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Ever since the advent of antibiotics in commercial use in the year 1930, different bacteria have been trying to overcome their efficacy by developing resistance against them. These resistant bacteria are known as ‘superbugs’.

Superbugs neutralize the effect of antibiotics by producing certain enzymes

They neutralize the effect of antibiotics by producing certain enzymes or by undergoing different types of mutations. The latest to join this ever growing army of resistant bacteria is the ‘New Delhi -1 metallo B lactamase (MDM-1) superbug’.

How does NDM-1 gene confer resistance to the infected bacteria?

B- lactam antibiotics, like penicillin have a ring like structure which when introduced inside a bacterium, stops it from replicating. Similarly, the NDM-1 gene when incorporated in the DNA of the bacterium makes them drug resistant. It produces an enzyme which destroys this ring. Hence, the antibiotic is rendered ineffective in controlling the multiplication of bacteria. What is even more worrying about the NDM-1 gene is that it is found on plasmids. The latter are DNA structures which can be easily replicated and passed on from one bacterial strain to another. This means that the antibiotic resistance facilitated by the NDM-1 gene can spread amongst different bacterial strains. If it latches on to a bacterium which is already multi drug resistant, the result can be catastrophic. To treat the infection thus produced would be next to impossible. Another perturbing fact about the NDM-1 gene is that till date it has been found only on gram negative bacteria. Antibiotics against these bacteria are few and far between. The picture looks gloomier when we compare the bacteria containing NDM-1 gene with Methicillin resistant Stapphylococcus Aureus (MRSA) which is a gram positive bacterium and has more antibiotics working against it.

In a hospital environment, there is ample scope for bacteria to thrive and multiply. There are so many open wounds, accidental or intentional as in surgeries, which can allow the bacteria to enter the human body. They can even enter along with the tubes, scopes and catheters if proper asepsis is not maintained. The overall immunity of the patients is also depressed. The bacteria normally present in the human body as in the gut are wiped out because of the use of various broad spectrum antibiotics. Now imagine the scenario if some drug resistant bacteria with the NDM-1 gene gain a foothold in the hospital. The implications can be terrifying.

NDM-1 gene affects Klebsiella pneumoniae and E.coli bacteria

Genetic studies done so far suggest that there are three regions on the DNA of Klebsiella pneumonia in a 180-kb plasmid which are responsible for the development of resistance to various anti bacterial drugs. It is on the third region that the new metallo  B lactamase gene, called the NDM-1 has been found. It lies in the middle with K. pneumoniae DNA on one side and an Abridged IS26 element on the other side. This portion of the DNA carrying the three resistance conferring regions can be transferred easily from one bacterium to another. It imparts resistance against almost all antibiotics. Apart from having certain distinct residues near its active site, the NDM-1 gene has a unique extra appendage incorporated between positions 162 and 166, which is not present in other metallo B lactamases.

NDM-1 gene has also been found on a 140 kb plasmid on the DNA of a strain of E.coli bacteria.

The menace of NDM-1 gene mutation

Normally carbapenems are used as the “last resort” antibiotics with maximum infection coverage rate and with the lowest drug resistance rate. This group of antibiotics is used only in a crisis and against multi drug resistant bacteria like Methecillin Resistant Staph Aureus (MRSA) and Clostridium difficile. The fact that bacteria with NDM-1 gene mutation are resistant even to the carbapenem group of antibiotics has terrified health professionals.

Apart from polymixins and to a lesser extent tigecycline, all other antibiotics have proved ineffective against NDM-1 superbug. The effect of fosfomycin, arbekacin and isepamicin against these bacteria is still under investigation.

Is the prevention against superbugs possible?

In the absence of proper antibiotics, prevention is the best method available at present to fight this menace. Creating awareness and maintaining standard methods of hygiene and asepsis, and implementing infection control methods are the only means of stopping further progression of these bacteria. Reckless and indiscriminate use of antibiotics must be checked and guidelines for antibiotic usage should be strictly adhered to. It is also of vital importance to quickly identify the producer of the resistant bacteria and keep him isolated to prevent the transmission of resistance to other bacteria.

Debatable points regarding NDM-1 superbug infection

Bacteria mutated with NDM-1 gene have so far been detected in 34 British nationals. Three American citizens have also been identified. As chance would have it, a few of these patients had returned after undergoing cosmetic surgery in India and Pakistan. Hence, the name ‘New Delhi 1 metallo B lactamase’ has been given to the superbug. The entire medical tourism industry in India has been discredited and is being held responsible for the evolution of this resistant strain of bacteria. However, this is debatable. So far, the superbug has not been isolated from any hospital in New Delhi. Therefore the naming of the bacteria has caused a furore in the country. Moreover, this resistant gene has also been identified in countries like Australia, Canada, the US, Netherlands and Sweden. Because of international travel, and because of the easy transfer of resistance from one bacterium to another, this bug has the potential to spread all over the world rapidly. It is very difficult to say whether the patients have picked up the bug in India or they were already carrying it before their travel to this country. Unless analysis of samples from all over the world is carried out in a scientific manner, the place of origin of the bug is just a matter of speculation.

Moreover, development of resistance to antibiotics is not a new phenomenon. Bacteria started developing resistance against the penicillin group of antibiotics almost immediately after the latter’s introduction in medical practice. New York City hospitals were in focus about 10 years ago for infection with other bacteria which were resistant to carbapenem group of antibiotics. Only the mechanism of development of resistance was different that time, because of a different kind of mutation. Bacteria have for long been developing resistance against the antibiotics available to us and NDM-1 is just another example of that. Researchers have been prompted to develop newer antibiotics to counter this attack. NDM-1 is making more waves as compared of other types of resistances because this time gram negative group of bacteria has been on the target. We have loads of antibiotics against gram positive bacteria like Methicillin resistant Stapphylococcus Aureus (MRSA) but are woefully short of antibiotics against the former. Only two new medicines are in the pipeline against these infections. Who knows this superbug may jolt our pharmaceutical industry to invest in research for antibiotics against gram negative bacteria?

We shouldn’t forget the fear of ‘pandemic due to swine flu’ that had gripped us just a year back. Even WHO had to scale down its perceived threat. As far as the generalized fear against NDM-1 superbug is concerned, it appears to be exaggerated. It too will settle down when some other new resistance or disease rises from the horizon.

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