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How Personalized Wound Care Diagnostics and Treatment Can Change Your Practice

Modern molecular pathology laboratory practices are bringing their cutting edge genetic and molecular diagnostic techniques to contain costs in wound care. Customized pathogen panels offer the rapid detection of a multitude of microorganisms and treatment resistance assessment, with biofilm analysis, which can be coupled with a wound specialty pharmacy’s recommendation that specifies an appropriate custom compounded medication for each patient's wound. As these authors detail, the result is a substantial decrease in cost to treat, days to heal, and hospital readmittance rate.

Cost containment: the phrase is not new, yet the approach to cost containment in 2021 should be. The traditional focus on revenue growth continues to be derailed through decreases in reimbursements, increased regulatory scrutiny, COVID-19, and growing health care administrative compliance burdens. Solely focusing on growth will not mask cost challenges because there is not infinite room for growth.

Traditionally cost containment is left to financial analysts of hospital groups or office managers of wound clinics to price shop line items that show up on the expenses within their profit and loss (P&L). In 2021, hospitals and wound clinics alike should be taking a multidisciplinary approach with the clinical and administrative personnel working alongside wound-focused specialty pharmacies and pathology laboratories. The result is making actionable decisions that decrease cost of care while improving patient outcomes. The cost containment strategy is not just identified in a director level meeting. Empowering practitioners, nurses, physical therapists, and other personnel in the wound care team to take responsibility for all performance metrics of the wound care unit can increase patient and physician satisfaction census and scores while dropping costs.1

Wound clinics specifically need to double down on containing all wound care costs—not just wound care supplies and calculating full time equivalents (FTEs). If the staggering amount of wound supply manufacturers, distributors, and products in the market are not enough to make your head spin, procuring objective data to compare product efficacy and healing outcomes will. Using the wrong dressing or wound-healing product for the patient and wound can lead to infection, complications, and stalled healing—all of which increase wound care costs. Non-healing wounds are frequent and increase wound care costs exponentially.

Contrary to popular belief, wound supply costs aren’t the only cost to consider when looking at medications. It’s important for clinics, physicians, supply chain managers, and hospital executives to understand that it’s more than just the straight cost of any one supply that matters to the big picture. Realistic costs take into account the entire journey of care, rather than siloed information from each hospital department. This leads to a longitudinal database and an analytics solution that can identify higher-level reports, tying in wound care data to metrics such as readmissions and length of stay. Perhaps a higher-cost pharmacy grade wound care product will actually save the hospital and wound practice revenue due to quicker recovery and decreased hospital readmission, thereby preserving revenue integrity.2,3

Cost Containment: Precision Medicine

Precision medicine in wound care offers one effective solution to decreasing costs and improving patient outcomes. It’s important to point out that precision medicine means different things to different practitioners. To oncologists, it means pairing the correct therapy with a specific mutation in a given cancer. To pulmonologists treating chronic obstructive pulmonary disease (COPD), it means the right blend of behavioral, physiologic, and pharmacologic therapies to improve patient performance and outcomes. In the context of wound care, precision medicine means three things: rapid identification of microorganisms; the detection of microbial genes that confer organism resistance; and integrated reporting by wound care pathologists with expertise in immunology, wound repair and infectious disease.

Microorganisms have distinct genetic “markers” to identify both species and subspecies specifically and reliably. Wound pathology labs can leverage the genetic basis of these organisms and cutting-edge technologies to identify organisms rapidly in an infectious process. The advantages this has over the conventional culturing or organisms are the following:

1.    Rapid turnaround time. These assays can be performed within 24 hours from the receipt of a specimen in a clinical lab. This is significantly faster than the average of 5 days for the incubation and growth time using traditional lab methods for growing the organisms before the results are “finalized.”

2.    Many wounds are polymicrobial. Genetic analysis of a wound’s organism population would provide a precise identification of the entire wound milieu as well as quantification of the organisms. Wound pathology labs can use the current methodologies to track the microbiome of the wound over time. For example, with a wound harboring 3–4 organisms, treatment may only successfully target 2 of the major organisms, allowing for the minor populations to exploit the resultant microenvironment and expand to fill the resultant void. Often, these microorganisms are more pathogenic than the original wound biome. Unlike traditional culture, wound pathology labs can see this change occurring over the evolution of the wound in real time, whereas culturing organisms is not sensitive enough to capture the displacement of and replacement by other competing organisms in a timely fashion.

3.    Empirical prediction of biofilms. At the present time, we cannot routinely detect the biochemical fingerprint of a clinically relevant biofilm outside of the research lab. We are left to predict the presence of such biofilms based on the combination of organisms such as Pseudomonas, Enterococcus, and Candida species, alone or in combination. While this is accurate 60–70% of the time, clearly there is room for improvement. However, documenting and initiating the treatment of biofilms is critical for tissue repair and wound improvement. Wound care providers and payors need to understand the biochemical complexity of the wounds, not just their biophysical parameters to ensure the accurate patient placement within a correct reimbursed care group. Wound complexity is also key to managing patient expectations and education as we rely more and more on patient adherence, follow-up, and telehealth evaluations.

