infectionNet Blog

When can bacteremic patients be switched to oral therapy?

Jessica Otte is a tireless improver and her work with Choosing Wisely led her to a very pragmatic question. When can admitted bacteremic patients be safely switched to oral therapy? Here are some pearls.

Urinary tract infections

Pyelonephritis is the most common source for bacteremia. Many of these patients can be changed to oral therapy quite quickly. By the time ID and susceptibility information is available, the change can be safely made if there has been clinical improvement and there is no worries about oral absorbtion.

Bacteraemic Pneumococcal pneumonia

Many of these patients can be safely and effectively changed to oral therapy if they are obviously improving. There has been a push toward shorter courses of therapy in general for CAP with 5 days now being “standard”. While bacteremia is a predictor of bad outcomes in these patients the ones that do poorly generally do so from the outset. The ones who improve promptly usually do well and oral therapy is appropriate.

Biliary source (usually coliform)

Most often this is associated with obstruction and surgical intervention is commonly needed. After obstruction has been sorted out (stenting etc.) change to oral or even discontinuation can be considered for those with good clinical change.

Beta-hemolytic streptococcus bacteremia from obvious cellulitis or erysipelas.

Once clear that it is not a necrotizing infection requiring urgent debridement, this can be treated in the same fashion as non-bacteraemic cases with the advantage of being able to use very targeted therapy (usually PenV). When systemic signs of infection have abated it is safe and effective to change to oral therapy. And remember that the leg almost always looks worse for several days before it looks better. If the patient FEELS better and is systemically improving, the leg will follow…

S. aureus

Be very careful with S. aureus. It is almost always associated with an occult source that may be hard to identify and that commonly needs surgical attention. A parenteral course of at least 14 days is almost always needed and no generalizations about change to oral therapy can be made. Infectious Diseases consultation is highly recommended.

And as always, my colleagues and I are available 24/7 to help out with these difficult decisions. And if you aren’t familiar yet with Spectrum. Have a look here Spectrum Web Version also available through a link on the top menu bar in PowerChart and FirstNet) and you can download the app for smartphone here Spectrum App.

Is it time to revisit cefepime?

Not long ago serious infections with E.coli and K. pneumoniae were treatable with a wide variety of antibiotics. The evolution of ESBL and AmpC producing strains has changed things. Now it is common in Canada to see infections with strains that are resistant to all of the “workhorse” hospital antibiotics (ceftriaxone, piperacillin-tazobactam and ciprofloxacin) making carbapenems the primary agents. Carbapenem use is rising and carbapenemase producing organisms are appearing on our shores – a very large concern.

Cefepime first became available in 1994 and was marketed as the first “4th generation” cephalosporin with a spectrum of activity similar to ceftazidime but with standard Q12H dosing. It is approved for the treatment of pneumonia, urinary tract infections, skin and soft-tissue infections, intra-abdominal infections and febrile neutropenia. Despite its broad label indications it has never been used widely in Canada. On the current BC provincial hospital formulary it is restricted to febrile neutropenia and cystic fibrosis.

Cefepime is the cephalosporin that is most stable to AmpC beta-lactamases of chromosomal or plasmid origin. There is growing clinical evidence of efficacy even in the context of hyperproduction of AmpC enzymes See

With the only alternative therapy often being carbapenems, cefepime is being advocated as a “carbapenem-sparing” strategy for SPICE organism and AmpC E.coli, K. pneumonia and P. mirabilis infections.

It may be time to utilize cefepime more fully in BC.

Antimicrobial Stewardship in Acute Care Settings

Antibiotics have been used since the 1960s and have been essential in the evolution of modern hospital care. Safe, effective, and relatively inexpensive, their use expanded markedly during the 1970s and 1980s when many “new and improved” antibiotics became available; they were convenient and had a broad range of uses. One new antibiotic, for example, often replaced two or three older ones.

As the use of antibiotics grew, so did antibiotic resistance, especially with regard to hospital-associated micro-organisms. This became increasingly worrisome to the health care sector. Coupled with budgetary pressures, antibiotic resistance prompted utilization reviews, which led to antimicrobial stewardship programs in some organizations. These programs are defined in the Accreditation Canada Required Organizational Practice (widely known as “ROP”) as:

“…an activity that includes appropriate selection, dosing, route, and duration of antimicrobial therapy. The primary focus of an antimicrobial stewardship program is to optimize the use of antimicrobials to achieve the best patient outcomes, reduce the risk of infections, reduce or stabilize levels of antibiotic resistance, and promote patient safety” (Accreditation Canada, 2013).

