Carbapenem-resistant Enterobacterales (CRE) are gram-negative bacilli of the order Enterobacterales (most clinically Klebsiella pneumoniae, Escherichia coli, Enterobacter species) that have developed resistance to carbapenem antibiotics (meropenem, imipenem, ertapenem, doripenem)—the traditional last-line β-lactams for serious gram-negative infections. CDC designates CRE as one of the 'urgent threats' in its 2019 Antibiotic Resistance Threats Report; WHO classifies them as 'critical priority' pathogens for new antibiotic development. Resistance mechanisms include carbapenemase enzymes (most clinically important): Klebsiella pneumoniae carbapenemase (KPC, Ambler class A, common in US and Europe), New Delhi metallo-β-lactamase (NDM, class B/MBL, common in India/Pakistan), oxacillinase-48 (OXA-48, class D, common in Mediterranean), Verona integron-encoded metallo-β-lactamase (VIM), and imipenemase (IMP); non-carbapenemase mechanisms include AmpC or ESBL combined with porin mutations (OmpK35/36 loss).
Epidemiology: CRE causes bloodstream, urinary tract, intraabdominal, respiratory, and surgical site infections, primarily in hospitalized and long-term care residents, immunocompromised patients (cancer, transplant), with prior antibiotic exposure (especially carbapenems, fluoroquinolones, third-generation cephalosporins), invasive devices (central lines, ventilators, urinary catheters), and recent travel to endemic regions. Mortality rates 40-50% for bacteremia and 30-40% overall, double or triple that of carbapenem-susceptible infections.
Treatment principles: rapid identification (PCR/Carba-NP/lateral flow immunoassays for carbapenemase type) and susceptibility testing guide therapy. Novel β-lactam/β-lactamase inhibitor combinations: ceftazidime-avibactam (active against KPC, OXA-48; not NDM/VIM/IMP unless combined with aztreonam), meropenem-vaborbactam (KPC; not OXA-48/MBL), imipenem-relebactam (KPC; not OXA-48/MBL); cefiderocol (siderophore cephalosporin active against most carbapenemases including MBLs); plazomicin (aminoglycoside resistant to most ribosomal modifying enzymes); aztreonam-avibactam (under development, MBL coverage); polymyxins (colistin, polymyxin B—high toxicity, last resort); fosfomycin (synergy partner); tigecycline (synergy partner; not for bacteremia or UTI). Combination therapy is common for severe infections. Source control (drain abscess, remove infected device) is essential. Prevention: active surveillance cultures of high-risk patients, contact precautions, hand hygiene, environmental cleaning, antimicrobial stewardship, and judicious carbapenem use.