Use Of Topical Antimicrobials Research Articles

Infections in critically ill burn patients

Severe burn patients are one subset of critically patients in which the burn injury increases the risk of infection, systemic inflammatory response and sepsis. The infections are usually related to devices and to the burn wound. Most infections, as in other critically ill patients, are preceded by colonization of the digestive tract and the preventative measures include selective digestive decontamination and hygienic measures. Early excision of deep burn wound and appropriate use of topical antimicrobials and dressings are considered of paramount importance in the treatment of burns.Severe burn patients usually have some level of systemic inflammation. The difficulty to differentiate inflammation from sepsis is relevant since therapy differs between patients with and those without sepsis. The delay in prescribing antimicrobials increases morbidity and mortality. Moreover, the widespread use of antibiotics for all such patients is likely to increase antibiotic resistance, and costs. Unfortunately the clinical usefulness of biomarkers for differential diagnosis between inflammation and sepsis has not been yet properly evaluated.Severe burn injury induces physiological response that significantly alters drug pharmacokinetics and pharmacodynamics. These alterations impact antimicrobials distribution and excretion. Nevertheless the current available literature shows that there is a paucity of information to support routine dose recommendations.

Topical spraying of cefazolin and gentamicin reduces deep sternal wound infections after heart surgery: a multicenter, large volume, retrospective study.

The use of topical antimicrobials applied to the sternum during cardiac procedures in combination with intravenous agents to prevent mediastinitis has been reported to yield good results. The objective of this study is to provide optimal method of topical antimicrobials for the prevention of sternal wound infection after cardiac surgery. We retrospectively evaluated the patients undergoing adult cardiac surgery at five institutions between January 1994 and August 2013 for the incidence of deep sternal wound infection (DSWI). The patients were sprayed with a solution of cefazolin and gentamicin into the surgical site several times during surgery. The incidence of DSWI was evaluated. Four major risk factors [diabetes mellitus (DM), emergency operation, dialysis and prolonged operation] were also evaluated for their implications in the outcome with the antimicrobial spraying. Totally, 6960 patients were analyzed. The incidence of DSWI was 0.46% in the spraying group versus 1.7% in control group (p < 0.0001). There is no significant difference of the incidence of DSWI between DM and non-DM groups (p = 1.00), emergency and elective operation groups (p = 0.25) under usage of antimicrobial spraying. However, there is significant difference of the incidence of DSWI between dialysis and non-dialysis groups (p = 0.0222), longer than six-hour duration and lesser than six-hour duration operation groups (p = 0.0269). Topical spraying of cefazolin and gentamicin reduces deep sternal wound infections after cardiac surgery. DM and emergency operation were not the risk factors of DSWI when antimicrobial spraying is administered. Considering the benefits, antimicrobial spraying could be used intermittently during such procedures.

Approach to chronic wound infections.

Infection is the likeliest single cause of delayed healing in healing of chronic open wounds by secondary intention. If neglected it can progress from contamination to colonization and local infection through to systemic infection, sepsis and multiple organ dysfunction syndrome, and it can be life-threatening. Infection in chronic wounds is not as easy to define as in acute wounds, and is complicated by the presence of biofilms. There is, as yet, no diagnostic for biofilm presence, but it contributes to excessive inflammation - through excessive and prolonged stimulation of nitric oxide, inflammatory cytokines and free radicals - and activation of immune complexes and complement, leading to a delay in healing. Control of biofilm is a key part of chronic wound management. Maintenance debridement and use of topical antimicrobials (antiseptics) are more effective than antibiotics, which should be reserved for treating spreading local and systemic infection. The continuing rise of antimicrobial resistance to antibiotics should lead us to reserve their use for these indications, as no new effective antibiotics are in the research pipeline. Antiseptics are effective through many mechanisms of action, unlike antibiotics, which makes the development of resistance to them unlikely. There is little evidence to support the theoretical risk that antiseptics select resistant pathogens. However, the use of antiseptic dressings for preventing and managing biofilm and infection progression needs further research involving well-designed, randomized controlled trials.

