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Sunnybrook's test program to place closer monitoring on the delivery of antibiotics is already showing benefits.

Resistance is futile - or at least that's the future goal of a Sunnybrook team working to fend off drug-resistant bacteria by cutting down on the use of antibiotics

It happens in every hospital: a critically-ill patient develops an infection. One example is ventilator-associated pneumonia, a common and serious infection in critical-care patients.

Not knowing which bug is causing the infection, the attending physician starts the patient on one or two or possibly even three broad-spectrum antibiotics, medications that are most likely to cover any potential culprits.

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The patient's samples are sent to the lab. Two days later, the results come back and the bacteria responsible for the infection are identified. Now - in the interests of reducing antibiotic resistance - it may be time to switch the patient to a narrower, more exact antibiotic to target the specific bug.

"We want a drug that is active against that one bug. We don't want to use a sledgehammer when a nail file will do the job," says Dr. Andrew Simor, head of the department of microbiology at Sunnybrook and a senior scientist at the Sunnybrook Research Institute.

Sunnybrook has been a leader in making sure antibiotics are used efficiently and with precision, a practice that helps control antibiotic resistance. And an exciting new initiative is improving antibiotic prescribing even more.

The Antimicrobial Stewardship Program began as a pilot study in Sunnybrook's critical care unit in 2009. The unit was a good place to start, since that is where patients are sickest and potentially exposed to the most procedures, devices and infections.

Antibiotic resistance has increased over the last many years in society and in hospitals, explains Dr. Simor. One of the drivers of this increase is excessive use of antibiotics, also known as antimicrobials.

To steward antibiotic use requires a collaborative effort. The lead investigators for the initiative were Dr. Simor, along with infectious-disease physician Dr. Nick Daneman, pharmacy and infectious-disease expert Dr. Sandra Walker and infectious disease pharmacist Marion Elligsen.

Here's how the stewardship program works: When a patient receives antibiotic treatment, the pharmacy is notified. On day three the team reflects on whether the patient is receiving the appropriate antibiotics. "By then," says Dr. Simor, "we have received labs and cultures, and have much more information on how the patient is doing."

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The infectious-disease pharmacist reviews the situation. Is there an infection? What germ is responsible? Is the patient still critically ill? Are there side effects? How is his or her kidney function? Is the dosage and frequency correct? Should we switch from intravenous to oral? Are there any allergies that might affect the choice of medication?

"Based on that review," says Dr. Simor, "the pharmacist may decide that is still the best drug. Or they may say, we know this organism can be easily treated with a narrower-spectrum antibiotic. We don't need the big guns."

Having made this decision, the pharmacist then reviews the case with the infectious disease physician, who may agree or disagree. They then communicate their recommendation to the physician who is attending to the patient, known as the critical care doctor. "We are only making suggestions," says Dr. Simor. "The critical care doctors should be the final arbiters; in our study, we found they complied with our suggestions 90 per cent of the time. We had excellent cooperation and buy-in."

The program has thus reduced antibiotic use by more than 20 per cent and quelled some resistant bacteria in the Sunnybrook Critical Care Unit. "We have demonstrated significant overall reduction in utilization and reduction in broad spectrum antibiotic use, which has resulted in a decrease in drug costs," says Dr. Simor. "And, even more significantly, there is some evidence of a decrease in the markers of antibiotic resistance and a decrease in C. difficile, compared to other parts of the hospital where rates stayed the same."

Dr. Simor and his team also studied whether tighter control over antibiotics had any undue effects on patients. "Did we affect the length of stay or in-hospital mortality? We studied that and believe the answer is no.

"We don't believe we did any harm and we do believe we have done some good. We have been able to show with scientific elegance that it does make a difference. I've been delighted at our success."

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Sunnybrook's Antimicrobial Stewardship Program was such a successful collaboration that in the fall of 2010, it received funding to be not only continued, but expanded into other departments in the hospital.


Why do antibiotics stop working against certain bacteria?

Bacteria evolve quickly to survive - faster than humans can create new antibiotics. "Bugs are much smarter than we are. They have been around for millions of years, whereas antibiotics have only been around for about 60 years," says Dr. Simor.

Bacteria have three ways to outfox antibiotics: by producing enzymes that change or destroy an antibiotic, by changing their basic structure so that an antibiotic is no longer effective, or by developing an outer shield against the antibiotic. "Every time we develop a new antibiotic, sooner or later some bug will develop resistance," says Dr. Simor.

Broad-spectrum antibiotics, such as the newer cephalosporins and fluoroquinolones, are capable of attacking many different types of bacteria. "In general, the more broad spectrum the antibiotic, the more likely they are to cause resistance," says Dr. Simor. Ideally, doctors prescribe more narrow-spectrum antibiotics to target the exact bacterium, such as penicillin, amoxicillin or a sulfa drug.

Once a "superbug" becomes highly resistant, doctors have to try different antibiotics until they find one that works. "It may add up to a germ being no longer treatable. These are still few and far between, but that's the danger," says Dr. Simor.

Some of the nastiest antibiotic-resistant organisms:

• Methicillin-resistant Staphylococcus aureus (MRSA), which causes skin and soft tissue infections, pneumonia and bloodstream infections.

• Vancomycin-resistant Enterococcus (VRE), a bug that lives in the bowel.

• Clostridium difficile (C. difficile), which causes diarrhea.

• Pseudomonas aeruginosa, an infection that is resistant to many antibiotics, such as quinolones and carbapenems. Hits the bladder, lungs and blood, and occurs most often in hospital.

• Multidrug-resistant Acinetobacter baumannii, which can cause pneumonia and infections in the urinary tract.

• New Delhi metallo-beta-lactamase (NDM-1)-producing E. coli. Resistant to almost every available antibiotic.

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