The Role of Systemic Antibiotics for Biofilm Removal in Chronic Wounds
The project is an investigative work on the role and efficacy of systemic antibiotics in treating chronic wounds. One of the reasons underlining this is the fact that chronic wounds represent a significant burden to healthcare professionals, patients, and the US healthcare system in general. Chronic non-healing wounds affect an estimated 5.7 million American patients and costs the country and an estimated 9 billion dollars annually (Naidoo et al., 2009). The implementation of treatments for wound biofilm has created a new perspective so that chronic wounds can be treated more efficaciously and potentially save the lives of many patients (Wolcott, & Dowd, 2008; Naidoo et al., 2009).
Biofilms are delaminated as a structured community of microbial cells enclosed within a self-produced polymeric matrix that is adherent to an inert or living surface. According to Percival and Cutting (2010), the appropriate definition of a chronic wound is a wound that does not heal within the expected timeframes as it is trapped in the inflammation phase of healing. Many reasons have been posited for this, including the presence of necrotic tissue, microorganisms – primarily bacteria that secrete the biofilm, alongside tissue ischemia, hypoxia and edema in the wounds (Zhao et al., 2013; Mihai et al., 2015). Most dermal wounds are colonized with aerobic and anaerobic microorganisms, which predominantly originate from mucosal surfaces of the oral cavity and gut. Biofilms are present in up to 90% of chronic wounds and 6% of the acute ones (Mihai et al., 2015).
Akiyama et al. (2004) explain that for many years past, the significance of microorganisms in the healing process of wounds has formed the basis of discussions in wound healing. Chronic wounds include surgical site-associated wounds, pressure ulcers, traumatic wounds, diabetic foot ulcers, and venous foot ulcers (Appendix B). According to Naidoo (2009), their chronicity is defined by the inability to complete the reparative process that allows for wound healing and return to normal functional and anatomical integrity within a span of 3 months. These wounds are commonly characterized by an arrest in the inflammatory phase of healing and are often associated with bacterial infections. Bacteria in Chronic wounds are frequently present as biofilm and mostly affect the elderly population. Patients with chronic wounds are commonly treated with either systemic or topical antimicrobial therapy. Although adequate systemic antibiotics are requisite for the healing of clinically infected and worsened wounds, there is controversy over the relevance and use of antibiotics (systemic or topical) in the treatment of cicatricial delayed wounds that do not show clinical signs of infection (Phillips et al., 2010).
According to Rhoads, Wolcott, and Percival (2008), the role of bacteria in the geneses and perpetuation of chronic wounds remains weakly apprehended. Characteristically, the bed of a chronic wound includes a compound microenvironment laden with more than a single species of bacteria. In a clinical setting, a hurdle thereof is present on correctly determining the presence of bacteria (or any other planktonic material) within the wound that impedes normative healing processes to justify the institution of interventions (Naidoo et al., 2009). Indications for antibiotic therapy use and better treatments are not very well defined.
Why consider systemic antimicrobial therapy for chronic wounds if many topical antibiotics are currently available on the market? In daily primary practice, wound care nurses, and in collaboration with the doctors in charge of the periodic assessment of chronic lesions present in a large group of patients who have been treated throughout their profession. They had noticed that patients, to whom a regimen of systemic antibiotic treatment has been added to their topical treatment, have experienced a significant improvement in the characteristics of this type of wounds. The primary goal of this study is to demonstrate that patients with chronic wound who receive systemic antibiotics will have greater clinical improvement of the wound features than those treated with topical agents.
Background and Significance of the Problem
Chronic wounds are arrested in the inflammatory phase of healing. The presence of foreign materials, necrotic tissues, or bacteria impedes the ability of the wound to heal by inducing the production of pro-inflammatory cytokines, excessive neutrophils and elevation of matrix metalloproteinases (Wolcott & Dowd, 2008; Phillips et al., 2010). In the process, the necessary building blocks (chemoattractants, growth factors, and mitogens) for normative wound healing are either destroyed or rendered inert (Rhoads, Wolcott, & Percival, 2008).
The necessity of the project is underlined by the fact that chronic wounds represent a significant burden to healthcare professionals, patients, and the US health care system; with an additional huge financial implication. In light of this, the project aims at demonstrating the role of systemic antibiotics in chronic non-healing ulcers as it pertains to elimination and disruption of biofilms at the wound surface – allowing for the progression of a wound from the inflammatory to the proliferative phase.
