H1N1 vaccine

Health Care Workers

I believe all health care workers should be immunized against H1N1 and that includes clerks and residents. All health care workers should be immunized annually with seasonal vaccine as well. Healthcare workers have a societal obligation to be available during times of need. The potential large societal benefit outweighs the individual risks.

General Population

Should all of the general population be immunized against H1N1? I am not so categorical here. I understand the position of the Public Health Agency of Canada concerning universal immunization. However, the large majority of illness has not been severe during the first part of this pandemic and a decision to decline immunization is a defendable one. This is certainly true with respect to those above 65 in which there has been very few infections suggesting considerable immunity.

Any risk/benefit analysis is predicate on quantification of risk and this is where things are less clear. The risk associated with this vaccine is undeniably small or it would not have been licensed by multiple national licensing bodies including our own. However, there are legitimate concerns over the level of safety owing to the obvious need for rapid evaluation. The quantification of safety needed for approval was very necessarily less than the level required for vaccines and other drugs that are not needed in as time-sensitive a fashion.

Controversies

The primary safety concerns pertain to the non-viral components of the vaccine as the viral antigens are produced in identical fashion to seasonal influenza vaccines. The Canadian vaccine Arepanrix from GlaxoSmithKline contains the preservative thimerosol and the adjuvant AS03, both of which are somewhat controversial.

Thimerosol
Thimerosol is used in the current vaccine because of the need for multi-dose vials to which adjuvant must be added shortly before administration. It is not practical to add adjuvant one dose at a time. It is a mercury containing preservative that has long been vilified by anti-vaccination groups (especially as a putative cause of autism) and has also been the subject of much study that has vindicated its safety. Despite this large safety data the scepticism persists and the last decade has seen a large reduction in its use especially in childhood vaccines.

My take: Thimerosol is NOT a significant concern.

AS03 Adjuvant
Adjuvants are substances added to vaccines to enhance immunologic response and in the case of H1N1 vaccine are needed to increase the supply of vaccine as much less viral antigen is needed per dose. Arepanrix contains 3.75 micrograms of influenza antigen while Non-adjuvanted vaccine needs 15 micrograms of antigen.

AS03 is one of 2 commercial “new generation” adjuvants that are similar but not identical. The other is MF59 from Novartis for which there is much more experience as it is part of Fluad – a seasonal influenza vaccine that has been widely used in Europe since 1997. The observations of long-term safety pertain to this use of MF59 and are extrapolated to AS03. Both AS03 and MF59 are oil-in-water emulsions containing squalene – a naturally occurring precursor to cholesterol and steroids that is plentiful in shark liver oil, the primary source of commercial squalene (The shark liver origin is the source of fear of problems in people with fish allergy. This is a theoretic problem that has never been reported).

Squalene is particularly controversial in the United States. It was implicated as the cause of “Gulf War Syndrome” when a study of sufferers reported a high incidence of anti-squalene antibodies. Despite much evidence to the contrary and the World Health Organization publishing an extensive report on the safety of squalene containing adjuvants, the US FDA has never approved a squalene-containing adjuvant and the issue may come to a head as H1N1 vaccine shortages loom large in the US.

My take :Early experience with AS03 suggests that is safe and large long-term experience suggests MF59 is very safe. Squalene appears to be a safe component of adjuvants. AS03 has not been used widely and definitive safety information remains to be generated.

Question your doctor about your antibiotic prescription

I gave a talk at the Canadian Society for Laboratory Science annual general meeting today concerning antibiotic resistance. In it I suggested that everyone has a role in the solution to the problem. Afterward someone asked me if they should question their physician more thoroughly when they are given a prescription. It is something I have been asked before and have generally been reluctant to suggest that questioning their doctor’s prescription decision was appropriate. I have been very conscious of the need for a cooperative, blameless approach.

I have changed my mind.

Everyone should demand very specific information about all antibiotic prescriptions. You should be aware of the exact diagnosis, the expected course of illness and symptoms that would suggest need for further medical assessment. Discussions of alternatives are completely appropriate. If your doctor can’t or won’t give you the information you want consider another opinion.

