Infections and Prophylaxis in Pediatric Trauma Patients
June 1, 2020
AUTHORS
Trahern (TW) Jones, MD, Fellow, Division of Pediatric Infectious Diseases, Adjunct Instructor, Department of Pediatrics, University of Utah Health, Salt Lake City
Shannon Brady, MD, Pediatric Resident Physician, University of Utah School of Medicine, Salt Lake City
PEER REVIEWER
Robert W. Schafermeyer, MD, FACEP, FAAP, FIFEM, Associate Chair, Department of Emergency Medicine, Carolinas Medical Center, Charlotte, NC; Clinical Professor of Pediatrics and Emergency Medicine, University of North Carolina School of Medicine, Chapel Hill
EXECUTIVE SUMMARY
• Survivors of pediatric trauma most frequently experience such infectious complications as abscesses and wound infections, followed by pulmonary infections, bacteremia, as well as peritonitis, osteomyelitis, and sinusitis.
• Patients with HIV and immunocompromising conditions who have grossly contaminated wounds should receive tetanus immunoglobulin regardless of their prior immunization status.
• The timing of antimicrobial prophylaxis in extremity wounds is another important consideration. Studies suggest a higher infection rate when prophylactic antimicrobials are given after three hours following an injury vs. a rate of 4.7% when given within three hours.
• Risk factors for the development of endophthalmitis following eye trauma include metal (rather than glass) as the penetrating material, the retention of intraocular foreign bodies, lens disruption, and delayed closure of an open globe or penetrating injuries greater than 24 hours old. Among both pediatric and adult patients, environmental Bacillus species are an important and frequent cause of post-traumatic endophthalmitis, along with coagulase-negative staphylococci, and, among children, streptococcal species.
• Individuals with burns are at significant risk of infections due to the breakdown of the skin, which serves as the body’s natural defense and primary immunologic barrier. It is not the toxic effect of thermally injured skin that places patients at risk of significant mortality, but the metabolic and bacterial consequences of a large open wound.
• All burns should undergo thorough cleansing and debridement, estimation of extent and depth, and coverage with appropriate topical antimicrobial agents within eight hours of injury.
• Topical antimicrobials recommended for all depths of burns include mafenide acetate or silver sulfadiazine. Mafenide is a topical sulfonamide with broad-spectrum Gram-positive and Gram-negative activity, including activity against Pseudomonas spp. It also has the ability to penetrate through eschar.
• Silver-impregnated dressings are another recommended option for burns and have the advantage of requiring fewer dressing changes, having better patient tolerance, and providing equivalent antimicrobial benefits.
• Cat scratches pose a risk for cat scratch disease from Bartonella henselae, symptoms of which include fever, enlarged and tender lymph nodes, and a pustule at the scratch site. Cat scratch disease should be treated with azithromycin.
The emergency medicine physician serves a critical role for trauma and surgical patients. Early recognition of infections and understanding the indications for prophylaxis are critical for management of pediatric trauma patients. The authors explore the most common etiologic agents by body system and prophylactic and therapeutic strategies.
— Ann M. Dietrich, MD, FAAP, FACEP
Traumatic injuries can disrupt the body’s natural barriers against invasive pathogens, particularly the skin and mucosal surfaces. Depending on the location of the initial trauma, the trajectory of possible ballistic components, the epithelial surfaces disrupted, the pathogenic and opportunistic organisms that colonize such surfaces, and the presence and nature of contaminants accompanying the external insult, a broad spectrum of infections may develop in any given trauma patient.
Fortunately, the practitioner may approach such injuries with a logical framework to anticipate the most likely pathogenic organisms at hand. Although there are no specific guidelines available for post-traumatic infections and prophylaxis in pediatric patients, it is possible to extrapolate the most likely organisms to colonize and infect wounds from a variety of literature, including case series, prospective trials, reviews, the American Academy of Pediatrics (AAP) Red Book, as well as some information from the Infectious Diseases Society of America’s (IDSA) guidelines for the prevention of infections associated with combat-related injuries.1,2 With such an approach, prophylactic antibiotics may be selected as appropriate for the patient’s injuries and the context of the trauma. (See Table 1.) In patients who develop post-traumatic infections, the rational deduction of likely pathogens based on the considerations mentioned earlier will help in selecting empiric therapy until definitive microbiological identification can be provided. This article will summarize such considerations and recommendations for a variety of traumatic injuries in pediatric and adolescent patients.
Table 1. General Pathogen Considerations and Recommendations for Antibiotic Prophylaxis for Trauma Related to Regional/System Anatomy |
||
Region/System |
Pathogen Considerations |
Recommended Prophylaxis |
|
Extremities |
Staphylococcus aureus, Group A Streptococcus, coagulase-negative staphylococci, Gram-negative bacilli |
|
|
Penetrating eye injury |
Environmental Bacillus species, coagulase-negative staphylococci, streptococcal species |
|
|
Maxillofacial |
Staphylococcus aureus, Gram-negative bacilli, oropharyngeal flora |
PLUS
|
|
Thoracic without esophageal involvement |
Staphylococcus aureus, alpha- and beta-hemolytic streptococci, Gram-negative bacilli |
|
|
Thoracic with esophageal involvement |
Staphylococcus aureus, alpha- and beta-hemolytic streptococci, Gram-negative bacilli, oral and enteric anaerobes |
PLUS
|
|
Abdominal |
Escherichia coli, other Gram-negative, Gram-positive, and anaerobic polymicrobial components, including Enterococcus spp., Bacteroides spp., and Enterobacter cloacae |
PLUS
|
|
Central nervous system |
Staphylococcus aureus, coagulase-negative staphylococci, beta-hemolytic streptococci, other Gram-negatives and some clostridial species |
PLUS
|
|
Bite Wounds |
See Table 4 |
|
|
* If patients have a previous history of anaphylaxis to β-lactam antibiotics, clindamycin is an acceptable alternative. In cases where cefazolin and metronidazole are recommended in combination, clindamycin may replace both agents. **Moxifloxacin is also an acceptable alternative in adult patients, but is not approved for pediatric use. ***Other regimens include cefoxitin with or without gentamicin; gentamicin plus metronidazole and ampicillin; meropenem monotherapy; other acceptable combinations typically used for perforated appendicitis. ****Other acceptable regimens in allergic patients include oral trimethoprim-sulfamethoxazole plus clindamycin. Adapted from: Hospenthal DR, Murray CK, Andersen RC, et al. Guidelines for the prevention of infections associated with combat-related injuries: 2011 update: Endorsed by the Infectious Diseases Society of America and the Surgical Infection Society. J Trauma 2011;71(2 Suppl 2):S210-S234. Kimberlin DW, Long SS, Brady MT, Jackson MA, eds. Red Book 2018 Report of the Committee on Infectious Diseases. 31st ed. American Academy of Pediatrics; 2018. Gilbert DN, Chambers HF, Eliopoulos GM, et al, eds. The Sanford Guide to Antimicrobial Therapy 2019. Antimicrobial Therapy, Inc.; 2019. |
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Epidemiology
Injuries and accidents are among the leading causes of morbidity and mortality for children of all ages, and they predominate especially among children > 1 year of age.3 The leading causes of accidents and injury-related deaths in each age group vary, but motor vehicle accidents, burns, homicides, suicides, and firearm-related deaths account for the majority, along with drowning deaths. (See Table 2.)