Statement of the Problem
The aggregation of microbes within a wound creates a distinct biofilm with differing characteristics so that a clinical approach has to be tailored to the specifics of the given biofilm. Importantly, the definition of the specific features of the biofilm and then designing a therapeutic option particular to that biofilm is currently getting defined. Therefore, the role of systemic antibiotics in improving the healing process of a chronic wound will be explored.
Project Purpose
The primary objective of this research is to compare changes in surface area of non-healing chronic ulcers treated with local therapy and systemic antibiotics versus treatment of non-healing chronic ulcers treated with local therapy alone. The wounds healing process will be assessing by periodically measuring the wound surface area in both groups.
The primary goal of this study is to demonstrate that there is a role in the use of systemic antibiotics in disrupting the wound biofilm in patients with chronic non-healing ulcers. Patients treated with systemic antibiotics will have greater clinical improvement as demonstrated by a decrease of wound surface area to those treated with topical agents alone.
Hypothesis
The institution of systemic antimicrobial therapy in conjunction with topical antimicrobial therapy is important in the disruption of biofilms within chronic wounds, and thereof will improve the healing process.
Aim of the Project/Outcomes to Achieve
With the position that systemic antimicrobial therapy is useful in eliminating surface biofilms, the principal objective of this project is to demonstrate the efficacy of using of systemic antibiotics in conjunction with topical treatment over the effectiveness of using just topical agent therapy for chronic ulcers. Expected changes will be:
- A decrease in the size of the wound.
- A reduction in the exudate produced
- Formation/growth of a granulation tissue in the wound bed within three weeks.
PICOT Question
For patients with biofilm colonized chronic wounds in nursing homes (P), how does the institution of both systemic and topical antimicrobial therapy (I) compared to the non-institution of systemic antimicrobial therapy (C) to influence the normal wound reparative processes (O) within a period of three weeks (T)?
Relevant Literature Review
Immune Responses to Biofilms
In-vitro research conducted demonstrates that human leukocytes do overcome Staphylococcus aureus biofilms (Kirketerp-Moller, Zulkowski, & James, 2011). In murine models of acute wound infections, Akiyama et al. in Kirketerp-Moller, Zulkowski, and James, (2011) found out that the efficacy of antimicrobials against biofilms of organisms S. aureus was substantially better in normal mice than in those whose leukocytes had been depleted. The primary mechanism of antimicrobial therapy in mice was then thought to be through the incursion of PMNs into the biofilm (Schultz et al., 2010). For films caused by Pseudomonas aeruginosa, the generation of extracellular polysaccharides, alginate, augured adequate protection from human leukocyte phagocytosis (primarily monocytes) mediated by Gamma Interferon (IFN-y) (Mihai et al., 2015). Similarly, Staphylococcus epidermidis bacteria were protected by polysaccharide intercellular adhesion (PIA) against phagocytosis and subsequent destruction by polymorphonuclear leukocytes (PMNs). (Mihai et al., pg. 376). Thus, seemingly extracellular polysaccharides give a certain impression of a being a major factor in the resistance of biofilms to PMN phagocytosis. Additionally, S. epidermidis PIA were protected against the antibacterial peptides of human b-defensin 3, cathelicidin/hCAP18 and dermcidin (Bjarnsholt et al., 2008). Biofilms produced by P. aeruginosa in addition to limiting the effectiveness of innate immune factors led to the destruction of PMNs through the elucidation of rhamnolipids (Kirketerp-Moller, Zulkowski, & James, p. 19). S. aureus also has the capability of cranking out leukotoxins, including the Panton-Valentine that has been linked to severe cutaneous infections.
Non-healing chronic wounds have often proved to show elevated levels of pro-inflammatory cytokines such as Interleukin 1 (IL-1), Tissue Necrosis Factor-alpha (TNF-a), Alpha Interferon (IFN-a), and Gamma Interferons(IFN-y) (Zhao et al., 2013; Mihai et al., 2015). Such cytokines are commonly elucidated in response to the virulence determinants of bacteria, including peptidoglycans, lipopolysaccharides, and DNA (Schultz et al., 2010). Within the substance of chronic wounds also are elevated levels of matrix metalloproteinases (MMPs) including gelatinases and collagenases which are produced by PMNs and commensurately low levels of inhibitors of these tissue metalloproteinases (Naidoo et al., 2009). These wound characteristics thereof, the literature suggests are as a result of the presence of biofilms (Akiyama et al., 2004).
