Case History: Rise of the superbugs

PUBLISHED : Tuesday, 09 October, 2012, 12:00am
UPDATED : Tuesday, 09 October, 2012, 9:44am

Madam Thila's health worsened dramatically after a fall at home. It left Thila (whose name has been changed for patient confidentiality reasons) with acute subdural haematoma, or bleeding in the brain, a potentially fatal condition where blood fills the skull cavity, pressing on the brain.

Doctors in her home province of Punjab, India, battled for three months to save the 54-year-old's life, and to stabilise her condition. She underwent repeated surgery, including craniotomies (where a piece of skull is temporarily removed to allow access to the brain) and a tracheotomy (where a hole is made in the windpipe to help get air into the lungs).

Because of her many operations, she had to be given several courses of antibiotics to stave off infection. Unfortunately, Thila was allergic to penicillin and penicillin-like antibiotics, and hence was given a class of antibiotics called carbapenems.

According to Dr Tsang Kay-yan, an infectious diseases specialist at the Hospital Authority Infectious Disease Centre at Princess Margaret Hospital, carbapenems are meant for serious infections that resist all other antibiotics and need to be used with great discretion.

Overuse or inappropriate use of them can lead to the development of bacteria that are resistant to the superdrug. What doesn't kill the bacteria makes them stronger. Part of the need for judicious use of carbapenem, says Tsang, is because no other antibiotics are being developed, and carbapenems are our last defence against severe bacterial infections.

Thila's condition was far from ideal and she remained bedridden. The bleeding had damaged part of her brain, and she was unable to speak or respond much.

Her son lived and worked in Hong Kong, and decided to bring her here to be treated.

A few days after she arrived in Hong Kong, Thila developed a fever, sudden shortness of breath and severe vomiting. She was admitted to Princess Margaret Hospital.

Doctors found that her blood pressure had fallen, and there were low levels of oxygen in her blood - she had to be put on a ventilator and was placed in intensive care.

Chest X-rays showed that Thila possibly had a chest infection (pneumonia) so they tested her sputum for bacteria. As she had some bedsores, doctors took a swab from a wound in her thigh for tests.

A vigilant nurse noted that Thila was recently admitted to hospital overseas - and regulations require such patients, as long as their admission was within the past six months, to be screened for carbapenem-resistant bacteria.

This was in response to the growing worldwide threat of such pathogens. A rectal swab was taken, according to protocol.

Three days later, the report from the sputum, leg wound and rectum specimens returned with alarming results. Different pathogens were found in all the three tests. But one chilling characteristic linked them all: every pathogen was carbapenem-resistant.

Thila was transferred to the Infectious Disease Centre, where she was cared for in isolation. Tsang was called in to help manage her treatment.

He needed to know more about the mechanism by which the pathogens were able to resist the drug, so further tests and gene sequencing of the pathogens were performed. The results filled Tsang with dread. Thila's gut bacteria had the New Delhi metallo-beta-lactamase 1 (NDM-1) gene.

Pathogens with this DNA produce an enzyme called carbapenamase that inactivates the carbapenem antibiotic, rendering it ineffective. They were virtually unassailable.

NDM-1 bacteria are the most feared, not only because they can destroy the super-antibiotic but because they can transfer the NDM-1 gene between strains of bacteria. If the NDM-1 gene is transferred to another antibiotic-resistant bacteria, it could lead to a potentially untreatable - and deadly - infection. That infection could easily spread from human to human. An epidemic of untreatable infections would be unthinkable.

Thankfully, the strains of bacteria in Thila's lungs and leg wound were not NDM-1 positive. Still, Tsang needed to find a way to address the infection that was ravaging her body. Moreover, bacteria had now infected her blood.

Thila's was Hong Kong's first known symptomatic NDM-1 case. A previous discovery of NDM-1 was made from a patient's urine sample but, by then, the patient had no symptoms and was not ill.

Tsang and his team scoured medical journals and reports for other known NDM-1 cases. As of June 18 this year, there have been 306 reported cases of NDM-1 worldwide and 12 deaths.

Surprisingly, colistin - an old antibiotic that has dropped out of favour in the medical community because of its potential to impair renal function - was one of the very few antibiotics known to be effective against NDM-1 pathogens.

Thila was placed on a two-week course of colistin. That helped to bring down her fever and allowed her blood pressure to slowly return to normal. But colistin was unable to eradicate the NDM-1 bacteria. Thila continued to test positive for the bug for five months.

Tsang says it is imperative that the medical community use antibiotics with great care - not all infections need antibiotic treatment. Viral infections do not respond to antibiotics.

When symptoms persist, swabs should be taken to test for the type of pathogen is causing an infection, says Tsang. Simple bacterial infections can be treated using simple antibiotics. Using higher classes of antibiotics to treat simple infections could lead to creating superbugs that are too tough to kill.