Sunday September 7, 2008
When bugs outwit drugs
By LIM WEY WEN
The battle against bacteria is far from over as we scramble to keep up with the resilience of antibiotic-resistant microorganisms.
WE CAN argue till the cows come home about Darwin’s theory of evolution, but Darwin may be right about natural selection: the most flexible and adaptable organism will have a better chance of surviving the forces of nature.
Dr Steven Chow... The use of potent antibiotics kills off the bacteria that are of protective value for your overall immune system. The theory is somewhat intuitive. After all, German philosopher Friedrich Nietzsche had later observed in his famous quote, “That which does not kill us makes us stronger”.
However, it spells trouble to doctors and infectious disease experts who spend all their lives trying to keep bacteria who lived by the same maxim away from their patients.
Antibiotic resistance (AR) – when the overuse and misuse of antibiotics lead to the increase of microorganisms which are resistant to antibiotics – is a long-standing problem in hospitals as well as in the community as doctors run out of effective drugs to treat infections that were once easy to cure.
XBug it!
The subject of antibiotic resistance is not new, but it remains a problem until today.
Shy of two decades after his serendipitious discovery of the antimicrobial properties of penicillin in September 1928, Alexander Fleming saw the emergence of AR bacteria coming.
A year after he won the Nobel Prize for Medicine for his discovery, he wrote in 1946 that “the administration of too small doses (of penicillin)? leads to the production of resistant strains of bacteria.”
His warning turned out to be true. Only a few years after drug companies started mass-producing penicillin in 1943, microbes began appearing that it could resist penicillin [2].
Now, penicillin resistance is so widespread it can be found everywhere. Even for Malaysia, where antibiotic use has a less extensive history compared to countries in the West, an estimated 90% of the bacteria Staphylococcus (which is a common cause of skin infections) are resistant to penicillin, says professor of pathology Prof Dr Victor K. E. Lim.
Through existing qualities or mutations of their genes, bacteria possess or acquire their abilities to evade the killing mechanisms of antibiotics. These “abilities” include, among others, being able to chemically modify the antibiotic or alternatively render it inactive by physically removing antibiotic molecules from the bacteria’s cell.
Over the years, the infamous “superbug” – Methicillin-resistant Staphylococcus aureus (MRSA), the multiple-drug resistant enterococci, and many others, including the bacteria Acinetobacter baumannii (causes hospital-acquired pneumonia), Pseudomonas aeruginosa (causes hospital-acquired pneumonia, urinary tract infection and blood infection), Streptococcus pneumoniae (causes community-acquired pneumonia) and Clostridium difficile (causes antibiotic-associated colitis) have been found to show resistance towards various classes of antibiotics.
Dr Victor D. Rosenthal ... By advocating good hand hygiene compliance (hand washing and the use of alcoholic hand rubs) and the usage of gauze dressings for intravenous or catheter sites, hospitalacquired infections and antibiotic resistance can be reduced. But as Darwin asserts in his theory of natural selection, the emergence of AR bacteria may only be natural.
“I don’t think you can prevent antibiotic resistance,” says Dr Lim as he recounts a recent study of soil bacteria which exhibits antibiotic resistance even though they are relatively unexposed to antibiotics and modern, man-made chemicals.
“It is difficult to prevent antibiotic resistance, maybe, because – as this study shows – the resistance has been there long before antibiotics were discovered,” says Dr Lim.
Even so, he is quick to note, that “if you use selective force, it will aggravate the situation.”
In other words, the widespread inappropriate use of antibiotics – the selection force that promotes the growth of resistant bacteria - is fuelling an increase in antibiotic-resistant bacteria, says the US Centers for Disease Control and Prevention (CDC) [1].
The use of potent antibiotics kills off the bacteria that are of protective value for your overall immune system, says President of the Federation of Private Medical Practitioners Association of Malaysia (FPMPAM) Dr Steven Chow.
“Such bacteria prevent the more dangerous bacteria from over-colonising your system and overpowering your immune mechanism,” he adds.
With long term use of low-dose antibiotics, the strains that were originally sensitive to the antibiotic will gradually develop mechanisms that can neutralise the antibiotics and subsequently, the AR strains (will) then populate the system.”
Overcoming resistance
Antibiotics are different from other drugs because it has a societal aspect to it, Dr Lim stresses. “The way in which a doctor uses an antibiotic has far-reaching consequences. If we don’t use it properly and cause resistance, we will be (denying) other patients, now and in the future, from the benefit of this antibiotic.”
On top of that, AR infections also has economic implications. According to the CDC, the cost of treating AR infections place a significant burden on society. Individuals infected with drug resistant organisms are more likely to require hospitalisation, to remain in the hospital for a longer time, and to have a poor prognosis.
Beyond clinics and hospitals, appropriate antibiotic use should also be practised in animal husbandry. - Reuters photo It has been estimated that the in-hospital cost of hospital-acquired infections (HAI) caused by just six common kinds of resistant bacteria in 1992 were at least US$1.3 billion (RM4.5 billion) per year excluding other costs such as the cost of lost workdays, post-hospital care or resistant infections in the outpatient or extended care facility settings.
Although it is unlikely for AR to be prevented completely, the reduction of its contributing factors – infection transmission coupled with the inappropriate use of antibiotics due to lack of knowledge by healthcare providers, patient demands for antibiotics and the use of antibiotics in animal husbandry – can prolong the useful life of an antibiotic, says Dr Lim.
