Despite the availability of various topical antimicrobials, most practitioners are not sure what to use on acute and chronic neonatal and pediatric wounds, especially due to a lack of robust supporting literature regarding concerns and side effects.
Skin infections. Impetigo is a common superficial bacterial skin infection that is often caused by S aureus and/or Streptococcus pyogenes. Clinically, there are 2 main syndromes: the more common nonbullous impetigo (impetigo contagiosa) and the less common bullous (blistering) impetigo. Nonbullous impetigo typically manifests as small intraepidermal blisters, which subsequently form yellow-brown crusted lesions around the face, particularly the nose and mouth. It is most common in children aged 2 to 5 years, and although self-limiting, it is generally treated with antibiotics to reduce symptom duration and to prevent further transmission of causative bacteria.3 Impetigo can be treated with topical antibiotics and/or systemic antibiotics, and the decision of which therapy to use is generally based on the number and extent of lesions, with minor disease usually treated with topical agents.3
Despite an estimated global prevalence in children of approximately 162 million, there is limited high-quality evidence to guide the appropriate empirical topical treatment of impetigo.3 A meta-analysis conducted in 2012 to assess interventions for impetigo included 24 randomized controlled trials (RCTs) that compared topical antibiotic therapy (mupirocin or fusidic acid) to placebo.12 Overall, the authors of that analysis concluded that topical antibiotic therapy achieved significantly higher cure rates than those with placebo and that there was no significant difference between the 2 main topical antibiotics used. However, the quality of the included studies was variable, with most being conducted more than a decade ago, making resistance patterns noncontemporary.
There remain several knowledge gaps regarding the most appropriate topical treatment for impetigo. For example, given that impetigo is generally regarded as a self-limiting condition, there are relatively few trials comparing topical antibiotic treatment to treatment with placebo. Normally, laboratory testing is not a part of the routine work-up for mild impetigo; therefore, true rates of resistance in causative pathogens are largely unknown. Thus, caution should be exercised in extrapolating results of studies conducted in low-resistance settings, as it is possible that clinical and microbiological cure rates differ among settings.3 Given the current evidence, it is important for practitioners to consider prescribing topical antibiotics for impetigo for the shortest possible duration of therapy and being aware of the microbial local resistance patterns.
Wounds. Whether surgical, traumatic, or iatrogenic, wounds have always been the primary target of topical antimicrobials. Both chronic and acute wounds in pediatrics are commonly covered by bacitracin or Neosporin (neomycin, polymyxin, and bacitracin zinc; Johnson & Johnson). Almost every cutaneous procedure in the emergency department or an outpatient office is followed by the application of one of those antibiotics, and they are included in the discharge instructions. Many studies have shown their efficacy over placebo in decreasing skin colonization and infection development, yet others demonstrated no difference and enhanced epithelization just from the presence of an emollient base.1–3
In addition to traumatic wounds, infections following burn injuries represent a major area of interest. Cutaneous injury, coupled with vascular insufficiency and often an inadequate immune system, may create a perfect storm for colonization and multiplication of microbes. Numerous topical antimicrobial agents have been used for infection prophylaxis, but the strength of data is moderate. A systematic review in 2013 reviewed the effectiveness of topical prophylaxis for burn-related infections in adults; it included 26 RCTs, evaluating a range of topical agents such as silver sulfadiazine, neomycin, bacitracin, polymyxin B, and mafenide acetate.10 The authors found no evidence to support the use of topical antimicrobials (compared with either no intervention or any other intervention) for the prevention of infections. Moreover, a subanalysis of 11 RCTs (with 645 participants) involving the use of 1% topical silver sulfadiazine found that patients treated with silver sulfadiazine actually had a higher risk of infection and a longer hospital stay than those treated with either dressings or skin substitutes.3 Frequent and potentially painful applications of these topical agents complicate care even further. It is the author’s opinion that modern dressings, including impregnated foams, skin substitutes, surfactant-based burn gel, medical grade honey, and hydrophobic gel-based dressings, offer safer, noncytotoxic, and patient-friendly solutions.
