Hatching superbugs

In 1945, after receiving the Nobel Prize for his chance discovery of the miracle cure – penicillin antibiotic – Alexander Fleming issued a warning. "There is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug, make them resistant," he said. Since the discovery of penicillin, scientists have made antibiotics to cure multitudes of diseases – tuberculosis, typhoid, urinary tract infection, septicaemia, and the list goes on. But Fleming's warning continues to haunt them. More so, because antibiotics are no more restricted to humans nor limited to treating diseases. In poultry, for instance, the industry has found another use for antibiotics: as a growth promoter. Chickens are fed antibiotics so that they gain weight and grow fast.

Public health experts have long suspected that such rampant use of antibiotics could be a reason for the increasing antibiotic resistance in India. But, the government has no data on the use of antibiotics in the country, let alone on the prevalence of antibiotic resistance. A recent study now confirms what has for long been suspected. Delhi non-profit Centre for Science and Environment (CSE) has found residues of antibiotics in 40 per cent of the chicken samples it tested. This suggests that the chickens were exposed to antibiotics throughout their short life cycle of 35-42 days. The Pollution Monitoring Laboratory of CSE tested 70 chicken samples procured from 16 markets in Delhi and the National Capital Region. Three tissues – muscle, liver and kidney –were tested for the presence of six antibiotics widely used in poultry: oxytetracycline, chlortetracycline and doxycycline (from class tetracyclines); enrofloxacin and ciprofloxacin (from fluoroquinolones) and neomycin, an aminoglycoside.

The residues of five of the six antibiotics were found in the chicken samples. The antibiotic residues were detected in all the three tissues. They were in the range of 3.37-131.75 µg/kg. Of the 40 per cent samples found tainted with antibiotic residues, 22.9 per cent contained residues of only one antibiotic while the remaining 17.1 per cent samples had residues of more than one antibiotic. Liver samples contained the maximum antibiotic residue, followed by muscle and kidney tissue. To understand any seasonal variation in the levels of antibiotic residues, CSE researchers conducted the study in two phases: first during September-October 2013, and then between May and June 2014.

The findings were alarming in both the phases. They suggest an indiscriminate use of antibiotics in poultry. "Repeated and prolonged exposure to antibiotics lead, by natural selection, to the emergence of resistant strains of bacteria," says Neil Schluger, chief scientific officer, World Lung Foundation, New York. These mutated robust strains bypass toxic effects of antibiotics, making them ineffective. They can easily spread among the flock raised in squalor and contaminate the food chain. They can also alter the genetic material of other bacteria, often pathogenic ones, making them resistant to several drugs and thereby, resulting in a global pandemic.

Humans are at a double threat. The mutated robust microbe strain can invade the body and cause diseases that are difficult to treat. Second, antibiotic residues present in the meat can directly unleash an assault on the microbes in humans. "Residues of antibiotics present in meat can easily find their way into the human body, where they can create resistant microbes," says Randeep Guleria, professor of pulmonary medicine at the All India Institute of Medical Sciences, Delhi

The scale of the threat can be gauged from the fact that antibiotics are frequently pumped into chicken during its life cycle: they are occasionally given as a drug to treat infections, regularly mixed with feed to promote growth and routinely administered to all birds for several days to prevent infections, even when there are no signs of it.

To ascertain the linkage between the overuse of antibiotics in poultry farms and antibiotic resistance in humans, CSE researchers reviewed 13 studies conducted by various government and private hospitals across the country between 2002 and 2013. The result was startling. The resistance was very high against ciprofloxacin, doxycycline and tetracycline. In certain studies reviewed by CSE, almost all of Pseudomonas, Enterobacter, Escherichia Coli and Klebsiella were found to be resistant to ciprofloxacin.

"Resistance to antibiotics is a major crisis that is going to hit the healthcare sector soon," says Devi Shetty, cardiac surgeon and founder of Narayana Health, a charitable hospital. These drug-resistant bacteria could nullify the gains of modern medicine by compromising the success of organ transplants, high-end surgeries and cancer chemotherapy.

"Not long ago, I treated a patient with drug-resistant tuberculosis," says Schluger. "What could have been a simple six-month course of treatment turned into a two-year ordeal which involved drugs that damaged the patient's hearing and nerves. A major surgery was required to remove the diseased areas of his lung," he adds.

With drugs losing their effectiveness, the world would need newer antibiotics. Unfortunately, no new class of antibiotic has hit the market since the late-1980s. In the US, more than two million people suffer from antibiotic-resistance-related illnesses every year; 23,000 of them succumb to the diseases. Annual healthcare cost due to antibiotic resistance is estimated to be as high as $20 billion, with an additional productivity loss of up to $35 billion in the US.

No such estimates are available for India, but cases of high antibiotic resistance are emerging from across the country. Vipin Vashishtha, who runs Mangla Hospital in Bijnor, Uttar Pradesh, writes on the pervasiveness of antibiotic resistance in the February 2011 issue of Indian Paediatrics. Bacteria found in 14 infants at his hospital were resistant to all classes of antibiotics – cephalosporins, aminoglycosides, monobactams, quinolones, piperacillin-tazobactam combination and carbapenems. These children were administered expensive antibiotics like polymyxin B and colistin, but only eight could be saved. Four of these eight developed complications like meningitis and arthritis, he wrote.

Guleria elaborates. Antibiotic resistance leads to two problems –mild infections require stronger dosage and no effective antibiotics are left for treating severe infections. The resistance to a class of antibiotics, for instance, fluoroquinolone, has fatal consequences. Fluoroquinolone antibiotics are prominently used to combat infections in intensive care units. Treating fatal diseases like sepsis, pneumonia and tuberculosis (TB) are becoming tough because microbes that cause these diseases are increasingly becoming resistant to fluoroquinolones. "We are receiving reports of multi-drug-resistant TB (MDR-TB) and extreme-drug-resistant TB (XDR-TB)," he adds.

Replying to a question in the Parliament recently, Union health minister Harsh Vardhan said that the number of MDR-TB cases in the country has increased five times to 23,325 between 2011 and 2013. "Almost one-third of all MDR-TB cases are resistant to fluoroquinolone, which forms the backbone of MDR-TB treatment," says Anuj Bhatnagar, a doctor at Rajan Babu Institute of Pulmonary Medicine and Tuberculosis, Delhi. "These patients are just one step short of XDR-TB, at which the options of treatment are seriously limited."

CSE study found two fluoroquinolone antibiotics—enrofloxacin and ciprofloxacin—in 28.6 per cent chicken samples tested. "This is just the tip of the iceberg," say CSE researchers. "We have tested chicken samples only for six widely-used antibiotics in the country. There are many more antibiotics that are routinely used in poultry."

For example, Skylark Hatcheries, an integrated poultry company in Jind, Haryana, uses Enramycin. Venky's uses bacitracin in its feed Bamylate, while Vetline India uses furazolidone antibiotic in its feed Furavet. Some European countries banned the use of bacitracin and furazolidone as growth promoters. Antibiotics from classes of cephalosporins, penicillins and macrolides are also among the most popular antibiotics used in poultry farms in India. WHO classifies these antibiotics as critical for human use.

(The views expressed belong strictly to those at Down to Earth.)