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Mutiny in the Body
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By Pauline Jestadt
When penicillin was introduced almost 60 years ago, it was considered a medical miracle. Along with vaccines, it virtually wiped out many infectious diseases, which until then, had threatened communities around the world. By 1996, over 26 million prescriptions for penicillin and other oral antibiotics were being dispensed each year in Canada, making this the second most common class of drugs after heart medicines. But as prescription of antibiotics became commonplace, the first signs of resistance emerged, meaning the bacteria were becoming more or completely unaffected by the drugs. To help prevent the growth of resistance, it is important that antibiotics be used appropriately. That’s why grassroots programs have been set up across the country to educate health professionals and the public that patients don’t need an antibiotic every time they have a cough or cold. Antibiotic prescriptions use in this country has fallen by close to 10 percent in recent years. Is this enough? the Health Journal turned to the following experts to find out:
Dr. Donald Low, Microbiologist-in-Chief at Toronto’s Mount Sinai Hospital, and the Toronto Medical Laboratories Professor at the University of Toronto
Leanne MacFarlane, PhC, manager of professional services at Managed Health Care
Services Inc. (MHCSI), and a Halifax pharmacist
Dr. John Stewart, family physician, Port Perry, Ont.
Dr. Kathleen Tobler, clinical associate in the intensive care unit of Alberta Children’s Hospital and a Calgary pediatrician
The Health Journal (HJ): Is antibiotic resistance a serious problem in Canada?
Dr. Donald Low: Over the past five years, there’s been a striking increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA). Staph aureus is an organism recognized throughout history as being able to cause infectious disease with marked morbidity and mortality in the hospital setting. It’s probably the most important health-care problem today when we talk about resistance. We’re also seeing an increase in vancomycin-resistant enterococci (VRE), following the huge increase in use of the antibiotic vancomycin both in the U.S. and Canada and its misuse in animal feed in Europe.
Leanne MacFarlane: With MRSA and VRE, we’re getting to the point where we’re starting to see resistance to the last reserve in therapy; the final lines of defense are rapidly coming to an end. That’s scary. It’s happening primarily in hospitals where these organisms are more easily passed around.
HJ: Have there been lethal outbreaks in hospitals?
Dr. Low: In hospitals across the country, we probably see about 2,000 deaths a year related to antibiotic resistance. Ten years ago, this number was significantly less. It’s mostly immunocompromised patients who are very sick, perhaps an HIV patient, someone undergoing cancer chemotherapy or a patient with multiple organ failure in the intensive care unit. These patients are on the edge, and an infection from a multi-drug-resistant organism is enough to push them over the edge.
HJ: Is the problem restricted to hospitals?
Dr. Low: No. In the community, we’re mostly concerned about Streptococcus pneumonia, the most common cause of bacterial infections of the middle ear and the central nervous system, and of pneumonia. In the past, this organism was exquisitely sensitive to the penicillins, but that’s changed dramatically in a very short period of time. In 1988, resistance was less than two percent; by 1994 it had gone up to seven or eight percent, and now it’s about 16 percent — in some places in Canada it’s as high as 40 percent. That has a major impact on how we treat meningitis, and eventually could affect how we treat children with middle ear infections.
MacFarlane: As a pharmacy consultant for a third-party administrator, I’ve seen an increase in the number of drug claims processed and a shift towards the use of second-line agents over first-line agents. And as a community pharmacist, I see a lot of people come in with a viral cold or flu, still believing they require an antibiotic to treat it.
HJ: What are first- and second-line agents?
Dr. John Stewart: First-line agents are the drugs that should be used most of the time for a bacterial infection, drugs like the penicillins. The second-line agents, such as cephalosporins, are newer, more expensive, but also very effective. Over the years, it’s become more common to grab one of these second-line antibiotics that will kill everything. It saves time and there’s a certain amount of patient expectation. The desperate two-income family comes into the office with a sick child and the mom can’t afford to take time off work and day care doesn’t want a sick kid. They need something they know is going to work.
Dr. Kathleen Tobler: Take pediatric otitis media as an example. The first-line antibiotic to treat this acute ear infection is ampicillin, which is easily tolerated and inexpensive. It will cover most of the bacteria that could be responsible for the infection, which is Streptococcus pneumonia in about 35 percent of cases. You would use second-line antibiotics only if ampicillin had failed or if the patient is allergic to the penicillins.
HJ: Is the goal then to control use of antibiotics or to insist on first-line agents?
