A 72-year-old woman from Delhi with chronic kidney disease (eGFR 28 mL/min/1.73m²) and recurrent urinary tract infections presents with fever, chills, and altered mental status. She was hospitalized 10 days ago for acute kidney injury and received multiple broad-spectrum antibiotics. Blood cultures grow a gram-negative rod identified as Klebsiella pneumoniae. Antibiotic susceptibility testing shows resistance to all β-lactams including carbapenems (imipenem MIC >16 μg/mL), fluoroquinolones, and aminoglycosides. The isolate is negative for ESBL production by double-disk synergy test and cephalosporinase testing. Polymerase chain reaction (PCR) and DNA sequencing confirm the presence of a blaKPC gene. Which of the following best describes the mechanism of carbapenem resistance in this isolate?

Explanation

## Carbapenem-Resistant Enterobacteriaceae (CRE): KPC Mechanism **Key Point:** The blaKPC gene encodes KPC (Klebsiella pneumoniae carbapenemase), a Ambler class A serine carbapenemase that hydrolyzes the β-lactam ring of carbapenems, third-generation cephalosporins, and other β-lactams. Unlike ESBLs, KPC is NOT inhibited by clavulanic acid and is resistant to β-lactamase inhibitors. ## Carbapenemase Classification | Class | Enzyme | Inhibitor | Substrate | Gene Location | Organism | |-------|--------|-----------|-----------|---------------|----------| | **A** | KPC, GES, SME | Clavulanic acid (partial) | Carbapenems, cephalosporins | Plasmid | K. pneumoniae, E. coli | | **B** | VIM, IMP, NDM | EDTA | Carbapenems | Plasmid | P. aeruginosa, Acinetobacter | | **D** | OXA-48, OXA-181 | Clavulanic acid | Carbapenems | Plasmid | K. pneumoniae, E. coli | **High-Yield:** KPC is the most common carbapenemase in Enterobacteriaceae worldwide, particularly in healthcare settings. The blaKPC gene is typically located on plasmids, enabling rapid horizontal transfer between species and strains. ## Clinical Features of KPC-Producing K. pneumoniae 1. **Resistance pattern:** Pan-resistant (resistant to all β-lactams, fluoroquinolones, aminoglycosides) 2. **ESBL test:** Negative (KPC is not an ESBL; it is a carbapenemase) 3. **Cephalosporinase test:** Negative (KPC is not an AmpC enzyme) 4. **Genetic confirmation:** PCR for blaKPC gene is positive 5. **Treatment options:** Colistin, tigecycline, or aminoglycosides (if susceptible); newer agents like ceftazidime-avibactam may be effective ## Mechanism of Carbapenem Hydrolysis ```mermaid flowchart TD A[KPC carbapenemase enzyme]:::outcome --> B[Serine residue in active site]:::action B --> C[Nucleophilic attack on β-lactam carbonyl]:::action C --> D[Acyl-enzyme intermediate forms]:::action D --> E[Hydrolysis of acyl bond]:::action E --> F[Inactive acyl product released]:::outcome F --> G[Bacterial cell resistant to carbapenem]:::urgent ``` **Clinical Pearl:** This patient requires isolation and contact precautions. Empiric therapy should be colistin or tigecycline pending susceptibility testing. Carbapenems are contraindicated despite the patient's presentation with sepsis. **Mnemonic:** **KPC = Kills Penicillins and Carbapenems** — a plasmid-encoded serine protease that hydrolyzes all β-lactams.