A blood culture isolate of Klebsiella pneumoniae from an ICU patient shows resistance to all carbapenems (MIC meropenem >8 µg/mL). Carbapenemase testing by modified carbapenem inactivation method (mCIM) is positive. The EDTA-modified CIM (eCIM) is POSITIVE (synergy with EDTA). What class of carbapenemase is most likely present, and what is the therapeutic implication?
- A Class B metallo-beta-lactamase (MBL, e.g., NDM, VIM, IMP); EDTA inhibits zinc-dependent MBLs; treat with aztreonam-avibactam or ceftazidime-avibactam plus aztreonam ✓
- B Class A serine carbapenemase (KPC); treat with ceftazidime-avibactam or meropenem-vaborbactam
- C Class D OXA-48-like carbapenemase; eCIM positivity confirms OXA-48; treat with temocillin
- D Class C AmpC beta-lactamase hyperproducer; eCIM positivity indicates AmpC; treat with cefepime
Explanation
The eCIM (EDTA-modified CIM) is positive when EDTA — a metal chelator that inhibits zinc-dependent enzymes — restores carbapenem activity, indicating a Class B metallo-beta-lactamase (MBL). Examples include NDM (New Delhi metallo-beta-lactamase), VIM, and IMP. MBLs hydrolyse all beta-lactams INCLUDING carbapenems but are NOT inhibited by standard serine-beta-lactamase inhibitors (avibactam, vaborbactam). However, they do NOT hydrolyse aztreonam (a monobactam). Therefore, aztreonam-avibactam (avibactam protects aztreonam from co-expressed serine-beta-lactamases) or ceftazidime-avibactam plus aztreonam are the key therapeutic options. Class A (KPC) is not inhibited by EDTA — eCIM negative in KPC. Class D OXA-48 is also eCIM negative.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.