The complex science of antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD) creates challenges for clinicians attempting to select the optimal therapy for sick patients. The app PK-PD Compass aims to simplify the decision making process and may serve as a valuable educational tool to antimicrobial stewardship programs.
Interview By: Timothy P. Gauthier, Pharm.D., BCPS-AQ ID
[Last updated 9 October 2016]
A while back a fellow infectious disease pharmacist sent me an E-mail message in which he excitedly described a new iPhone app he had come across, which assisted in simplifying the antibiotic decision making process. The app was called PK-PD Compass.
PK stands for pharmacokinetic and PD stands for pharmacodynamic. Together, they are referred to as PK-PD and both are under the umbrella of pharmacology (the study of drugs). Pharmacokinetics relates to drug exposure and is the science of how a drug moves through the body (i.e., absorption, distribution, metabolism, excretion). Pharmacodynamics relates to the patient’s response and is the science of the effects a drug has on the body. In infectious diseases, PK-PD can be very complicated and confusing, so to hear of a new tool I could download and use on my iPhone was very exciting.
Fast-foward to today and in the setting of seemingly insurmountable antimicrobial resistance challenges worldwide, tools like PK-PD Compass are more relevant to medicine than ever before. In turn, to assist in spreading the message about this helpful tool I reached out to Dr. Paul Ambrose and the folks at PK-PD Compass for an interview. They were kind enough to oblige and the result is the following, which is meant to provide insight on the back-story, current ongoings and future plans for PK-PD Compass.
Dr. Paul Ambrose (Pharm.D., FIDSA) serves as President of the Institute for Clinical Pharmacodynamics (ICPD). He has held academic appointments at the University of Oxford and the University at Buffalo. Primarily, Dr. Ambrose’s area of expertise is the application of pharmacokinetic-pharmacodynamic PK-PD principles within infectious diseases. He is pictured here.
PK-PD Background
PK-PD has long served as a tool for pre-clinical drug evaluation along with dose and dosing interval selection for early-stage clinical development programs. For instance, the use of laboratory PK-PD models (in vivo and in vitro) in conjunction with human PK data (concentrations in blood over the course of therapy) facilitates discrimination between potential dosing regimens. Ultimately, this increases the probability of positive clinical outcomes while minimizing the potential for drug-related toxicities.
ICPD has successfully utilized this approach for support of regulatory decision-making and as support for susceptibility breakpoint determinations (e.g., susceptible, intermediate, or resistant). ICPD’s mission is to bring this approach to clinicians (PharmD’s and MD’s alike) by improving their access to PK-PD information and significantly lowering the barriers preventing their use of PK-PD analyses. The end goal is to better inform antibiotic dosing regimen selection where it is needed most, at the patient’s bedside. The PK-PD Compass is the manifestation of this goal.
The PK-PD Compass is a first-of-its kind educational mobile antimicrobial stewardship program to help clinicians make better antibiotic decisions. This application utilizes PK-PD data and analyses to educate clinicians about antimicrobial therapy and dose optimization.
Use of the application involves an intuitive, step-wise process guiding users through inputting pathogen and patient specific information to ultimately yield the probability of attaining drug exposures associated with efficacy for user-selected antibiotic-pathogen pairs. The approach is known as PK-PD target attainment analysis. The PK-PD Compass also allows users to record antimicrobial stewardship events and outcomes. Once an antibiotic dosing regimen is selected, a user may select to receive a follow-up reminder after 48 hours to review the patient’s status and adjust therapy accordingly.
What motivated the creation of the PK-PD Compass?
At ICPD, we serve one person — the patient. We have decades of experience working with numerous drug developers in the anti-infective space, but our primary goal has always been to ensure patient safety and elevate the care they receive. The PK-PD Compass was a natural step toward this goal.
We knew PK-PD had a lot to offer medical practitioners of all levels, but the data needed is often buried in textbooks and medical literature, not to mention the mathematical and programming skills needed can be daunting. There is simply not enough time in the day to set everything in place.
