Are We Approaching the End of Antibiotic Therapy?

The emergence of a new antibiotic resistance mechanism in India, Pakistan, and the United Kingdom represents a potentially major global health problem, and possibly signals the end of effective antibiotics treatments, according to a new study.

Researchers at the University of Madras (Chennai, India), Cardiff University (United Kingdom), and other institutions investigated the prevalence of carbapenem resistant gram-negative Enterobacteriaceae conferred by the New Delhi metallo-beta-lactamase 1 (NDM-1) resistance gene; the multidrug-resistant bacteria is found in India, Pakistan, and the U.K. The researchers isolated the bacteria from two major population centers in India--Chennai (in south India), and Haryana (in northern India)--and referred them to the U.K. National Reference Laboratory (NRL; Weymouth). Antibiotic susceptibilities were assessed, and the presence of the NDM-1 resistance gene was established by polymerase chain reaction (PCR). Isolates were typed by electrophoresis of genomic DNA, and plasmids were analyzed by S1 nuclease digestion and PCR typing. The researchers also reviewed case data regarding the UK patients to look for evidence of travel and recent admission to hospitals in India or Pakistan.

The researchers identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan. NDM-1 was mostly found between E. coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. Most of the isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable from one bacterium to the other, whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries. The study was published in the August 10, 2010, issue of Lancet Infectious Diseases.

"In many ways, this is it,” said coauthor Professor Tim Walsh, Ph.D., of the department of infection, immunity, and biochemistry at Cardiff University, in an interview published in the Guardian "This is potentially the end. There are no antibiotics in the pipeline that have activity against NDM 1-producing Enterobacteriaceae. We have a bleak window of maybe 10 years, where we are going to have to use the antibiotics we have very wisely, but also grapple with the reality that we have nothing to treat these infections with.”

"A lot of modern medicine would become impossible if we lost our ability to treat infections. The emergence of antibiotic resistance is the most eloquent example of Darwin's principle of evolution that there ever was,” added coauthor Professor David Livermore, Ph.D., of the UK Health Protection Agency (HPA; London). "It is a war of attrition. It is naive to think we can win.”

Beta-lactamases are enzymes produced by some bacteria responsible for their resistance to beta-lactam antibiotics like penicillins, cephamycins, and carbapenems. These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam. The lactamase enzyme breaks that ring open, deactivating the molecule's antibacterial properties.

Related Links:
University of Madras
Cardiff University
UK National Reference Laboratory
UK Health Protection Agency