Drugs vs Bugs

Cut to 2010: It took a report in Lancet about a bug named after New Delhi to give India a wake-up call and make “antibiotic resistance” a household word.

For a country stubbornly resistant to what doctors call “judicious use” of drugs,the affront was prodigious. How can a superbug be named after New Delhi? After all,buying the latest antibiotics without prescription in the city—and in the rest of the country—is as easy as buying a pack of band-aids. It is precisely this cavalier attitude,which,say doctors,is responsible for the rise of antibiotic resistance in bugs.

But that is only a part of the story—and the most recent part.

“It is important to remember that pathogenic (disease causing) bacteria and the organisms from which many antibiotics are made (like Penicillium chrysogenum in case of penicillin) have been living side by side in the universe for thousands of years,” says Dr Yogesh Souche,scientist from Pune’s National Institute of Cell Sciences,who has been studying the spread of antibiotic resistance in bacteria through markers in the environment. “They have been used to sharing a complex environment and their survival mechanism gets activated very fast…sometimes even a year after a new drug begins to circulate.”

Fleming had conducted some of his tests on a penicillin-resistant strain of Staphylococcus aureus which he had indeed developed in the laboratory. But the first official case of clinical resistance to penicillin was recorded in 1947,nearly four years after the drug was introduced in hospitals.

The bug in question was Staphylococcus aureus again—‘Staph’,the bane of hospitals across the world. Staph can cause a host of maladies—from skin infection to sepsis,pneumonia,osteomyletis and even heart failure. And it is the same Staphylococcus aureus,which has become resistant to methicillin today and has gained notoriety across the globe as MRSA—methicillin-resistant Staphylococcus aureus— giving the medical communities in Europe and the US a headache. The strain,according to the US Centers for Diseases Control,caused over 2,500 more deaths than AIDS in the US in 2005.

Between penicillin and methicillin,the bugs have managed to get the better of around a dozen antibiotics and then some more. The latest entrant in the drugs arsenal,daptomycin,approved for use in September 2003,has been vanquished too. And the strongman of antibiotics,Carbapenem,has been felled by Acinetobacter baumanii,a hospital-acquired infection that was written about as late as March 2010 in the journal Infection Control and Hospital Epidemiology.

Bugs and resistance

How do bugs employ the resistance factor? As opposed to the 21 chromosomes in the human body which compose the DNA, bacteria have only one,says Souche. “They have only one big chromosome that comprise the DNA. But they also have an extra chromosome that is about 1,000 times smaller,which they can pass onto other bacteria regardless of species. This is the fast efficiency one,which also contains the chemical weapons against antibiotics. And this the key that makes bacteria the king of its environment.”

It is one of these extra chromosomes—an antibiotic-resistant enzyme which has become infamous as NDM1—which is giving doctors the nightmares. The fear is that the enzyme can jump from one strain of bacteria to another and piggybacking onto them,spread outside hospitals and give rise to a host of untreatable diseases.

What is ironical is that most of these bacteria are born and bred in hospitals. Inevitable perhaps,given that it the place where they have the most chance of meeting and beating whole ranges of antibiotics.

“In the hospital environment,bacteria acquires immunity against antibiotics much faster and these resistant strains proliferate in hospitals,” says Pinak Srikhandey,a doctor in the Critical Care Unit of Fortis Hospital in Vasant Kunj,Delhi. Thanks to them,there are incidences of post-op wound infections,blood infections,ventilator-related pneumonia,and skin and urinary infections among patients whose immunity is already low. And visitors to the hospital and the healthcare workers act as conduit,unwittingly carrying the pathogens from patients inside to healthy people outside—and sometimes even fall sick themselves.

What Srikhandey is so ready to acknowledge is something the medical community rarely talks about. Hospital-acquired infections—otherwise known as ‘nosocomial infections’—is almost a taboo subject in India. “While doctors do discuss it internally,that such a thing exists is mostly unknown among the general population,” says Souche. “While such incidences are regular in all hospitals,no operation theatre is ever said to be closed because of an infection outbreak. It is always attributed to other reasons.” And it is understandable,he adds,since no one wants to create panic among patients and give the hospital a bad name. In contrast,a chunk of data on the subject is available for hospitals in the US and the UK. And awareness is high among people—so much so that the subject is exploited regularly to churn out medical thrillers.