Most stewardship programs began in large, academic medical centres that had specialists in medical microbiology, infectious diseases, and clinical pharmacy. Programs often depended on the interests of local experts, were generally pharmacy-based, and were subject to the competitive pressures of rising expenses in all drug classes. Very little acute care antimicrobial stewardship occurred outside these centres.

In the mid-1990s, the Canadian Infectious Disease Society and Health Canada co-sponsored a two-day conference called “Controlling Antimicrobial Resistance: An Integrated Action Plan for Canadians.” Experts and policy makers came together and made numerous recommendations including the establishment of “…antibiotic stewardship and antibiotic use teams in all Canadian hospitals by incorporating them into accreditation standards.” Unfortunately, very little happened after that for a number of years.

Then, in 2005, a seminal report was published by Dr. Jacques Pépin, describing a large increase in the incidence and severity of Clostridium difficile (C. difficile) in Quebec. The report claimed that C.difficile was responsible for an estimated 2,000 deaths, a claim that quickly put hospital infections in the public and political spotlight. C. difficile and Severe Acute Respiratory Syndrome (SARS) had exposed serious shortcomings in infection prevention and control(IPC) in hospitals, and the response was swift. Investments in IPC were made across Canada—infrastructure was improved, more IPC personnel were hired, and some decreases in the rates of hospital-acquired infections were noted. Antibiotic stewardship was recognized as an appropriate response to C. difficile but there were few changes outside Quebec.

The quality and safety movement

The Canadian Patient Safety Institute was established in 2003 as a federal response to the increasing focus on patient safety. Since that time, there has been a slow and steady increase in provincial and acute care infrastructure to promote safety practices. Most jurisdictions have established health quality councils or undertaken a similar initiative within government. It is vital that central structures (e.g., health authorities, provincial governments) and experts actively support the administrative functions, such as policy and priority setting, of antimicrobial stewardship programs.

Many new and robust IPC programs were created under quality and safety portfolios and their creation helped move quality and safety agendas forward. Accreditation Canada, for example, as an independent, third-party organization, markedly increased the IPC requirements in its standards to support quality improvement.

Human resources

Who then is integral to these antimicrobial stewardship portfolios? Clinical pharmacists are the backbone of acute care infrastructure. Much of the day-to-day delivery of antimicrobial stewardship programs is performed by clinical pharmacists with guidance from senior clinical pharmacists and physicians. Clinical pharmacy programs are generally well established in academic health science centres and less so in smaller health care centres because antimicrobial stewardship often has to compete against other clinical pharmacy services for resources. Quantifying a need and establishing stable funding for clinical pharmacists is an essential step in establishing antimicrobial stewardship programs.

Physicians are integral to antimicrobial stewardship programs. A local champion with specific medical knowledge can help develop and maintain these programs. Yet, most infection specialists (infectious disease specialists, medical microbiologists) work in large centres; it will be important to find ways to interest local clinicians in working on programs at smaller centres.

It will also be necessary to reconsider medical human resources as they relate to consultation and expert guidance in case management. The use of remote technology for consultation will facilitate the expansion of antimicrobial stewardship programs into more remote communities. Because of the concentration of medical expertise in large, urban centres, and the size of Canada, it will be important to develop region-specific solutions that will likely involve remote technology to support human resources.

Information technology and data collection

Two types of information are essential to antimicrobial stewardship—antimicrobial use and antimicrobial susceptibility (i.e., laboratory testing of the effectiveness of an antimicrobial agent). Most Canadian institutions do not have well-developed systems to meet these data needs. Some of this is happening as facilities are modernized and upgraded, but it is essential that the needs of antimicrobial stewardship programs be considered during laboratory or pharmacy technology upgrading efforts.

The development of provincial data collation and interpretation centres could also play a role in supporting standardized measurement of success and areas that need improvement.

Quality and safety—the connection with IPC

Administrative support for antimicrobial stewardship falls naturally within the quality and safety portfolios, and these are clearly aligned with IPC. Synergy among IPC programs can be realized quickly, as many physician champions are involved in both IPC and antimicrobial stewardship. Of course, the microbiology laboratory is also an essential partner.

Some international programs have been moving toward infection management teams, with more integration of infection prevention, diagnosis, and therapy. This may be the next logical step in Canada.

