Why topical antibiotics for burns

Aside from the recognized threat of burn wound sepsis, burn wound infections also may lead to wound conversion, skin graft failure, and prolonged hospitalization. The introduction of topical antimicrobial agents was a major advancement in burn care and proved to be responsible for important reductions in mortality from burn wound sepsis [ 2 , 3 ]. Currently, while the problem of invasive burn wound infection has largely been eliminated by early surgical excision and closure of deep second-degree and third-degree burns, topical antimicrobial control in these wounds prior to definitive surgical debridement is still necessary.

Even superficial burns which are expected to heal may benefit from the use of topical antimicrobial agents since microbial proliferation in a burn wound has the potential to significantly delay healing [ 4 ], the main consequence of which is increased scarring. Therefore, regardless of burn depth, topical antimicrobials are most importantly indicated when there is clinical suspicion of risk of infection, or when a wound infection is evident.

Paradoxically, many of the topical antimicrobial agents currently in use also have cytotoxic effects on keratinocytes and fibroblasts and have the potential to delay wound healing. Thus, while topical antimicrobial agents are indicated for most if not all burn wounds, the choice of a topical agent must consider many factors such as the wound depth, anticipated time to healing, need for surgical intervention, and the known cytotoxicity of the agent.

The appearance of microbes in the burn wound follows a predictable pattern. Initially, but only transiently, the wound is sterile. Within 48 h of injury, gram-positive bacteria that are normally found in the skin such as Staphylococcus aureus , Corynebacterium , and Streptococcus species colonize the wound surface. These are usually gram-negative organisms such as Pseudomonas aeruginosa , Enterobacter species, Proteus , and Escherichia coli. Unfortunately, the full spectrum of emerging antibiotic-resistant bacteria including methicillin-resistant Staphylococcus aureus MRSA and multiresistant Acinetobacter are now frequently encountered in the burn wound at this stage.

Later, yeasts and fungi may appear [ 5 , 6 ], which is always an ominous sign connected with heightened mortality [ 7 ].

While almost all burn wounds will become colonized with microorganisms, this does not always cause harm. Since superficial burns have a preserved blood supply and perfusion through much of the dermis, they typically will become colonized but less frequently develop invasive burn wound infections.

In contrast, deeper burns are covered by an avascular layer of moist and protein-rich dead skin the eschar , which fosters bacterial proliferation and invasion, leading to burn wound infection. Furthermore, generalized immunosuppression associated with major burn injuries predisposes the patient to local burn wound infection. When bacteria in the eschar penetrate surrounding uninjured tissues and invade the bloodstream, fatal sepsis may result.

Hence, there is an important need to suppress bacterial growth with topical agents, especially in deeper burns, to prevent invasive burn wound infection and its life-threatening consequences. Infection will delay wound healing [ 11 ]. Bacteria produce numerous endotoxins, exotoxins, and proteases which inflict further tissue injury. The microbial population also has metabolic requirements and consumes resources necessary for wound healing [ 4 ]. Finally, a heavy bioburden stimulates an increased inflammatory response, the by-products of which may cause injury to healthy tissue [ 4 ].

These problems are particularly germane to more superficial burns that are attempting to heal spontaneously and provide the rationale for the use of topical antimicrobial agents in this setting. Many topical antimicrobial agents are cytotoxic to keratinocytes and fibroblasts, and as such have the potential to delay wound healing [ 12 , 13 ]. It is not surprising that in systematic reviews of controlled trials comparing biosynthetic skin substitutes to topical antimicrobial dressings for superficial partial-thickness burns, faster healing was observed with the use of skin substitutes [ 14 , 15 ].

Consequently, the choice of a topical antimicrobial agent must be a delicate balance between the need to control microbial growth in the burn wound, and the potential risk that the topical agent may impair wound healing. In practical terms, among more superficial burns that are expected to heal on their own, it is more important and difficult to strike this balance.

In these burns the goal is healing within 2—3 weeks of injury to reduce the likelihood of hypertrophic scarring [ 16 ]. Conversely, in a deeper burn that is not expected to heal spontaneously and which will be excised and closed surgically, there is a greater emphasis on suppressing microbial growth and less emphasis on optimizing conditions for spontaneous healing.

