A study appearing in the Aug. 11 issue of Lancet Infectious Diseases indicates that a new gene, NDM-1, is creating resistance in bacteria to almost all known antibiotics, including carbapenems, and there are no new drugs in the pipeline to combat a potential new superbug.
Because of the growing trend of medical tourism, resistant bacteria are spreading quickly; the Lancet study identified 37 colonized individuals who returned to the United Kingdom after having surgery in Bangladesh, India or Pakistan. According to experts, NDM-1 has been associated with E. coli bacteria, the most common cause of urinary tract infections (UTIs).
Karthikeyan K. Kumarasamy, MPhil, of the Department of Microbiology at the University of Madras in Chennai, India, and colleagues, explain, "Bacteria from clinical and non-clinical settings are becoming increasingly resistant to conventional antibiotics. Ten years ago, concern centerd on Gram-positive bacteria, particularly meticillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp. Now, however, clinical microbiologists increasingly agree that multidrug-resistant Gram-negative bacteria pose the greatest risk to public health. Not only is the increase in resistance of Gram-negative bacteria faster than in Gram-positive bacteria, but also there are fewer new and developmental antibiotics active against Gram-negative bacteria and drug development programs seem insufficient to provide therapeutic cover in 10 to 20 years."
Kumarasamy, et al. (2010) explain further, "The increase in resistance of Gram-negative bacteria is mainly due to mobile genes on plasmids that can readily spread through bacterial populations. Standardized plasmid typing methods are enhancing our understanding of the host ranges of these elements and their worldwide distribution. Moreover, unprecedented human air travel and migration allow bacterial plasmids and clones to be transported rapidly between countries and continents. Much of this dissemination is undetected, with resistant clones carried in the normal human flora and only becoming evident when they are the source of endogenous infections. The CTX-M-15 extended-spectrum -lactamase (ESBL) encoded by blaCTX-M-15 was first reported in India in the mid-1990s. The gene jumped from the chromosome of its natural hosts, Kluyvera spp, to plasmids that have subsequently spread widely, establishing CTX-M-15 as the globally-dominant ESBL and the primary cause of acquired resistance to third-generation cephalosporins in Enterobacteriaceae. "
Studies have identified ESBLs in 70 percent to 90 percent of Enterobacteriaceae in India, according to the researchers, making the widespread use of reserved antibiotics such as carbapenems necessary. They add, "Rates of cephalosporin resistance are lower in other countries but the growing prevalence of ESBL producers is sufficient to drive a greater reliance on carbapenems. Consequently, there is selection pressure for carbapenem resistance in Enterobacteriaceae, and its emergence is a worldwide public health concern since there are few antibiotics in reserve beyond carbapenems. Already Klebsiella pneumoniae clones with KPC carbapenemase are a major problem in the U.S., Greece, and Israel, and plasmids encoding the VIM metallo-carbapenemase have disseminated among K pneumoniae in Greece."
Kumarasamy, et al. (2010) report on this new type of carbapenem resistance gene, designated blaNDM-1, explaining that a patient, repatriated to Sweden after admission to hospital in New Delhi, was colonized with K pneumoniae and Escherichia coli with blaNDM-1 on plasmids that transferred between bacterial strains in vitro. The researchers sought molecular, biological and epidemiological data on New Delhi metallo- -lactamase 1 (NDM-1) positive Enterobacteriaceae in India and Pakistan and investigated importation of the resistance gene into the UK by patients returning from the Indian subcontinent.
The researchers note that the ease of transmissibility "implies an alarming potential to spread and diversify among bacterial populations," and they express concern that most of the Indian isolates were from community-acquired infections, suggesting that blaNDM-1 is widespread in the environment. The researchers add, "Several of the UK source patients had undergone elective, including cosmetic, surgery while visiting India or Pakistan. India also provides cosmetic surgery for other Europeans and Americans, and blaNDM-1 will likely spread worldwide ... The potential for wider international spread of producers and for NDM-1-encoding plasmids to become endemic worldwide, are clear and frightening."
Reference: Kumarasamy KK, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. The Lancet Infectious Diseases, early online publication. August 11, 2010. doi:10.1016/S1473-3099(10)70143-2.