Taking antibiotics is serious business and deserves serious personal consideration. The more questions asked the better.

Are you a clinical ecologist?

We physicians have an obligation to be ecologists. Our collective actions are having measurable effects on the evolution of the microorganisms that live with us and occasionally infect us. Have a read of this paper I wrote with Dr. David Patrick of the BC CDC to see how you can be part of the solution to this ever-escalating problem.

Click here to check it out.

Overcrowding and Understaffing Keys to MRSA Transmission: The Lancet ID

A recent article from The Lancet Infectious Diseases, July 2008, raises the issues of overcrowding and understaffing as key contributors to the rise in MRSA rates.

  1. The drive towards greater efficiency by reducing the number of hospital beds and increasing patient throughput has led to highly stressed health-care systems with unwelcome side-effects
  2. The economic benefits of downsizing health-care systems are likely to have been offset by the increased burden of adverse events, such as MRSA infection, leading to a false economy.
  3. MRSA can compound problems of understaffing in hospitals through its effect on staff workloads and staff availability.
  4. Large outbreaks of epidemic MRSA, or those that cannot be brought under control, might result in ward closure, the consequences of which can be seen as an extreme example of bed blocking.

Feel free to download, read and distribute the full pdf .

Abstract:

Recent decades have seen the global emergence of meticillin-resistant Staphylococcus aureus (MRSA), causing substantial health and economic burdens on patients and health-care systems. This epidemic has occurred at the same time that policies promoting higher patient throughput in hospitals have led to many services operating at, or near, full capacity. A result has been limited ability to scale services according to fluctuations in patient admissions and available staff, and hospital overcrowding and understaffing. Overcrowding and understaffing lead to failure of MRSA control programmes via decreased health-care worker hand-hygiene compliance, increased movement of patients and staff between hospital wards, decreased levels of cohorting, and overburdening of screening and isolation facilities. In turn, a high MRSA incidence leads to increased inpatient length of stay and bed blocking, exacerbating overcrowding and leading to a vicious cycle characterised by further infection control failure. Future decision making should use epidemiological and economic evidence to evaluate the effect of systems changes on the incidence of MRSA infection and other adverse events.

Other key points include:

  1. In Australia, the requirement for hospital beds is predicted to increase by 70–130% by 2050.
  2. fewer people in some high-income countries seem to be choosing nursing as a career, potentially contributing further to the ageing and diminishing size of the health-care workforce.
  3. In the USA, these factors have led to an increase in the average age of registered nurses from 37.4 years in 1983 to 41.9 years in 1998 and 46.8 years in 2004.

From Lancet Infect Dis 2008; 8: 427–34

Superbugs and Discrimination

There has been a large amount of media attention afforded to infections caused by antibiotic-resistant “superbugs”. This is an opportunity to examine the consequences of the increasingly common practice of labeling people as colonized with superbugs for the purpose of applying special isolation precautions intended to minimize spread. By far, the most important of the current superbugs is methicillin-resistant Staphylococcus aureus or MRSA which is the focus of this opinion piece.

MRSA

Staphylococcus aureus (staph) is a normal human-associated bacteria (germ) that lives on the skin and, particularly, in the front part of the nose. All people are said to be “colonized” with staph – i.e. all people have staph in and on them. However, staph sometimes causes infections, most commonly in skin that has been damaged. It is the most common bacteria causing boils, abscesses, infected hangnails and infections in cuts and scrapes. Everyone has experienced at least a minor staph infection. More importantly, it is also responsible for many serious infections, in particular in hospital after surgical procedures. In the 1950’s when antibiotics were first available most bacteria were easily killed by most antibiotics. The bacteria that commonly caused infections in people including Staphylococcus aureus were susceptible to the effects of early antibiotics like penicillin and tetracycline. However the miracle of antibiotics soon started to fade as bacteria became resistant to antibiotic effects and the race to find “new and improved” antibiotics began. The 1960’s through 1980’s were a time of heady optimism when the many new antibiotics that became available “solved” the problem of resistance. Methicillin (and related antibiotics) easily treated staph infections.

