We're running out of new antibiotics to treat common infections

WHO has been sounding the alarm over the increasing number of pathogens resistant to antibiotics for a number of years now. — Pixabay

Covid-19 left a devastating trail of destruction in 2020.

While vaccines are touted to provide some relief by helping to control the pandemic in 2021, there are also other health threats that need to be addressed urgently.

One of the biggest global public health threats of this century is antimicrobial resistance (AMR).

AMR occurs when bacteria, viruses, fungi and parasites change or mutate over time and no longer respond to medicines, making infections harder to treat and increasing the risk of disease spread, severe illness and death.

The development of antibiotics, antivirals and antimalarials are some of modern medicine’s greatest breakthroughs.

However, as a result of AMR, these drugs are no longer as effective as they used to be.

Infections such as pneumonia, tuberculosis, gonorrhoea and salmonellosis are getting harder to treat.

According to the World Health Organization (WHO), resistance to tuberculosis drugs is a formidable obstacle in fighting a disease that causes 10 million people to fall ill and 1.6 million to die yearly.

In 2017, around 600,000 cases of tuberculosis were resistant to rifampicin – the most effective first-line drug.

Not only that, an alarming 82% of these patients had tuberculosis that was resistant to multiple drugs.

Drug resistance is driven by the overuse of antimicrobials in people and in animals, especially those used for food production, as well as in the environment.

WHO estimates that at least 700,000 people die each year due to AMR, and this figure is expected to rise to 10 million a year by 2050.

Says University Malaya Medical Centre (UMMC) infectious disease consultant Associate Professor Dr Sasheela Ponnampalavanar, “We are running out of antibiotics to treat common infections such as respiratory tract and urinary infections.

“We use whatever we have and hope for the best.

“Despite so many sophisticated treatments available now for, for example, transplantations and cancer, patients still succumb to these multidrug-resistant organisms.

“It is everybody’s responsibility to reduce the resistance level and practise good infection control to prevent these infections from happening.”

Losing their potency

Secondary bacterial infections are common among ICU patients, especially if their stay is prolonged. — Reuters

A few years after the first antibiotic, penicillin, became widely used in the late 1940s, penicillin-resistant infections emerged that were caused by the bacterium Staphylococcus aureus.

These “staph” infections range from urinary tract infections to bacterial pneumonia, and bone and heart valve infections.

Methicillin, one of the strongest in the arsenal of drugs to treat staph infections, is no longer effective against some strains of S. aureus.

Vancomycin, which is the most lethal drug against these resistant pathogens, may also be in danger of losing its effectiveness as some strains of S. aureus that are resistant to vancomycin have been reported.

“Mortality for this infection is 30% and if it’s a resistant staph, it could go up to 60%.

“Even if the patient survives, he will need a lot of time (being treated) in hospital,” points out Assoc Prof Sasheela.

A main challenge in this region is treating carbapenem-resistant Acinetobacter baumannii.

This bacteria mostly affects patients in the intensive care unit (ICU), causing pneumonia and bloodstream infections. It has a high death rate.

The UMMC infection control department head says, “Most new antibiotics are more effective against strains that are not common in our region.

“We have some old antibiotics that can still be used, but because they are so old, there were no proper randomised controlled trials when they were first tested.

“They may have some sensitivity, but we have no idea how effective they are.

“Also, some of these old drugs have adverse effects, so there are limitations (to their use).”

There are potent drugs that are toxic and damaging to the kidney, which are sometimes used in combination with other medicines, as a last resort.

“When Covid-19 first appeared, none of us knew how to treat it, so when patients came in with community-acquired pneumonia – we treated them for that, so there was a lot of antibiotic use.

“We do have point-of-care tests (e.g. PCR tests for the SARS-CoV-2 virus) that we use to differentiate between viral and bacterial infection.

“But it was not widely used in government hospitals until recently because it is an expensive test.

“So now we are able to reduce the use of antibiotics upfront,” she says.

While most Covid-19 patients are not at risk of a secondary bacterial infection, the handful of such patients who develop severe symptoms and end up needing ventilator support in the ICU for a prolonged period will be at risk of such a secondary infection.

She explains, “They end up getting hospital-acquired pneumonia, depending on what bug is circulating in the hospital.

“And in the ICU, the microorganisms are mostly multidrug-resistant.

“We can still treat them with antibiotics, depending on how much antibiotics the patients were exposed to before.

“If their stay is prolonged, then we will eventually have nothing to treat them with.”

With all the Covid-19 standard operating procedures (SOPs) in place, the level of bacterial infection in the community has decreased, but in the hospital setting, the risk has gone up, she notes.

“Our mentality is such that we are so preoccupied with Covid-19.

“When an infected patient comes in, we put on our personal protective gear and observe hand hygiene.

“But the universal hand hygiene standards (involving non-Covid-19 patients) are not there yet.”

Lack of new drugs

The World Health Organization is urging countries to restrict the use of antibiotics in food animal production. — TNS

The clinical pipeline of new antimicrobials is scarce.

In 2019, WHO identified 32 antibiotics in clinical development that address the organisation’s list of priority pathogens, but only six of which were classified as innovative.

