What is the treatment for Klebsiella pneumoniae with KPC resistance?

Treatment for Klebsiella pneumoniae with KPC Resistance

For Klebsiella pneumoniae with KPC resistance, ceftazidime/avibactam or meropenem/vaborbactam should be used as first-line treatment options. 1, 2

First-Line Treatment Options

• Ceftazidime/avibactam or meropenem/vaborbactam are strongly recommended as first-line treatments for KPC-producing K. pneumoniae infections (STRONG recommendation, MODERATE certainty of evidence) 1, 2
• These novel β-lactam/β-lactamase inhibitor combinations have demonstrated superior clinical outcomes compared to older treatment regimens 2
• In the TANGO II study, meropenem/vaborbactam monotherapy showed higher clinical cure rates, decreased mortality, and reduced nephrotoxicity compared to best available therapy 1

Alternative Treatment Options

• Imipenem/relebactam and cefiderocol may be considered as alternatives for KPC-producing K. pneumoniae (CONDITIONAL recommendation, LOW certainty of evidence) 1, 2
• For infections involving metallo-β-lactamase (MBL) producing strains, ceftazidime/avibactam plus aztreonam is preferred 3
• Fosfomycin-containing combination therapy may be considered, particularly in combination with tigecycline, polymyxin, or carbapenems 1

Site-Specific Considerations

• For respiratory infections (pneumonia), meropenem/vaborbactam may be preferred due to better epithelial lining fluid concentrations (intrapulmonary penetration ratios of 63% for meropenem and 65% for vaborbactam) 1, 2
• For central nervous system infections, consider agents with adequate CNS penetration 2

Special Populations

• For critically ill patients, therapeutic drug monitoring (TDM) should be considered, especially when using polymyxins or aminoglycosides 1
• In patients with renal dysfunction, dose adjustments are necessary for most antimicrobial agents 1

Monitoring and Follow-up

• Daily clinical assessment for treatment response is essential 2
• Follow-up blood cultures should be obtained to document clearance of bacteremia 2
• Monitor for emergence of resistance, particularly with ceftazidime/avibactam (resistance rates range from 0% to 12.8%) 1

Important Considerations and Pitfalls

• Rapid molecular testing should be used to identify specific carbapenemase types to guide appropriate therapy 2, 3
• KPC-producing organisms are often misidentified by routine susceptibility testing and may be incorrectly reported as sensitive to carbapenems 4
• Resistance to ertapenem is common and may be a better indicator of KPC production 4
• KPC variants (e.g., mutations in the blaKPC-3 gene, D179Y variants) can confer resistance to ceftazidime/avibactam; in such cases, meropenem/vaborbactam may be a therapeutic option 1
• The emergence of strains resistant to all available agents (including newer β-lactam/β-lactamase inhibitor combinations) is concerning and requires careful antimicrobial stewardship 5

Duration of Therapy

• For uncomplicated bacteremia, a minimum of 7-14 days of appropriate therapy is recommended 2
• For complicated bacteremia with metastatic foci, longer courses (14-21 days) are typically required 2
• In immunocompromised patients, therapy should continue at least until immune recovery 2