With reports of bacteria having breached a last resort antibiotic called colistin, global heads are being urged to act fast before infections become untreatable.
In a strongly-worded article published in the journal Science on March 17, two officials from the World Health Organisation wrote that to slow down antibiotic resistance, it may not be enough to limit our use of the existing drugs but also to develop new ones. Their warnings come in response to the slew of cases of bacteria showing resistance to what is considered a last resort antibiotic, colistin.
Colistin first came to use in the 1950s to treat certain bacterial infections. Its use declined in the 1970s when it was shown to have harmful side-effects on the kidney, but lately it’s made a depressing comeback.
Enzymes called carbapenemases have made bacteria resistant to most common antibiotics used to treat infections. Infections by these multi-resistant bacteria kill tens of thousands of people each year, according to Marc Sprenger and Keiji Fukuda, authors of the article. Colistin is one of the only drugs that work on such bacteria. So, the antibiotic has begun to reappear on the medical shelves – not because it is any less harmful – but because it is sometimes the only option left.
Cons of colistin
Colistin is quite prominent in India, too. “Although minimal, recently there is an increase in its use in the healthcare setting,” said Balaji Veeraraghavan, a clinical microbiologist at Christian Medical College, Vellore, via email. But colistin’s use is not restricted to clinics. As Dr. Veeraraghavan mentioned, India is listed among the largest producers of colistin for veterinary use and for export to European countries. “Many companies in India sell colistin, which costs about Rs 5,000/kg, for non-human use and is freely available like fertilisers,” he added.
As colistin becomes more frequently used around the world, it would not be long before the bacteria learnt to overcome this obstacle as well. Last July, a team of Italian scientists reported a colistin-resistant bacteria outbreak in a hospital in their country. The resistance seemed to be caused by a chromosomal mutation. Mutated bacteria are able to spread within and between hospitals, but a strict infection control strategy is sufficient to tackle these types of outbreaks.
However, a Chinese study published a few months later in November gave us a new reason to panic. While doing a routine surveillance of antibiotic-resistant E.coli bacteria in food animals in China, researcher Yi-Yun Liu and team made a startling discovery. They found that a sub-type of E.coli contained a gene called mcr-1 which was making them colistin-resistant. The scary thing about mcr-1 is that it can spread from one strain of bacteria to another by a mechanism called plasmid-mediated transfer.
Running out of options
The danger, explained Olivia Lawe Davies from WHO via email, is if mcr-1 spreads to bacteria that are already resistant to other antibiotics. “This would result in bacteria that are resistant to all antibiotics causing infections that are effectively untreatable.”
The mcr-1 gene was found in multiple settings in China: in E.coli isolated from pigs at a farm, in pork and poultry meat from slaughterhouses and supermarkets and subsequently in samples from patients admitted in two different hospitals. Soon after, findings by researchers from France and Denmark confirmed that mcr-1 was present in their countries as well.
Dr. Veeraraghavan calls this development a public threat. “Rate of colistin resistance has been reported to be as high as 20% in Greece among K.pneumoniae, 21% in A.baumanii. This is a major concern.”
With their article, Marc Sprenger and Keiji Fukuda, from WHO’s Antimicrobial Resistance Secretariat, bring back the spotlight on the objectives of the Global Action Plan on antimicrobial resistance that emerged at the World Health Assembly in May 2015. They say that while preserving and regulating existing antimicrobials is crucial to protect their effectiveness, the present situation is dire enough to warrant an accelerated search for new antimicrobial agents that can compensate for the fall of colistin.
“There has been no new class of antibiotics developed in 30 years, and none of the antibiotics currently in the development pipeline are expected to be effective against the most dangerous bacterial mutations that have emerged,” warned Lawe Davies. Dr. Veeraraghavan agreed: “Drugs with new mechanisms of action are need of the hour.”
Experts concede that even if we do discover a new antibiotic, the development of resistance is inevitable. “We need to work to preserve all antibiotics, new and old,” said Lawe Davies. It’s a tall task – one that the WHO believes cannot be solved by the human health sector alone. Sectors as diverse as human health, agriculture, environment, trade and education will need to collaborate to come up with the best strategies. Some of these are expected to be agreed upon by global heads of state at the UN General Assembly in New York in September this year.