Carbapenemase

Carbapenemase

Carbapenemase is a type of beta-lactamase enzyme that confers resistance to carbapenem antibiotics, which are often used as a last resort for treating severe bacterial infections. These enzymes are produced by certain bacteria, rendering them resistant to a broad spectrum of beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems.

Mechanism of Action

Carbapenemases hydrolyze the beta-lactam ring of carbapenem antibiotics, thereby inactivating the drug and preventing it from exerting its antibacterial effect. This enzymatic activity is a significant concern in the treatment of infections caused by Gram-negative bacteria, such as Escherichia coli and Klebsiella pneumoniae.

Types of Carbapenemases

Carbapenemases are classified into different classes based on their molecular structure and mechanism of action:

• Class A carbapenemases, such as KPC (Klebsiella pneumoniae carbapenemase), are serine beta-lactamases that use a serine residue in their active site to hydrolyze the beta-lactam ring.
• Class B carbapenemases, also known as metallo-beta-lactamases (MBLs), require zinc ions for their activity. Examples include NDM-1 (New Delhi metallo-beta-lactamase) and VIM (Verona integron-encoded metallo-beta-lactamase).
• Class D carbapenemases, such as OXA-48-like enzymes, are oxacillinases that also use a serine residue for hydrolysis but have a different structure compared to Class A enzymes.

Clinical Significance

The emergence and spread of carbapenemase-producing organisms pose a significant challenge to public health due to limited treatment options and increased mortality rates associated with infections. These organisms are often resistant to multiple classes of antibiotics, making infections difficult to treat.

Detection and Diagnosis

Laboratory detection of carbapenemase production is crucial for infection control and appropriate antibiotic therapy. Methods include phenotypic tests, such as the modified Hodge test, and molecular techniques, such as PCR assays, to identify specific carbapenemase genes.

Treatment Options

Treatment of infections caused by carbapenemase-producing bacteria often requires the use of combination therapy and newer antibiotics, such as ceftazidime-avibactam and meropenem-vaborbactam, which are designed to overcome resistance mechanisms.

Also see

• Antibiotic resistance
• Beta-lactam antibiotics
• Multidrug-resistant bacteria
• Infection control