A 72-year-old woman from Mumbai is admitted with sepsis secondary to a hospital-acquired pneumonia. She was hospitalized 2 weeks ago for hip fracture surgery and received multiple courses of broad-spectrum antibiotics including ceftazidime and piperacillin-tazobactam. Sputum culture grows a gram-negative rod identified as Klebsiella pneumoniae. Antibiotic susceptibility testing reveals resistance to ceftazidime, cefepime, imipenem, and meropenem, but susceptibility to colistin and tigecycline. The organism produces a positive result on the Hodge test. Which of the following mechanisms best explains this resistance pattern?

Explanation

## Carbapenem Resistance and the Hodge Test **Key Point:** A positive Hodge test indicates carbapenemase production. The Hodge test detects the ability of the organism to hydrolyze a carbapenem (typically imipenem), which is characteristic of carbapenem-resistant Enterobacteriaceae (CRE). ## Clinical Presentation of CRE This patient presents with the hallmark resistance pattern of a carbapenemase-producing organism: - **Resistant to:** 3rd-generation cephalosporins, 4th-generation cephalosporins, AND carbapenems (imipenem, meropenem) - **Susceptible to:** Polymyxins (colistin), tigecycline, sometimes aminoglycosides - **Confirmatory test:** Positive Hodge test (indicates carbapenemase activity) ## Carbapenemase Mechanisms ```mermaid flowchart TD A[Carbapenem-resistant Enterobacteriaceae]:::outcome --> B[Carbapenemase production]:::action B --> C[Serine carbapenemases]:::action C --> D[KPC, OXA variants]:::outcome B --> E[Metallo-beta-lactamases]:::action E --> F[NDM, IMP, VIM]:::outcome A --> G[Porin loss]:::action G --> H[Reduced outer membrane permeability]:::outcome B --> I[Hydrolysis of carbapenems]:::action I --> J[Resistance to imipenem, meropenem]:::outcome ``` **High-Yield:** Carbapenemases are fundamentally different from ESBLs. While ESBLs are inhibited by beta-lactamase inhibitors and cannot hydrolyze carbapenems, carbapenemases actively cleave the carbapenem ring structure. The most common carbapenemases in India are NDM (New Delhi Metallo-beta-lactamase) and KPC variants [cite:Indian Council of Medical Research Guidelines on Antimicrobial Stewardship]. ## Why Colistin and Tigecycline Remain Effective - **Colistin:** Works via membrane disruption, not inhibited by beta-lactamases - **Tigecycline:** A broad-spectrum tetracycline that bypasses beta-lactamase resistance through ribosomal binding **Clinical Pearl:** Hospital-acquired CRE infections carry high mortality. The Hodge test is a rapid, inexpensive bedside method to detect carbapenemase production and guide empiric therapy toward polymyxins or tigecycline.