Emerging proteomics methods will employ new markers to directly detect or confirm the presence of biofilms in the future. As the developing genomics and proteomics testing methods yield more complete assessments of the constellation of organisms present in a wound, their characteristics, including resistance genes, and a number of other factors and markers that determine the host response to the organisms, the entire microenvironment will be profiled to provide a more complete treatment regimen tailored to the patient.

Microbial genes of resistance are also useful markers that we can use to rapidly tailor local therapy for each patient. The key to biofilm management is this targeted, compounded approach to topical antibiotic therapy with the correct biofilm disruptor—both chemical (different active ingredients to be discussed later on in this article), and mechanical (negative pressure wound vacuums and debriding dressings of last resort). Resistance mechanisms against a specific antibiotic class frequently confer increased susceptibility to other antibiotic classes, a process known as collateral sensitivity (CS).

An informed switch of an antibiotic may thus enable the efficient treatment of resistant strains. Multiresistant variants via the process of collateral sensitivity of pathogenic bacteria can evolve through consecutive genetic changes or by acquiring plasmids that carry several resistance genes. The molecular identification of these determinants (which transitional culture and sensitivity testing cannot do) is critical to successful antimicrobial planning—switching or adding antimicrobials before these determinants are delineated can expand and result in global resistance to a host of organisms and different classes of antimicrobials. Resistant bacteria may be efficiently eradicated by switching treatment to a different antibiotic class towards the microbe harboring collateral sensitivity. Sequential multidrug treatments that cycle between antibiotics with collateral sensitivity to each other may potentially reduce the rate of resistance evolution. This process could be serially repeated in a sequential multidrug treatment regimen so as to maintain antibiotic susceptibility in the pathogens.

Data volume and density is of major value in modern medicine. The role of the wound care pathologists is to help synthesize and make actionable these data in a succinct way for the various stakeholders in the wound care process. We bring together infectious organisms, their biofilm potential, and their resistance genes in a synoptic form that conveys complexity and a potential clinical pathway for treatment. These treatment pathways represent the surgical pathology equivalent of guiding the wound care providers’ hands to either validate their existing treatment plan or assisting with treatment optimization. Additionally, these integrated reports are designed to inform the entire treatment vertical—from the patient to a specialist, to provider extender, and finally to the payor.

Cost Containment: Tailored Topical Treatments

The treatment of chronic wounds is a major challenge for health care providers, with a high failure rate leading to amputation, sepsis, and death.4 One of the major reasons for this failure is the formation of bacterial biofilms, which are present in 60% of chronic wounds.5,6 Biofilm formation can make bacteria up to 1,000 times more resistant to antibiotics, antimicrobial agents and disinfectants, and also difficult for the host immune system to resolve by itself.7

Most, if not all, antibiotics and antiseptics fail to eradicate mature biofilms, and today, the poor efficiency of available antibiotics is a major challenge for the successful treatment of chronic infections.8

Most wound care products available are not formulated to effectively work against biofilms.

The most commonly used topical antibiotic therapies used for wound care include bacitracin, silver sulfadiazine, gentamicin, and mupirocin. Unfortunately, these topical treatments often are ineffective for 2 reasons: Many of the wounds have polymicrobial infections, and the culprit pathogens are resistant to these medications. Secondly, these topical preparations must be applied numerous times a day for proper antibiotic dose absorption. Adherence to multiple treatments is a longstanding problem in wound care.9

Ultimately, anti-biofilm therapies have the potential to significantly increase the ability of health care providers to treat wound infections effectively. It is important for all wound clinics and wound providers to switch immediately to a dressing that has active ingredients that are clinically proven to work against biofilm. Some example active ingredients are:

EDTA (ethylenediaminetetraacetic acid) chelates and potentiates the cell walls of bacteria and destabilizes biofilms by sequestering calcium, magnesium, zinc, and iron.10,11

Citric acid effectively eradicates biofilms due to its ability to penetrate the biofilm matrix and the cell membrane.12

Xylitol inhibits different stages of biofilm formation via chemotaxis of bacteria outside of the biofilm (posing as a source of food).12

Do Targeted Compound Medications Work?

As Moulavi and colleagues note, the antibiotic treatment and its delivery method can directly affect the complex healing process.9 “Why are oral, intravenous, and intramuscular the delivery routes of choice in wound-treatment protocols? If the infection is local, why use systemic therapy? What is the role of compounded prescriptions in wound treatment?” As the authors say, inappropriately prescribing oral antibiotics can increase both microbial resistance and increase health care costs. In addition, due to poor vascular supply in the infected area and other patient comorbidities, oral antibiotics often do not reach the infection site. The most commonly used topical antibiotic therapies used for wound care include bacitracin, silver sulfadiazine, gentamicin, and mupirocin. However, the authors note these topical treatments often are ineffective, as many of the wounds have polymicrobial infections, and the culprit pathogens have resistance to these medications.

Furthermore, Moulavi and colleagues say many of the available prescription topical antibiotic therapies (such as mupirocin, bacitracin/polymyxin B, and gentamicin ointments and creams) require application at least twice daily.9 Additionally, many bacteria are resistant to these agents, and they become more liquefied when exposed to increased body temperature and wound drainage, which causes periwound maceration.

