What are Carbapenems?

Carbapenems are a very powerful class of beta-lactam antibiotics that are structurally related to the penicillins. They are broad-spectrum antibiotics and act against gram-negative, gram-positive bacteria and those that grow in the absence of oxygen. These drugs are generally used in cases of infection by multiple types of bacteria or when the invasive bacteria are resistant to other types of antibiotics. There are strains of bacteria that have developed a gene for resistance to the carbapenems, alarming the medical community with fears of a worldwide superbug.

Beta-lactam antibiotics all have a ring structure composed of three carbon atoms and one nitrogen atom. They interfere with bacterial cell wall synthesis by interfering with a crucial step of synthesis. These compounds block penicillin-binding proteins (PBP). This leaves bacterial cell wall intermediates loose. It tricks the cell into producing enzymes that degrade its own cell wall, killing the organism.

Many bacteria produce enzymes that degrade beta-lactam antibiotics. Such enzymes are known as beta-lactamases. It is common practice to prescribe this type of antibiotic with a beta-lactamase inhibitor, so the bacteria cannot degrade the antibiotic. With carbapenems, the beta-lactamase inhibitor used is cilastatin.

There are a number of different kind of carbapenems used in clinical practice. The first compound to be used was imipenem, which is commonly prescribed with cilastatin. Later types of inhibitors do not need to be used with this beta-lactamase inhibitor. These compounds vary in which PBP they bind to, which gives some selectivity towards different types of organisms. For instance, those that inhibit PBP3 are specific for the opportunistic pathogen Pseudomonas aeruginosa.

Carbapenems are the most powerful antibiotics known, since they are able to contain such a diverse array of bacterial infections. They are usually saved for use as a measure of last resort, so as not to encourage the development of resistance against them. Such antibiotics are typically administered intravenously in hospitals.

This class of antibiotics is able to kill most bacteria that produce beta-lactamase inhibitors, because its structure is slightly different than the other classes of beta-lactam antibiotics. New strains of enteric bacteria have developed, however, that do carry a resistance gene that enables them to degrade the beta-lactamase of carbapenems. Enteric bacteria are gram-negative bacteria such as Escherichia coli. The new resistance gene is known as NDM-1. It is a beta-lactamase with a metallic ion as a cofactor and was first isolated in New Delhi, India. Hence, the name stands for New Delhi metallo beta-lactamase.

A number of patients in the United Kingdom have been hospitalized with strains of bacteria containing this resistance gene. Some have died. Most had been to the Indian subcontinent, predominantly for cosmetic surgery. Others had contracted their disease from other patients in the hospital. Infections have also occurred in the United States, Canada, and several other countries.

There is no other antibiotic class that can replace carbapenems. The NDM-1 gene can be transferred between different types of bacteria. If it ends up in a strain that is resistant to all antibiotics and spreads easily between patients, that would be a serious threat to human health.