But the “bugs” continued to become more resistant to the effects of even new antibiotics. Particularly problematic was the development and spread of methicillin resistance in Staphylococcus aureus. The options for treating staph infections became very limited, often reduced to a single antibiotic – vancomycin, that is only available in intravenous form. Methicillin-resistant types of Staphylococcus aureus (MRSA) became increasingly common, particularly in hospitals, and spread from patient to patient was well described.

Solutions to the “MRSA Crisis”

With spread of MRSA occurring in many hospitals, experts in Infection Control were challenged to find rapid solutions. However, the root of the problem was a very basic one. Canadian hospitals were physically inadequate to control the spread of any kind of bacteria. Basic principles of hygiene had been eroded by many years of “belt tightening”. Reductions in bed capacity had left hospitals commonly operating at greater than 100% capacity. The smaller numbers of patients admitted to hospital were much sicker on average. Cleaning and maintenance staffing levels had dwindled.

With real solutions (investment in infrastructure and human resources) not imminent, approaches turned to identifying the people that had the problem bugs (MRSA in particular) to apply special precautions aimed at limiting spread to other patients. Measures include use of private rooms, physical barriers (gloves, gowns etc), and increased cleaning of the environment near patient. The general term used is “contact precautions” for this above-normal attention to hygiene and signs are used to identify the special rooms. In order to apply this different level of hygiene to only those with MRSA a system of “flagging” patients was necessary. In most Canadian hospitals anyone found to have MRSA is identified in the hospital computer system and contact precautions are initiated when they present for their next episode of care.

Screening for Colonization

In the beginning, patients with MRSA were only identified when they had an infection. Soon, however, a process of seeking out patients that may be colonized with MRSA was advocated. This involves sampling material from the nose and skin for MRSA. This “screening” process was first used to check for spread of MRSA to patients that were close to someone that had a proven infection with MRSA. Typically, the patients sharing the same room would be screened and if MRSA found in their nose or on their skin they, too, would be isolated and flagged in the computer system. These colonized people do not have an infection but still can potentially be the source of spread to more patients. It is not known how long an individual will remain colonized but it may be a very long time or even forever. (Remember that staph is a normal human-associated bug and lives in and on everyone. The only difference between MRSA and other kinds of staph is that MRSA is more resistant to antibiotics).

The advocates of screening encouraged more widespread application culminating in screening of all patients being admitted to hospital as practiced in several Ontario hospitals and reported in the Globe and Mail a few months ago. Millions of dollars are being spent on increased staff and infrastructure to accomplish the task of separating patients presenting to healthcare institutions as the “Clean” (without MRSA) and the “Unclean”(with MRSA) for differential application of precautions to limit spread.

At present in Canada many thousands of individuals are labeled as having MRSA and registered in various databases in hospitals. This has very large implications.

Discrimination Issues

In hospital
Patients on “contact precautions” often get inferior care. Several reports have described the problem access to services. Less Xrays, less physiotherapy, less timely surgery are examples. Because of fears on the part of healthcare workers there is a natural tendency to avoid contact with patients identified as potentially infectious. It does not help that the term “superbug” is commonly used.

Patients on “contact precautions” get fewer visitors. This can be devastating especially to patients needing long stays. Family member fears can be extreme and near impossible to assuage.

Outside of Hospital
Analogous to the initial irrational fears surrounding patients infected with HIV, systematic discrimination in many areas is possible.

Employment
This is particularly troublesome especially for those employed or seeking employment in health care.

Housing
Access to group homes and shelters may be adversely affected for example.

Public services
Access to public transportation may by affected. Limited disabled person transportation in a community may put “superbug” people to the bottom of the priority list for example.

Education
“Superbug” status may be considered in acceptance criteria for all types of training.

As an expert in Infection Control I feel very strongly that the current direction of identifying individuals for special attention as a primary approach to the complex issue of antibiotic resistance is immoral.

