MRSA breakthrough may spell the end for drug-resistant bacteria

A stealthy enemy

To Kao, S. aureus is a stealthy enemy. About one-third of people worldwide have some in their nose or on their skin. This pattern of coexistence is decades old, but the pathogen rarely attacks the host.

Staph infection only happens when the bacteria penetrates the body, either through a break in the skin or through the digestive or respiratory tracts. The infection causes damage ranging from minor skin lesions to more serious conditions such as pneumonia or endocarditis, an infection of the heart's inner lining.

In 2009, Ho Pak-leung, honorary consultant at Hong Kong's Queen Mary Hospital, confronted an intimidating MRSA infection.

A 42-year-old man who had A-type swine flu (aka H1N1) acquired MRSA in the community - known as CA-MRSA - and died two days after being admitted to the hospital.

"We treated him using aggressive medications, but they were of no help," Ho recalled. "The patient died of pneumonia."

MRSA not only destroyed lives, it drove up medical costs, mainly due to patients' prolonged stays in hospital. According to a 2013 California study, the average hospital cost was around $14,000 per MRSA case, around twice the cost of other hospital stays.

Before, most MRSA occurrences emerged from hospitals or healthcare institutions, where the risk of infection was higher, and were identified as hospital-associated MRSA, or HA-MRSA.

Though Hong Kong's first official CA-MRSA case was recorded in 2004, Ho said the first case actually occurred in March, 2001, when an 8-month-old boy who displayed a number of severe illnesses died 26 hours after being hospitalized.

Since then, Ho, chairman of the Health Protection Program for Antimicrobial Resistance at the Centre for Health Protection, has been monitoring and observing the transmission of the superbug.

Ho, a close colleague of Kao, is an avid researcher. He contributed to Kao's non-antibiotic study, and both men believe the overuse of antibiotics has helped S. aureus develop resistance to many of them.

Growing use

In the first half of this year, Hong Kong saw 632 CA-MRSA infections, according to the Center for Health Protection, more than twice the number reported during the whole of 2008.

According to a recent survey, about 49 percent of 1,200 people questioned in the city said they took antibiotics last year, up from 34.6 percent in 2011.

In a separate study, 97.9 percent of 1,255 interviewees said they obtained antibiotics from a physician.

The percentage should have been lower, given that only 10 percent of flu symptoms are caused by bacterial infection and antibiotics act against bacteria but not viruses. Therefore, it seems likely that a large number were prescribed to treat viral infections, such as common colds, sore throats and flu.

On the positive side, antibiotics have been prescribed as preventive measures. Patients with viral infections have weakened immune systems, which makes them vulnerable to secondary bacterial infections. Antibiotics may help to prevent that, Kao said.

Margret Ip, honorary consultant at the Department of Microbiology at Prince of Wales Hospital, said Hong Kong's public hospitals imposed vigorous regulation of antibiotic prescription after SARS, so antibiotic misuse may be rife in the private health sector.

As pathogens keep evolving and become more complex, the symptoms of bacterial and viral infections are now more indistinct, Ip said: "It's possible that doctors in private clinics, without sufficient and updated patient data to refer to, mistakenly prescribe antibiotics for the wrong ailments."

She suggested establishing a platform to share information between hospitals and clinics, so family doctors can keep track of changes in contagious diseases and the best remedies to employ.

Hong Kong's private practitioners can log antibiotic prescriptions on an electronic health record system, but it's voluntary.

The city is using the platform to monitor antibiotic use in private clinics, but many people have questioned its effectiveness because physicians rarely report excessive prescription if it is not mandatory to do so.

Rising consumption

Globally, surveys indicate that antibiotic consumption in high-income economies was relatively constant from 2000 to 2015, and the rise was predominantly driven by low-and-lower-middle income economies, such as India, China and Pakistan.

Moreover, humans are not the major consumers. Instead, animals account for large amounts of antibiotics that are used to treat or prevent disease, or fatten them for market.

In 2013, global use of antibiotics in food animals was around 131,100 metric tons, and is projected to rise to around 200,000 tons by 2030.

"It would be best to ban all antibiotic applications on farms. However, that would lead to rising food prices and make life tougher for people on lower incomes," Kao said. "Most poultry in Hong Kong is imported, and in light of that it's hard to impose controls."

Last year, the Ministry of Agriculture on the Chinese mainland issued measures to reduce antibiotics in poultry and livestock, and authorities intend to abolish more than 100 high-risk drugs currently used on animals. By 2020, more than 97 percent of poultry, livestock and aquatic products on the mainland are likely to qualify as secure food sources, with antibiotic residues well within safety standards.

In November, the Hong Kong government published a five-year plan to combat drug resistance.

By 2022, it aims to bar breeders from using antibiotics on livestock unless the drugs are prescribed by vets. In addition, the Agriculture, Fisheries and Conservation Department will stop issuing antibiotic permits that allow farmers to purchase and possess antibiotics used on farm animals.

Greater recognition

Recent lab tests on mice show that those infected with CA-MRSA had a 40 percent survival rate after seven to 10 days. A separate group, injected with non-antibiotic M-21, Kao's breakthrough, all survived.

The findings were published in July in the journal Proceedings of the National Academy of Sciences of the United States of America.

Ip, of Prince of Wales Hospital, supports Kao's approach. "In light of today's sweeping antimicrobial resistance arising from antibiotics, the non-antibiotic approach is the way to rein in the problem," she said. Ip is exploring natural compounds in herbs such as skullcap root and Chinese goldthread to see if they can produce drugs to beat superbugs.

However, Qian Pei-yuan, chair professor of the Division of Life Science at the Hong Kong University of Science and Technology, said MRSA may still acquire the ability to fend off M-21, as it did antibiotics.

This year, he identified an enzyme called D-stereospecific resistance peptidases, seen in many bacteria, which is a key factor in MRSA's ability to break down peptide antibiotics, including vancomycin.

Kao anticipates that M-21 will be manufactured as a medication and undergo clinical trials after five years, before being tested on human patients. If it's proven safe, he expects the first batch of M-21 to be used to treat patients with CA-MRSA.

The M-21 breakthrough, a quantum leap in the fight against antimicrobial pathogens, earned Kao's team first prize at the Innovation Academy Awards at the International Consortium for Prevention & Infection Control last year.

The consortium is a leading platform for scientists from more than 100 countries to discuss measures to tackle antimicrobial resistance.

"The award demonstrates that global infectious disease experts are giving the nod to our non-antibiotic approach. They see it as a promising way to possibly iron out problems arising from rampant drug-resistant bacteria," Kao said.