Reply

We appreciate the comments by Silvestri et al. about our article.1 We agree that a selective intestinal decontamination (SID) strategy with nonabsorbable antibiotics is especially attractive for preventing the selection of multiresistant pathogens. As stated by Silvestri et al., SID strategies based exclusively on the use of topical antimicrobials (eg, tobramycin and polymyxin in combination) have shown efficacy in the prevention of some severe infections, such as ventilator-associated pneumonia in critically ill patients.2 However, the reduction in mortality for these patients has been achieved with SID schemes that also generally include systemic antibiotics.3, 4 Unfortunately, there is little information about SID with tobramycin and polymyxin in liver transplant recipients, although similar results would be expected in this population. Therefore, we also encourage the design of specific studies in order to establish the optimal strategy for preventing early bacterial infections in liver transplant recipients while minimizing the risk of selecting multiresistant pathogens. Rafael San-Juan M.D.*, Jose Maria Aguado M.D.*, * Infectious Diseases Unit 12 de Octubre University Hospital Madrid, Spain.

Topical antiseptics in wound care: time for reflection

Topical antiseptics in wound care: time for reflection

PHMB as a topical antimicrobial in veterinary wound management

There are currently no new antibiotics on the horizon, and this fact should cause concern for all involved in both human and veterinary medicine. The use of topical antimicrobials should be considered as the alternative to systemic antibiotics in wound infection in order to minimize their use. Polyhexamethylene biguanide (PHMB) is a relative newcomer to the veterinary market, having been used as an antiseptic/antimicrobial in a variety of industries for over 60 years. PHBM has been incorporated into a range of wound dressings and is highly effective as an antimicrobial as it destroys the outer and cytoplasmic membranes of the bacteria, destroying them. These dressings are able to rapidly reduce the bacterial load in the wound and represent the first line in the management of the bacterial burden of a wound.

Topical antimicrobials for burn wound infections.

Throughout most of history, serious burns occupying a large percentage of body surface area were an almost certain death sentence because of subsequent infection. A number of factors such as disruption of the skin barrier, ready availability of bacterial nutrients in the burn milieu, destruction of the vascular supply to the burned skin, and systemic disturbances lead to immunosuppression combined together to make burns particularly susceptible to infection. In the 20th century the introduction of antibiotic and antifungal drugs, the use of topical antimicrobials that could be applied to burns, and widespread adoption of early excision and grafting all helped to dramatically increase survival. However the relentless increase in microbial resistance to antibiotics and other antimicrobials has led to a renewed search for alternative approaches to prevent and combat burn infections. This review will cover patented strategies that have been issued or filed with regard to new topical agents, preparations, and methods of combating burn infections. Animal models that are used in preclinical studies are discussed. Various silver preparations (nanocrystalline and slow release) are the mainstay of many approaches but antimicrobial peptides, topical photodynamic therapy, chitosan preparations, new iodine delivery formulations, phage therapy and natural products such as honey and essential oils have all been tested. This active area of research will continue to provide new topical antimicrobials for burns that will battle against growing multidrug resistance.

Coverage of Large Pediatric Wounds With Cultured Epithelial Autografts in Congenital Nevi and Burns: Results and Technique

The use of cultured epithelial autografts (CEA) for the treatment of large burn wounds has gained popularity in recent years. This technique may circumvent the restrictions of limited donor site availability and hasten permanent wound coverage for large TBSA burns. The availability of a large amount of skin from a small donor site with the promise of permanent wound coverage suggests its use in other conditions such as giant congenital nevi (GCN) as well. The risk of malignant transformation of GCN to melanoma although somewhat controversial is significant enough to warrant early excision in childhood. Cultured keratinocytes may provide one-stage coverage of these large wounds, lessening the number of surgeries and the inherent staging problems of tissue expansion or autografting. A retrospective single institution review of was done for 29 children (20 burns and 9 patients with GCN) who underwent coverage of their large surface area wounds with CEA over an 18-year period. Excellent take rates were noted; 76.4% for burn patients and 66% for patients with GCN. Several strategies in preoperative, perioperative, and postoperative care have been standardized and have helped improve outcome. The keys to success with the CEA technique have been aggressive control of wound sepsis, surgical technique, specific use of topical antimicrobials, dressings, and the standardization of nursing and physiotherapy care. Although the cost of CEA is high, the benefits to patient care make this technique an appealing choice for large wound coverage in the pediatric population.