While I recognize that some institutions have had short-term success in limiting the spread of MRSA using a “screening and isolating” approach, it is discriminatory and fails to address root cause. What is needed is renewed infrastructure and investment in human resources so that all Canadians needing institutional healthcare receive it in a safe fashion at all times. If all patients were in private rooms there wouldn’t be need for different precautions for MRSA patients because EVERYONE would be appropriately accommodated. If all rooms were cleaned as we now clean rooms housing MRSA patients there would be no need to identify any room as special.

MRSA is not the last antibiotic-resistant bug that will be a problem for Canadians. It is certainly not the only bug that is spread in inadequate healthcare facilities. This complex and exceedingly important issue will not have a simple solution.

Until such time as we find sensible, sustainable, equitable approaches, we must recognize the large sacrifices made by the unfortunate persons identified with “superbugs”. All efforts to mitigate any negative consequences must be made. This may include identifying “superbug” status as prohibited grounds in human rights legislation.

The case for a national Antibiotic Drug Plan

Antibiotic resistance is rapidly escalating and is a threat to us all. It is the “global warming” of medicine and just as energy consumption will necessarily continue, so will consumption of antibiotics. Resistance to antibiotics can’t be completely “fixed” but must be actively managed – forever. As antibiotic consumption cannot be optimized by market distribution active regulatory control is the only option.

At present there are many uncoordinated levels of regulation of drug distribution in Canada. Federally, a new drug must be approved for sale by Therapeutic Products Directorate (TPD). Once approved (given a “notice of compliance” with regulations) a manufacturer can market the drug to prescribers. However, the central marketing effort is directed toward large governmental and third party payers as the vast majority of human drugs in Canada are payed for by these institutional drug plans.

Each province and territory has their own drug plan and their are several large private plans that provide coverage to employees of private companies, unions members, government employees, and some individuals. The provincial drug plans vary widely in structure, eligibility, coverage, administration and means and levels of cost sharing. Once a company is successful in having their drug covered marketing efforts rapidly shift to influencing prescribers. Physicians are “detailed” – visited by pharmaceutical company representatives and provided with promotional materials and samples. Educational events are organized and often enticed with dinners, trips etc. with speakers recruited from the ranks of the “infection expert elite” who are payed with money, or by support for research or other programs directed by the speaker. The majority of the Canadian “infection expert elite” are directly or indirectly involved in pharmaceutical company marketing efforts and not in governmental programmatic approaches to optimizing utilization.

Because of this disparate structure antibiotic consumption varies widely in Canada. The highest consuming province consumes at a rate that is almost double the lowest consuming. Rates of individual drug consumption vary by several hundred percent in many cases. And once added to the formulary of a drug plan there is very little scrutiny of changing consumption. Antibiotics are relatively inexpensive when compared to several other classes of drugs. Rapidly increasing costs of cardiac, gastrointestinal, cancer and neurologic / psychiatric drugs have commanded all of the drug utilization attention.

What is the answer to this obviously ineffective, inefficient system? A national Antibiotic Drug Plan – a completely rational and economically sound response that would distinguish these publicly essential drugs from all other pharmaceuticals. Buying power would lower overall costs. The provinces would welcome federal guidance especially if accompanied with funding. Drug approvals and post-marketing surveillance activities could be tightened. Provincial differences in utilization would be scrutinized and drive an agenda of research into “best practice” of antibiotic use. Professional bodies could be engaged to participate in government supported targeted research into new agents and approaches to infections.

Several years ago at their first ministers conference the premiers unanimously called upon the federal government to establish a national drug plan. It was rapidly dismissed as a money grab by the provinces and simply too expensive for the federal government to consider. I feel it was an opportunity squandered. The idea should be resurrected, limited to antibiotics and federally funded. This bold step would position Canada to become a world leader in the management of antibiotic resistance.

We can’t cleanse populations of antibiotic resistant organisms

The current infection control mantra advocating actively seeking out the humans harboring antibiotic resistant bacteria and “decolonizing” them with antibiotics is fabulously flawed and shortsighted. More antibiotics will certainly not be a fix for the complex problem of antibiotic resistance.

