The Benefits of Dual Therapy for Gram-Negative Infections: An Assessment of the Guidelines

Prior to the kick off of ID Week 2018, the Society of Infectious Disease Pharmacists (SIDP) hosted their 2018 Annual Meeting in San Francisco, California. The SIDP meeting included several exciting presentations on trending topics and issues in infectious disease pharmacy.

As part of the program, Julie Ann Justo, PharmD, MS, BCPS-AQ ID, clinical professor at the University of South Carolina School of Pharmacy, gave a presentation on the use of combination therapy for gram-negative agents.

Dr. Justo sat down with Contagion^® to discuss her presentation, which reflected on the Surviving Sepsis guidelines, hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) recommendation guidelines, as well as national guideline recommendations and primary literature.

“What I tried to do was to focus on what’s new in combination therapy and discuss some of the limitations of the large body of evidence that we have and really try to focus on why are we still debating this topic after many years of research.” Dr. Justo explained. (see video).

The most recent HAP/VAP guidelines were updated in 2016 and encourage more customization of when to use combination-gram negative therapy based on local epidemiology. The recommendations also support the use of hospital antibiograms, including unit specific antibiograms.

Although customization is encouraged in some elements of the guidelines, a specific recommendation encourages the use of combination gram-negative therapy for the initial management of septic shock in the empiric setting.

Dr. Justo commented on the severity of illness, explaining that it is important to acknowledge because available data evaluating combination in comparison with monotherapy for gram-negatives mostly favors monotherapy or indicates that combination therapy does not have to provide an advantage. (see video).

“You start to see the benefit of combination therapy when you start looking at subgroups or specific studies that really focus on patients that need vasopressors, have failed fluid resuscitation, and have hemodynamic instability,” Dr. Justo stressed. “In those patients, it really seems like getting a second agent on board that in some cases would be active for that gram-negative in those first crucial 3 days of therapy—that really can be life-saving.”

In addition to discussing combination therapy, the presentation highlighted that the HAP/VAP and Surviving Sepsis guidelines fail to provide strong, specific recommendations about incorporating relevant factors into risk score algorithms.

Dr. Justo discussed the importance of considering antimicrobial history and microbiological history. (see video).

Furthermore, she emphasized the need to improve antimicrobial history information by collecting data about the recency of exposure and duration of exposure to treatments which can provide more information about the risk of resistance.

In regard to microbiological history, the guidelines state that a history of colonization or prior infection with multidrug-resistant gram-negatives indicates that a patient is going to be at a higher risk for multidrug-resistant gram-negatives with current infections, but information on how to incorporate the information into algorithms is lacking.

According to Dr. Justo, the microbiology and antimicrobial history will go a long way in determining the risk of resistance. Infectious disease pharmacists can include more information that can help better predict resistance as well, she stressed.