: It is the beginning of the end. Hospitals in India are now recording cases of infections resistant to colistin, the last antibiotic available in the world, which was brought back from a 40-year exile in 2005 to treat increasing number of infections resistant to other high-end antibiotics.
For now, colistin is the only cannon left in the medical armoury to treat bacterial infections, mainly those acquired in the hospital that no drug can treat. The number of cases resistant to colistin is still rare, but worrisome, say doctors.
The first-ever evidence of pan-drug resistant cases has now been recorded by three Chennai-based doctors. Their paper: 'Emergence of pan-drug resistance amongst gram negative bacteria! The first case series from India', published in the latest issue of Journal of Microbiology and Infectious Diseases, maps 13 colistin-resistant cases recorded over 18 months. It concludes that pan-drug resistant infections, particularly those in the blood stream, have a higher mortality.
Tertiary care hospitals across the country are recording cases of infections that even colistin can't treat. Colistin resistance has been detected at 4 to 5 % in Delhi hospitals. In Pune's state-run Sassoon General Hospital, of the 799 drug-resistant bacteria tested between January and July in 2014, 36 were found to be colistin resistant. Stray cases have been reported at Ruby Hall Clinic in Pune and doctors at Tata Memorial Hospital in Mumbai recall one case in the last three to four years.
"Colistin resistance is still rare. It is carbapenem (the strongest class of antibiotic) resistance that is increasing across the world. Colistin is used to treat cases that are resistant even to carbapenem. It is an emerging problem. Doctors in Greece had published colistin-resistance data in 2006, and the US recorded it two years ago," said infectious diseases consultant Dr Abdul Ghafur, one of the authors of the paper on the 13 cases, and also the coordinator of Chennai Declaration that has laid out guidelines for hospitals and doctors on antibiotic use.
Ramanan Laxminarayan, vice president for research and policy at the Public Health Foundation of India said the use of colistin itself is a concern. "It is not a preferred antibiotic. In Vietnam, it was used only in animals till a few years ago," he added.
Such concerns notwithstanding, India has little choice but to use the drug, that was in exile since 1970 for its toxicity, to treat the rising resistance to carbapenem, a third-generation antibiotic used to treat cases resistant to lower drugs.
Most hospitals are still wary of reporting colistin-resistance figures, but doctors now admit that it is time to acknowledge the problem so that corrective measures can be taken.
Understanding colistin
It became available for clinical use in the 1960s, but was replaced in the 1970s with other antibiotics owing to its toxicity
However, with antibacterial resistance on the rise, colistin is increasingly being used to treat severe, multidrug-resistant gram-negative bacterial infections, particularly among intensive-care patients
Colistin is used when all or almost all other drugs have failed and is often a patient's last hope for survival.
Factors fuelling resistance
Exposure to infections in hospitals and the practice among many doctors to prescribe strong antibiotics even for common flu is fuelling resistance to antibiotics.
Quoting reports, Dr Prachee Sathe, head of critical care, Ruby Hall Clinic, said hospitalised patients acquire 11 to 83% of infections, and that 30% of total sepsis deaths are due to antibiotic resistance. Long hospital stay, use of in-dwelling catheter and overuse of antibiotics add to resistance, she added, pointing out that sepsis accounts for more than half of all hospital deaths.
Dr J V Divatia, professor and head of department of anaesthesia, critical care and pain at Tata Memorial Hospital, Mumbai, said community-acquired infections, such as pneumonia, are still sensitive to antibiotics. "But the resistance is high in hospital-acquired infections. The resistance to carbapenem is 50 to 60%. In the case of acenotobacter (a hospital bug) seen in ICU patients, the resistance is 70 to 80%," he said.
The only superior drug to carbapenem is colistin and medical journals refer to it as the 'last-line' therapeutic drug against multidrug-resistant gram-negative pathogens in the 21st century.
But bacteria that people were once exposed to only in the hospital, are now being reported in the safe environs of homes. Dr Divatia mentioned resistant E coli found in stool samples of even people whose only exposure to the hospital had been that of a regular health check.
Dr Sathe recalled a case of an otherwise healthy patient who came for pneumonia treatment and was put on the ventilator, but was detected with two bacteria - MRSA and klebsiella -infections that are usually reported after a long hospital stay.
