Says Prof. Jacques Acar, chairman of the WHO Working Group on Monitoring and Management of Bacterial Resistance to Antimicrobial Agents: "Resistance is epidemic in many countries and multi-drug resistance leaves doctors with little room for manoeuvre in the treatment of an increasing number of diseases."
At the same time, the drug-defying homunculi—pneumococci, staphylococci, enterococci and strains of tuberculosis bacilli—are spreading with unexpected rapidity. And with no new antibiotics in the offing, they are going to have a field day.
India is one of the hot zones of the microscopic marauders. Take the latest avatar of mycobacterium tuberculosis, for instance. It's almost invincible against the most lethal cocktail of drugs—rifampicin, isoniazid, pyrazinamide, and ethnabutamol. Known as multi-drug resistant (MDR) strain in medical parlance, it's been around for a while and is proliferating—it reigns over a significant 13 per cent of Delhi's total TB patients and may eventually destroy them. But, alarmingly, not before it has colonised many more in the unhygienic environs of our crowded hospitals, homes and cities. While no survey has yet documented the nationwide spread of MDR TB, almost all major hospitals in metros have reported its presence. Experts fear smaller towns and villages may be harbouring hundreds more.
What's worse, there is no hope of a new TB drug in the near future. "Once you've got MDR TB, your immune system is your only hope," says J.N. Pande, head of the department of medicine at AIIMS. "Luckily our immune systems usually get the better of these invaders, but in cases where immunity is compromised—diabetics, HIV patients, chronically ill patients, the elderly—a small platoon of these germs may snowball into a ruthless army of TB homicides."
Though MDR TB is being treated with a powerful cocktail of drugs, the success rate is a sad 30 per cent. Says P.R. Narayana, director, Chennai-based Tuberculosis Research Centre, "the treatment is expensive: 2.5 lakh for the entire course. For another, the drugs are too toxic for anybody's patience."
Worse still, studies by the National Institute of Immunology in Delhi suggest the local mutants are not only dissimilar to but also more varied than those found in the US or Europe. "This is real bad news," says Ashok Rattan, a microbiologist at AIIMS, "because it means detection kits and drugs developed abroad to tackle MDR mutants may not work here." The diversity of MDR mutants also implies one kind of diagnostic kit wouldn't do. Researchers will have to engineer multiple kits so as not to let any MDR mutant escape unnoticed.
Malarial parasites too have launched a 'disobedience movement' against chloroquine, the reigning antimalarial drug. Says R.K. Gupta, a consultant physician at Ganga Ram hospital, Delhi: "Till recently, only plasmodium falciparum could resist chloroquine; now we see even P vivax defying it. Increasingly, we have to resort to stronger and more expensive drugs like mefloquine to fight these microbes."
TB and malaria mutants are not the only microbes celebrating victory over antibiotics. There are many other life-threatening diseases whose agents have pulled off major coups against antibiotics. Says a worried Gupta: "I'm getting an increasing number of cases resistant to as many as six antibiotics. Often I'm left with no option but to use potent antibiotics with dangerous side-effects. And they are extremely expensive, costing anywhere between Rs 300-2,000 per day."
In fact, most of the first-generation antibiotics—penicillin, streptomycin, chloroquine, chloromycetin, cephalosporin—are fast losing their edge over the microbes. Says Gupta: "Most of the pathogens I encounter in Ganga Ram are 50-80 per cent resistant to almost all the major antibiotics." This is evident from increasing consumption of state-of-the-art antibiotics-like cephalosporins, quinolones and vancom-ycins. The story in other referral hospitals is no different. "If nothing is done now to check drug resistance, more and more people will die and healthcare costs may soar into billions of rupees," warns Gupta.