Table 2. Leading Causes of Injury Deaths by Age Group, United States – 2018 |
|||||
Rank/Age |
< 1 year |
1-4 years |
5-9 years |
10-14 years |
15-24 years |
|
1 |
Unintentional suffocation |
Unintentional drowning |
Motor vehicle accident |
Suicide suffocation |
Motor vehicle accident |
|
2 |
Homicide unspecified |
Motor vehicle accident |
Unintentional drowning |
Motor vehicle accident |
Unintentional poisoning |
|
3 |
Motor vehicle accident |
Homicide unspecified |
Fire/burn |
Suicide firearm |
Homicide firearm |
|
4 |
Homicide, other specified |
Fire/burn |
Homicide firearm |
Homicide firearm |
Suicide firearm |
|
5 |
Undetermined suffocation |
Unintentional suffocation |
Unintentional suffocation |
Unintentional drowning |
Suicide suffocation |
|
Adapted from Centers for Disease Control and Prevention. Ten Leading Causes of Death and Injury. Updated March 30, 2020. https://www.cdc.gov/injury/wisqars/LeadingCauses.html |
|||||
The mechanisms associated with these causes of death also may lead to substantial risk of infection among survivors of such injuries. In general, infections are a frequent cause of in-hospital complications among trauma and burn survivors, and are significantly associated with increased length of hospital stay and mortality.4,5
Data from the 1990s demonstrated that survivors of pediatric trauma most frequently experienced such infectious complications as abscesses and wound infections, followed by pulmonary infections, bacteremia, as well as peritonitis, osteomyelitis, and sinusitis.6 Isolates from these infections included predominantly Staphylococcus aureus, followed by Gram-negative species such as Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, with a smaller number of Streptococcus pyogenes isolates as well.6 Although aerobic pathogens were isolated most frequently, anaerobes were not uncommon, and many infections were polymicrobial in nature.
This article will detail initial management in wound infection prevention, followed by specific considerations for different body sites and situations.
Wound Cleansing, Debridement, and Irrigation
Irrigation is a vital component of any initial wound management. This primarily involves the application of a nontoxic fluid to remove debris and wound exudate to promote wound healing.7 Normal saline (0.9%) typically is favored, because it is an isotonic solution and does not interfere with normal healing processes, and does not damage tissues or alter the normal bacterial flora of the skin.8 The choice of tap water vs. sterile saline has been debated, with multiple studies performed to compare infection rates. In terms of acute wounds, animal studies have not found a difference in infection rates in acute soft tissue wounds cleaned with tap water compared with sterile saline.9,10 Likewise, authors of a study of 530 pediatric patients with simple lacerations did not find a significant difference in infection rates between tap water and sterile saline irrigation,11 suggesting that tap water may be an effective alternative in the prehospital or emergency department setting.
Pressure lavage is an important component of wound cleansing, and multiple experimental studies consistently have demonstrated its ability to prevent infection.8 In terms of mechanism, it is thought that a pressurized stream of water may overcome microbial adhesion mechanisms associated with bacteria that are bound to the surface of host tissues on the wound surface. The most effective pressure for removal of bacterial contamination is not precisely known; however, most authors recommend pressures of 5 to 8 PSI.12 This pressure can be achieved by using a 19-gauge syringe or catheter on a 60-cc syringe.13 Pressures greater than 15 PSI are likely to lead to both soft tissue and bone injury.14 The risk of infection has been found to increase with higher lavage pressures, likely secondary to tissue damage.15 Overall, however, there is a paucity of quality evidence to support the use of pressure irrigation.8
There are limited data on the most effective volume of irrigant to use. A frequently cited rule of thumb is 60 mL of irrigant per centimeter of wound length.16 Others suggest irrigating simple wounds with 250 mL of fluid total.10 Current IDSA guidelines for removing contamination recommend irrigation of wounds with normal saline or sterile water under low pressures (5 to 10 PSI with a bulb syringe or gravity flow), with additional volume recommendations to use 3 liters for Type I, 6 liters for Type II, and 9 liters for Type III extremity fractures.1
Tetanus Toxoid Considerations
Tetanus is a rare but potentially lethal infectious complication of any injury. Clostridium tetani is an obligate anaerobe found ubiquitously in soil, as well as in human and animal gastrointestinal tracts.17 The spores of this organism may contaminate any wound. As the bacillus replicates within the injury site, tetanospasmin toxin is elaborated and produces its effects on the motor end plates of skeletal muscle and synapses of the spinal cord. Deep wounds that may encourage anaerobic respiration, as well as those that are grossly contaminated with soil or feces, often have been considered to be particularly at risk, but past studies have indicated that up to 80% of cases are produced in instances with relatively insignificant wounds.17,18 As tetanospasmin is produced, the patient begins to experience worsening muscle spasms from inhibition of acetylcholine from nerve terminals in muscle tissue. Sometimes these muscle spasms may occur locally surrounding the infected site, but the toxin usually produces general manifestations, including trismus (lockjaw); spasms of the neck, back, and abdomen; and rigid posturing (opisthotonos), leading to generalized tonic seizures and eventual death in the absence of medical care.17
Tetanus is rare in the United States, largely because of the success of almost universal vaccination of the population. Between 2009 and 2017, the United States experienced only 264 cases of tetanus, and nearly every case was in someone who either never received the tetanus toxoid vaccine or who did not stay up to date on their recommended 10-year booster shots.19 However, tetanus remains a pertinent concern throughout the developing world, with the World Health Organization reporting more than 15,000 cases globally in 2018 alone.20
Tetanus is averted primarily through receipt of the initial vaccination series. The immunization history of the patient is the most important consideration when managing postinjury tetanus prophylaxis. The Centers for Disease Control and Prevention recommends that unvaccinated patients or those with an unknown vaccination history begin a primary series of tetanus-toxoid-containing vaccine. Additionally, they should be assessed for the need for tetanus immunoglobulin (TIG).19 (See Table 3.) Of note, patients with HIV and immunocompromising conditions who have grossly contaminated wounds should receive TIG regardless of their prior immunization status.