Everyone – not just healthcare professionals – has a role to play.
In hospitals, antibiotic and infection control committees are being set up to monitor and control antibiotic usage and infection transmission.
“Antibiotic resistance is still a problem, and we have to be alert at all times. If we are not, it is going to get worse,” says senior pharmacist P. Devashanti, who sits on her hospital’s antibiotic subcommittee.
In our hospital, surveillance on AR include the monitoring of infections, where doctors will take cultures and liaise with the microbiology unit from time to time, especially when there is a difficult infection or an infection outbreak, says Devashanti.
Every four years, the subcommittee will review the hospital’s antibiotic use and its guidelines to prevent its abuse and development of antibiotic resistance in the future.
As for doctors, Dr Chow says: “For the medical profession, there is indeed an accepted clinical practice guidelines that have been produced by the Academy of Medicine Malaysia together with the Ministry of Health and the Malaysian Society for Infectious Diseases and Chemotherapy, which is the basic guide for rational use of antibiotics in various clinical settings.”
It is important to note that antibiotics should be used only for bacterial infections, and not viral infections.
Although doctors are given guidelines on the rational use of antibiotics, the overuse or misuse of antibiotics can result from patient demand, says Dr Lim.
“Patients or their parents do expect an antibiotic to be given, especially so if the patient is unwell for more than a few days... This is not a new phenomenon,” says Dr Chow.
When some patients go to see a doctor, they ask for an antibiotic. And if you do not give it to them, they go to see the next doctor, says Dr Lim.
That is why, he says, many doctors choose to give in to the patient’s demands rather than give a 10 minute health education lecture. “So, it is also important for patients to learn that they should not demand for antibiotics,” he explains.
Patients can take time to discuss with their doctors whether an antibiotic is really needed and make sure they follow their doctors’ instructions to finish the course of antibiotics prescribed. This is because even if you are feeling better, some bacteria may survive and re-infect you if treatment stops too soon.
Beyond clinics and hospitals, appropriate antibiotic use should also be practised in animal husbandry.
According to Dr Khaw Eng Sun, the market development manager of the Federation of Lifestock Farmer’s Associations of Malaysia (FLFAM), farmers use antibiotics to treat sick animals under the guidance of veterinarians. The use of antibiotics for growth promotion in lifestock is not allowed.
Antibiotics that are harmful will be banned by the Department of Veterinary Services and farmers will not have access to the antibiotic, he says.
Besides, the department also supervises the antibiotic use in animals by placing its officers in meat processing plants to check for antibiotic residue.
“In Malaysia, it is allowed to treat bacterial infection (in lifestock). We can’t just kill the animals when they are sick because we have to be fair to the animals,” says Dr Khaw, who is a veterinarian by training.
Following treatment, farmers should wait for the antibiotic to be excreted before the chicken is sold.
Prudence and prevention is key
With big pharmaceutical companies shifting their focus towards developing drugs for chronic diseases, the way forward to managing antibiotic resistance is to control the use of current antibiotics and practise good hygiene, says Dr Lim.
As the past two decades only saw two new classes of antibiotics being introduced for clinical use, antibiotic prudence and infection prevention is likely the most viable measure.
“If you have very good infection control, to a certain extent you can keep down the resistant rates; and if you have very good antibiotic control, you can also keep down the resistant rates. (That is why) usually, what we do is to tackle them both at the same time.
“Firstly you try and educate doctors on how to use antibiotics properly (antibiotic stewardship), and secondly, you improve infection control,” he explains.
For International Nosocomial Infection Control Consortium Chairman Dr Victor D. Rosenthal, the best approach is to prevent the infection by the bacteria rather than pay attention to the resistance of the bacteria.
“The idea is to attack the problem at the source, not the consequence,” says Dr Rosenthal.
The best way to address the problem of HAI and the associated AR is to prevent the transmission of infection, says Dr Rosenthal.
By advocating good hand hygiene compliance (hand washing and the use of alcoholic hand rubs) and the usage of gauze dressings for intravenous or catheter sites, HAIs and AR can be reduced.
“The risk of having a HAI is the same, the only difference is (when you are infected with an antibiotic resistant bacteria), you have less effective antibiotics,” he explains.
“I have always reduced the bacterial resistance rates (in hospitals) without any extra programmes by reducing the transmission of infection.
“It is more effective,” he says.
While AR is likely to stay, the challenge is to find a way to manage the problem. Washing our hands properly and using antibiotics responsibly is a good start.
References:
1. US Centers for Disease Control and Prevention (2007, September 23). If you Have a Cold or Flu, Antibiotics Won’t Work For You! CDC Features. www.cdc.gov/Features/GetSmart
2. Lewis, R. (2005, September). The Rise of Antibiotic-Resistant Infections. FDA Consumer Magazine. www.fda.gov/Fdac/features/795_antibio.html
3. Omilusik, K. (2004, August). From Dye to Peptides: The Evolution of Antibiotic Drugs. The Science Creative Quarterly. www.scq.ubc.ca/from-dyes-to-peptides-the-evolution-of-antibiotic-drugs
4. Yim G. (2007, September). Attack of the Superbugs: Antibiotic Resistance. The Science Creative Quarterly. www.scq.ubc.ca/attack-of-the-superbugs-antibiotic-resistance
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