A Scottish model

The Scottish Antimicrobial Prescribing Group (see SAPG) was created to facilitate implementation of a 2008 action plan on antimicrobial resistance. Numerous lessons can be learned from its success. See

One of the primary lessons is that dedicated funding is essential—new money was identified to create the SAPG infrastructure and to fund clinical pharmacists in all of the regional boards. The same type of investment is required in Canada.


In the past decade, quality and safety portfolios have become increasingly important in Canadian health care organizations, better positioning Canada to tackle the difficult challenge of managing antibiotic resistance using antimicrobial stewardship programs. With serious attention and investment, antimicrobial resistance is manageable.

The perils of pet rats


In my 18 months of taking my turn overseeing the Vancouver Island Health Authority diagnostic microbiology laboratory I have been involved in the diagnosis of 3 cases of Streptobacillus moniliformis infection.

All three were quite serious requiring several days of hospital care. All three involved pet rats. At least 2 of them were not associated with a bite but were associated with very intimate “face to face” contact with the rat. I believe there have been four more cases within the last 3 years diagnosed in our lab. Seven cases in one small city in three years associated with pet rats without bites.

Rat bite fever is a serious infection that can be fatal. All rats have S. moniliformis in their mouths. All rat owners are at risk. It is clear that close contact without a bite can transmit this infection. It seems reasonable that an attempt be made to inform rat buyers of the risk and that there is a role for public health.

Likewise physicians need to be aware of the possibility and ask febrile patients specifically about rat contact.

The most recent case is summarized here Rat Bite Fever

Stewardship is Structure

Certainly in the Canadian context, Antimicrobial Stewardship is a public service.

public service noun

  1. : the business of supplying a commodity (as electricity or gas) or service (as transportation) to any or all members of a community
  2. : a service rendered in the public interest

It fulfills both of these dictionary definitions perfectly. Stewardship programs provide a service to members of communities — The community of healthcare providers to aid in their provision of care and to the community at large to provide the ongoing benefits of the availability of effective antimicrobials. This is very much in the public interest.

More established public services such as the police, fire fighting and waste removal are easy to conceptualize and understand. Others such as fisheries and forest management are more difficult. Few would dispute that the management of common resources is important, however. Common to all are several elements.

Could the Department of Fisheries perform its’ functions without information? Of course not. Just as information about fish stocks is necessary to define sustainable fish harvest quotas, information is necessary to manage antibiotics. Fortunately, much of the information needed to manage antibiotic use is readily available. Millions of susceptibility tests are performed and all antibiotics distributed for human use are under prescription and have records associated. We haven’t yet done a good job of collation, redistribution and display but it is only a small amount of idea and resource away.

Nothing ever prospers as a “side of the desk” endeavour. Why would Antimicrobial Stewardship be any different? It needs dedicated thoughtful people with appropriate skill sets – just like anything else. The good news is that evaluations of established AS programs have shown cost savings even after taking account the increased expenditures on manpower. Antimicrobials have been so poorly managed that there is much wasted resource. There is a large potential to turn misused antimicrobials into excellent, well-paid, stable jobs for Canadians.

Policies and Procedures
Policies are informed by principles and guide procedures. Goal statements and metrics for evaluation are central. Nothing unusual about this. However, this is new in Canada and much trial and error is to be expected. The principles should be firmly established but procedures will necessarily be diverse as Canadian health delivery is diverse.

The cornerstone of sustainability. All established conservation programs become easier to enact as the benefits are recognized by more and more people. They become the norm.

Canada is poised for a Antimicrobial Stewardship revolution. We have the enthusiasm, the people and the need. We just need some structure.

Canada’s big antibiotic problem

Canadians prescribe and take a lot of antibiotics and why not? They are safe. They are effective. They are inexpensive. All good? Not at all.

There is a complicated reason why sensible, well-meaning Canadians are making decisions that are harmful to themselves, their neighbours and their children – antibiotic resistance.

The more antibiotics we all take, the more likely that they won’t work for any of us. This makes for a very difficult problem. We need to use antibiotics very well as a group which is very different from how people generally think about things. Drugs are personal, given one prescription at a time by one doctor to one patient. People naturally do not fear antibiotic resistance, they fear personal illness and death.

There are, quite literally, hundreds of thousands of scientific papers describing antibiotic resistance. A search in Google Scholar for “antibiotic resistance” returns “about 1,000,000″ articles. There are also thousands of descriptions of antibiotic misuse in every conceivable area that they have been used. We have not been careful.