Treatment roadblock
India drafted the antibiotic policy in 2011 and hospitals have only now started implementing it. Now, there are clear guidelines on the judicious use of antibiotics. While tertiary-care hospitals, at least the major ones in the country, have an infection control mechanism in place, on many occasions patients reach them after they have been exposed to infections and antibiotic overuse in smaller hospitals, point out experts.
"The biggest problem we face is that patients come to us after visiting a general practitioner who would have started treatment with high-end antibiotics. So we have to first de-escalate the antibiotic dosage to identify which organism is growing and which is sensitive," said Dr Vishnu Reddy, former chairman of the infection control committee of Yashoda Hospitals in Hyderabad.
A high-on-antibiotics treatment only derails quick response to a resilient infection, say doctors. Add to that the time it takes to zero down on the infection-causing bug. Much like the nail-biting diagnosis marathon of Dr House with his team, it is an excruciating wait to zero down on the infection-causing bug, almost three days, during which time doctors start what they call empirical treatment (particularly when the patient is critical), which includes administering a broad spectrum antibiotic to eliminate a range of bugs. However, it often ends up killing the sensitive bacteria, and pushes the growth of resistant ones.
Dr Sathe said the overuse of antibiotics that too targeted at incorrect bacteria, only strengthen the resistant ones. There are molecular techniques coming up that can give reports within six to 24 hours, but it could well take time for them to hit the market.
The way ahead for now is combination therapies that doctors are already using, and the hope for new research and a new antibiotic to be developed.
Among those working on it is Hyderabad-based Vista Pharma. "We are focussed on developing novel antibiotics, novel drugs that work on any sort of resistant organism because the compounds have never been used on the bacteria before. We are in the pre-clinical, R&D phase to identify good, effective safe molecules for infections resistant to carbapenem and last-line antibiotics," said Radha Rangarajan, founder and CEO of Vitas. Till then, colistin is the only option with doctors.
Why self-medication is a public health issue
In the story of antibiotic resistance are bigger public health concerns that need immediate attention-self-medication with antibiotics for treating as routine infections as cough, cold and fever to over-the-counter availability of even high-end antibiotics to mixing antibiotics in poultry feed being some of them.
Using antibiotics inappropriately, such as stopping dosage mid-course, also breeds resistance and so does the quality of the drug being consumed.
Experts note antibiotic resistance is not just the hospital's responsibility. "It is each individual's responsibility and also that of the veterinary industry," says Dr Renu Bharadwaj, head of department of microbiology at B J Medical College in Pune.
"The resistance to antibiotics is very low in Norway, Sweden and Finland because of their judicious use in the line of treatment and very good infection control practices," said Dr Suneetha Narreddy, infectious diseases consultant with Apollo Hospitals, Hyderabad. She also expresses concern about the promotion of generic drugs, with the same drug diversely priced between Rs 250 and Rs 3,000, but without any quality indicator.
How to tackle resistance
Antibiotics should be avoided to treat common ailments such as cough, cold and fever, unless advised by doctor
Antibiotic dosage should not be stopped midway as it breeds resistance of infection-causing bacteria
If the doctor suggests discharge from hospital, leave immediately. Longer stay only increases exposure to hospital infections
For hospitals
Hospitals should have a good infection control mechanism in place
They should follow the antibiotic policy, which suggests judicious use of drugs
Prescribing and dispensing the right antibiotic
For veterinary industry
Judicious use of antibiotics in animal feed
Record antibiotic usage
Better management and housing of animals to reduce infection possibility
WHO recommends
Policymakers can help tackle resistance by:
Strengthening resistance tracking and laboratory capacity
Regulating and promoting appropriate use of medicines
Fostering innovation and research and development of new tools
Promoting cooperation and information sharing among all stakeholders
India's policy
Observations:
* A major factor responsible for this is the widespread use and availability of practically all anti-microbials over the counter for human as well as animal consumption
* In India, antibiotics are used widely in food animals as growth promoters and to prevent and treat infection.
Non-therapeutic usage of antibiotics has been especially common in poultry production. However, there is no regulatory provision regarding the use of antibiotics in livestock
Suggestions:
Establish intersectoral coordination committee with experts from various sectors. Develop regulations on usage of anti-microbials in poultry and other animals as well as the requisite labelling requirements in food.
Promote appropriate use of antibiotics through various interventions to stop unnecessary prescribing and misuse of antibiotics