Positive patch test reactions to gentamicin show sensitization to aminoglycosides from topical therapies, bone cements, and from systemic medication

A history of prolonged use of topical antimicrobials is common among patients with positive patch test reactions to gentamicin and to aminoglycosides. The aim of this study was to show sources of gentamicin sensitization in patients with positive patch test reactions to gentamicin. About 7814 patients were patch tested with a baseline patch test series and 620 of them were further tested with gentamicin. The clinical histories, concurrent contact sensitivities, and sources of sensitization are analysed among these patients. Positive patch test reactions to gentamicin were seen in 29/620 patients, most of whom (18/29) also reacted to neomycin and to kanamycin (7/29). Mean age of the gentamicin-positive patients was 62 years, but three young operating room nurses with hand dermatitis had a history of gentamicin exposure from bone cement. Among the 11/29 neomycin-negative patients, a history of exposure to different aminoglycosides was apparent, and one patient had a history of systemic netilmicin-medication-associated exanthema. Positive patch test reactions to gentamicin reflect sensitization to different aminoglycosides for which gentamicin seems to represent a sensitive indicator. Gentamicin sensitization may result from occupational exposure to gentamicin containing bone cements or from systemic medication with aminoglycosides.

Postoperative Topical Antimicrobial Use

Allergic contact dermatitis associated with topical antimicrobial agents is an increasing problem in the postoperative wound care period. We reviewed the topical antimicrobial agents most commonly used postoperatively in North America and Europe, examined the incidence of allergic contact dermatitis from each agent, and provided guidelines for the use of topical antimicrobials on closed and open wounds in the postoperative period. Neomycin was the most common cause of allergic contact dermatitis both in the general patch-tested population (11%) and in the postsurgical population. Bacitracin was also a common culprit, although at a lower rate (8%). There is a risk of co-reactivity between these two agents. Polymyxin B and mupirocin were not significant allergens. The rate of postoperative infectious complications in dermatologic surgery (1-2%) was similar to the rate of allergic contact dermatitis from topical antimicrobials (1.6-2.3%). We concluded that for closed wounds, the use of topical neomycin postoperatively should be avoided. White petrolatum is an efficacious and cost-effective alternative for closed wounds. For open wounds, topical antimicrobials that do not contain neomycin should be recommended.