Table 3. Tetanus Toxoid Recommendations |
||||
Past number of doses of previous tetanus toxoid-containing vaccines |
Clean, minor wound |
Any other wound, including those
|
||
|
DTaP, Tdap, or Td |
TIG* |
DTaP, Tdap, or Td |
TIG |
|
|
Unknown or < 3 |
Yes |
No |
Yes |
Yes |
|
≥ 3 |
No** |
No |
No*** |
No |
|
*Patients with HIV or severe immunocompromise with grossly contaminated wounds should receive TIG regardless of past immunization status **Yes, if it has been 10 years or greater since the patient’s last tetanus toxoid-containing vaccine ***Yes, if it has been 5 years or greater since the patient’s last tetanus toxoid-containing vaccine Adapted from: Centers for Disease Control and Prevention. Tetanus: For Clinicians. Updated Jan. 23, 2020. https://www.cdc.gov/tetanus/clinicians.html |
||||
Extremity Wounds
Pathogens introduced via traumatic extremity wounds can result in skin, soft tissue, and/or bone infections. The major pathogens associated with trauma-related extremity soft tissue and skin infections are Group A Streptococcus (S. pyogenes) and S. aureus.21 Pyomyositis and osteomyelitis may develop in the setting of an extremity trauma via contiguous spread of infection to the bone from adjacent soft tissues. Along with S. aureus and S. pyogenes, aerobic Gram-negative bacilli also should be considered in deep soft-tissue infections secondary to extremity injuries.21,22 Additionally, puncture wounds of the plantar aspects of the feet and wounds contaminated with water and soil may be infected with Pseudomonas spp. and Aeromonas spp.23,24
The selection of appropriate antibiotic prophylaxis is an important consideration when managing extremity wounds. Some sources suggest that antibiotic selection should vary based on the extent of injury and the presence and degree of open fracture as defined by the Gustilo-Anderson open fracture grading system.25 Briefly, Type I open fractures are associated with clean (non-contaminated) wounds less than 1 cm in length; Type II open fractures are associated with lacerations greater than 1 cm in length without extensive soft tissue damage, flaps, or avulsions; and Type III open fractures are associated with either an open segmental fracture, an open fracture with extensive soft tissue damage, or a traumatic amputation. Currently, coverage for Gram-positive skin flora is recommended most frequently for Type I and Type II open fractures.1
Studies have demonstrated that broader-spectrum Gram-negative coverage (such as would be achieved with fluoroquinolones or aminoglycosides) in these types of traumatic extremity wounds does not improve outcomes and actually increases the rates of resistant Gram-negative infections.26 Cefazolin serves as adequate prophylaxis in trauma-related injuries against Gram-positive skin flora and methicillin-susceptible S. aureus.1,27,28 If patients have a previous history of anaphylaxis to β-lactam antibiotics, clindamycin is an acceptable alternative. Some authors have suggested that Type III open fractures are associated with increased morbidity and risk of infection because of compromised vascularity, wound contamination, and fracture instability.25 For these injuries, some guidelines recommend Gram-negative coverage with ceftazidime and gentamicin, which is supported by researchers who found a higher rate of infection for Type III fractures treated with ciprofloxacin compared to those treated with ceftazidime/gentamicin.29 This contrasts with common practice taken from IDSA combat-related trauma guidelines, which support the exclusive use of cefazolin for all types of fractures.1 For penetrating injuries through the sole of the foot, particularly through the shoe or with concern for soil contamination, fluoroquinolones should be considered for prophylaxis because of the possible introduction of Pseudomonas spp.23,24
The timing of antimicrobial prophylaxis in extremity wounds is another important consideration. Studies suggest a higher infection rate (7.4%, 49 of 661 patients) when prophylactic antimicrobials are given after three hours following an injury vs. a rate of 4.7% (17 of 364 patients) when given within three hours.22 The ultimate duration of antimicrobial prophylaxis is not clearly defined, but prospective studies suggest therapies as short as one day may be effective, which is in contrast to the traditionally recommended five days of therapy.30 Current IDSA guidelines recommend a one- to three-day course of prophylaxis for all extremity wounds, including those with open fractures.1
Eye, Maxillofacial, and Neck Wounds
Eye trauma may lead to disruption or penetration of ballistic or foreign material into the globe. This potentially may introduce pathogenic bacteria into the otherwise sterile anatomic planes and spaces of the eye, leading to endophthalmitis or other vision-threatening infections. Prior work with adult patients suggests that in the absence of antibiotics, 3% to 10% of ocular trauma cases may be complicated by endophthalmitis.31,32 Although this rate is relatively low, endophthalmitis is vision-threatening, and the administration of appropriate prophylactic antibiotics may reduce the rate of post-traumatic infectious endophthalmitis to less than 1%.32 Risk factors for the development of endophthalmitis include metal (rather than glass) as the penetrating material, the retention of intraocular foreign bodies, lens disruption, and delayed closure of an open globe or penetrating injuries greater than 24 hours old. Among both pediatric and adult patients, environmental Bacillus species are an important and frequent cause of post-traumatic endophthalmitis, along with coagulase-negative staphylococci, and, among children, streptococcal species.31,33,34 Rarely, Gram-negative bacilli and environmental molds have been described as an infectious etiology. Outcomes may be poor with any etiologic organism, but especially in the case of Bacillus species.35 Ophthalmology consultation is critical in any suspected or confirmed case of ocular trauma, penetrating injury, or infectious endophthalmitis.
