New Delhi metallo-beta-lactamase (NDM-1) is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. News of this new resistance factor has been percolating in smaller medical reports since June 2010, including the weekly bulletin of the US Centers for Disease Control and Prevention. NDM-1 is the designation for carbapenemases found in enterobacteriaceae. Bacteria that produce carbapenemases are often referred to as “superbugs” because infections caused by them are difficult to treat e.g. Klebsiella pneumoniae. Such bacteria are usually only susceptible to polymyxins and tigecycline.
NDM-1 was first detected in a Klebsiella pneumoniae isolate from a Swedish patient of Indian origin in 2008. NDM-1 have been isolated till now in K pneumoniae, Escherichia coli, Citrobacter freundii, Enterobacter cloacae, and Morganella morganii.
The most common bacteria that make this enzyme are Gram negative such as Escherichia coli and Klebsiella pneumoniae. This enzyme belongs to plasmids- a snippet of DNA, not on a chromosome, that reproduces on its own and can be transfered freely between different bacteria.
The Misuse of Antibiotics
The first clue to the presence of a carbapenemases like NDM-1 comes from the increased minimum inhibitory concentration (MIC) values of these bacteria. Doctors in subcontinent have always used high profile antibiotics and high doses for even the most minor diseases. This gives the bacteria an opportunity to be more and more exposed to these antibiotics and compeling them to make new resistance factors.
The virtual nonexistence of antibiotic policies and guidelines in India & Pakistan is a major driver of the emergence and spread of multidrug resistance in subcontinent. 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 and government.
In August 2010, the first reported death due to a bacteria expressing the NDM-1 enzyme was recorded as a Belgian man who had become infected while being treated in a hospital in Pakistan. He died despite being administered colistin, a powerful antibiotic. A doctor involved in his treatment said, “He was involved in a car accident during a trip to Pakistan. He was hospitalised with a major leg injury and then repatriated to Belgium, but he was already infected”.
Cost to Human Race
Imagine that it will take about 10 years, and about $1 billion dollars, to get a new antibiotic through the development pipeline and into the market. And then imagine that — as has been shown for a number of dru
gs, most recently the new antibiotic daptomycin — bacteria begin developing resistance to your drug within a year of its deployment in patients. And after that, imagine — as has been cited in a number of papers — that once local resistance to your antibiotic appears in approximately 20% of isolates, physicians will cease prescribing your antibiotic, for fear their patient will be one of that 20%.
So, to recap: 10 years, $1 billion; short course; short market life; rapid obsolescence.
Who will take the responsibility to stop bacteria from developing resistence?