Acute bacterial conjunctivitis – benefits versus risks with antibiotic treatment

Acute bacterial conjunctivitis – benefits versus risks with antibiotic treatment

Gene Therapy to Fight Infection in Skin Transplants

Wound closure can be problematic in patients with massive burns covering a large area of the body and in diabetic patients suffering from chronic ulcers. Insufficient donor sites in severely burned patients results in delayed wound closure and increases the likelihood of infection, which is a major cause of burn wound mortality [1]. Complications in patients wi th diabetic foot ulcers, most commonly resulting from infection, lead to as many as 50,000 amputations annually in the USA [2]. Tissue-engineered skin substitutes have been developed to begin to meet the needs of these patient populations [3]. The most basic skin substitutes are synthetic, acellular materials that act primarily as barriers to fluid loss and microbial invasion. Among the most innovative products are those containing cultured skin cells. Commercially available cellular skin substitutes, such as Apligraf ® , contain allogeneic dermal fibroblasts and epidermal keratinocytes, derived from donated neonatal foreskin, combined with a bovine collagen matrix. Apligraf is indicated for use in the treatment of venous leg ulcers and diabetic foot ulcers, increasing the percentage of wounds healed and decreasing the time required for wound closure [4–6]. However, as it is prepared using allogeneic cells, Apligraf and similar products act as biological bandages. Cells within the graft secrete growth factors and other proteins that facilitate wound healing and provide a matrix for cell migration, but the grafted cells do not persist indefinitely. Multiple applications are often required for complete wound healing. For burn patients, epidermal sheet grafts such as Epicel ® can be prepared with patient-derived keratinocytes for permanent wound coverage [7]. These grafts contain only epidermal cells; thus, they are prone to blistering and scar formation [7]. Cultured skin substitutes (CSS) are a bilayered autologous skin substitute currently in Phase II clinical trials. Comprised of cultured autologous keratinocytes, fibroblasts and biopolymers, CSS are used as an adjunctive treatment for coverage of burn wounds of greater than 50% of the body’s surface area, and have also been used to treat chronic wounds [8–10]. Despite the clinical successes observed with skin substitutes, they exhibit anatomical deficiencies, such as delayed vascularization, when compared with native skin autograft, which increase the risk for destruction due to microbial contamination. The use of topical antimicrobials in combination with skin substitutes can enhance engraftment and facilitate wound healing, but may contribute to the emergence of resistant strains of microorganisms. The development of a bioengineered skin substitute with increased innate resistance to microbial contamination could reduce or eliminate the requirement for exogenous antibiotics. Hypothetically, this could be achieved using a cutaneous gene therapy approach. Gene-encoded antimicrobial peptides, including members of the α- and β-defensin families and cathelicidins, have demonstrated antimicrobial activity against a wide variety of pathogens. Significantly, antimicrobial peptides have been shown to act against microorganisms commonly found in burns and chronic wounds, including multiply-resistant strains. As their mechanism of action is distinct from pharmaceutical antibiotic agents, defensins and related peptides represent a novel approach for treatment or prevention of infection. Antimicrobial peptides are effectors of the innate immune system and represent the body’s first line of defense against infection. Various antimicrobial peptides are expressed in neutrophils and in tissues that serve as interfaces with the environment, such as gut and lung epithelia and skin [11,12]. Rather than relying on specific antigen recognition, as in adaptive immunity, mediators of innate immunity take advantage of shared structural and functional characteristics of microorganisms. Antimicrobial peptides are cationic, allowing them to interact with the anionic lipid bilayer of microbial cell membranes through electrostatic interactions [13]. Following adsorption, the peptides disrupt the integrity of the outer cell membrane; irreversible injury of the target cell can result from entry of the antimicrobial peptide and other normally excluded molecules and leakage of essential cell components. Defensin-related cell death has also been linked to interference with protein synthesis and

Role of biological membranes in the management of Stevens Johnson syndrome—Indian experience

Erythema multiforme minor (EM), Stevens Johnson syndrome (SJS), and TEN are a group of severe exfoliative diseases of the skin and mucous membranes. Most authors consider SJS and TEN to be the same disease entity, differing only by the area of involved skin. TEN and SJS both seem to be caused by immunologic reactions to foreign antigens. Drugs are implicated in many cases. Anti bacterials, anti fungals anticonvulsants analgesics, non steroidal anti-inflammatory agents and even cortico steroids have been suspected of causing the disease process. The histologic characteristics of TEN include dermo epidermal separation resembling a blistering scald, followed by necrosis and shedding of the epidermis. The general recommendation for treatment of severe cases of TEN is the removal of necrotic epidermis and topical treatment of the wounds. The wound in TEN resembles superficial partial thickness burns though there is histological variation between the two. In TEN the affected areas heal within a week whereas it takes 2 to 3 weeks in partial thickness burn. To reduce the rate of infections and protect the unhealed areas as well as to reduce pain, several protocols have been suggested. These involve the use of topical anti microbials and the coverage of wounds with biological dressings. The most

The use of topical antimicrobials in wound bioburden control

The control of wound bioburden is believed to be valuable in avoiding possible deterioration into infection; in reducing critical colonization; and in treating frank infection. While the immune response is the governing factor in the development of infection, the reduction of bioburden – if achieved to a sufficient degree and for sufficient duration – can enable host defences to regain control. Topical antimicrobial agents, carefully selected and correctly dosed, can help achieve these goals. This review examines the value of topical antiseptics and antibiotics in various formulations in controlling the bioburden of acute and, predominantly, chronic wounds. The currently held perception of antibiotic misuse is reinforced and reiterated. Topical antibiotics must be used with caution and only for specific, limited indications. Topical antiseptics have a much broader range of applications and are generally safer when used appropriately. Conditions and circumstances of use are provided for these agents.

