Compounded Prescription Wound Therapies: Safe, Therapeutic, and Cost-Effective

ABSTRACT: The objective of this study was to assess the effectiveness of treating bacterial load in a wound using topical, compounded, prescription antibiotics. Using evidence-based guidelines, we sought to learn whether prescription compounded antibiotics were effective for the care of wounds, whether adverse effects were associated with their use, and whether their use is cost-effective. We also sought to evaluate the outcomes of topical, compounded, prescription antibiotics in clinical practice. Based on the results of our study, we conclude that topical, compounded, prescription antibiotic therapy for wounds are easy to use, cost-effective, and effective in bacterial load suppression or eradication, which can allow wounds to successfully heal faster with reduced patient discomfort.

KEYWORDS: Wound care, antibiotics, bacterial load, topical compounded antibiotics, chronic wounds, bacterial infection, microbial resistance, cost-effective care

Chronic and acute wounds have an enormous economic and social impact and are a substantial burden on the US health care system. Chronic wounds affect an estimated 6.5 million individuals in the United States and cost more than $25 billion annually to treat. As the age of the US population increases and the prevalence of these wounds continues to rise, this cost is projected to increase.¹

The development and persistence of chronic wounds is promoted by nonhealing. One of the major factors that delays wound healing is the presence of bacteria. Patients with chronic wounds are at increased risk for wound infection due to associated comorbidities such as decreased blood supply to the area, advanced age, diabetes mellitus, obesity, malnutrition, and the use of corticosteroids and other immunosuppressant therapies.¹

Bacteria can affect a wound in varying degrees, from an asymptomatic contamination or colonization to an infection. Although inflammation is a physiologic part of wound healing, the presence of bacteria can prolong this phase and prevent normal repair from occurring. Additionally, bacteria that form biofilms can resist treatment and further delay the healing process. Infections in wounds increase the number of hospitalizations and can become expensive to manage.² A much less expensive alternative to inpatient care is treating wounds at home with prescription topical treatments.

Wound Treatment Background

In this article, the term wounds is used to include diabetic ulcers, pressure ulcers, vascular ulcers, surgical wounds, traumatic wounds, skin tears, and localized cellulitis as seen in lymphedema and in acute and chronic wounds. All of these wound types have been included in our evaluation of topical compounded antibiotic treatment. The challenge is to explore the various ways bacterial loads can be suppressed or eradicated at the wound site to allow the body to proceed to wound healing without bacterial impediment.

The question is, why is the gold standard treatment for a localized infection oral, intravenous (IV), or intramuscular (IM) antibiotics? Why expose a patient to systemic treatment when the infection is localized, and when bacterial resistance is on the rise?

There are many reasons for why a given wound does not heal or heals slowly. Formation of granulation tissue can be directly reduced with bacterial-load interference. Diabetic ulcers have been noted to have a reduced number of stem cells, and these cells can be less effective; their morphology is altered, growth is decreased, and more dysfunctional cells are present in these wounds. As the average age of the US population increases, so too will the presence of these less functional stem cells. Providing a healthier wound environment with a reduced bacterial load allows for better healing to occur. Preparing a wound prior to acellular or cellular therapies can be done with topical antibiotic therapy, with the goal of reducing the bacterial load and stimulating collagen growth.

The antibiotic treatment and its delivery method can directly affect the complex healing process. Why are oral, IV, and IM 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?

One of the challenges to wound care has been the lack of an adequate antibiotic delivery system that clings to the tissue to assure surface absorption and deliver the medication over a 24-hour period. Many of the available prescription topical antibiotic therapies (such as mupirocin, bacitracin/polymyxin B, and gentamicin ointments and creams) require at least twice daily changes; furthermore, many bacteria are resistant to these agents, and they become more liquefied when exposed to increased body temperature and wound drainage, causing periwound maceration.

Our Wound Care Problem

Many of the primary care providers who care for patients prescribe oral antibiotics for the treatment of chronic wounds. However, current guidelines suggest that systemic antibiotics can be ineffective, and topical antibiotics should be used.² Inappropriate prescribing of oral antibiotics can increase microbial resistance and increase health care costs; moreover, oral antibiotics often do not reach the site of infection due to poor vascular supply in the area and other patient comorbidities. Additionally, the risk of potentially fatal Clostridium difficile infection increases with the use of oral antibiotics.