Systemic levofloxacin or moxifloxacin is the recommended prophylaxis after open-globe ocular trauma, with relatively lower rates of post-traumatic endophthalmitis described after use of these medications.1,36 Prophylaxis should be continued for at least seven days, or until appropriate ophthalmology evaluation. Empiric treatment of post-traumatic endophthalmitis will require intravitreal antibiotics and possible vitrectomy, and thus ophthalmology consultation is critical. Empiric systemic therapy should include vancomycin or ciprofloxacin.37
Maxillofacial and neck injuries may involve a relatively wide variety of pathogens in post-trauma infections. These have not been well-characterized, but studies from combat situations and civilian surgeries have suggested that S. aureus predominates, although Gram-negative organisms and oropharyngeal flora also may cause infection.38,39,40,41
Current guidelines recommend post-traumatic injury prophylaxis with intravenous (IV) cefazolin for at least one day based on studies centered on head and neck surgical prophylaxis, with the addition of metronidazole if disruption of the oral or pharyngeal mucosa is suspected.1,28 Clindamycin is an acceptable alternative for those with confirmed allergy or other intolerance to cefazolin. When true post-traumatic infections of the head and neck develop, Gram-negative upper respiratory isolates and anaerobes should be considered alongside Gram-positive flora and S. aureus as potential causative agents.41 Consultation with otolaryngology surgical services is critical in all maxillofacial injuries and post-traumatic infections.
Thoracic Wounds
Penetrating thoracic trauma or thoracic trauma management requiring the use of a chest tube may introduce pathogenic bacteria into typically sterile anatomic compartments, notably the pleural potential space, as well as the mediastinum, pericardial sac, lung parenchyma, etc. The use of prophylactic antibiotics may reduce the rate of empyema and other post-traumatic infections in such situations.1,42 Surgical consultation is recommended in all situations of penetrating trauma to the chest.
The need for specific antimicrobial regimens in thoracic trauma may be distinguished further based on the flora that may contaminate such wounds — essentially by whether the esophagus has been disrupted or involved in the injuries. Without esophageal involvement, S. aureus, alpha- and beta-hemolytic streptococci, and Gram-negative bacilli, among others, are expected pathogens contributing to post-traumatic empyema and other infections, which frequently are polymicrobial in nature.43,44 IV cefazolin for at least 24 hours is recommended for prophylaxis in chest wounds without esophageal involvement.1 In the event of post-traumatic empyema or other infection in this context, empiric therapy must take into account the high likelihood of staphylococcal (and potential methicillin-resistant S. aureus [MRSA]) involvement, as well as possible contributory Gram-negatives.
In the event of post-traumatic thoracic injuries with disruption or perforation of the esophagus, concern is raised for the possible introduction of oropharyngeal and enteric anaerobes into the pleural, mediastinal, and pericardial spaces. Contamination or superinfection with staphylococci and Gram-negatives still is a pertinent concern. For these reasons, both cefazolin and metronidazole are recommended for prophylaxis for at least one day following definitive washout.1 Alternatives to this regimen include ertapenem or moxifloxacin. For infections that develop in patients with esophageal involvement, empiric therapy must include anaerobic coverage, as well as take into account the high likelihood of staphylococcal or Gram-negative involvement.
Abdominal Wounds
Penetrating abdominal injuries are highly concerning for disruption of hollow viscus organs and leakage of their contents into otherwise sterile anatomic compartments. The high burden of potentially pathogenic organisms in these injuries accounts for high rates of post-traumatic infection. In case series of soldiers injured on World War I battlefields (and hence, prior to the antibiotic era), injuries with colonic perforation led to infection in 60% to 75% of cases.45,46 More recent data from civilian trauma centers suggest that, even with appropriate postoperative antibiotics, penetrating abdominal injuries may lead to infections in 30% of all cases and in 70% of cases with colonic perforation.47,48 Data from American military operations in Iraq and Afghanistan likewise confirm such high rates of sepsis and infection following penetrating abdominal injuries.49 Based on a recent Cochrane review of studies regarding antimicrobial prophylaxis following abdominal trauma, the duration and precise regimen of antibiotics remain uncertain and supported by relatively low-quality evidence.50 Later, this article will discuss likely pathogenic species to be targeted, and regimens supported by surgical prophylaxis and combat-related studies, as well as recommendations from the AAP.
When approaching patients with penetrating abdominal trauma, a high priority must be placed on addressing the microbiological burden of such injuries. Gross fecal contamination must be addressed at the time of primary surgical repair to reduce overall contamination to the sterile compartments of the peritoneum and retroperitoneum. IDSA guidelines recommend against skin closure if colonic perforation or tissue destruction accompanies such injuries to avoid infectious complications.1 E. coli predominates in the microbiological profile of all post-traumatic infections, often alongside other Gram-negative, Gram-positive, and anaerobic polymicrobial components, including Enterococcus spp., Bacteroides spp., and Enterobacter cloacae.51
For prophylaxis following penetrating abdominal injuries, IDSA guidelines recommend the use of cefazolin and metronidazole to target such enteric Gram-negative and anaerobic organisms, administered for at least 24 hours following surgery.1 Alternative regimens suggested by these guidelines include single-dose ertapenem or moxifloxacin. Recommendations from the AAP include cefoxitin with or without gentamicin, or gentamicin, metronidazole, and ampicillin, meropenem alone, or any other regimen deemed appropriate for the congruent situation of perforated appendicitis.28
When encountering post-traumatic infections of the abdomen, providers should tailor therapy to target polymicrobial components, including Gram-negative, Gram-positive, and anaerobic commensals and pathogens. Recent data from a civilian trauma center in Southern California suggest that Gram-negatives frequently are susceptible to third-generation cephalosporins, carbapenems, and quinolones, while enterococci frequently are susceptible to penicillins in such cases.51 Complicated intra-abdominal infections following trauma require surgical and pediatric infectious disease consultation.
