(From the February 2015 Issue of Research Now)
Existing research has demonstrated that delays as short as an hour in correct antibiotic administration can impact patient outcomes from critical infections, but evidence and guidelines to inform antibiotic decisions are lacking for critically ill children. A recent study published by clinician-scientists at Nationwide Children’s Hospital is the first to use patient-specific risk factors to design and implement a protocol to appropriately select and time antibiotics administered to critically ill children in the pediatric intensive care unit (PICU).
“Previously, less than two-thirds of patients that ultimately had positive bacterial cultures actually received an antibiotic that covered the organism prior to the culture results returning,” says Todd Karsies, MD, a critical care physician at Nationwide Children’s and lead author of the study, which was published in the Annals of the American Thoracic Society. “Use of the new protocol resulted in a significant increase in the rate of appropriate empiric antibiotics, with 90 percent of patients receiving the correct antibiotic, and it also decreased the time until appropriate antibiotics were prescribed.”
Researchers evaluated all of Nationwide Children’s PICU patients with suspected infection in the year prior to and for one year after protocol implementation. They examined appropriate selection of empiric antibiotics and time elapsed between collecting a bacterial culture and administering appropriate antibiotics, in light of individual risk factors and culture results.
“There is growing evidence suggesting that giving correct antibiotics to critically ill patients with suspected infection, as quickly as possible, is vital in ensuring the best patient outcomes,” says Dr. Karsies. “However, we are seeing rising rates of antibiotic-resistant bacteria, and there are almost no pediatric guidelines to help determine which children in the PICU are at high risk for resistant bacteria, which can make correct antibiotic selection challenging — particularly since using inappropriately broad antibiotics can lead to toxicity and antibiotic resistance.”
By using individual risk factors as part of the decision-making process, researchers were able to limit the use of extremely broad antibiotics in one-third of patients who were low-risk, potentially decreasing the development of antibiotic resistance or toxicity related to antibiotic overuse.
“Our main intervention was the implementation of an empiric antibiotic protocol covering all patients in the PICU with suspected infection,” explains Dr. Karsies. “The most important component of the protocol was the creation of two pathways: one for patients felt to be at low risk for resistant or health care-associated Gram-negative pathogens, and another for those felt to be at high risk for these organisms.”
To evaluate this risk, the clinician-researchers created a set of risk factors that reflected high exposure to the health care system, such as a recent hospitalization, that would indicate a greater potential for infection with a resistant pathogen. High-risk patients were prescribed broader spectrum empiric antibiotics, including two anti-pseudomonal agents, which are used to treat infections resulting from Pseudomonas aeroginosa, an antibiotic-resistant bacteria commonly encountered in health care settings. Low-risk patients were prescribed narrow-spectrum drugs designed to cover typical, community-acquired pathogens.
“There are no pediatric guidelines to help clinicians make empiric antibiotic choices in the PICU,” explains Mark Hall, MD, a critical care physician at Nationwide Children’s and senior author of the recent study. “This work offers the first risk-based framework in which to make these decisions and is a first attempt at tailoring antibiotic choices to patients’ individual needs.”
The research team is currently evaluating modifications of the individual-level risk factors to further reduce the number of patients who are prescribed broad-spectrum antibiotics without diminishing the rate of appropriateness or time until correct antibiotics are administered. Much of the delay in appropriate antibiotics occurs prior to ICU admission, Dr. Karsies explains, so they are also studying the impact of this protocol when applied to critically ill patients pre-ICU, in the emergency department.
Karsies TJ, Sargel CL, Marquardt DJ, Khan N, Hall MW. An empiric antibiotic protocol using risk stratification improves antibiotic selection and timing in critically ill children. Annals of the American Thoracic Society. 2014 Dec, 11(10):1569-1575.