In addition to the primary innate immune mechanism discussed above Kirketerp-Moller, Zulkowski, and James, (2011) posit that S. aureus biofilms can also elicit adaptive immune responses, which may lead to the development of biofilm-specific diagnostics, treatments and possible vaccines.
Diagnosis of Chronic Wound Biofilm Infection
Depending on the availability of laboratory tests in wound care facilities, these listed laboratory and clinical feature may become handy in the diagnosis of biofilms: (1) failure of antibiotic treatments and recurrence of infections. (2) The presence and persistence of clinical signs of infection, especially for more than seven days (Edwards-Jones, 2016). (3) The reappearance of systemic signs and symptomatology associated with infection after the cessation of antibiotic therapies (Naidoo et al., 2009). (4) Microscopic evidence of microbial aggregates and biofilm structures, surrounded by inflammatory infiltrates (Zhao et al., 2013). (6) The detection of mucoid P. aeruginosa, a biofilm-specific microbial phenotype. (7) Positive molecular diagnostic methods – including Polymerase Chain Reactions, Next-Generation Sequencing, Fluorescence In-Situ Hybridization, or, Pyrosequencing (Kirketerp-Moller, Zulkowski, & James, 2011; Wolcott, & Dowd, 2008; Percival, & Cutting, 2010). (8) specific immune response to the identified microorganisms, as expected after two weeks of biofilm infection (Mihai et al., 2015).
The utility of aerobic culturing techniques of samples superficially collected from infected sites in the diagnosis of chronic wound biofilm infection has been questioned in some of the literature reviewed (Rhoads, Wolcott, & Percival, 2008). These may yield false-positive results in cases where the samples are contaminated with skin microflora. Additionally, false-negative results may appear despite the suggestive clinical signs of infections, due to the presence of non-culturable bacteria with low rates of metabolism, due to increased adherence of biofilm bacteria to the surrounding tissues and due to the impossibilities associated with the diagnosis of anaerobic microorganisms (Phillips et al., 2010). Edwards-Jones, (2016) notes that traditional culturing techniques come short in differentiating between biofilm or planktonic bacteria.
The most recent guidelines on the diagnosis of biofilms recommend that in cases of moderate to severe soft tissue infections, it is imperative to perform a tissular biopsy from the bed of the debrided wound then followed by histopathological exams (Schultz et al., 2010; Kirketerp-Moller, Zulkowski, & James, 2011). Whereas this reliable technique can objectivate the aggregation of microorganisms, as well the accumulation of PMNs at the site of infection, it cannot adequately identify the specific causative organisms and contributes thereof to the therapeutic approach (aerobic culturing) (Rhoads, Wolcott, & Percival, 2008; Mihai et al., 2015).
Aerobic culturing though has garnered standards of formerly being considered the gold standard for diagnosing wound infections; the technique may still prove useful when associated with antibiotic susceptibility testing to guide antibiotic therapy, particularly when there is a risk of systemic infection by dispersed biofilm bacteria (Bjarnsholt et al., 2008). However, the results obtained from antibiotic susceptibility testing may be misleading in some biofilm infections due to their characteristic tolerance of therapeutic agents (Phillips et al., 2010). The Calgary Biofilm Device has been designed to detect in a standardized, reproducible and repeatable method the minimum biofilm eliminating/eradication concentration (MBEC) (Kirketerp-Moller, Zulkowski, & James, 2011).
Naidoo et al., (2009) explains that in cases of acute infections, such as urinary tract infection, a quantitative microbiological assessment guides the institution of therapies (presence of more than 105 bacteria/mm3). In chronic wound infections and wound healing, there exist no clear relationships established yet between the clinical signs of infection and the bacterial load. Critical colonization is used to quantify bacteria present in non-healing, non-infected wounds, involved in the pathogenesis of skin lesions (Rhoads, Wolcott, & Percival, 2008; Kirketerp-Moller, Zulkowski, & James, 2011).
Optimal Treatment of Chronic Wounds
For one to effectively treat chronic wound infections, the approach should be initially tooled to focus on the prevention of the attachment of microbes and development of biofilms, followed by a careful selection of therapeutic agents with an increased delivery to the biofilm target (Percival, Thomas, & Williams, 2010; Phillips et al., 2010). For the achievement of optimal functionality results, adverse reactions such as intolerance or allergies should be rapidly diagnosed. The emergence of resistant strains should be assessed carefully by periodic microbiological examination of samples obtained from the wound, as associated by antibiograms for the isolated bacteria (Kirketerp-Moller, Zulkowski, & James, 2011).
