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Indian Journal of Medical Microbiology, Vol. 28, No. 3, July-September, 2010, pp. 265-266 Correspondence New Delhi metallo-beta-lactamases: A wake-up call for microbiologists BVS Krishna Department of Clinical Microbiology, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom New Delhi metallo-beta-lactamases (NDM) is a nomenclature that Indians cannot be proud of, NDM-1 is the designation for carbapenemases found in enterobacteriaceae isolated from patients in the United Kingdom and elsewhere who have had healthcare contact in India or Pakistan. [1],[2] Carbapenems (imipenem, ertapenem, meropenem, doripenem) are a class of beta-lactam antibiotics with a broad spectrum of activity against gram-positive, gram-negative, and anaerobic bacteria. Carbapenemase enzymes belonging to Ambler molecular classes A to D have been detected in various clinical isolates. Of these the class B enzymes are clinically the most significant. They are the metallo-beta-lactamase (MBL) enzymes of the IMP or VIM series that have been reported worldwide. MBL enzymes, whose genes are plasmid and integron located, hydrolyze virtually all beta-lactams except aztreonam. [3] Many of the carbapenemase producers are frequently resistant to fluroquinolones and aminoglycosides. NDM-1 was first detected in a Klebsiella pneumoniae isolate from a Swedish patient of Indian origin in 2008. The gene coding for this unique enzyme blaNDM-1 was found in one of the three resistance-carrying regions of an integron. NDM-1 shares very little identity with other MBLs. As well as possessing unique residues near the active site, NDM-1 also has an additional insert between positions 162 and 166, which is not present in other MBLs. NDM-1 has a molecular mass of 28 kD and is monomeric. [4] NDM-1 have been isolated from K pneumoniae, Escherichia coli, Citrobacter freundii, Enterobacter cloacae, and Morganella morganii. [2] Other classes of carbapenemases have already been found in K pneumoniae, E cloacae, Pseudomonas aeruginosa, and Acinetobacter baumannii. [5] The first clue to the presence of a carbapenemase comes from the increased minimum inhibitory concentration (MIC) values or frank resistance of the enterobacteriaceae to ertapenem, imipenem, or meropenem. NDM-1 is inhibited by EDTA like other MBL enzymes; this has been demonstrated by the EDTA-disc synergy test. The carbapenemase activity can be screened for by the modified Hodge test. [6] Further characterization and identification of the enzyme can be done only by molecular methods. Treatment of infections caused by pathogens producing carbapenemases, including NDM-1, poses a serious challenge as these infections are resistant to all commonly used antibiotics. [5] Treatment of patients should be guided by the susceptibilities of the individual pathogens, and clinical laboratories must test for a wide range of antibiotics, including tigecycline, colistin, polymyxin, and aztreonam. The use of antibiotic combinations may have to be considered in desperate cases. Carbapenems are the only reliably active antibiotics against many multiresistant gram-negative pathogens, particularly those with extended-spectrum beta-lactamases (ESBLs) and AmpC enzymes. [7] The emergence and diversity of carbapenemase-producing strains is therefore a major concern and one that Indian microbiologists cannot afford to ignore. The virtual nonexistence of antibiotic policies and guidelines in India to help doctors make rational choices with regard to antibiotic treatment is a major driver of the emergence and spread of multidrug resistance in India. This is augmented by the unethical and irresponsible marketing practices of the pharmaceutical industry, and encouraged by the silence and apathy of the regulating authorities. Poor microbiology services in most parts of the country add to the problem. Microbiologists in India have a very important role in the prevention of spread of these dreaded multiresistant pathogens across the world. They should actively participate in the clinical decision making with regard to the treatment of infections, influence the policies and approach to infections and antimicrobials by the government, develop guidelines for antibiotic therapy in their local hospitals, become infection-control doctors, set up surveillance systems for drug-resistant organisms, and educate healthcare workers and the general public about the dangers of multidrug resistant organisms, including hospital-acquired infections. References
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