There will always be bacteria circulating in human populations. Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae have been living in and on humans since the inception of humanity. When a new or “re-circulated” type (strain) enters a population, as is happening now with so-called community-associated MRSA (USA type 300 or Canadian type CMRSA 10), some people will become ill with relatively minor illness. An unfortunate few will have serious illness. Many more will become immune without illness. The strain will spread widely and over time will appear to be less virulent (able to cause disease) as the immunity of the population increases. It will be transmitted less efficiently as there will be fewer people with overt disease and fewer susceptible individuals. Another strain will emerge that has an advantage and the complex story will write its next chapter.

It is simply not possible to fundamentally change this circumstance by focussing on the individual “bad” organism and killing it with more antibiotics. While “decolonizing” has a well-defined benefit in particular circumstances (the use of antiseptics and antibiotics prior to surgery is the best example), it certainly can’t be viewed as a rational public-health response to a continuously changing world-wide ecologic problem. The extreme efforts focussing on individual organisms are stifling the debate on fundamental solutions for managing (not eliminating) antibiotic resistance and infections caused by antibiotic resistant microorganisms. Firstly, we need much more attention to antibiotics at all levels. Programmatic approaches to optimizing their distribution are essential. Secondly, we need a major renewal of healthcare infrastructure engineered to limit the spread of microorganisms. There is absolutely no reason why Canadians can’t address these issues and become world leaders.

The antibiotic resistance file must be elevated on all agendas.

It is all about design

Everybody pees. Urinals are poorly designed. Pee ends up on shoes and pants and floors.

Someone in the Netherlands tackled this problem and designed a urinal that efficiently catches pee and uses a clever bit of psychology to help the boys leave the maximum amount of pee in the urinal. A fake fly is etched on the porcelain in precisely the right spot.

By the time it is realized that the fly doesn’t move the pee is collected – simply brilliant.

A Bee in the Urinal

Sink design to blame for outbreak

One patient, one room, one bed, one sink goes the infection control rhyme. That was until a Pseudomonas aeruginosa outbreak between December 2004 and March 2006 at Toronto General Hospital killed 12 transplant patients.

The issue: tall, high pressure ‘gooseneck’ sinks drove water straight into the drain hole of the sink without getting water into the basin.

The problem: sludge in the bottom of the sink containing Pseudomonas aeruginosa was splashed out of the drain when the high pressure water hit it and transported around the room when people washed their hands.

The solution: Who knows best on this one? The doctor? The Infection Control Practitioner? The epidemiologist? The engineer?

The answer is likely all of the above.

First things first

Design is important and needs to be first. Before cost, before space, before time, before everything else, things need to be designed and evaluated. Things seem to get designed these days to fill a space, or fit along a wall, or to be this tall by this wide, and once the right ratio of tall-ness to wide-ness is achieved, the evaluation is over.

Design is how it works, not how it looks.

Dying for a toilet (or lack there of)

Since the 1980s Clostridium difficile colitis had been recognized as a, generally manageable, adverse consequence of antibiotic therapy. Not surprisingly, outbreaks in hospital were associated with shared bathrooms. Patients usually responded well to therapy and infection control efforts focused on cleaning and providing a private room and bathroom to those affected. Most often outbreaks were relatively easily managed. It was a regularly recurring nuisance type of problem for infection control practitioners.

However, the evolution and spread of an extremely virulent strain of C. difficile (referred to as NAP1 in Canada) has changed the landscape. The likelihood of severe disease ending with colectomy or death has markedly increased. Overall incidence has increased and outbreaks sustained. Canadians are truly dying for the lack of a toilet. Primary prevention is essential.

Canadian hospitals are aging and a cycle of renewal is beginning. We must make sure that acute care hospitals are constructed with a one patient: one toilet ratio. The added capital costs will be recovered many fold in infection avoidance. We need standards that explicitly state the requirement for a toilet for each patient and a maximum of 2 patients per room – Provincial standards and National standards. Lets make it the law.