Systemic antimicrobial drugs are not recommended because they are ineffective against colonization and infection of the burn wound [ 15 ].

Avascular eschar and the presence of biofilms are the main impediments that limit the delivery and effectiveness of systemic antimicrobials, and the routine use of systemic agents only leads to the emergence of dangerous multiresistant microbial strains. In contrast, topical antimicrobials are delivered directly to the burn wound, and to varying degrees penetrate eschar and limit the development of infection.

Although microorganisms are capable of developing resistance to topical agents, this is much less common than to systemic antibiotics.

This may be in part related to the route of delivery. However, one study found that while many multidrug-resistant organisms MDROs are susceptible to commonly used topical agents, higher rates of resistance were seen than to non-MDROs [ 17 ].

While antimicrobial resistance to topical antimicrobials is less common than to systemic agents, practitioners should always consider this possibility as well as strategies to deal with this problem. One approach is to know the common or endemic organisms within the burn care facility and to avoid use of topical agents that are ineffective against those microbes. For example, where fungus is endemic, mafenide acetate may not be a good choice due to its inactivity against fungus.

Another strategy may be to rotate use of various topical agents rather than employ only one agent. The ideal topical antimicrobial for burn wounds would have the following properties: It would have a broad spectrum of coverage and would not stimulate the development of resistance. It would be able to penetrate well into the burn eschar while being painless to apply and requiring infrequent dressing changes or reapplication. Finally, it would not inhibit wound healing and would be non-absorbable and free of systemic adverse effects.

Unfortunately, none of the currently available topical antimicrobial agents meet all these criteria. Silver has been known for centuries to have antimicrobial properties, and it is the foundation of established topical antibacterial agents for the burn wound such as silver nitrate solution, silver sulfadiazine cream, and silver-releasing dressings.

Silver ions are toxic to bacteria, yeasts, and fungi through several mechanisms. These include inhibition of enzymes necessary for metabolism and respiration of the microorganism, disruption of the cell membrane or cell wall of the microbe, and interference with DNA and RNA preventing replication of the microorganism [ 18 , 19 , 20 ].

Microbial killing is strongly correlated with the concentration of free silver ions [ 18 ]. Resistance to silver is uncommon, presumably because silver acts by multiple mechanisms, but there is some evidence that suggests that chronic exposure to very low concentrations of ionic silver can induce resistance. Thus, it is recommended that dressings or agents that release high levels of ionic silver are preferable, from the standpoint of avoiding development of silver resistance [ 4 ].

Although ionic silver is an effective antimicrobial agent, in vitro studies have found that it is also cytotoxic to cells essential for wound healing such as keratinocytes and fibroblasts, and silver has been shown to delay healing of second-degree burns in vivo [ 20 , 21 , 22 , 23 , 24 , 25 ].

Ionic silver dissociates from AgNO 3 to effectively inhibit a broad spectrum of microorganisms on the burn wound including Staphylococcus species, some gram-negatives including Pseudomonas and some yeasts. However, the liberated free silver ions readily precipitate with chloride and any other negatively charged molecules, inactivating the silver, and creating inert silver salts.

Consequently, silver ions do not penetrate deeply into the eschar and must be frequently replenished by keeping the gauze dressings on the wound continuously wet with the 0. Poor eschar penetration and labor intensiveness are considered the main drawbacks of AgNO 3.

Bacterial conversion of nitrate to nitrite may rarely lead to methemoglobinemia [ 26 ]. Silver sulfadiazine SSD is applied universally as a topical antimicrobial for burns. Silver sulfadiazine is effective against numerous microorganisms commonly found in the burn wound including gram-positive bacteria e. This effect has been observed in many clinical studies where SSD was compared to alternative dressings or topical antimicrobials [ 14 , 29 ].

While much of this evidence is low quality, there seems to be a consistent pattern showing that SSD delays healing of superficial burns [ 14 ]. A minority of patients experience cutaneous hypersensitivity to SSD, and the agent cannot be used in patients who are allergic to sulfonamides. Application to the burned face is relatively contraindicated due to the risk of ocular irritation or injury. While silver is readily absorbed, systemic silver toxicity to specific organs such as the liver or the kidney through silver deposition is exceedingly rare but theoretically should be considered when SSD is repetitively applied to large surface areas [ 30 ].

