Appropriate Initial Therapy and Mechanism of MDR Bacteria

Ryan Shields, PharmD, MS, discusses the importance of appropriate initial therapy, patients at increased risk for multidrug resistance, and the mechanisms that lead to multidrug resistance.

Ryan Shields, PharmD, MS: Among patients with bacterial infections, there are several factors that are associated with worse outcomes for the patient. These include things like severity of illness at the onset of infection, the number of comorbid or underlying diseases that the patient has, older age, and, importantly, receipt of the wrong antibiotics initially. Now, of all these factors, there’s only one that’s modifiable, and that’s the antibiotics we prescribe for the patient. We know that this is critically important for their outcome. Specifically, among patients with bacteremia, if they received the wrong antibiotic initially, they’re at a much higher likelihood for in-hospital mortality or death.

An important key for clinicians is how to identify the patients who do receive the wrong antibiotic initially, and this is where multidrug-resistant pathogens have a huge impact. Because we know infection due to a multidrug-resistant pathogen is the single strongest predictor of a patient receiving the wrong antibiotic initially, because these multidrug-resistant pathogens are resistant to many of the frontline antibiotics we use to treat infections initially.

So, if we take these 2 concepts together, multidrug-resistant pathogens are associated with empiric inappropriate antibiotic therapy. And this is associated with the worst outcome for your patient, including in-hospital mortality. We really have to be judicious in finding out which patients are at the highest likelihood for infection due to multidrug-resistant pathogens.

In this setting, there are 2 important factors that are associated with multidrug-resistant pathogens. Generally speaking, these are exposure to health care settings and exposure to antibiotics. Now, there are very specific patient populations in which oftentimes you find these factors with both health care exposure and antibiotic exposure. These include our immunosuppressed patients, such as those receiving solid organ transplantation, as well as our patients from nursing homes or long-term care facilities who present to the hospital having been exposed to antibiotics and lots of health care settings. For these patients specifically, it’s incumbent upon clinicians to do a detailed history at the time of their presentation to not only find their history of prior infections, but to look at their microbiology records to identify resistant pathogens and also to look at their recent exposure to antibiotics. Taking these factors into consideration will help you decide which is the best antibiotic regimen for this patient initially once you know more about their history.

Several factors contributed to the growing threat to multidrug-resistant pathogens. From a public health perspective, our societal overuse of antibiotics has led to many of the problems that we see now. In the community setting, for instance, we tend to overuse antibiotics to treat things like viral infections. And even when we identify bacterial infections, oftentimes we pick the wrong antibiotic—maybe one associated with more adverse effects—or not the right antibiotic for the patient. Cumulatively then, all this overuse of antibiotics leads to selection pressure for more resistant bacteria, and those patients oftentimes come to our hospital.

Another important consideration from a public health perspective is the amount of antibiotics we use in agriculture, particularly livestock and in farming. By metric ton, the total number of antibiotics we’re using in those settings is much greater than the total number of antibiotics we’re using for patients directly. So, these things also contribute to the burden of antibiotic-resistant infections.

International travel is another contributor from a public health perspective. Patients in other countries infected or colonized by resistant bacteria can now travel the globe more readily than they ever had been before. And these are patients who oftentimes come from other countries presenting to our hospitals and bringing in new mechanisms or new bacteria with new mechanisms of resistance.

Once those patients present inside the hospital, there’re a number of factors that contribute to the threat of multidrug-resistant pathogens. We know that resistant bacteria are spread in the hospitals through nosocomial transmission. This is done through health care workers seeing different patients, and also medical instruments can transmit resistant bacteria as well.

The local epidemiology of your hospital also influences the threat of multidrug-resistant pathogens. If you practice in a hospital that has high rates of drug-resistant bacteria, you know patients presenting in that hospital are going to be at greater risk. Also, local-prescribing practices of antibiotics can influence how readily resistant bacteria are selected for in your hospital.