According to Rhoads, Wolcott, and Percival, (2008), the consideration of an ideal antimicrobial approach for a patient with chronic wounds should accomplish the following: promote the healing of a wound, prevent and treat the prevalent wound infection and improve the patient’s quality of life. Additionally, an ideal antimicrobial agent should either remove all the pathogenic bacteria or at least lower the bacterial load to way below the critical colonization limit, spare the commensurate microflora and support the defense mechanisms of the host (Naidoo et al., 2009).
While the resistance of antibiotics is a genetic acquisition, and thereof irreversible, the tolerance of the biofilm to therapeutic agents may revert to susceptibility after phenotypic changes to free-floating status (Phillips et al., 2010). In chronic wound infections, the institution of standard antimicrobial therapy alone cannot eradicate biofilm infections (Appendix A). This is because the Minimum Inhibitory Concentrations (MICs) of biofilms are 1,000 times than the ones for planktonic bacteria; attaining such levels in humans has potential adverse effects and toxicity (Mihai et al., 2015). Due to horizontal gene transfers and hypermutability, biofilm communities generate resistant bacterial strains at higher rates (Schultz et al., 2010)
In cystic lung infections caused by P. aeruginosa, it has been documented that there exist a so-called “window of opportunity” during phenotypic changes. Such is a signification of a period of microbial vulnerability to an aggressive antibiotic therapy (Schultz et al., 2010; Kirketerp-Moller, Zulkowski, & James, 2011). Such is a suggestion that the utility of an antibiotic based pulse therapy, that is repeated periodically, to maintain the bacterial load at non-harmful levels is a preemptive treatment. However, there exist no evidence to support the use of systemic antibiotics to prevent or treat biofilm wound infection despite their common use in clinical practice (Rhoads, Wolcott, & Percival, 2008). Additionally, the role of tetracycline in the treatment of biofilms is being examined. Questions are being asked on the efficacy of tetracycline in treating biofilm bacteria formations (P. aeruginosa, Klebsiella species, Bacillus pumilis, K. pneumoniae and Achromobacter Spp.) within 3-5 days, and chloramphenicol showing efficacy in 5-8 days (Naidoo et al., 2009).
There exists limited available evidence regarding the: (1) optimal therapeutic approach to treat chronic wound infections with immature and mature biofilm. (2) The context for the initiation of topical antibacterial agents – wounds with clinical signs of infection versus non-healing non-infected wounds. (3) Or the specific antimicrobial target – sparing the “good” fungi or bacteria versus the sterilization of a wound (Schultz et al., 2010). Thereof, Hoiby et al. in Kirketerp-Moller, Zulkowski, and James, (2011) suggest that the institution of a combined therapy is more effective (two different classes of antimicrobials, systemic and local therapy, local antiseptic and local antibiotic) than a single therapy. Also, the application of antimicrobial therapies on a debrided wound if effective as it removes the residual free-floating bacteria, the primary source of biofilm restoration (Percival, Thomas, & Williams, 2010; Mihai et al., 2015).
Therapeutic decisions should not only be based on the price of a single product but rather a thorough evaluation of the full cost of treatment, with the premises that it would take place on an extended period, and it should achieve wound healing. The overuse of antibiotics, the primary cause of the rising prevalence of microbial resistance, should be prevented by continued education of bit healthcare practitioners and patients (Rhoads, Wolcott, & Percival, 2008). The efficacy of antimicrobial therapies is optimally assessed by objective clinical measures of wound progression, using standardized questions such as the Wound Healing Index as compared to the removal of the microorganisms from ulcers (Kirketerp-Moller, Zulkowski, & James, 2011).
Research Question
What is the efficacy of systematic antibiotics in treating bacterial biofilms within chronic wounds in a controlled sample?
Methodology and Research Design
Setting/Sample Design
A sample of 50 participants will be randomly selected from the health center population, where n = 25 (50%) will be males and n = 25 (50%) females. The study will be a double-blinded, conducted with a randomized assignment to one of the two cell therapy dose groups (n = 25, 25). The setting is a home facility, termed PPNRC. Eligible patients will be adults aged 18 years and above experiencing complex chronic wounds (Appendix B). Included wound sizes will range from 2 cm2 to 12 cm2, with a duration of 7 – 100 weeks. The team will pilot-test the predefined eligibility criteria using a random sample of 20 patients.