Pharmaceutical companies have stopped searching for and developing new antibiotics. There is very little incentive for many reasons:

  1. Antibiotics cure infections quickly. Small amounts are taken for a short time. Drugs taken for chronic conditions are taken continuously for long times making them much more profitable.
  2. Antibiotic resistance can occur quickly making the antibiotic ineffective. This is unpredictable.
  3. Antibiotics must be extremely safe because a large amount of antibiotics are taken for non-serious illness. For example, if one person in a million dies from liver toxicity from an antibiotic taken for sore throat the drug will be removed from the market. Several recent antibiotics have “died” after regulatory approval in recent times for this reason after hundreds of millions of dollars of development costs.

The antibiotics we have are being used poorly and resistance to them is increasing. There are almost no new ones being developed. Disaster is looming.

What is the Canadian response? Basically, there isn’t one. Certainly no concerted one. There is no federal leadership of any kind. There is no coordinated measurement of antibiotic resistance. There is no coordinated measurement of antibiotic use. No drug plan, provincial or third-party, regularly evaluates the appropriateness of the antibiotics they pay for. Physicians are not evaluated in their antibiotic knowledge or prescribing practices by anyone. Instruction in medical schools concerning antibiotics is very sparse.

Current drug regulations don’t work for antibiotics

Despite the very obvious differences, antibiotics are subject to the identical regulatory structures that govern cholesterol drugs, diabetes drugs, blood pressure drugs and erectile dysfunction drugs. The process works this way:

  1. A new drug must be approved by the Therapeutic Products Directorate (TPD) of Health Canada.
  2. Once approved (referred to as being given a “notice of compliance” with the Food and Drugs Act and Regulations) legal marketing, prescription, and dispensing can occur.
  3. Companies then lobby to get the new drug covered by provincial and large private drug plans (e.g. Blue Cross).

Each province and territory has their own drug plan and several large private plans provide coverage to private company employees, government employees, unions members and some individuals. A very large proportion (~90%) of drugs in Canada are payed for by these plans. It is at this level that control over drug use can be affected by regulation, education and monitoring but there is very little attention afforded to antibiotics because of their relatively small cost. Cardiac, gastrointestinal, cancer and neurologic / psychiatric drugs command all of the drug utilization attention. The individual provinces don’t have the economic interest or the infrastructure to develop antibiotic optimization strategies.

National pharmacare

In 2005 the first ministers conference saw a plea for a national pharmacare plan endorsed by all premiers. It was widely discredited as a provincial grab for federal money as a response to pharmaceuticals being the most rapidly expanding sector of healthcare expenditure. It was scoffed at by the federal government and deemed to be “too expensive” for consideration. This despite overwhelming evidence that the buying power and reduced bureaucracy afforded by cooperation would result in significant savings.

What if it was limited to antibiotics?

The federal expense would not be prohibitive. Outpatient antimicrobials total less than a billion dollars annually. It could lay the groundwork for future expansion to other classes of drugs and most importantly it would distinguish antimicrobials as needing special regulatory attention.

A framework Australia’s Pharmaceutical Benefits Scheme is

Key Recommendations in the Executive Summary of the Report of the Advisory Committee on Animal Uses of Antimicrobials and Impact on Resistance and Human Health

  1. Make all antimicrobials used for disease treatment and control available by prescription only.
  2. Develop an extra-label use policy which ensures that this practice does not endanger human health. Such a policy should include the ability to prohibit the extra-label use of specific drugs of critical importance to human health.
  3. Evaluate, register and assign a DIN to all antimicrobials used in food animals, whether manufactured domestically or imported. This include antimicrobials imported in bulk Active Pharmaceutical Ingredients (APIs), which should be allowed into Canada only under permit. The intent of this recommendation is to stop the direct use of APIs in food animals.
  4. Stop the importation, sale and use of antimicrobials not evaluated and registered by Health Canada. The intent of this recommendation is to stop the “own use” loophole.
  5. Evaluate antimicrobials for growth promotion or feed efficiency using sound risk analysis principles and rapidly phase out antimicrobial claims not fulfilling the following criteria: demonstrably effective; involving products rarely, if ever used in human therapy; and not likely to impair the efficacy of any other prescribed antimicrobial for human infections through the development of resistant strains.
  6. In consultation with the provinces, other federal agencies and industry groups, design and implement an ongoing, permanent, national surveillance system for antimicrobial resistance arising from food-animal production. Surveillance should include indicator and pathogenic bacteria isolated from animals, foods and imported animal products.