New Delhi metallo- -lactamase-1 in Enterobacteriaceae: emerging resistance

Abstract

Let us consider the following hypothetical scenario. A 48-year-old man with a history of type 2 diabetes mellitus was recently on vacation in Calcutta, India. Three days into his stay, he was involved in a motor vehicle accident, for which he was admitted to the local general hospital. He underwent open reduction and internal fixation of a comminuted fracture of the left tibia. His postoperative care was unremarkable except for a urinary tract infection. He was given cefazolin intravenously for five days. After 12 days in hospital, he was discharged and was assessed by an orthopedic surgeon upon his return to Canada. Radiographic examination showed loosening of the prosthetic hardware. He was admitted to hospital for revision of the hardware. Intraoperative cultures grew Klebsiella pneumoniae that showed resistance to β -lactam antibiotics, fluoroquinolones, cephalosporins and carbapenems. A modified Hodge test to detect carbapenemase gave a positive result. The isolate was forwarded to the local public health laboratory, where the presence of the gene for New Delhi metallo-β-lactamase-1 (NDM-1) was confirmed by polymerase chain reaction and DNA sequencing.T he carbapenem class of antimicrobials, which comprises imipenem, meropenem, ertapenem and doripenem, are often the last resort for the safe and effective treatment of infections caused by multidrug -resistant gramnegative bacteria. Resistance to carbapenems occurs through several mechanisms, including the production of carbapenemases. One such example is the newly described NDM-1, which is found on mobile genetic elements and confers resistance to all β-lactam antibiotics available in Canada.1 These mobile genetic elements (strands of DNA able to transfer from one bacterium to another, such as a plasmid or transposon) typically carry genes that confer resistance to fluoroquinolones, aminoglycosides and trimethoprim-sulfamethoxazole. MethodsWe searched PubMed using the term "NDM-1" for all relevant scientific articles published up to and including October 2010. Twenty-three research articles were identified, most of which were case reports or case series. Four of these articles were used in this review, and 19 articles were excluded because they lacked new information or because they were not available in English. Each of the included articles was reviewed by at least two of the authors. A Google News search of the lay press using the terms "NDM-1" or "medical tourism" was also conducted. Given the recent emergence of NDM-1, we included all articles that were deemed credible by the authors. Additional information was obtained through personal communication with relevant experts. Emergence of carbapenem resistanceCarbapenems are increasingly used because of the emergence of extended-spectrum β -lactamases in Enterobacteriaceae, particularly in Escherichia coli and K. pneumoniae. Review CMAJ • New Delhi metallo-β-lactamase-1 is a bacterial enzyme that renders all current β-lactam antibiotics inactive.

Emergence of Potential Superbug Mycobacterium Tuberculosis , Lessons from New Delhi Mutant-1 Bacterial Strains

“…The newly described NDM-1 enzymes are found on mobile genetic elements, and able to confer resistance to all available β-lactam antibiotics. (24) These mobile genetic elements are DNA strands usually plasmids or transposons which typically carry genes that confer antibiotic resistances and able to transfer from one bacterium to another. Nucleotide and protein based studies have identified the gene encoding for NDM-1 as bla NDM-1 gene which was found on a 140 kb plasmid isolated from an Escherichia coli strain found in the Swedish patient's feces.…”

Isolation of Genetically Unrelated bla NDM-1 -Positive Providencia rettgeri Strains in Israel

“…bla NDM-1 was first described in 2009 in a Klebsiella pneumoniae isolated in a Swedish hospital from a patient previously hospitalized in a medical institution in India (2). Since then, the isolation of bacterial species carrying the bla NDM-1 gene has been reported in several countries, usually from patients who traveled to the Indian subcontinent (3)(4)(5)(6).…”

Toxicity of β-Lactam Antibiotics: Pathophysiology, Molecular Biology and Possible Recovery Strategies

“…Pollini and coworkers reported that a metallo-β-lactamase-producing P. aeruginosa identiied in a cystic ibrosis patient was resistant to carbapenems [33]. Furthermore, New Delhi β-lactamase-1 (NDM-1) producing Enterobacteriaceae infections have been found in patients sufering from type 2 diabetes mellitus infections [34]. Bacteria that produce NDM-1 have been dealt with resistance also in other classes of antimicrobials and virulently restrict treatment options [34].…”