Finally, SSD has a relatively short duration of action and penetrates only the superficial part of the burn eschar [ 31 ]. Therefore, SSD may need to be reapplied more than once per day to preserve a sufficient reservoir of the compound to maintain continuous dissociation of silver onto the wound surface, although daily vs more than once-daily application of SSD has never been formally studied. This has implications for all burn patients but especially children who would be subjected to repetitive painful dressing changes when this agent is chosen.

The latest way to deliver silver to the burn wound is the silver-releasing dressing. There are numerous silver-releasing dressings which can be broadly classified as follows [ 19 , 32 , 33 ]:. Activated charcoal dressings with silver work by adsorbing bacteria into the dressing where they are then destroyed by silver in the dressing.

In vitro, nanocrystalline silver dressings have shown antimicrobial activity against a broad spectrum of bacteria, antibiotic-resistant organisms, as well as yeasts and fungi [ 34 , 35 , 36 ].

A major advantage of these dressings is that their sustained release of ionic silver provides an effective antimicrobial effect while potentially requiring fewer painful dressing changes as compared to more traditional approaches such as silver nitrate dressings [ 37 ]. This might be especially beneficial in the pediatric burn population.

Similar findings of reduced hospitalization and cost by use of outpatient nanocrystalline silver dressings as opposed to inpatient SSD for pediatric patients with scald burns have been reported [ 40 ]. At present, there is insufficient evidence from randomized clinical studies which predominantly involve partial-thickness burns to confidently determine that silver-releasing dressings prevent burn wound infections [ 41 ]. Similarly, there is conflicting evidence on whether silver-releasing dressings impede or promote re-epithelialization [ 42 , 43 , 44 ].

Canonsburg PA, USA is a topical sulfonamide antibiotic that can penetrate deep into eschar and tissues, and it is active against many gram-positive and gram-negative organisms. This capability was originally harnessed to successfully counter the problem of invasive burn wound infection and fatal septicemia from gram-negative species, especially Pseudomonas [ 2 , 3 ].

The most common use of mafenide acetate MA is for deep or infected burns where penetration of the antibiotic into the eschar is advantageous. For the same reason, the cream is also used for deep burns of the ear to prevent invasive infection leading to suppurative chondritis of the ear cartilage [ 45 ].

One problem with MA is its lack of antifungal activity. Addition of nystatin to MA is used to avoid fungal overgrowth with prolonged use of MA. Another disadvantage is that MA is painful on application, especially on more superficial wounds.

To some extent, this problem has been reduced by using the 5 and 2. Like other topical antimicrobials, MA is cytotoxic to fibroblasts and keratinocytes and may impede wound healing. In vitro studies suggest that concentrations as low as 0. Another adverse effect is that MA is a carbonic anhydrase inhibitor and may cause severe metabolic acidemia with compensatory hyperventilation when it is repetitively applied to large surface areas.

For this reason, mafenide acetate cream is usually reserved for smaller deep burns, or it is alternated with SSD on larger burns. Finally, MA may occasionally cause a local rash or skin irritation [ 48 , 49 ].

An antibiotic ointment contains an antibiotic within a water-in-oil emulsion where the volume of oil exceeds that of the water. Thus, such ointments provide not only an antibacterial effect but also they create a moist wound healing environment. Hence, these agents are optimally suited for superficial burns where spontaneous healing is expected. While the spectrum of bacterial coverage tends to be limited, these agents are relatively free of complications. In general, the ointments are applied two to three times daily as a thick layer for moisture retention and then are covered with a non-adherent dressing layer followed by gauze [ 48 ].

Mostly they are soothing to apply, easier to clean off than creams such as SSD, and tend to be reasonably well tolerated by children. Bacitracin is a topical agent effective against gram-positive bacteria but not gram-negative bacteria or yeasts.

Bacitracin ointment is contained in a petroleum base which helps to maintain a moist wound healing environment. Usually, bacitracin is applied to superficial burns, especially those on the face. Due to the lack of fungal coverage, prolonged use, especially after re-epithelialization has occurred, may lead to overgrowth of yeast causing a rash.