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. Numerous studies have shown that the most common organism present in chronic wounds is Staphylococcus aureus (methicillin-resistant and -susceptible strains). Interestingly, our study findings showed that many of our patients’ culture test results showed the presence of Escherichia coli due to incontinence and shower and bathwater exposure to the wound. 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.

We needed a topical application of a prescription antibiotic that would cling to the wound no matter the position of the wound, as well as deliver a steady dose of medication over 24 hours. Compounded antibiotics, when prepared according to protocol, provided our practice with this treatment option.

Evidence-Based Study, 2009-2015

Our study’s patient population comprised male and female Medicare recipients between 50 and 104 years of age, with nonhealing wounds, and with a variety of comorbidities that included but were not limited to lymphedema, spinal cord injury with paralysis, venous stasis, arterial occlusive disease, diabetes, renal failure, coronary artery disease, chronic obstructive pulmonary disease, Parkinson disease, idiopathic pulmonary fibrosis, Alzheimer disease, and dementia. Among the challenges to wound care in this population were advanced age, muscle atrophy, reduced vascular flow, body composition changes (further reducing vascular flow over bony structures), and poor nutrition.

The majority of study participants had been referred to us, usually in a chronic state, with wounds that were not responding to typical treatment. The topical compound antibiotic treatments, which varied according to the species of bacteria present in the wound, were administered to patients whether their treatment plan was aggressive or palliative.

More than 1139 compounded topical antibiotic prescriptions were written and used in our medical practice during the study period from 2009 to 2015. We continue to use this topical method of treatment in our practice as part of our wound care protocol.

Study treatments

Topical compounded prescription antibiotic treatments in 3 different formats (hydrolysable powder, thermoreversible gel/solution, or ointment) were used to deliver antibiotics. The percentage of each ingredient was ordered within pharmacology guidelines to prevent toxicity. Vascular stimulants, collagen, and lidocaine were added to various compounded antibiotic treatments according to individual patients’ signs, symptoms, and wound care needs. Topical treatment was limited to 2 to 4 weeks during a treatment period. Before and during topical compounded antibiotic treatment, serial sharp debridement was used to remove devitalized tissue that can harbor bacteria and delay wound healing.

The hydrolysable powder dosage form was used for incorporating solid pharmaceutical ingredients. The powder selected was Methocel E4M Premium CR (Dow Chemical Co), a hydroxypropyl methylcellulose powder. This powder forms a water-soluble, hydrophilic matrix upon hydroxylation of exudates from the wound. The hydrolyzed matrix system is highly mucoadhesive and adheres well to wounds. This powder base has an extensive, well-understood history and an excellent safety record. Any additional drug in the powder mixture was incorporated into the hydrophilic matrix system upon hydrolyzation and was available via diffusion (mimicking the process of an extended-release dosage form, most of which use a methylcellulose matrix). Among the disadvantages of this delivery method are that liquid ingredients (such as insulin) cannot be incorporated, and that the final product needs specialized systems if sterilization is required.

The hydrogel delivery was compounded using hydrolyzing poloxamer 407. This substance is widely used in the pharmaceutical industry and makes a unique thermoreversible matrix that is in a solution phase at low temperatures and a gel phase at room temperature and/or body temperature. In the solution phase, it can be placed easily into sinus tracts. At higher concentrations, the hydrogel can absorb wound exudates and still maintain its gel state. The poloxamer makes a mucoadhesive matrix that can incorporate even poorly dissolvable drugs (such as nifedipine) and allows the incorporated drugs to have a prolonged release from the matrix. The poloxamer itself has shown to have disrupting effects on biofilms and, without any additional ingredients, may promote normal wound healing. The drawbacks include that it is not very convenient for use on shallow ulcers; it may be compressed out of deeper wounds on the buttocks, when the patient’s weight shifts; and internal use of the poloxamer in studies has been associated with negative lipid profiles and possible renal toxicity.

The ointment base was compounded using commercially available Eucerin (Beiersdorf Inc) when a barrier was needed. Ointments do not have the depot effect that the powder and the poloxamer base have; thus only the drug that is in the film surface adjacent to the wound has the ability to be used, and any additional drug outside of this narrow layer is trapped and is not available to tissues via diffusion during the healing.

