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Infection After Orthopaedic Trauma: Prevention and Treatment

Yun, Heather C. MD; Murray, Clinton K. MD; Nelson, Kenneth J. MD; Bosse, Michael J. MD

Journal of Orthopaedic Trauma: October 2016 - Volume 30 - Issue - p S21–S26
doi: 10.1097/BOT.0000000000000667
Supplement Article

Summary: Trauma to the extremities is disproportionately represented in casualties of recent conflicts, accounting for >50% of injuries sustained during operations in Iraq and Afghanistan. Infectious complications have been reported in >25% of those evacuated for trauma, and 50% of such patients were treated in the intensive care unit (ICU). Osteomyelitis has been reported in 9% (14% of intensive care unit patients), and deep-wound infection in 27% of type III open-tibia fractures. Infections complicating extremity trauma are frequently caused by multidrug-resistant bacteria and have been demonstrated to lead to failure of limb salvage, unplanned operative take-backs, late amputations, and decreased likelihood of returning to duty. Invasive fungal infections of extremities have also presented a unique challenge in combat-injured patients, particularly in those with blast injuries with massive transfusion requirements and high injury severity scores. Infection prevention should begin at the time of injury and, although context-specific depending on the level of care, includes appropriate irrigation, surgical debridement, wound care and coverage, fracture fixation, and antibiotic prophylaxis, in addition to basic infection prevention measures. Clinical practice guidelines to address infection prevention after combat trauma (including extremity infection) were developed in 2007 and revised in 2011, with endorsement from the Surgical Infection Society and the Infectious Disease Society of America. Nevertheless, significant challenges remain, including austere environments of care, multiple transitions of care, and lack of coordinated efforts in prevention. Treatment of established infections is optimally multidisciplinary, particularly when deep wounds, bone, and joints are involved. Surgical debridement of overtly infected or necrotic tissue is necessary, with particularly aggressive margins if invasive fungal infection is suspected. Infected nonunion frequently requires the use of prosthetic materials for fixation, potentiating biofilm formation, and complicating medical therapy. Antibiotic therapy should be targeted at results of deep wound and bone cultures. However, this is complicated by frequent contamination of wounds, requiring differentiation between potential pathogens in terms of their virulence and decreased culture recovery in patient who have frequently received previous antibiotics. Lessons learned in infection prevention and treatment of orthopaedic trauma from combat can serve to inform the care of patients injured in natural disasters and noncombat trauma.

*Department of Infectious Disease Service, San Antonio Military Medical Center, JBSA-Fort Sam Houston, Houston, TX;

Uniformed Services University of the Health Sciences, Bethesda, MD;

Department of Orthopaedics and Rehabilitation, Womack Army Medical Center, Fort Bragg, NC; and

§Department of Orthopaedics, Carolinas Medical Center, Charlotte, NC.

Reprints: Heather C. Yun, MD, MCHE-ZDM-1, 3551 Roger Brooke Lane, JBSA-Fort Sam Houston, TX 78234 (e-mail:

The authors report no conflict of interest.

Accepted July 19, 2016

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Infectious complications of combat trauma have been reported throughout history. Recent experiences in Iraq and Afghanistan have demonstrated that despite significant advances in combat casualty care, infections remain a tenacious problem. Prospective data from the Trauma Infectious Disease Outcomes Study have shown a 27% rate of infectious complications in patients evacuated from the operation theater by the time of discharge from a US-based military hospital; this rate increases to 50% if only intensive care unit (ICU) patients are considered.1 Infections of skin, soft tissue, and wounds account for the bulk of these (18% and 28%, respectively), occurring a median of 12 days after injury, with severity ranging from superficial surgical site infections to deep-space infections requiring drainage and sometimes with resulting sepsis and bacteremia. Given the disproportionate distribution of extremity wounds, and the high rate of vascular trauma compared with previous conflicts, a high incidence of extremity infections among these patients is unsurprising.2 Recent advances in body armor have led to decreases in thoracic and abdominal injuries in recent conflicts, but extremity injuries still account for 54%, not significantly different from 58% in World War II, and the vast majority (82%) of long-bone fractures are open.3

Data from the Trauma Infectious Disease Outcomes Study cohort indicate that osteomyelitis occurs in 9% of combat-injured patients from recent casualties (14% of ICU patients).1 Earlier retrospective data evaluating causes of osteomyelitis and frequency of relapse or recurrence estimated a frequency of 15% in patients with extremity injuries, 17% of whom would relapse.4 Type III open-tibia fractures present particular risk, with 27%–77% complicated by deep-wound infection.5–7 Given the frequent need for retaining hardware for fracture stabilization, the high frequency of multidrug-resistant (MDR) pathogens associated with such injuries, and the need for prolonged antimicrobial therapy, such infections are considerably challenging to treat.