Prevention of postsurgical wound infections is another area of concern. Most practitioners will administer preoperative antibiotics, followed by postoperative systemic antibiotics. Some may recommend topical antibiotics to the incision area as prophylaxis. There is limited evidence to support the administration of topical antibiotics directly at the surgical site.12 In adults, an analysis concluded that locally applied topical antibiotics had a probable benefit in reducing postsurgical infection rates in joint arthroplasties and ophthalmic surgery and a possible benefit in reducing the rates in cosmetic breast augmentation and in obese patients undergoing abdominal surgery.8 In addition, a Cochrane review13 evaluated the use of locally applied topical antibiotics in the prevention of surgical wound healing by primary intention. The overall quality of the evidence was poor, however, but a mild positive effect was elucidated in the surgical site infection rate. Personally, the author worries about this practice in pediatrics because data are limited and it may continually add to antimicrobial resistance.
Decolonization. In addition to systemic antibiotics, contemporary infection prevention strategies often involve the application of a topical antibiotic (mupirocin) to the nasal mucosa to eradicate preoperative S aureus carriage and antiseptic body washes (chlorhexidine) to reduce the bacterial load on the skin. The available evidence suggests that prophylactic nasal and skin decolonization is an effective strategy for preventing S aureus infections following surgical procedures, predominantly orthopedic and cardiac surgeries. This reduction is observed for both methicillin-susceptible S aureus (MSSA) and methicillin-resistant S aureus (MRSA).3 MRSA colonization in the general population is widespread (approximately 1.5% of the population).6,8 Neonates are likely to acquire S aureus through the birth canal, breastfeeding, and contact with people and the surrounding environment.6,11 Neonatal colonization rates of S aureus were reported to be 40% to 50% during the first 8 weeks of life, followed by a gradual decrease to around 20% at 6 months of age, with anterior nares being the predominant site of MRSA colonization.6 Other parts of the body, such as the umbilicus, pharynx, axilla, groin, and perineum, harbor MRSA to a lesser extent. Current data demonstrate a higher MRSA colonization rate in hospitalized neonates than in the general neonatal population, ranging from 3.9% to 32% among institutions.11,14 Approximately 1 of 5 neonates colonized with MRSA may develop an infection, with the onset ranging from 4 to 9 days.8 Prematurity is the single largest predisposing factor.8
The clinical manifestations of MRSA infections range from mild focal infections to more severe forms, such as toxic shock syndrome, and invasive infections, such as sepsis, necrotizing pneumonia, meningitis, endocarditis, osteomyelitis, liver abscesses, and urinary tract infections. The mortality rate of MRSA infections varies widely among institutions, ranging from about 2.9% to 28%.8,14 Although there seems to be no difference between MRSA and MSSA in terms of their clinical presentation and mortality rate, neonates infected with MRSA may have a higher readmission rate and a longer infection course than those with MSSA.14
Untreated colonization increases the risk of MRSA infection by 6% daily.15 Therefore, most neonatal intensive care units have adopted active surveillance cultures plus MRSA decolonization strategies using nasal mupirocin with or without antiseptic bath along with frequent handwashing. Many studies have shown the success of this practice in both children and adults, but frequent recolonization occurs in neonates.11,14–17 In the author’s experience, many neonates require a second and third course of mupirocin, leading to the current 30% mupirocin-resistant rate. Most neonates tolerate the application well; therefore, many courses are easily administered without always checking strain sensitivity or the potential effectiveness of mupirocin.
It is known that the mupirocin molecule is unstable in the enteric form.9,15 In cutaneous application, it is successful in eradicating MRSA/MSSA by targeting bacterial isoleucyl-tRNA synthetase.9 In adults little evidence exists for transcutaneous absorption, based on the level of monic acid (the cleavage of the mupirocin molecule produces monic acid) in the urine or the lack thereof.8,9 Neonates may absorb mupirocin to a greater extent, given their skin immaturity, leading to a greater exposure and potentially more widespread resistance. While it is important to prevent MRSA infections and eliminate MRSA/MSSA colonization, practitioners have to be cognizant of resistance development, minimalize unnecessary exposure, develop tests helpful in determining mupirocin efficacy, and adhere to strict hygiene measures.
Dr. Boyar is director of Neonatal Wound Services, Cohen Children’s Medical Center of New York, New Hyde Park, and associate professor of Pediatrics, Zucker School of Medicine, Hofstra/Northwell, Hempstead, NY. This article was not subject to the Wound Management & Prevention peer-review process.