Bacitracin should therefore be terminated as soon as the wound has epithelialized [ 48 , 49 ]. Like Bacitracin, Polymixin B sulfate is impregnated in a thick petroleum-based ointment that helps with moisture retention. The antibacterial spectrum covers many gram-negative bacilli including Pseudomonas , but activity against gram-positives is limited.

Absorption and systemic toxicity such as nephrotoxicity or neurotoxicity are uncommon but could be seen with repeated application to large surface areas [ 5 ]. This aminoglycoside antibiotic ointment covers gram-negative bacilli such as Escherichia coli and Enterobacter , along with some gram-positive species.

Unlike the other antibiotic ointments, bacteria tend to develop resistance to neomycin more frequently and local skin irritation is seen more frequently. Absorption following application to large surface areas may lead to systemic toxicity including nephrotoxicity and ototoxicity [ 48 , 49 ]. The limited antibacterial spectrum of the individual agents described above is partly overcome by combining them. This topical agent is highly effective against gram-positive skin flora including Staphylococcus aureus , and importantly, it is the only topical ointment that can suppress MRSA.

Antiseptic solutions are chemical agents that are externally applied to wounds and tissues. These agents typically have a broad spectrum of activity and act through multiple simultaneous mechanisms, which may be the reason that microorganisms do not develop resistance to these agents as readily as to antibiotics.

Many antiseptic solutions are also able to disrupt biofilms [ 50 ]. Thus, these agents were originally used on chronic wounds but more recently they have been utilized for microbial control on acute burn wounds. Most of these agents are cytotoxic to keratinocytes and fibroblasts and can impair wound healing.

In general, the optimal solution concentration that provides an acceptable balance between microbial killing and avoidance of cytotoxicity is unknown for most of these agents. Concentrations as low as 0. However, in vitro cytotoxicity to fibroblasts and keratinocytes has also been reported in this concentration range [ 12 , 13 , 51 ].

Patients should be directed to continue using wound dressings until the wound shows signs of healing and should always be advised to seek medical care for wounds that do not exhibit signs of healing after 5 days of self-treatment or if the wound shows signs of infection. Preassembled kits can be purchased, or patients can assemble them themselves. Many kits also contain medications such as oral and topical antihistamines, OTC topical hydrocortisone cream, OTC pain relievers, and calamine lotion.

It provides handy first-aid tips and the 10 most common myths about first aid. Self-Treatment of Minor Wounds and Burns. May 3, Yvette C. Terrie is a clinical pharmacist and medical writer based in Haymarket, Virginia. References Bernard D. Minor burns, sunburns and wounds. Handbook of Nonprescription Drugs. Factors Affecting Wound Healing. Journal of Dental Research.

Acute wound management: revisiting the approach to assessment, irrigation, and closure considerations. International Journal of Emergency Medicine. How to clean and protect a cut or scratch in 2 simple steps. Band Aid website. The conclusions we are able to draw regarding the effects of prophylactic antibiotics in people with burns are limited by the volume and quality of the existing research largely small numbers of small studies at unclear or high risk of bias for each comparison.

The largest volume of evidence suggests that topical silver sulfadiazine is associated with a significant increase in rates of burn wound infection and increased length of hospital stay compared with dressings or skin substitutes; this evidence is at unclear or high risk of bias. Currently the effects of other forms of antibiotic prophylaxis on burn wound infection are unclear. One small study reported a reduction in incidence of pneumonia associated with a specific systematic antibiotic regimen.

Infection of burn wounds is a serious problem because it can delay healing, increase scarring and invasive infection may result in the death of the patient. Antibiotic prophylaxis is one of several interventions that may prevent burn wound infection and protect the burned patient from invasive infections.

There were no restrictions with respect to language, date of publication or study setting. All randomised controlled trials RCTs that evaluated the efficacy and safety of antibiotic prophylaxis for the prevention of BWI.

Quasi-randomised studies were excluded. Two review authors independently selected studies, assessed the risk of bias, and extracted relevant data.

Risk ratio RR and mean difference MD were estimated for dichotomous data and continuous data, respectively.