Wounds Involving the Central Nervous System
Penetrating injuries to the brain and spine may lead to indriven fragments of bone, debris, and the offending bullet or other material responsible for the injury. This may lead to contamination of the otherwise sterile brain and spinal cord, and, in the case of the latter, the preceding ballistic track may cross through the hollow viscus organs of the peritoneum, introducing Gram-negative and anaerobic organisms. Prior studies based on military casualties with central nervous system injuries and infections from World War II, the Vietnam War, the Lebanese Civil War, and the Iran-Iraq War have suggested a variety of microbial pathogens may contaminate such wounds and cause post-traumatic infection in the central nervous system.52,53,54,55,56 Chief among these are staphylococcal species, especially S. aureus, but coagulase-negative staphylococci, beta-hemolytic streptococci, other Gram-negatives, and some clostridial species may be involved as well. In both military and civilian case series, penetrating trauma to the cranium and central nervous system from any mechanism may cause meningitis, osteomyelitis of the skull, and brain abscesses as infectious sequelae.57 While superficial infections frequently are caused by S. aureus, deep-seated infections, such as brain abscesses, also may be due to Gram-negative bacteria.
Current guidelines from the IDSA, supported by surgical prophylaxis recommendations from the AAP, recommend that patients with penetrating injuries to the central nervous system undergo prophylaxis with intravenous cefazolin, with the addition of metronidazole if the wound is contaminated with organic debris, or if there is suspected association of a hollow viscus injury with a spinal cord injury.1,28 The ultimate duration of prophylaxis is determined primarily by the time to definitive closure of any cerebrospinal fluid leaks, but five days are recommended as a minimum duration.
Treatment of post-traumatic infection of the central nervous system must involve neurosurgical expertise to determine if debridement of the scalp or drainage/aspiration of deep-seated abscesses is possible. Antibiotic therapy should take into account the high prevalence of staphylococci in such infections, as well as the possible presence of Gram-negative facultatively aerobic bacteria. Treatment of such infections also should ensure adequate dosing and antibiotic selection to achieve central nervous system penetration because of the unique pharmacodynamic characteristics of the blood-brain barrier. Consultation with a pediatric infectious disease specialist is recommended.
Burns
Individuals with burns are at significant risk of infections due to the breakdown of the skin, which serves as the body’s natural defense and primary immunologic barrier. It is not the toxic effect of thermally injured skin that places patients at risk of significant mortality, but the metabolic and bacterial consequences of a large open wound.58 Complications in burn patients arise primarily due to secondary infections; therefore, topical antimicrobial prophylaxis should be initiated at the beginning of burn treatment.59 Systemic effects of secondary infections (e.g., systemic inflammatory response syndrome) can be difficult to distinguish in burn injuries, since such injuries themselves often lead to a hyperdynamic, hypermetabolic, and proinflammatory state.60
Current guidelines emphasize mechanical cleansing with irrigation as a critical component to all burn injury care.1,61 International guidelines state that tap water and sterile saline both are appropriate choices, as long as thorough irrigation occurs, especially with low-pressure lavage.61 All burns should undergo thorough cleansing and debridement, estimation of extent and depth, and coverage with appropriate topical antimicrobial agents within eight hours of injury.1 More extensive burns — deep partial-thickness and full-thickness — should undergo early (within five days) excision and grafting.
Topical antimicrobials are recommended for burns of all degrees of severity.1 Topical therapy has the advantage of producing high concentrations of the active agent at the site of injury. This is particularly true after mechanical cleansing via irrigation, which disrupts bacterial biofilms and matrices, thus making infectious agents more “accessible” to any given topical antimicrobial.61 Practitioners also should bear in mind that systemic absorption and delivery of oral antimicrobial agents may be compromised in deeper burns secondary to disruption of blood vessels, and, thus, topical formulations hypothetically may be more effective in situ.
Topical antimicrobials recommended for all depths of burns include mafenide acetate or silver sulfadiazine.1 Mafenide is a topical sulfonamide with broad-spectrum Gram-positive and Gram-negative activity, including activity against Pseudomonas spp. It also has the ability to penetrate through eschar.60 Silver is a staple in burn management and is found in numerous topical products, including silver nitrate, silver sulfadiazine, and silver-based dressings. Elemental silver and silver-based compounds have been known to have bactericidal properties as early as 1000 B.C.,when they were used for medicinal purposes and to render water potable.62 Silver’s antimicrobial properties include activity against Gram-positive, Gram-negative, and fungal organisms. The mechanism of this activity is secondary to interactions with thiol groups, release of intracellular potassium, direct cellular membrane disruption, and microbial DNA interaction.62 Silver-impregnated dressings are another recommended option and have the advantage of requiring fewer dressing changes, having better patient tolerance, and providing equivalent antimicrobial benefits. Silver-impregnated dressings require changes every three to five days. In contrast, topical antimicrobials must be applied twice daily with dressing changes. In all situations, topical antimicrobial therapy should be used until all burn injuries are successfully covered with healed skin.1
Systemic antimicrobial prophylaxis for burn injuries generally is discouraged unless there are concomitant injuries for which antibiotics would be indicated.1,61 A Cochrane systematic review of 36 randomized, controlled trials of systemic and topical antimicrobial prophylaxis in burn injuries failed to demonstrate any evidence that systemic antibiotic prophylaxis reduces the risk of local infection, sepsis, or infection-related mortality.63 However, IDSA guidelines allow for consideration of systemic antimicrobials for perioperative prophylaxis during excision and grafting procedures.1 If used, cefazolin 2 g IV every six hours to eight hours is appropriate for skin flora coverage. Pediatric patients should receive the same antimicrobial agents as adults (topical and systemic), with the exception of mafenide acetate, which should not be used in neonatal patients because of a risk of kernicterus with sulfonamides. Dosing of systemic antimicrobial agents should be weight-based in children less than 40 kg.