Dr. Tobler: Both. For example, 80 to 85 percent of throat infections are caused by viruses. Of the remaining 15 percent, only some are caused by group-A Strep, the primary organism physicians are attempting to treat with antibiotics. It’s not only a waste of money to treat most of these infections with antibiotics, it also promotes resistance. It’s easy to culture the throat to determine the need for antibiotics in most cases. Otitis media is different: it’s more difficult and invasive to get a culture from the middle ear. Even though spontaneous recovery may occur in 70 to 90 percent of cases, in Canada we still treat it with antibiotics to avoid the serious complications you can have if you’re not in the spontaneous recovery group. In this case, the issue is the use of first-line agents versus broad spectrum second-line antibiotics.
HJ: What causes drug resistance?
MacFarlane: Bacteria communicate with one another, so they can share things they’ve learned about antibiotics. And when you give an antibiotic, you’re not only affecting whatever organism you’re hoping to treat, but you’re also affecting whatever normal flora exist in the body.
Dr. Stewart: If you wipe out all your normal bacteria by taking antibiotics, then if you come across one of the more potent bugs in the next three to four months, you’re more at risk of picking it up and having a very serious disease.
HJ: Is resistance the fault of physician prescribing habits?
MacFarlane: No. It’s a multi-pronged problem caused by a lack of good education and information for patients. Physicians are very busy and are trying to treat patients as effectively as possible, but they don’t always have lab results to go on, so they may empirically decide what to do. Pharmacists are filling prescriptions without necessarily knowing what the diagnosis is, again losing that ability to screen and determine if the most appropriate therapies are being selected. Everyone has to play a role in controlling antibiotic misuse.
Dr. Tobler: Part of the problem is patient preference; parents know certain antibiotics taste better and only have to be taken once a day as opposed to twice or three times a day. We need to take the time to educate patients about good antibiotic choices.
HJ: How do you know that reducing the number of prescriptions will translate into less antibiotic resistance?
Dr. Low: When Finland and Iceland had a resistance problem with group-A Strep in the late 1980s they instituted a policy of reducing prescriptions and actually saw a reduction in the amount of resistance. We hope that has set a precedent and that the same trend can be applied in our case.
HJ: What, other than the questionable prescription practices, is causing drug resistance?
Dr. Low: We can also blame the simultaneous cut in resources. Laboratories are being downsized and merged, and staff required to do more work in less time. Laboratory technologists are responsible for a wider spectrum of testing, for biochemistry and hematology, as well as microbiology, so they’re losing their expertise. This can result in inadequate surveillance to identify patients who might be carrying these organisms. In microbiology, there’s an incredible amount of expertise required of the bench technologist to identify these problems so we can do something about them.
HJ: Are there initiatives to turn around this trend?
Dr. Low: A clinical score helps doctors decide whether to prescribe an antibiotic to patients with an upper respiratory tract infection and sore throat. The score is based on answers to questions about the presence of fever, tender lymph nodes, throat swelling, pus on the tonsils and the age of the patient. The physician checks off each question and counts the score. A low score means there’s only a slight chance of bacterial infection, in which case there’s no need for a culture and the physician shouldn’t prescribe an antibiotic. With slightly higher scores, they might take a culture but wait until it comes back before giving out an antibiotic. People with viral colds or flu don’t need antibiotics.
Other initiatives include encouraging people to stay up to date with immunizations and flu shots. Health-care professionals need to work as a team to ensure the right antibiotic is selected, that people are using the appropriate doses and that they comply with instructions.
HJ: Should the pharmaceutical industry play a role in controlling antibiotic resistance?
Dr. Low: It obviously has a major interest in this because of the consequences. Growing resistance to the older penicillin or ampicillin can mean that newer drugs aren’t going to work either.
MacFarlane: The pharmaceutical industry must continue to develop more effective antibiotics. It’s coming to the point where some bugs are going to be resistant to the last thing available to treat them. As technology improves, the industry will probably get better at finding things that work in a much more targeted way, but it’s a very lengthy process and this type of research requires a lot of resources.
HJ: What’s the government doing?
Dr. Low: The Ontario government is currently working on looking at the feasibility of instituting a strategic plan for the reduction of antibiotic use. The plan would create a surveillance committee, an antibiotic-use committee and an infection-control committee. These three committees will try to set province-wide standards and policies for the control of antimicrobial resistance and the reduction of antibiotic use. We hope we can set a standard to be copied by other provinces.
Dr. Stewart: There are already other initiatives. In Newfoundland, for example, they’re auditing physician charts to see if they’re adhering to developed standards. In Alberta, they’ve written guidelines for antibiotic use and guidelines are under review in B.C.
HJ: Anything federal?
Dr. Stewart: In May 1997, Health Canada held a meeting in Montreal to study bacterial resistance. At that meeting, it set a goal to reduce antibiotic prescriptions by 25 percent within three years — I believe we could cut much more than that. After that meeting, the federal government established a permanent secretariat to monitor the extent of the problem, to be aware of projects that are in place and to ultimately look at ways of funding projects that have potential to make significant change.