UK Office of Health Economics director emeritus Prof Dr Adrian Towse notes that: “We have a few new antibiotics, but we haven’t had any new classes of drugs, which have a different mode of operation that makes it harder for the bugs to develop resistance.

“The new ones are not coming forward at the rate that we’re losing the old ones.

"So the resistance of the old ones is accelerating at a greater pace.

“Fewer and fewer companies are interested in developing antibiotics as we’re not sending the right commercial signals.”

In most countries, the value of a new drug is assessed via clinical superiority in randomised controlled trials, and the focus is on the immediate health impact on the treating patient.

He says, “The problem with the new drugs is that we don’t have superior evidence in randomised controlled trials because of the difficulty in recruiting patients.

“The newer drugs are expensive, so people are looking for evidence that they contribute more – that’s what we have to rethink: the sorts of evidence we look at.

“We should be willing to look at the microbiological evidence if we cannot get the clinical evidence.

“The second part, i.e. health benefits, should not be viewed just from the patient’s point of view.

“Even though they are drug-resistant, we may still be saving their lives (with the new treatment).

“But the knock-on effects are that we’re stopping the transmission from spreading in the community.”

Prof Towse emphasises the importance of keeping the health system going.

“An antibiotic takes about 10 years to develop.

“Governments and the industry have set up various funds to encourage research and development.

“But when companies get to the expensive part of development, i.e. phase 3 clinical trials, they look at the commercial aspect and realise they may not be able to go the full length.”

He cites the case of an American company that developed a promising new antibiotic, but went bust because the sales were so low.

One main reason is that doctors tend to keep the latest and most effective drugs in reserve and only use them on patients who are resistant to all the older antibiotics.

This is to help maintain its efficacy for as long as possible, as the less it is used, the less likely microorganisms are able to develop resistance to it.

Says Prof Towse, “We want to use the new drugs as little as possible and keep them for those drug-resistant patients who cannot be treated with older antibiotics.

“The volumes may be low, but even if we have a relatively high-priced drug, it picks up some of these other elements of value.

“But the returns to the company are very low, so there needs to be another way of pulling up the company.”

He adds, “Our problem is that we need new antibiotics, but our pricing and reimbursement mechanisms, combined with infection control and stewardship programmes, mean that we’re not sending the right signals to the companies.”

Adds Assoc Prof Sasheela: “No matter what antibiotic we come up with, resistance will eventually develop, so we’ve got to use what we have judiciously.”

She explains that when a new antibiotic arrives, it is tested on various microorganisms in the lab, “and surprisingly, even when the antibiotic has just reached our shores, there is already resistance to it”.

Poor awareness

While antibiotics are safe to use, their misuse will eventually rebound to hurt us all. — AFP

In a 2019 telephone survey conducted by the National Antimicrobial Resistance Committee with 1,005 Malaysians on their antibiotic usage and knowledge (Pengetahuan dan Amalan Pengunaan Antibiotik di Kalangan Rakyat Malaysia), results showed that only half had adequate knowledge on antibiotic usage, with 74.2% knowing that different antibiotics were needed for different ailments.

However, 69.2% erroneously believed that antibiotics could hasten their recovery from fever and colds, with 52.2% saying antibiotics were effective against viral infections.

On the bright side, 96% said they consulted their doctors before taking antibiotics.

But 11% would go to a different doctor for a new prescription if the initial doctor they consulted refused to give them the drugs they wanted.

Assoc Prof Sasheela, who revealed the results during a recent webinar, shares that: “A third of the participants believed long-term use of antibiotics was harmful and stopped taking the drugs when they felt better; 15-20% had no problems asking the doctor to prescribe antibiotics and would keep the unfinished, old ones for future use; and another 10-15% said they could buy antibiotics easily from pharmacies without a prescription, and willingly shared their drugs with friends.

“Attitude-wise, 72% felt they needed to take antibiotics if they felt unwell or as a preventive measure, which is wrong.

“What is more worrying is that only a small fraction of participants knew antibiotics cannot treat mumps, headaches, body aches, sore throats, fever, coughs and colds.”

As for the leftover antibiotics, it would be disposed into the dustbin (49%), reused when similar symptoms occur (19%), flushed down the toilet (17%), shared with others (14%), used as fertiliser for trees (9%) or given to pets (5%).

Only 21% rightfully returned the unused portions to the nearest pharmacy, clinic or hospital.

A whopping 74% did not know that antibiotics are used in the agricultural sector.

Clearly, our general awareness on AMR and antibiotics is poor.

Assoc Prof Sasheela offers these tips to combat AMR:

• Do not take antibiotics without a doctor’s prescription
• Do not ask your doctor to prescribe antibiotics without proper clinical reason
• Finish your dosage of antibiotics as prescribed, even if you already feel well
• Do not share your antibiotics with anybody else
• Be realistic – no bacterial infection can be cured in a day, and
• Return all your unused antibiotics to the nearest pharmacy, clinic or hospital for them to dispose of properly.

She says, “Antibiotics were always thought to be something safe, but we know that if they are not used properly, there are adverse effects.

“Acting against AMR is a shared responsibility and if we don’t take action now, the AMR impact could be far more devastating than Covid-19 in the future.”