Burn injury infections occur with less frequency than in the past, given the use of early debridement and topical antimicrobial application as recommended by current guidelines.1 However, early signs of infection are important to recognize. Specific microorganisms should be considered based on the presence of eschar separation and color change in the wound. Pseudomonas colonization may create a yellow/green exudate. Invasive Pseudomonas infections often are black. In general, fungal infections are more insidious in nature, and may not be obvious immediately in the acute phase. Candida infections typically are more purulent. Aspergillus species infections may appear gray-brown, while Mucor species infections may appear black.60 In all cases of infectious complications following burns, burn specialists and infectious disease consultation are recommended.
Wound Contaminants and Retained Foreign Bodies
All penetrating wounds have the potential to introduce environmental microorganisms. Important considerations include wounds contaminated by water (fresh water and salt water) and organic material, such as soil.
Both superficial and deeper invasive infections can occur after contamination of open wounds by fresh water or salt water.64 Much of the data surrounding the epidemiology and microbiology of aquatic injuries and infections comes from disaster research. Data from the 2004 tsunami in Thailand found that the majority of early-onset soft tissue infections were polymicrobial, with Gram-negative bacteria as the most commonly isolated organisms, including Aeromonas species, E. coli, K. pneumoniae, P. aeruginosa, and Proteus species.65 Further data demonstrated that late-onset infections were caused mostly by rapidly growing marine mycobacteria that required specific antimycobacterial antimicrobials.66 Of the early-onset infections, Aeromonas species are some of the most common.64 This organism lives in fresh and brackish water, with an increased incidence of infections during warmer months. Commonly, it is seen after near-drowning accidents. Infections caused by Aeromonas species include cellulitis, pyoderma furuncles, and necrotizing infections.64 The majority of isolates are susceptible to aminoglycosides, third- and fourth-generation cephalosporins, fluoroquinolones, and imipenem.65 Vibrio vulnificus is a highly virulent Gram-negative curved bacilli that is found in marine environments, and causes multiple types of infections. It is a known cause of acute gastroenteritis and invasive sepsis, classically following meals of undercooked shellfish, but it also is a known pathogen in necrotizing wound infections following marine injuries.67 Antibiotic therapy, typically with a third-generation cephalosporin plus doxycycline, should be initiated empirically with any concerns for V. vulnificus infections.68
Soil may contain varying amounts of bacteria depending on the amount of sunlight, temperature, pH, and nutrients in a given sample. Microorganisms in soil can be indigenous or introduced from animal waste, flooding, or sewage.69 A classic soil-related infection is wound botulism, caused by the toxin-producing, anaerobic, rod-shaped, spore-forming bacteria, Clostridium botulinum. C. botulinum and its spores are found ubiquitously in soil, dust, and marine and freshwater sediments.70 Wound botulism occurs when C. botulinum contaminates disrupted tissue planes, followed by bacterial replication and toxin production.71 The production of toxin leads to systemic symptoms of botulism, which is a neuroparalytic disorder that manifests with acute, afebrile, symmetric, descending flaccid paralysis. Antimicrobial agents are not prescribed routinely in cases of botulism, and some (such as aminoglycosides) actually may potentiate the paralytic effects of the toxin. Instead, therapy is focused on supportive care and the use of botulism antitoxin.71
The botulism antitoxin approved for use in the United States is Botulism Antitoxin Heptavalent, which is a mixture of immune globulin fragments. It is approved for use for the treatment of symptomatic botulism following exposure to botulinum neurotoxin serotypes A, B, C, D, E, F, or G in adult and pediatric patients.72 The adult dose is one vial, starting at an infusion rate of 0.5 mL/min for the first 30 minutes and doubling the rate every 30 minutes to a maximum of 2 mL/min. The pediatric dose is 20% to 100% of the adult dose, starting at 0.01 mL/kg/min, increasing by 0.01 mL/kg/min every 30 minutes to a maximum dose of 0.03 mL/kg/min. For infants younger than 1 year of age, the dose is 10% of the adult dose, regardless of body weight, with a starting rate of 0.01 mL/kg/min, increasing by 0.01 mL/kg/min to a maximum infusion rate 0.03 mL/kg/min.72
Penetrating wounds also may introduce foreign bodies, which can lead to inflammation, delayed healing, damage to surrounding tissues, and infection. Imaging modalities most helpful for detecting foreign bodies include plain film radiographs, computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound.73 Plain films are the preferred imaging method for detecting foreign bodies, especially when dealing with radiopaque foreign bodies, such as metal, glass, and gravel.73 Multi-view radiographs are most helpful in identifying the relative positions of foreign bodies in three dimensions. Radiolucent objects, such as wood, plastic, and plant matter, are not visualized easily using plain radiographs.74 CT is more useful for identifying an object’s precise location to aid in removal; however, CT scans are limited by metallic artifacts. MRI cannot be used if an object’s composition is unknown due to imaging artifacts and the potential harm to the patient if the object is ferromagnetic in nature. Ultrasound has the advantages of portability and lack of radiation exposure; however, it is mostly useful for detecting only superficial foreign bodies.74
Human and Animal Bites
Human and animal bites warrant special consideration in post-traumatic prophylaxis and infection. Animal bites may occur from many different species beyond domestic dogs and cats, and the risk for different bites depends on many factors, including living conditions, locally indigenous species, and exposure to animals.75 In the United States, dog bites account for the majority of all such injuries (80% to 90%), followed by cats (5% to 15%), and rodents (2% to 5%). The remainder of bites are from rabbits, ferrets, farm animals, monkeys, and reptiles.75 The most common complication from all types of bites is infection, the rates of which vary based on the animal causing the injury. Even with early presentation, the infection rate among all dog bites is much lower (< 20%) when compared to cat bites (> 50%).76 In addition, the rate of infection seems to rise with increasing time to presentation. Because of this, it is recommended that cultures be obtained from all bites that are older than eight hours and from all human bites.75
Animal bites can cause a variety of injuries based on the animal causing the bite. Dog bites typically cause abrasions, puncture wounds, lacerations, and crush injury to tissues. Cat and rodent bites often cause puncture wounds that may penetrate into deep tissues. Human bites typically cause an occlusion-type injury (from upper and lower teeth coming together and sinking into the skin) or a clenched-fist injury (fight bites).58 Clinical signs and symptoms of bite wound infections can present as soon as several hours to days after the injury. Common signs and symptoms include pain, erythema, swelling, and purulent drainage. Lymphadenitis and fevers are less common. Complications of animal bite infections include cellulitis, osteomyelitis, tenosynovitis, and brain abscesses.76