A recent retrospective cohort study of 1,378 patients set out to compare healing outcomes in three large cohorts of wound patients managed universally for bioburden:13
●    standard of care group, which was prescribed systemic antibiotics on the basis of empiric and traditional culture-based methodologies
●    treatment group 1, which was prescribed an improved selection of systemic antibiotics based on the results of molecular diagnostics
●    treatment group 2, which received personalized topical therapeutics (including antibiotics) based on the results of molecular diagnostics.

The outcome was a resounding success. Patients in treatment group 2 had >200% better odds of healing at any given time point compared with the other cohorts. Implementation of personalized topical therapeutics guided by molecular diagnosis resulted in statistically and clinically significant improvements in outcome.

Incorporating a Wound Care Focused Pathology Lab and Pharmacy Partner

The future of wound care precision medicine is critical to improving outcome, decreasing cost, and providing a vehicle for rational innovation. There can be no doubt, given the cost, debilitation, and increasing prevalence of wounds in our population, that more advanced therapies will come to the fore—whether they be targeted small molecules to increase fibroblast proliferation, or transplants of cadaver immune stem cells to provide the optimal immunological conditions for wound repair. Molecular diagnostics, integrated reporting, and diagnostics specialists such as wound care pathologists will be critical for this next generation of wound care evaluation and personalized treatment. Additional examples of testing we envision of these next 3–5 years are:

1.    Biochemical identification and characterization of wound associated biofilms from Gram negative, Gram positive and specialized microorganisms.
2.    Immunologic profiling of wound exudate to understand optimal condition for wound repair.
3.    Host genetic determinates of wound repair, such as mutations in genes for extracellular matrix or receptors for fibroblasts growth.
4.    Host metabolomics for including diabetes and micronutrient deficiency.

If health care providers and health care executives are willing to acknowledge the powerful role data can play, the impact on both patient outcomes and revenue integrity can be tremendous. It begins with realizing that patients with chronic wounds cost hospital systems much more than wound clinics. Focusing on this niche will improve the hospital's bottom line and wound clinic’s bottom line through decreased cost of care, decreased hospital readmission rates, and decrease in days to heal.

A simple way to address cost containment today is to stop identifying chronic wounds by using traditional cultures and using wound dressings that do not disrupt biofilms or contain the anti-infective medications identified in diagnostic reports and start using next generation diagnostic tools and custom compounded treatments from wound specialty pharmacies that are readily available today.

Clinical Case

The patient is an 88-year-old female with end-stage dementia presenting with a 12.8 x 8.9 cm Stage 3 decubitus pressure ulcer with a 9-week history of treatment with MediHoney® (Derma Sciences) and Tegaderm® (3M). While necrotic tissue had been debrided, there was only a minor granulation tissue response noted. Molecular microbial identification and sensitivity was ordered with pharmacist evaluation for compounded antibiotic therapy if necessary. Results were positive for Proteus mirabilis with no genetic determinants of microbial resistance.  

Because of the extremely high biofilm association with this organism, both the pathologists and pharmacist made the recommendation of a biofilm disruptor. The pharmacist was able to compound a biofilm disruptor cocktail with the addition of tobramycin.

Treatment commenced as recommend and at two months the wound had reduced to 10.2 x 7.8 cm with improved granulation tissue response. At the end of two months repeat molecular testing was negative for microorganisms and the patient was returned to the original treatment plan. At five-month follow-up, a continued granulation tissue response was noted and wound reduction to 6.5 x 5.3 cm was documented.  

Survam Patel, PharmD, is a licensed pharmacist and the managing partner of Smithville Pharmacy in central Texas, specializing in customizing anti-infectives and pain treatments for wound providers and patients. For more information or a provider consultation, he can be reached at www.woundpharmacy.com.

Kevin Rosenblatt, MD, PhD, is Chief Medical Officer and Chief Scientific Officer of NX Prenatal, a prenatal diagnostics company developing assays for adverse pregnancy outcomes and conditions such as preterm birth. He is also currently President and Medical Director of Consultative Genomics, PLLC, a molecular pathology group specializing in Genomic and Proteomic clinical testing as applied to chronic disease, infectious disease, population health management, and personalized medicine. He is also a member and CMO of Healix Pathology, LLP, in Houston, Texas. Dr. Rosenblatt has more than 30 years of clinical and biomedical research and development experience in multiple settings, including academia, biotech, startups, and clinical practice, and he has published over 80 papers on cancer and neuronal biology, biomarker development, and clinical genomics and proteomics.

Peter Bryant-Greenwood, MD, is an anatomic and molecular pathologist with a focus on the immunology of infectious disease, chronic disease, and cancer. He is CMO of Phase2 Laboratories in Nashville, a partner in Consultative Genomics PLLC in Houston and a founder of Healix Pathology LLP in Houston.

Feature
Survam Patel, PharmD; Kevin Rosenblatt, MD, PhD; and Peter Bryant-Greenwood, MD
References

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