h 1
• Tigecycline 100mg IV loading dose, then 50mg IV q12h 1
• Eravacycline 1mg/kg IV q12h 1
• Duration: 5-7 days 1

Important Clinical Considerations

1. Infectious disease consultation is strongly recommended for managing infections caused by multidrug-resistant organisms 1

2. Prolonged infusion of β-lactams is recommended for pathogens with high minimum inhibitory concentration (MIC) 1

3. Rapid testing for carbapenemase type is crucial to guide appropriate therapy early 1

4. Combination therapy should be considered for:

   • Severe infections with CRE (particularly non-KPC producers)
   • CRAB infections
   • Critically ill patients with high risk of mortality 1

5. Carbapenem MIC matters: Patients infected with Enterobacteriaceae with carbapenem MICs of 2-8 mg/L have significantly higher mortality rates than those with MICs ≤1 mg/L, supporting lower susceptibility breakpoints 2

Common Pitfalls to Avoid

1. Avoid tigecycline monotherapy for CRAB pneumonia (strong recommendation) 1

2. Don't delay appropriate therapy - time to active antibiotic therapy influences outcomes in critically ill patients 1

3. Don't use routine combination therapy for DTR-PA unless specifically indicated 1

4. Avoid underdosing carbapenems - use high-dose extended infusion when needed 1

5. Don't forget susceptibility testing - treatment should be guided by antimicrobial susceptibility results 1

By following these evidence-based guidelines and considering the specific carbapenemase mechanism and infection site, clinicians can optimize treatment outcomes for patients with infections requiring carbapenem therapy.