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Antimicrobial resistance is a real threat, and while danger remains in the continued over-utilization of antibiotics, we can’t let this delay effective treatment for the highly sick.

The overuse of antibiotics has led to increasing worry about “superbugs” — bacterial infections with resistance to medication. This has spurred a necessary curb of their overuse, including inappropriate prescribing in viral infections such as cold or flu, and unnecessary applications in agricultural practices. However, it’s important that fear of antimicrobial resistance (AMR) doesn’t cause health care practitioners to hesitate to use appropriate antibiotics when treating seriously sick patients.

A recent study by Lodise et al. (2016) warns that a reluctance to treat high-risk patients with highly potent antibiotics may be just as dangerous as AMR itself. Lodise demonstrated that seriously ill patients who received delayed appropriate therapy (DAT) stayed in the hospital longer, had more hospital associated costs and an increase in mortality. Additionally, a seminal study by Kumar et al. (2006) showed a 7.6 percent decrease in survival for each hour of DAT in patients with septic shock.

Current practices

According to the CDC, at least 2 million people per year are infected by resistant bacteria in the United States, yet the same study by Lodise et al. shows that 46.2 percent of patients that have resistant infections — where the use of powerful antibiotics is not just appropriate but vital — are receiving DAT.

“Patients that are really in bad shape … if you’re wrong with the initial choice of antibiotic and have to wait a couple days to find the right one, the patient may not be savable at that point,” explains James Hackworth, senior vice president of corporate development for Shionogi Inc., a supporting voice for the need to find a more accurate way to properly utilize these powerful antibiotics in high risk cases.

Finding the balance

When deciding whether the concerns around DAT or the worry of overuse of antibiotics should prevail, doctors have to weigh two complementary risks. One is the risk that the patient has a resistant infection which is influenced by many factors such as prior antibiotic use, lengthy hospital stays and other factors. The other is the fragility of the patient and their likelihood they will have a poor outcome if appropriate antibiotic therapy is not initiated immediately.

This combination of risks — both risk of resistance and medical fragility — forces doctors into a tough choice of using their most potent antibiotics upfront versus waiting until resistance is confirmed.

Not only are doctors burdened with the responsibility of making the call between overall medical risks and the dangers of resistant infection, they’re doing so without a reliable, research-backed system. Right now, there’s no way of quantifying these risks to point to cases where treating with powerful antibiotics empirically outweighs stewardship concerns.

“Right now, there’s no quantifiable way of saying, ‘this is too risky of an infection,’ we must treat more aggressively. Every physician makes their own judgment call based on the information and therapeutic tools they have available to them,” explains Hackworth.  “The problem is [doctors] are often coming down on the side of not treating with the more potent drugs in some high-risk cases. They need more tools.”

A secondary problem is that even if there were a perfect system of identifying the appropriate high risk patients where the most potent antibiotics should be used upfront, currently there are no antibiotics that will cover resistant infections in all cases. Therefore, without greater knowledge of what bacteria are causing the infection, the threat remains that the wrong drug will be selected and not be effective. This is why more research is necessary in novel antibacterial agents that cover higher percentages of pathogens.

Towards a unified system

Those in the health care industry vested in forwarding antibiotic stewardship are hoping for more studies to be conducted to better understand how to quantify the combined effect of the risk of resistance and the risk to the patient of DAT, all the while balancing stewardship concerns. Striking this balance will be crucial to provide the right support to clinicians for their care of critically ill patients suspected to be battling a “superbug.”

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