Excluded will be pregnant and lactating mothers, wounds that expose tendons and bones, patients with known allergies to intervention drugs, patients with exposure to certain chemicals and exclusionary medical conditions. Exclusion during the run in will include patients with uncontrolled severe edema, patients with concomitant bodily infections or those with healing rates of equal to or greater than 0.350 cm per two weeks. Screening fails and withdrawal rates will be recorded.
The set agreement rate on review will be 90%. After its attainment, each patient (with their characteristic) will then be screened by two independent external members. Discrepancies will be resolved by discussions or the involvement of a third reviewer. The same process will be carried out for other identified eligible patients relevant to the study.
Interventions
The subject participants will receive systemic antimicrobials in conjunction with other standardized chronic wound treatment modalities – topical/alternative treatment (n = 25). The comparator groups will receive other chronic wound treatment modalities exclusion of systemic antimicrobials (defined as standardized topical/ alternative wound treatment mechanisms, n = 25). Alternative therapies: includes debridement and local wound treatment. Defined as the removal of necrotic devitalized tissue from a wound. This strategy will serve to minimize the tissue bioburden of the wound by decreasing the presence of microorganisms, thereof reducing the hypoxic part of the wound and diminishing the inflammatory response. The concept behind this is TIME (Tissue, Inflammation or Infection, Moisture balance, and Edge effect).
Timeframe
Considering that chronic wounds take time to heal, it is important that patients be carefully chosen. The study will be carried out for four weeks, (this is to be reviewed) after which the measuring of outcomes will commence. Treatments will be continued for 13 weeks or until the wounds healed, whichever occurs first.
Variables
Expected patient variables include:
- Patient demographics (age, sex, race, diabetes, peripheral neuropathy, body mass index, serum pre-albumin, HbAIC). Levels of serum pre-albumin and HbAIC are good indicators of the body’s response to chronic wounds (Naidoo et al., 2009).
- The size of the wound – in standard units.
- The location of the wound
- The area (in square centimeters) of the wound
- The specific quantities and species of bacteria
- Wound depth – in standard units
- Concomitant bodily illness (comorbidities)
Confidentiality
The confidentiality of patients is one of the primary duties in medical practice. It requires that primary patient healthcare providers keep the personal health information of a patient in private unless consent to release the information is provided by the particular patient (Bjarnsholt et al., 2008). The project will aim at creating a trusting environment by respecting the privacy of a patient, as it may increase the willingness of the patient to participate in the project to its end. The health care center obligates on patient confidentiality, and prohibits primary providers of healthcare from disclosing information on the patient’s case to other persons without permission, and thereof encourages health care professionals and the health care center, in general, to take precautions to ensure that only authorized access occurs.
Stakeholders
The project focuses on ensuring that all stakeholders at PPNRC are included in the study. Nurse Managers and nurses will play a great role in helping monitor patients to meet the objectives of the research. Further, patients who will also participate in the research will play a critical role to ensure the successful completion of the project.
Instruments/Scales of Measurement of Outcomes
Rather than focusing on the physiologic endpoints, (for example, the type of granulation tissue expected), the undertaking of this outcome assessment is meant to evaluate the effect of the instituted intervention on endpoints relating to the positive effects accrued by patients (Phillips et al., 2010). These include the status of patient satisfaction, health-related quality care, patient perspectives on the treatment modalities, the cost of the quality care instituted and the functional status of the patient (Soon & Chen, 2004).
Outcomes in the care of wounds may be broadly divided into three categories, a) health-related quality of life, b) measurement of clinical efficacy and c) health economics. The healthcare-related quality of life is then generally assessed using either the health status instrument, either may be “condition specific” or “generic” (Soon & Chen, 2004). Clinical efficacy measures thereof refer to the functional or physiologic endpoints that are considered significant from a nursing perspective but that do not directly elicit the patient points of view on the intervention. The proposed efficacy measure in the measurement of chronic wound care will include:
- The percentage of patients healed
- The type and amount of exudate produced before and after the intervention
- Percentage of wound areas debrided
- The rate of wound infection reduction
- Mean time taken to complete the healing
- The percentage change in wound dimensions (depth and area)
- Predominant tissue at the wound bed.
Wound healing related variables and patient demographics will be evaluated for their influences on the complete healing of all patients, as well as the subsets of control patients.
