SINGAPORE, June 6 — While Singapore has been fighting to contain the deadly Covid-19 pandemic, 64-year-old retiree Lee Soo Han has spent the past year battling a different type of life-threatening infection.

Since undergoing surgery in 2012 to repair a swelling of the abdominal aorta — the part of the artery that passes through the abdomen as it carries blood from the heart — Lee has had three bouts of superbug infections caused by Escherichia coli (E coli) and Klebsiella pneumoniae (K pneumoniae).

E coli and K pneumoniae are common causes of infections but the strains affecting Lee are particularly problematic. They are resistant to several types of antibiotics including carbapenems, a class of broad-spectrum antibiotics reserved for the treatment of multi-drug resistant infections.

He contracted his first superbug infection in 2012, and later in 2019 and December last year following operations to manage complications related to his first aneurysm episode.

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During his most “critical” bout of infection in 2019, when he was having continuous high fever, he was admitted to an intensive care unit.

Lee said: “At one stage, I was lying on the hospital bed and the doctors were trying different cocktails of antibiotics to see which one could work for my infection.

“When I realised that it was a superbug infection, I felt scared but I remained positive because I believed there should still be antibiotics to fight the bug.”

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When oral medications could not help him, doctors at the National Centre for Infectious Diseases (NCID) and Tan Tock Seng Hospital (TTSH) looked for alternative antibiotics.

Lee underwent intravenous antibiotics for almost a year at an outpatient antibiotic therapy clinic at TTSH.

Although the Covid-19 pandemic has been the top healthcare priority in the past year, a silent but deadly global health threat looms.

Lee is among those whose health has been impacted by infections that have become increasingly difficult to treat.

As drug-resistant infections rise, it means that drugs previously effective for an increasing range of common and complex illnesses may no longer work.

Experts told TODAY that the situation could be significantly impacted during the ongoing pandemic.

Dr Lee Tau Hong, head of the Antimicrobial Resistance Coordinating Office at NCID, said: “Globally, many patients with Covid-19 were treated with antibiotics (that do not work on the Sars-Cov-2 virus) as they were assumed to be infected or co-infected with bacteria. However this is often not the case.

“Another consequence of Covid-19 is that a subset of patients do develop superimposed bacterial infections that require the use of antibiotics. Thus Covid-19 pandemic may increase antibiotic use.”

What the figures show

Dr Lee said that antimicrobial resistance is often described as a “silent pandemic” because it is not immediately noticeable and not easily recognised.

In Singapore, one in nine hospital patients (11.9 per cent) have caught an infection while being treated for other conditions.

This was documented by a study here involving more than 5,000 adult patients in 13 acute hospitals from July 2015 and February 2016. It was published in the journal Clinical Infectious Diseases.

Associate Professor Hsu Li Yang, head of the infectious diseases programme with the Saw Swee Hock School of Public Health at the National University of Singapore (NUS), said that there are more than 8,000 infections caused by antibiotic-resistant bacteria each year in Singapore.

This excludes other drug-resistant infections caused by microbes such as fungi, viruses and parasites.

Dr Lee from NCID said: “Since the discovery and the use antibiotics in the last century, some of the antibiotics are losing their effectiveness over time as bacteria causing these infections have become more resistant.”

For instance, about a quarter of E coli and K pneumoniae isolated from infections in public hospital patients in 2017 were found to be resistant to ceftriaxone, a broad-spectrum antibiotic used to treat many types of bacterial infections.

Close to 40 per cent of E coli, a common cause of urinary tract infection (UTI) in public hospital patients, were resistant to ciprofloxacin, a common oral antibiotic that is prescribed for UTI.

“Worryingly, approximately 2 per cent of K pneumoniae are resistant to carbapenems, which is a class of antibiotics reserved for the treatment of multi-drug resistant infections,” Dr Lee said.

It is estimated that such infections could kill 10 million people worldwide each year by 2050, if nothing is done, he added.

Why drug-resistant infections are so common now

Doctors said that the misuse and overuse of antimicrobials, not just through medications for humans but also in activities such as agriculture and environmental contamination, have sped up the rate of resistance.

Assoc Prof Hsu said: “Unfortunately, the development of new antimicrobials and antibiotics has not kept pace with the speed of antimicrobial resistance development for decades.

“So, infections caused by antibiotic-resistant bacteria have become more difficult to treat, especially for the ‘critical’ and ‘high’ priority bacteria on the World Health Organization’s list.”

An example of a superbug labelled “critical priority” by the World Health Organization (WHO) include the carbapenem-resistant Acinetobacter Baumanii. When attacked by this bug, the person suffers from pneumonia and wound, bloodstream, and urinary tract infections.

Drug-resistant infections prolong the time needed for patients to get better and are more expensive to treat.