MacFarlane: There has to be unified international effort, too. Antibiotic resistance doesn’t exist within the borders of a country; these bugs can go anywhere around the world. It’s up to health-care providers internationally, as well as governments, to show leadership on this issue.
HJ: Are we winning the battle?
Dr. Low: It was about 1994 when we finally realized we had a problem. At that time we started educating physicians, and the public began hearing that the antibiotics heyday was over. By 1996, we began seeing a reduction in the number of prescriptions. That year saw a three-percent reduction, followed the next year by another three percent, and another again in 1998. Since 1996, use of oral antibiotics in Canada has dropped 10 percent.
Weaning off antibiotics
Dr. John Stewart is convinced that to control resistance against antibiotics, patients have to be part of the process. The huge increase in the use of antibiotics over the years, he says, stems partly from pressure by patients who want a quick fix for the cold or flu. Dr. Stewart, a family physician in Port Perry, Ont., was part of a 1994 provincial government panel to develop anti-infective guidelines.
“A busy general practitioner is vulnerable to patient expectations in the prescribing process,” Dr. Stewart stresses, “and unless there’s a strong reason why that should change, it’s not going to.”
Dr. Stewart drew up a unique model to try to break the trend. The model included just about everyone in his small community of 7,000 people, and others from surrounding areas. He developed a teaching program for health professionals that focused on appropriate prescribing for the most common infections — ear, urinary tract and upper respiratory tract. Dr. Stewart also organized town hall meetings where the public learned the difference between bacterial infections, which need an antibiotic, and the more common viral infections, which don’t. He answered questions about the increased risks of taking an antibiotic when it isn’t needed, and explained how it can wipe out all bacteria and leave people vulnerable to more potent “super bugs.”
If patients go to their doctor with a viral infection, intent on leaving with an antibiotic prescription in hand, instead of giving them the unnecessary drug, Dr. Stewart advises physicians to sign a prescription recommending alternative treatment. “It’s important to treat the symptoms effectively,” said Dr. Stewart. “One thing physicians can do is give patients a really decent prescription cough syrup so everybody gets some sleep at night.”
From October ’96 to March ’97, Dr. Stewart gathered information from 10,000 patient visits for the most common infectious diseases in the Port Perry area. He compared the number of antibiotic prescriptions issued in that six-month period to the previous six months in the same area, and also to antibiotic use across Ontario and across Canada during the two time periods.
“The total number of prescriptions went down significantly and within the prescriptions that were written, there was a significant shift to first-line agents, the agents that should be used most of the time,” Dr. Stewart recalls.
The program was clearly a success, but was that because it was a small rural community where Dr. Stewart was well known and influential? Could something like this work in a larger centre? Dr. Stewart set about to prove the program was portable by bringing it into east Toronto. All feedback indicates that this initiative will be just as effective. “Comments from the medical profession claim that this is the best medical education they’d ever had — very grassroots and very interactive,” Dr. Stewart says.
A third phase of the project will involve seven rural and urban communities surrounding Toronto. Dr. Stewart is working with leaders from these areas to adapt the program to their respective communities. He plans to eventually cover the entire province.
To address the problems caused by the inappropriate use of antibiotics, the National Information Program on Antibiotics (NIPA) was created in 1996. The partners include: The Canadian Infectious Disease Society, The Canadian Medical Association, The Canadian Paediatric Society, The Canadian Pharmacists Association, The Canadian Public Health Association, The Canadian Thoracic Society, The College of Family Physicians of Canada, and the Lung Association.
The “Antibiotics: Use them Wisely” program was launched to the public in January 1997. At that time, the results of a NIPA Gallup poll on attitude toward antibiotics revealed that 26 per cent didn’t finish prescriptions and 34 per cent forgot to take their medication on time or as scheduled. Last March, a NIPA poll on physicians’ attitudes revealed that 41 per cent were more likely to prescribe antibiotics because of pressure from parents or patients, even when they felt antibiotics weren’t necessary.
NIPA has developed new instructional tools to assist physicians and pharmacists in explaining the use and misuse of antibiotics to the public. These include a brochure for patients, a “non-prescription” pad for doctors to use to explain why an antibiotic is not appropriate and “to prescribe” other non-prescription therapies, and a pad of notes for patients who are prescribed antibiotics reminding them of the importance of completing the entire course of therapy.
Chair of NIPA, Dr. Ronald Grossman, professor of Medicine at the University of Toronto and a pulmonary physician at Mount Sinai Hospital, is very proud of the results of this initiative, to date. “Canada is the only industrial nation where prescribing antibiotics has gone down.” NIPA was initiated and is sponsored by an educational grant from Pfizer Canada, Montreal.
Pauline Jestadt is a medical writer based in Toronto.
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