Data Collection and Analysis

Treatment protocols were formulated and were documented in the electronic health record (EHR) system so the physicians and nurse practitioners were using the same treatment formularies, durations, and assessment tools. The templates were specialized to describe the prescriptions and the percentages used. The wounds were monitored every 7 to 14 days for signs and symptoms, size (length, width, depth, undermining, and tunneling), drainage (appearance), odor or lack thereof, periwound appearance, dermal appearance, and general overall progress or decline of the condition of the wound. Templates also were used in the EHR system so that charted data were easier to compare. Photographs of the wounds were taken after permission was obtained from the patient or through power of attorney.

Treatment Outcome

Treatment outcome is directly affected by the application technique, the frequency of application, and the prevention of reexposure to bacteria. Incontinence exposure was addressed and contained. The proper topper dressing was necessary for the proper activation of the compounded prescription treatment. Daily application was needed over at least 2 weeks but limited to 4 weeks. These limits were placed to prevent prolonged use of the compounded topical antibiotic treatment, which could lead to microbial resistance, while still providing adequate treatment.

No complications were associated with compounded antibiotic treatment during the study period from 2009 to 2015. We did not adjust patients’ warfarin intake (prothrombin time/international normalized ratio were not affected), and we observed no related incidence of C difficile or gastrointestinal tract distress, since the antibiotics were delivered topically. The patient or their caregivers reported no adverse effects, and no drug interactions were reported. During the treatment period, more than 95% of the wounds treated at our specialty medical practice were treated topically. Oral, IV, or IM treatments were used only for patients with systemic infection.

Patient, Caregiver, and Clinician Satisfaction

Throughout the study period, patients, caregivers, and skilled nursing staff reported ease of application and removal of the topical therapy. Although daily visits were required for an average of 2 weeks, family members often could assist with the dressing changes due to the ease of the treatment method. This decreased the time by skilled nursing for dressing changes.

The cost of the treatment (approximately $50 to $70 for the total treatment) was acceptable to 99% of our patients. Because this form of treatment was not covered by most Medicare Part D prescription drug plans in the United States, our patients paid for treatment themselves. All of the patients who received the topical compounded treatment agreed that it was worth the out-of-pocket cost they incurred.

Not only did the physicians and nurse practitioners at our practice report overall satisfaction with the treatment methods, but also home care agencies, primary care practices, assisted-living facilities, family members, and our patients responded favorably.

Conclusions

The data collected during the study period led us to draw the following conclusions:

• The use of topical, compounded, prescription antibiotics from a compounding pharmacy that follows proper preparation methods and national standards can successfully treat bacterial load in wounds.
• Compounded, topical antibiotic therapy is cost-effective and easy to apply and remove.
• Caregivers can easily learn how to use the compounded treatment correctly with minimal instruction.
• A reduction of the bacterial load through the surface of the dermis can be effective in wound healing.
• The topical compounded therapy reduced wound healing time.
• Biofilms can be removed with the use of topical, compounded, prescription antibiotics with the proper delivery base.
• Topical treatment with compounded prescription antibiotics is safe, is tissue-compatible, and is not cytotoxic if done within the guidelines for dosing, delivery, and duration.
• Microbial resistance has not been encountered since we started topical treatment plans starting in 2009 when used within the guidelines (protocols) for a duration of 2 to 4 weeks.

The results of this study provide evidence-based data to encourage thought  about and increased research on using topical, compounded, prescription antibiotic therapy to treat bacterial loads in chronic wounds. Further studies are needed to confirm whether these wound-care techniques are effective and can be used widely.

Not every wound is a candidate for this therapeutic option; nevertheless, a majority of wounds responded positively to the treatment method during our study. Based on our findings, we have concluded that topical, compounded, prescription antibiotic treatment for wounds is easy to use, cost-effective, and successful in bacterial load suppression or bacterial load eradication, which can allow wounds to heal successfully with reduced patient discomfort and in less time. 

Debbie Moulavi, MS, WOCN, MSN, NP-C, is a nurse practitioner and wound, ostomy, and continence nurse at Central Florida Wound and Skin Consultants in Orlando.

Thomas Slaughter, PharmD, is a compounding pharmacist at Mulberry Pharmacy in Mulberry, Florida.

Tabassum Merchant, WOCN, MSN, NP-C, is a nurse practitioner and wound, ostomy, and continence nurse at Central Florida Wound and Skin Consultants in Orlando.

References:

1. Singer AJ, Clark RAF. Cutaneous wound healing. N Engl J Med. 1999;341(10):738-746.
2. Collins N, Sloan C. Nutrition 411: strategies to enhance wound healing in frail elders. Ostomy Wound Manage. 2014;60(2):12-14.