The majority of infections due to animal bites are polymicrobial in nature. Prospective data on the microbiology of animal bites encountered in an emergency department identified an average of five different bacterial isolates per culture in dog and cat bites.77 Specific pathogenic considerations vary based on the species of animal responsible for the bite. (See Table 4.) The most common organism isolated from both dog and cat bites is Pasteurella species. Capnocytophaga canimorsus has been identified as a cause of severe infection and sepsis in immunocompromised and asplenic children.76 Human bites typically consist of anaerobic and aerobic microorganisms.76 Eikenella corrodens is a common cause of clenched-fist human bite injuries. Numerous other systemic infections may be caused by human and animal bites, including rabies, Bartonella, tularemia, brucellosis, leptospirosis, rat-bite fever, and hepatitis B and C virus infections.76
Table 4. Important Pathogenic Bacteria in Bite Wounds |
||
Type of Bite |
Aerobic Bacteria |
Anaerobic Bacteria |
|
Dog |
Pasteurella spp Streptococcus spp Staphylococcus spp Capnocytophaga canimorsus |
Fusobacterium spp Bacteroides spp Prevotella spp Propionibacterium spp Peptostreptococcus spp |
|
Cat |
Pasteurella spp Streptococcus spp Staphylococcus spp Moraxella spp |
Fusobacterium spp Bacteroides spp Porphyromonas spp Prevotella spp Propionibacterium spp |
|
Human |
Streptococcus spp Staphylococcus spp Eikenella corrodens Haemophilus spp |
Fusobacterium spp Prevotella spp Peptostreptococcus spp Veillonella spp |
|
Adapted from: Bula-Rudas FJ, Olcott JL. Human and animal bites. Pediatr Rev 2018;39:490-500. |
||
The management of bite wounds varies based on the type of animal bite, time from injury, and evidence of infection. Prophylactic antibiotics should be administered based on wound severity and host immune competence. Current guidelines demonstrate marginal benefit to prophylactic therapy in dog bites in otherwise immunocompetent individuals who present > 12 hours after injury. High-risk bites or immunocompromised individuals should receive preemptive antimicrobial coverage for three to five days. Examples of high-risk characteristics include puncture wounds or wounds to the face, hands, or feet.21 Antimicrobial coverage for both aerobic and anaerobic bacteria is imperative in the treatment of animal bites, and amoxicillin-clavulanate is used often in the outpatient and emergency department setting.21 Trimethoprim-sulfamethoxazole plus clindamycin is an alternative in individuals with serious allergic reactions to penicillins.78 When parenteral therapy is indicated, ampicillin-sulbactam or piperacillin-tazobactam are appropriate choices; vancomycin also should be added if there are any concerns for MRSA.76
Cat scratches pose a risk for cat scratch disease from Bartonella henselae, symptoms of which include fever, enlarged and tender lymph nodes, and a pustule at the scratch site.79 Cat scratch disease should be treated with azithromycin.21
Dog bites result in approximately 55,000 deaths globally per year from rabies. In the United States, more than 90% of rabies cases occur from wildlife bites, predominantly bats, followed by raccoons, skunks, and foxes.76 Prophylaxis for rabies includes the vaccine series and rabies immune globulin (RIG). Individuals who have received prior rabies immunizations who have rabies antibody titers should receive only a vaccine booster in the case of new exposure. Individuals without prior immunization should receive a four-dose series of rabies vaccines along with a dose of human RIG for post-exposure prophylaxis. The four-dose vaccine series is administered on days 0, 3, 7, and 14 following injury. RIG should be infiltrated around the wound.76 The need for rabies post-exposure prophylaxis varies according to the animal type. Dog, cat, and ferret bites require prophylaxis if the animal develops any signs of rabies in observation or if there is any suspicion of rabies. Rats, skunks, raccoons, foxes, and most other carnivores should be regarded as rabid unless the animal is proven negative, or unless the geographic area is classified as rabies-free.78
Primate bites are uncommon in the United States; however, they pose a risk of herpes B virus in research laboratory workers. Herpes B virus (Macacine alphaherpesvirus 1) closely resembles human herpes simplex virus (HSV) types 1 and 2, and is endemic in rhesus monkeys, pigtailed macaques, and cynomolgus monkeys.80 Herpes B virus is similar to HSV in that it resides in the trigeminal and lumbosacral sensory ganglia and periodically reactivates, causing intermittent asymptomatic shedding. Infections in humans are rare but can cause flu-like symptoms that progress to encephalomyelitis. If the infection is untreated, the death rate can be as high as 70% to 80%. Prompt antiviral post-exposure prophylaxis for monkey bites should be initiated with valacyclovir or acyclovir.80
Splenectomy Considerations
The spleen is a critical element of the human immune system. It regulates both the innate and adaptive immune system as both a phagocytic filter and a production center of human antibodies.81 Its critical importance was first illustrated by studies that reported cases of overwhelming infections caused by encapsulated bacteria in infants younger than 6 months of age who had undergone prior splenectomies.82 The spleen is particularly effective at protecting the body from encapsulated bacteria through Immunoglobulin M-mediated phagocytosis via memory B cells that are unique to the spleen.81
Incidents and conditions leading to splenectomy or functional asplenia include traumatic splenic rupture, anatomic defects, severe hemolytic anemia, immune-mediated cytopenias, metabolic storage diseases, sickle cell anemia, and secondary hypersplenism.58 The most significant post-splenectomy complications include sepsis, pneumonia, and meningitis. Rates of these infections vary, with prior analyses between 1966 and 1996 identifying a 3.2% prevalence of infections with a 1.4% mortality rate.83 The risk of infections is 50 times greater in splenectomized patients than the general population.84 Mortality can be as high as 50% in patients who develop postsplenectomy sepsis, most commonly from Streptococcus pneumoniae.85 The disease course in post-splenectomy patients can be sudden in onset with fulminant progression, and sepsis should be suspected in any asplenic patient presenting with severe or febrile illness.85
Splenectomy places patients at risk for infections and sepsis from encapsulated bacteria, especially S. pneumoniae, as highlighted earlier. Other encapsulated bacteria for which such patients are at higher risk include Haemophilus influenzae and Neisseria meningitidis. More rare pathogens include C. canimorsus, Babesia, and Bordetella holmesii.85 Preventing post-splenectomy sepsis depends on vaccination and prophylactic antimicrobial therapy and empiric antimicrobial therapy.