The appropriate use of topical antimicrobials and antiseptics in children.

The appropriate use of topical antimicrobials and antiseptics in children.

Utility of an intervention scoring system in documenting effects of changes in burn treatment

The consequences of the introduction of a program of consistent use of topical antimicrobials and early aggressive excision of deep burn wounds by utilizing a comprehensive, computerized patient registry/therapeutic intervention scoring system, were investigated. Prospectively, the clinical course, mortality, outcome and hospital costs were compared for the year preceding (89 patients) and the 4 years following (226 patients) the introduction of the new treatment program. It was found that mortality decreased from 10.1 to 4.6% after change in therapy ( P<0.001), despite an increase in mean burn extent. The length of hospital stay per % burn surface area declined from 1.2 to 1.0 days ( P<0.001). The number and complexity of therapeutic interventions and the associated costs, also declined. Patients in the new treatment program had a better level of physical and psychosocial function at follow up. In conclusion, the introduction of a program of consistent use of topical antimicrobials and early, aggressive surgical excision was associated with an improved outcome at lesser cost. The combined registry–intervention scoring system permits ready analysis of results using data entered on a daily, near-real time basis.

Prospective outcome analysis of a protocol for the surgical and rehabilitative management of burns to the hands.

Treatment protocols for the management of burned hands are essential for integrating team efforts and achieving optimal functional results. Standard protocols are especially useful during mass casualty incidents, when the admission of multiple patients with large burns and/or associated injuries may reduce the priority usually accorded the hands. We prospectively evaluated a surgical and rehabilitative treatment protocol for burned hands during a mass casualty incident, after which 43 burn patients with 82 burned hands were admitted to one burn center. Soft-tissue management was individualized to achieve, if possible, wound closure within 14 days, and included the use of topical antimicrobials, cutaneous debridement and/or tangential excision, biologic dressings, and split-thickness autografts. Range of motion therapy was based on daily measurement of active motion of the metacarpophalangealjoints. Static splinting alternating with continuous passive motion every 4 hours was utilized for sedated patients. Continuous passive motion alternating with active ranging and night splinting was utilized for metacarpophalangeal flexion <70 degrees. Active ranging and progressive resistance was utilized for metacarpophalangeal flexion > or =70 degrees. Sixty-four hands required excision and grafting, with 89 percent having at least one autografting procedure completed by postburn day 16. Total active motion of the hands treated averaged 220.6 degrees on discharge and 229.9 degrees at 3 months after injury. Mean hand grip strength was 60.8 pounds at discharge and 66.0 pounds at 3 months after injury. Adherence to a standard hand burn protocol resulted in timely wound coverage and recovery of hand function for a large group of patients treated at a single burn facility after a mass casualty incident.

Failure of infection control in intensive care units: Can sucralfate improve the situation?

Conventional infection control measures in intensive care units (ICUs) are aimed primarily at stemming cross-infections. The role of patients' endogenous flora in the pathogenesis of nosocomial infection and occasional lapses in aseptic technique in ICUs help to explain the frequent failure of the conventional approaches. Newer control strategies include avoiding gastric and oropharyngeal overgrowth of gram-negative bacilli by using sucralfate to avoid gastric alkalinization and/or suppressing nosocomial flora by use of topical antimicrobials.

The use of topical antimicrobials combined with biobrane in burn wound infections: L. Zachary, J. P. Heggers, M. C. Robson, et al. J Trauma 22:833–836, (October), 1982

The use of topical antimicrobials combined with biobrane in burn wound infections: L. Zachary, J. P. Heggers, M. C. Robson, et al. J Trauma 22:833–836, (October), 1982

The Use of Topical Antimicrobials combined with Biobrane in Burn Wound Infections

The Use of Topical Antimicrobials combined with Biobrane in Burn Wound Infections