Dr Lee said: “Alternative antimicrobials frequently require administration of injection, and this can increase the length of hospitalisation and overall cost for these patients.

“Patients receiving some of these alternative antimicrobials may develop more side effects than when treated with first-choice antimicrobials.”

How superbugs spread

There are many ways by which these superbugs can spread. They can be passed between people via contact or when picked up from the environment. Some infections are foodborne.

Anyone can get a superbug infection but people with a weakened immune system are at a higher risk.

For example, methicillin-resistant Staphylococcus aureus (MRSA), a well-known antibiotic-resistant bacteria, can colonise the skin and bodies of people who unknowingly pass it on to others.

Assoc Prof Hsu said: “In the hospital setting, it may be passed between patients by healthcare workers through touch, if they do not wash their hands properly between attending to patients.

“In the home setting, they can also be passed by touch or through part of the environment that becomes heavily colonised (by the bacteria) such as soft toys and blankets.

“There have also been numerous reports of MRSA passing between members of sports teams because they share towels or are involved in sports with heavy contact.”

Why it’s hard to get new effective drugs

To find a way out of the conundrum, Assoc Prof Hsu said that there is a need to encourage development of new classes of antibiotics.

Improving the appropriate use of antibiotics is one strategy to delay drug-resistance.

Yet the pipeline of new drugs that can effectively combat superbugs is running dry.

Compared to drugs for cancer or chronic diseases, for example, the pharmaceutical industry sees limited returns from antibiotic development, Assoc Prof Hsu said. This means there is little incentive for them to invest in research and development to create new drugs.A scientist in a microbiology laboratory working with E coli culture. — iStock via TODAY
A scientist in a microbiology laboratory working with E coli culture. — iStock via TODAY

Professor Adrian Towse, emeritus director and senior research fellow from the Office of Health Economics in the United Kingdom, said that drug-resistance infections are a “global issue that no one country can solve”.

Prof Towse’s research includes looking at new funding models to tackle antimicrobial resistance.

The UK, he said, is adopting a “subscription model” in which regular fixed payments are made for new antibiotics development regardless of the amount of antibiotics used.

“The usual ‘price-per-pill’ model will not give companies a return on their investment and so we will not get the new research and development we need to get the new antibiotics we need,” Prof Towse said, adding that Sweden has a similar system in place and the United States has a proposal for a subscription model.

“We need more innovative countries, including Singapore, to put in place such models that fit their own healthcare systems.

“While many countries have antimicrobial resistance action plans in place, most of them do not address the need to encourage the development and launch of new antibiotics.”

What is being done

To combat the rise of superbugs here, Dr Lee said that a collaborative, multi-pronged and multi-sector approach is required.

He said that in NCID and public hospitals here, there are teams that look at improving and monitoring the appropriate use of antimicrobials for patients.

Infection prevention and control teams are on hand to detect the rate of infections caused by antimicrobia-resistant organisms and implement control measures to prevent spread between patients.

At the national level, the National Strategic Action Plan on Antimicrobial Resistance was set up in 2017.

Several strategies have been implemented to tackle the issue. They include setting up a national coordinating office within NCID and initiating a systematic surveillance programme of drug-resistant bacteria in humans, animals and environment.

What people can do

The experts said that members of the public can also do their part by educating themselves on the issue.

Assoc Prof Hsu said: “Stop asking for antibiotics when seeing a doctor for an upper respiratory tract infection (like the common cold or flu).”

Dr Lee said: “We can all do our part to reduce the risk by maintaining good personal hygiene practices such as frequent handwashing and staying at home when unwell to minimise spreading infection to others. Cooking food properly before eating can prevent foodborne infections.”

Keeping vaccinations up-to-date may also reduce the chance of getting infections that lead to situations where antibiotics may be prescribed.

Assoc Prof Hsu pointed out that consumers should also be conscious that most meat in Singapore are from farms where antibiotics are used as growth promoters.

“As consumers, we can also send a signal that we value meat that is raised without antibiotic growth promoters. Ultimately, the aim is for antibiotics to be phased out as growth promoters worldwide, which has already occurred in the European Union,” he said.

Lee, who has suffered several superbug infections, is still on antibiotic treatment, received through an intravenous drip at home. He goes to an outpatient clinic once a week to review his condition.

He expressed his gratitude to his doctors for keeping him alive and counts his blessings that he is on his way to recovery.

“So far, I’ve not had complications (from the superbug infections). I am also able to carry out normal activities in moderation such as going out for some exercises although I avoid strenuous workouts,” he said.

“I am glad that medicine and science is quite advanced today, and that the doctors found a treatment that works for me, if not, I do not think I’ll be alive now.” — TODAY