We [Dr. Paul Ambrose, Dr. Sujata Bhavnani and Dr. Christopher Rubino] developed the PK-PD Compass with these issues in mind by building in the required PK-PD information and integrating these data with clinical practice guidelines and recommendations. We also took steps to remove the technical limitations I mentioned by automating a number of processes. Behind the scenes, the PK-PD Compass integrates population pharmacokinetics, exposure-response relationships, and pathogen susceptibility data, by using Monte Carlo simulation, but the user interface is so simple and straight forward you would never know it.
At the end of the day, we created a great tool which educates clinicians about PK-PD by comparing competing therapeutic alternatives through this lens.
When should pharmacists look to use the PK-PD Compass?
To date, the Compass supports 34 antibiotics commonly administered intravenously in a hospital setting. Pharmacists can use the Compass for educational purposes on a routine basis, but we suspect medical professionals will learn the most when evaluating antibiotic regimens in the context of antibiotic-resistance.
The Compass supports the evaluation of multidrug resistant Acinetobacter baumannii, E. coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The ability to educate clinicians about dosing regimens relative to the susceptibility of these extremely resistant organisms provides a lot value.
Available antibiotic susceptibility data is limited by a variety of factors. How does this most impact the utility of PK-PD Compass?
We like to think of susceptibility data as a relatively static tool. These data simply evaluate pathogen susceptibility on the basis of fixed drug concentrations without any consideration of patient-specific factors or dosing frequency.
Consider for a moment where susceptibility breakpoints come from. Breakpoints are derived on the basis of achieving efficacious drug concentrations and positive clinical outcomes for a typical patient population administered a typical dosing regimen. I’d dare to say there is no such thing as typical, every patient comes with his or her own unique set of circumstances.
Don’t get me wrong though — susceptibility information is highly valuable and has served the medical community well for over half a century, but this is only one component of what drives the PK-PD Compass.
As opposed to traditional susceptibility data, the Compass provides a more dynamic approach, integrating information specific to the patient and the susceptibility of their infecting organism. Moreover, the Compass outputs as many antimicrobial agents and dosing regimens as the user wishes. It’s at this point that the clinician can utilize what they have learned and exercise their professional judgment to select an appropriate antibiotic regimen for their specific patient.
Can the PK-PD Compass assist hospitals and nursing homes to meet the new Joint Commission standard on antimicrobial stewardship?
Absolutely! Regardless of whether a stewardship program is just getting started or has years of experience, the Compass will offer a unique perspective to practitioners on educating their selection of antibiotic regimens. The design process for the Compass had two primary focus points…
- To build a tool for antibiotic stewardship professionals and practices
- To create a program which educates and guides clinicians, enabling them to exercise their professional judgement to make the right decisions
…and our team of PharmD clinicians and scientists was well suited for the task.
The requirements proposed by the Joint Commission earlier this year put a great deal of emphasis on providing education to both medical staff and patients. This has served to validate that our guiding design principles align well with what healthcare regulators are looking for in a stewardship program.
What can we hope to see in the future from the PK-PD Compass?
We are constantly taking feedback and trying to come up with new features to better educate our users on antibiotic regimen selection. Our top priority right now is giving users the ability to select infusion times for beta-lactam agents. This feature is in development now and users should be expecting to see it in an update soon. We have also had discussions about expanding the Compass to be used for pediatrics and that is definitely a long-term goal of ours.
What really excites us is the opportunity to have the technology behind the Compass integrated into electronic health record systems. Doing so would allow the Compass to pull patient demographic and microbiologic susceptibility data from a patient’s record to automate the entire calculation process. Just imagine opening your susceptibility panel and seeing the typical list of antibiotics and their susceptibilities, but also accompanied by a set of dosing regimens and their respective percent probabilities of achieving efficacious drug concentrations. That is a truly patient-centric approach to informing antibiotic regimen selection, and it is a powerful thing.
To learn more and start using PK-PD compass, click here.
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