Prophylactic antimicrobial therapy is recommended for certain asplenic patients, including children and older individuals who have experienced an episode of post-splenectomy sepsis. The AAP recommends daily oral penicillin in asplenic children younger than 5 years of age and in older children and individuals for at least one year after splenectomy.86 Prophylactic penicillin should be initiated in infants with sickle cell disease as soon as a diagnosis is made. The duration of prophylactic therapy is not defined, but the AAP currently recommends discontinuation at 5 years of age in fully immunized children with sickle cell disease who have not had a severe pneumococcal infection. For other causes of asplenia, some experts continue prophylaxis throughout childhood and into adulthood.86 Lifelong prophylaxis is recommended for children and adults with a history of sepsis caused by encapsulated organisms.85 The antimicrobial agent of choice and doses vary by age. (See Table 5.)
Table 5. Post-Splenectomy Antimicrobial Recommendations |
|
Patient Characteristics |
Antimicrobial Choice |
|
Age < 3 years |
Oral penicillin V 125 mg BID |
|
Age > 3 years |
Oral penicillin V 250 mg BID |
|
Adults |
Penicillin V 250 mg BID or amoxicillin 500 mg BID |
|
Penicillin allergy |
Erythromycin 250 mg BID |
|
BID: Twice daily Adapted from: Rubin LG, Schaffner W. Clinical practice. Care of the asplenic patient. N Engl J Med 2014;371:349-356. |
|
Post-splenectomy patients who present with acute illness, including fever, must seek medical attention immediately and should be initiated on empiric antibiotics. Empiric coverage for adult and pediatric patients should include vancomycin and ceftriaxone or cefotaxime.87
Immunizations against S. pneumoniae, N. meningitidis, and H. influenzae type B (Hib) should be provided within 14 days of splenectomy.1 PCV13 followed eight weeks later by PPSV23 is recommended.88 Immunization recommendations vary based on age. (See Tables 6 and 7.)
Table 6. Post-Splenectomy Vaccination Recommendations for Adults (Age > 19 Years) |
||
Vaccine |
Primary Series |
Revaccination |
|
Pneumococcal vaccine - PCV13 plus PPSV23 |
1 dose of PCV13 followed by |
PPSV23 every 5 years |
|
Haemophilus influenzae type b vaccine - Hib |
1 dose |
None needed |
|
Meningococcal serotype ACWY vaccine - MenACWY |
2 doses at least 8 weeks apart |
Every 5 years |
|
Meningococcal serotype B - MenB-FHbp or MenB-4C |
2 doses of MenB-4C at least 1 month apart or 3 doses of MenB-FHbp at |
Not applicable |
|
Adapted from: Centers for Disease Control and Prevention. Asplenia and Adult Vaccination. Updated May 2, 2016. https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/asplenia.html |
||
Table 7. Post-Splenectomy Vaccination Recommendations for Children |
|||
Vaccine |
< 2 years old |
> 2 years old |
Revaccination |
|
Pneumococcus - PCV13 and PPSV23 |
4-dose series of PCV13 at 2, 4, 6, and 12 to 15 months of age |
1 dose PPSV23 ≥ 8 weeks after last dose of PCV13 |
PPSV23 every 5 years |
|
Haemophilus influenzae type b - Hib |
4- or 3-dose series depending on brand at 2, 4, 6 and 12-15 months of age |
Only if prior series not completed |
None needed |
|
Meningococcus serotype ACWY |
4-dose series at 2, 4, 6, and 12 months of age |
2 doses ≥ 8 weeks apart |
Every 5 years |
|
Meningococcus serotype B |
Not until age 10 years |
At age 10 years: 2 or 3 doses depending on brand |
None needed |
|
Adapted from: Centers for Disease Control and Prevention. Immunization Schedules for Health Care Providers. Updated Feb. 3, 2020. https://www.cdc.gov/vaccines/schedules/hcp/imz/child-indications-compliant.html |
|||
Conclusion
Injuries and trauma may cause a wide variety of disruptions in the body’s natural barriers and anatomic spaces, leading to contamination and infection. By considering the framework discussed earlier, and following applicable guidelines, practitioners may logically provide prophylaxis and treat secondary infections in trauma patients. Burns, animal bites, and grossly contaminated wounds all warrant additional considerations. Finally, practitioners should always consider tetanus prophylaxis, and whether additional immunization or prophylactic antibiotics are warranted in patients who have undergone traumatic or surgical splenectomy.
REFERENCES
A complete list of references can be found online at https://bit.ly/2WnQDhY.
The emergency medicine physician serves a critical role for trauma and surgical patients. Early recognition of infections and understanding the indications for prophylaxis are critical for management of pediatric trauma patients. The authors explore the most common etiologic agents by body system and prophylactic and therapeutic strategies.
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