College of American Pathologists

  Another resistance mechanism poses worldwide threat


CAP Today




September 2010
Feature Story

A worldwide health problem could be developing from the spread of NDM-1 (New Delhi metallo—β–lactamase 1) in multidrug-resistance Enterobacteriaceae in India, Pakistan, and the UK, according to an Aug. 11 article in the online journal The Lancet Infectious Diseases. “It’s pretty concerning,” says Jean Patel, PhD, of the Centers for Disease Control and Prevention. “The NDM-1 mechanism of resistance is clearly able to disseminate.”

The authors studied antibiotic susceptibilities of Enterobacteriaceae isolates from centers in India and the UK, and identified the carbapenem-resistant gene NDM-1 in isolates of E. coli and Klebsiella pneumoniae that were highly resistant to all antibiotics except to tigecycline and colistin. The study’s conclusion: Coordinated international surveillance is needed to prevent a worldwide public health problem caused by NDM-1 (Kumarasamy K, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infec Dis. 2010; published online Aug. 11).

“I think the concern raised in this Lancet article is valid and we’re probably having another group of rapidly spreading β-lactamase resistance on our hands,” Stefan Riedel, MD, PhD, director of clinical laboratories at Johns Hopkins Bayview Medical Center, Baltimore, told CAP TODAY. The CDC’s June 25 MMWR (Morb Mortality Wkly Rep. 2010;59) has already reported on three isolates of Enterobacteriaceae in the United States carrying the NDM-1 resistance mechanism.

This development is “extremely significant for our community,” Dr. Riedel says. The presence of metallo-β-lactamase (MBL) type resistance mechanisms with activities against carbapenems was known in parts of Europe and other countries, “but NDM-1 is a new mobile MBL so far not present in this particular group of organisms.” Unfortunately, this particular MBL is also linked to multidrug resistance, and since it’s plasmid-borne, the organisms described in the Lancet article have resistances to many other classes of antibiotics with the potential of easy spread to other organisms.

“If you compare outbreak data, we have seen spread of ESBL-producing gram-negatives and drug-resistant organisms in Europe as well as the U.S. more often in nosocomial settings, whereas these recently reported isolates in the UK, Pakistan, and India were actually from community-acquired infections,” Dr. Riedel says. That basically underscores the fact that a broad, indiscriminate community-based use of antibiotics, including over-the-counter, non-prescription use, can lead to development of those resistances.

Over the past 10 years, these scenarios have been occurring in other parts of the world and have made U.S. institutions more aware of the need to rethink their own practices to stem community outbreaks of highly resistant organisms. The organisms pose particular danger to patients, Dr. Riedel says, because pharmaceutical companies have focused recently more on gram-positive antibiotics. As there are not many newer gram-negative antibiotics in the pipeline, “we might fall short on treatment options,” he says.

“It’s important to recognize that multidrug-resistance in gram-negative organisms occurs more frequently, and that these newly described ­β-lactamases have the potential for global spread,” Dr. Riedel says. Laboratories in the U.S. need to be on the watch for these organisms, and in very close communication with their infection control department to identify cases or clusters early on. “Once there is an index case,” he says, “the key is to recognize the resistance pattern and to implement not only appropriate treatment but effective infection control measures to prevent further spread of these MDR organisms in our hospital settings.”

—Anne Paxton

Related Links Related Links