It is also doctors and hospitals who carry the burden of the other big factor in antibiotic resistance in bugs: indiscriminate prescription.

“Increasing resistance to a lot of antibiotics is due to a lot of misuse and overuse of drugs,” says Randeep Guleria,Professor of Medicine at AIIMS. “Most hospitals do not have a proper antibiotic policy. Open ICUs admit patients and multiple antibiotics are prescribed without much rationale.”

And for doctors,there is always a pressure to prescribe new,high-end antibiotics,he says—sometimes from pharma companies who just want to sell their drugs and sometimes from patients who want quick relief. The downside is that where a mild,small dose antibiotic would have controlled the bacteria—albeit a little slowly—it gets exposure to newer drugs and begins acquiring resistance against it.

“What is worse,” adds Souche,“is the private practitioners’ habit of symptomatic treatment—prescribing medicines without getting to know the source of the problem.” An infection can be caused by many different bacteria,but without pinning it down through identification and sensitivity tests—even quick tests are available these days—a broad spectrum antibiotic is prescribed at random. Add to it the patients who buy antibiotics over the counter indiscriminately and those who never complete the course of a prescribed drug,and you already have a lethal cocktail of wrong procedures.

Then there is the question of antibiotics filtering into the body through other sources,like animal products and plant products. Milk from a cow under antibiotic treatment can contain antibiotics,points out Souche. So can meat,or plant products where the plant had been getting water contaminated with antibiotics.

In July 2009,researchers from the Indian Institute of Toxicology Research (IITR),Lucknow,published an article in BMC Microbiology that noted the high levels of antibiotics in Ganga—a result of undigested antibiotics that flow into the river with sewage—and high levels of antibiotic-resistant pathogens. In February 2009,researchers from Sweden’s University of Gothenburg found high levels of antibiotics—ciprofloxacin and cetrizine among others—being released into the region’s waters through effluents of pharmaceutical plants in Patancheru near Hyderabad.

Plus,there is the question of whether the drugs available in the market are always safe. “Different companies sell the same drug,under different brand names with minor changes in formulations. But in the absence of a strict quality check,a lot of such products are suspect. Plus,the competitive price factor only ensures that people are ready to swallow strong medicines at the drop of a hat without any thought of consequences,” says Srikhandey.

The fightback

“The issue is multifactorial,” says Dr Chand Wattal,chairman,Department of Microbiology at Sir Ganga Ram Hospital in New Delhi. “The need of the hour is effective legislation and an antibiotic policy”.

Guleria agrees. “A comprehensive antibiotic policy needs to have a fine balance—benefit to the patient and society. It needs to be hospital-specific since each hospital has its own resistant strains and needs to be drawn up through consensus between the government,the hospital and the pharma companies,” he says.

Given the cost of developing a new drug—a decade,billions of dollars and the cost to the society meanwhile in terms of lives—doing anything less is criminal,feels the medical community.

“The silver lining here is that bugs have short memories,” points out Prof Gopal Nath,microbiologist with Benaras Hindu University,who is trying to develop an alternative to antibiotics. “If a bacteria is resistant to a particular drug and that drug is withdrawn today,it will regain sensitivity to that drug within a few years.”

“If that same drug is commissioned after a decade,it will again be able to control the same bacteria and this is also where an antibiotic policy can be of help,” says Wattal.

The other foolproof method of containing bacteria attack is thorough vaccination. Nath’s own research provides the third option: one in which a cocktail of “killer viruses” is unleashed against bacteria.

Bacteriophage literally means a ‘killer of bacteria’. The idea of using viruses to kill diseases is not new. In fact,in the Soviet Union till the 1980s,phage therapy was prevalent for common infections,with the George Eliava Institute of Bacteriophage,Microbiology and Virology in the Soviet Republic of Georgia at the centre of such research. Post cold war,experimentation with phage has begun afresh in the US and Western Europe and the viruses are being used even to find a solution for cancer.

The viral cocktail,Nath said,has been successfully used in case of Psuedomonas aeruginosa,an antibiotic resistant strain and though the experiments are still at the laboratory stage,phage therapy still holds out considerable hope for the future.