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NDM-1: new resistance mechanism in ESBL
An enzyme in gram-negative pathogens, which is developed by resistance genes, leads to resistances to almost all beta-lactam antibiotics, including carbapenems.
On 10 August, The Lancet Infectious Diseases published a study that generated wide media response: international researchers reported on a new resistance gene in multi-resistant gram-negative Enterobacteriaceae. The new resistance mechanism was first identified in patients who had been treated in India or Pakistan.
The gene initiates an enzyme (carbapenemase), the New Delhi Metallo-beta-lactamase (NDM-1).
Acting as chemical catalyst, this enzyme inactivates the beta-lactam antibiotics of the carbapenem class – antibiotics that are reserved for severe and persistent infectious diseases caused by other beta-lactam-resistant pathogens (extended-spectrum beta lactamases, or ESBL). However, NDM-1 cannot only inactivate carbapenems but also all other classes of beta-lactam antibiotics.
Among the gram-negative pathogens, NDM-1 was, according to the study, mostly found among Klebsiella pneumoniae and Escherichia coli. In NDM-1, the resistance genes are located on plasmids (circular DNA molecules) of different sizes. Hence, the genes can quickly “jump over” to other bacteria. This means that other bacterial species will most likely acquire the new resistance gene as well.
The phenomenon of the resistance to the carbapenem reserve antibiotics is not new. In addition to NDM-1, there are three other resistance genes known to produce different carbapenemases and to be able to cause a multi-resistance to gram-negative pathogens: VIM (reported in 1999), KPC (reported in 2001) and OXA (reported in 2004).
Experts at the National Reference Centre for Gram-negative Pathogens assume that in Germany there is no cause for concern: related to all K. pneumoniae isolates, the occurrence of NDM-1 or other carbapenemase genes are estimated to be below 0.1 per cent; for other ESBL species even less.
The main problem with pathogens generating NDM-1 is the limited options of therapy: there are only two active antibiotic ingredients – Polymyxin and Tigecycline. Both antibiotics do not possess an unlimited effect; there is even evidence that resistances to these reserved active substances already have appeared.
Up to now, four cases of NDM-1-producing bacteria have occurred (16 August 2010) in Germany. However, there are no specific recommendations yet.
On its website, the Robert Koch-Institute clearly states to adhere to the measures of hospital hygiene, especially hand hygiene.
Alcohol-based hand disinfectants are regarded as being absolutely effective, also against multi-resistant bacteria such as the new species producing NDM-1. According to current information, it can be assumed that the bactericidal activity which has been proven in accordance with prEN 13727 and EN 1500 also covers the activity against antibiotic-resistant bacteria. A study on the efficacy of Sterillium® against different multi-resistant bacteria, including multi-resistant gram-negative species such as E. coli and Klebsiella pneumonia, within 30 seconds also supports this conclusion.
Further information:
Abstract of the Lancet study
Kumarasamy K K et al.
Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological and epidemiological study.
Press Release of the Health Protection Agency
National Resistance Alert 3 of the Health Protection Agency
Kampf G, Hollingsworth A.
Validity of the four European test strains of prEN
12054 for the determination of comprehensive
bactericidal activity of an alcohol-based hand rub.
Journal of Hospital Infection (2003) 55, 226–231.
(Status: 18.08.2010)