Data Collection and Data Analysis
Data from the patients will be extracted after an agreed period – say on a weekly basis. Data from the selected sample patients will be reviewed by the team and an external examiner. Variables will be measured as follows:
- Wound area and depth – measured using the prevalent measurement techniques. For example, one technique is the use of a fixed focal length digital camera with dual lasers. Software integral to the device will then calculate the wound sizes and area.
- Wound location – defining the location of the wound.
- Peripheral neuropathy will be determined using a 10-g monofilament probe of the foot dorsum while averting the gaze of the patient.
- Measurement of wound bioburden will be carried out using a bacteriologic culture of up to 4 mm punched out tissular samples obtained from cleansed wounds during screening visits before run-ins. The performance of standard microbiology tests will be conducted at the (name here) laboratories, with an assay of the lower limit of quantification (measurement here – for example, 1.0 x 103) of the colony forming units per gram (Lantis et al., 2013).
- Specific bacterial species tests will be conducted to ascertain the microorganisms specifically associated with impaired healing.
- Body mass index – calculation using the weight in kilograms and height in meters
- Measurement of pre-albumin and HbAIC – collection of serum samples using serum separator tubes. Serum will be separated from venous blood via centrifugation and sent to the (name here) laboratory for analysis.
- Patient demographics – history of diabetes, body weight and height, wound duration and location, age, sex, and race. These will be obtained from patient histories, patient interviews, review of patient records and physical medical examinations
The distribution of baseline characteristics (patient demographics) will be tested using analysis of variance. The prospectively defined statistical analysis employ the commonly used tool of Cochran-Mantel-Haenszel test, which will be adjusted for the pooled sites, and for the proportion of patients achieving complete wound healing by the treatment modalities instituted during the 13 weeks of therapy. The missing outcomes will be imputed using the last observation as carried forward.
Wound survival analysis will be similarly evaluated based on a prospective plan using the Cox proportional hazard, adapted for the baseline wound areas. The Cochran-Mantel-Haenszel test as adapted for the pooled sites will be used to examine the treatment effects on the patients who received systemic antimicrobials to those who did not at each weekly visits. The tests will be performed separately for each pair of participants.
In the study, post hoc analysis of patient and wound variables will be carried out by combining all the patients involved; patients receiving systemic therapy in addition to another therapy (topical treatment and wound debridement) and patients who received alternative therapy exclusion of systemic therapy (topical treatment plus wound debridement). Quantitative continuous variables (BMI, wound duration, HbAIC, and wound area) will be tested using parametric analyses (t-tests) or, if not normally distributed (this will be based on the Shapiro-Wilk Test) by nonparametric analyses (exemplifying the Mann-Whitney rank-sum test) (Raffoul, 2008; Lantis et al., 2013).
Categorical variables present will be dichotomized as “0” or “1”; appropriately differentiated as non-healing versus healing, location on the hips versus location on the legs, whites versus nonwhites and monofilament sensation no versus yes. Dichotomous categorical variables will then be tested using the x2 and the Yates correction formulae. (Lantis et al., 2013). Both the coded and continuous dichotomous variables will be tested using multiple logistic regression, employing the maximum likelihood estimation. Adjustments for multiplicity will not be made. Relationships between the bioburden in wounds median wound duration will be tested using the Kruskal-Wallis one-way analysis of variance and rank.
Assumptions and Limitations
- Weekly sharp debridement is not necessary
- For each bacteria genus identifies, the proportion of culture-positive wounds that healed will be compared to the average healed for all the treated patients.
- In the testing of both the coded and continuous dichotomous variables using the multiple logistic regression, with the maximum likelihood estimation, appropriate adjustment for multiplicity will not be made
Conclusion
Whereas biofilms can adapt to selective stresses, some clinicians have posited that rotating regimens of selected treatment methodologies is advantageous (by rotation I mean changing a certain biocide to a new biocide after some time – for example after every four weeks). Furthermore, the institution of multiple antibiotic agents, which target the various colony species may also be used concurrently. In addition to the selective targeting of biofilms, it is important to address other barriers to healing such that complicate the disease, including edema, glucose levels, vascular integrity and repetitive trauma. Addressing these issues will help augment the host’s defenses, which when at their optimal performance, provide the best means of wound management. Protocol-driven, well-designed regimens are needed to organize the simultaneous use of these strategies. Importantly, concomitant strategies are needed to defeat such determined enemies.
References
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