Treatment of Carbapenem-Resistant Enterobacter cloacae Complex

Introduction to Treatment Options

The American College of Physicians and other medical societies recommend ceftazidime-avibactam 2.5 g IV every 8 hours infused over 3 hours as the first-line treatment for carbapenem-resistant Enterobacter cloacae complex infections, with meropenem-vaborbactam 4 g IV every 8 hours or imipenem-cilastatin-relebactam 1.25 g IV every 6 hours as alternative options 1, 2, 3.

For KPC-Producing Isolates, the Infectious Diseases Society of America recommends ceftazidime-avibactam 2.5 g IV every 8 hours infused over 2-3 hours as the first-line treatment 1, 3, 5.
For OXA-48-Like Producing Isolates, the European Society of Clinical Microbiology and Infectious Diseases recommends ceftazidime-avibactam 2.5 g IV every 8 hours 3.
For Metallo-β-Lactamase Producers, the Infectious Diseases Society of America recommends mandatory combination therapy with ceftazidime-avibactam 2.5 g IV every 8 hours PLUS aztreonam 6, 4.

Monotherapy is generally preferred for most carbapenem-resistant Enterobacter cloacae complex infections, with combination therapy reserved for specific high-risk scenarios, according to the Infectious Diseases Society of America 2, 3, 5.
For severe sepsis or septic shock, the Society of Critical Care Medicine recommends polymyxin-based combinations, which reduce mortality compared to monotherapy (35.7% vs 55.5% mortality) 1.

For bloodstream infections, the Infectious Diseases Society of America recommends treatment for 7-14 days, individualized based on clinical response 7.
For respiratory tract infections, the European Respiratory Society recommends treatment for typically 7 days for uncomplicated cases 6.

The American College of Physicians recommends dose reduction in renal dysfunction for imipenem-cilastatin-relebactam, with adjustments based on CrCl 1, 6, 7, 4.

The Infectious Diseases Society of America recommends avoiding first or second-generation cephalosporins against Enterobacter due to intrinsic resistance 4.
The European Society of Clinical Microbiology and Infectious Diseases recommends avoiding third-generation cephalosporins due to high likelihood of resistance development during therapy, particularly for E. cloacae 4.
The Infectious Diseases Society of America recommends avoiding ceftazidime-avibactam monotherapy for MBL-producers as avibactam lacks activity against Class B enzymes 3, 5, 6, 4.

For pneumonia, the Infectious Diseases Society of America recommends meropenem-vaborbactam may be preferred due to better lung penetration 4.
For urinary tract infections, the European Society of Clinical Microbiology and Infectious Diseases recommends single-dose aminoglycosides can be considered as alternative for complicated UTI 3, 5.
For bloodstream infections, the Society of Critical Care Medicine recommends avoiding tigecycline monotherapy; use newer β-lactam/β-lactamase inhibitors or combination therapy 1, 5, 4.