But what makes microbes resistant to drugs that once destroyed them? Two factors: their adaptive genius and our stupidity and hubris. Let's praise their genius first. Most microbes including bacteria are marvellously protean, always "changing clothes" to escape their enemies. This Darwinian hide-and-comeback strategy has paid off handsomely in their fight against antibiotics. Explains geneticist Joshua Lederberg, Nobel laureate and president-emeritus at The Rockefeller University in New York who was here last month to attend the Ranbaxy Science Foundation's symposium on drug resistance: "Any population of organisms, bacteria included, naturally includes variants with unusual traits—in this case, the ability to withstand an antibiotic's attack on a microbe. When a person takes an antibiotic, the drug kills the defenseless bacteria, leaving behind—or "selecting", in biological terms—those that can resist it. These renegade bacteria then multiply, increasing their numbers a millionfold in a day and establishing monopoly."
And it builds upon itself. The more frequent the bug-drug skirmishes, more and more organisms develop resistance to more and more drugs. Microbes possess an impressive bag of tricks to hoodwink antibiotics. For example, penicillin kills bacteria by attaching to their cell walls, then destroying a key part of the wall. The wall falls apart, and the bacterium dies. Resistant microbes, however, either alter their cell walls so penicillin can't bind or produce enzymes that dismantle the antibiotic. In another scenario, erythromycin attacks ribosomes, structures within a cell that enable it to make proteins. Resistant bacteria have slightly altered ribosomes to which the drug cannot bind. Many bacteria have become resistant to antibiotics tetracycline, streptomycin and gentamicin by blocking off the ribosomal route.
Most dangerously, a mutant can pass on its "resistance" genes to other bacteria. For instance, one bacterium may take up DNA from another bacterium. Penicillin-resistant gonorrhea results from transformation. That's not all. Viruses often act as couriers of drug resistance. Some viruses called bacteriophages attack bacteria and steal their DNA to make baby viruses.And if the bacterial DNA possesses "resistance" genes, they are all expressed in the identical copies of the virus. When these baby viruses molest new bacteria, they pass on these genes to them.
Bacterial bravura is bad enough, but we have made it easier for them with our inept use of antibiotics. Most doctors tend to over-prescribe them, and that too broad-spectrum ones, without ensuring if they may not have become effete. But more alarmingly, they tend to prescribe antibiotics for all kinds of viral infections. Pande emphasises: "Antibiotics kill bacteria, not viruses. There is no reason why you should take antibiotics for common ailments such as cold, bad throat and bronchitis. Overexposure to antibiotics is especially dangerous for children, for bacteria have far more opportunities to acquire resistance."
Self-medication, chemists posing as doctors, and the free availability of antibiotics over the counter make matters worse. Besides, says Gupta, "most patients stop medication as soon as the symptoms disappear. They don't realise there are still a few germs left to be killed, which then acquire resistance, multiply rapidly and mount a fresh attack."
This is precisely how MDR TB has arisen. Now, in a last-ditch offensive, the government, aided by the World Bank, has launched the Directly Observed Therapy Strategy, a new approach that would guarantee that patients comply with the therapy. The cure rate, say doctors, is about 95 per cent.
All this may still not be enough to contain the rebellious bugs if we can't stem the spread of infection. Says Pande: "With increasing urbanisation and worsening sanitation and hygiene, infectious diseases such as malaria, dengue, TB, bronchitis, cholera, diarrhoea, typhoid, pneumonia, have risen sharply in the last decade." Hospitals, believes Gupta, are a major source of infections. "Like in the US, we too must have a Clean Hands Operation in our hospitals to keep the germs in check."
So can we beat the bugs? Prophesies Lederberg: "Perhaps we are approaching an era, not unlike the last century, where disease is rife and there is no solution for common diseases which are curable today. This alarming thought could well become a reality unless solutions are developed rapidly."
Drug companies, of course, wouldn't abandon their search for newer drugs. But frankly, we can't really do much about the innate ability of bacteria to mutate. Meanwhile, policy makers and citizens can do their bit to fight drug resistance: prevent overuse of antibiotics through awareness, banning over-the-counter sale of antibiotics, and monitoring the spread and impact of antibiotic resistance.