The initial microbiology of deep-wound infections and osteomyelitis complicating these injuries in general reflects the overall microbiology of the theater's infectious complications. During operations in Iraq, this was most notably represented by MDR Acinetobacter baumannii-calcoaceticus complex.8 Initial microbiologic sampling of fresh combat wounds revealed predominantly usual skin flora, including coagulase-negative staphylococci and Staphylococcus aureus. However, by the time of established osteomyelitis, most infections were attributed to MDR A. baumannii-calcoaceticus (recovered in 70% of cases) and other gram-negative pathogens including Klebsiella pneumoniae and Pseudomonas aeruginosa.4 By the time of relapse, the microbiology had shifted, with S. aureus responsible for the majority of infections, and gram-negatives infrequently recovered. An early evaluation of infectious complications after open, type III tibia fractures revealed similar findings; nearly half of wounds initially infected with gram-negative bacteria developed subsequent infection with S. aureus after treatment.6

As the major theater of operations shifted to Afghanistan, the microbiology of the resulting bacterial infectious complications shifted away from A. baumannii-calcoaceticus complex and toward extended-spectrum beta-lactamase–producing organisms, most notably Escherichia coli. Surveillance culture data obtained during 2005–2009 revealed progressive reductions in A. baumannii-calcoaceticus complex colonization, whereas rates of other MDR gram-negative rods, including E. coli, K. pneumoniae, and Enterobacter aerogenes, accounted for 66% of gram-negative rod isolated from 2009 to 2012.9,10 The increase in combat operations in Afghanistan in 2010–2011 was also marked by an increase in complex blast injuries of the lower extremities caused by improved explosive devices, leading to an increase in multiple amputations, high above-the-knee amputations, and genital injuries. Invasive fungal infections (IFIs) of these wounds, in particular those sustained in the lushly vegetated, southern regions of Afghanistan, were noted to increase during the same time period, with rates as high as 12% in the ICU at the Landstuhl Regional Medical Center in Germany.11,12

Infectious complications of combat-related orthopaedic injuries are clearly associated with poor outcomes. Positive surveillance cultures, present in 64% of severe open-tibia fractures, have been associated with subsequent infection and amputation.5 This risk was further increased with 2 or more species of bacteria identified from colonization cultures. Patients with deep-wound infections or osteomyelitis had higher rates of amputation (40% and 34%, respectively) compared with those without infection (15%) and significantly higher reoperation rates and longer times to fracture union. Deep-wound infection or osteomyelitis has also been associated with decreased return-to-duty rates, hospital readmissions, and failure of limb salvage.7,13,14 IFIs are associated with high-level amputations (22% including both proven and probable cases), including hip disarticulations and hemipelvectomies, and crude mortality rates of 9% in these patients.15

These infectious complications are by no means limited to those whose injuries were sustained by combat. Although combat-injured patients are often unique in terms of mechanism of injury, site of care, and microbiology, similar rates of infection have been seen in civilian trauma. The Lower Extremity Assessment Project reported early wound infection rates of 34% and 23% in amputation and salvage groups, respectively, with a 9% rate of osteomyelitis in the latter group.16 These remain within the range of data reported by Gustilo et al17 for type III tibia fractures (6%–39%). Although early data indicated wound contamination predominantly by gram-positive organisms, later data suggested an increased role for gram-negative and polymicrobial infections, especially with type II and III fractures, which prompted recommendations for expanded antimicrobial prophylaxis.18

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Surgical Management

Irrigation and debridement to remove gross contamination and all devitalized tissues to limit bacterial replication is often the first step in the prevention of infection after injury. This should be performed as early clinically feasible after injury.19 Additives to normal saline (alternatively sterile or potable water can be used if needed) have not been found to improve outcomes, may add toxicity, and are not recommended. Clinical practice guidelines call for 3, 6, and 9 L of irrigation fluid for type I, II, and III fractures, respectively, to be delivered under low pressure.20 Basic science data from the US Army Institute of Surgical Research show higher rebound of bacterial loads in wounds treated with pulse lavage compared with bulb syringe.21 Recent data from the FLOW study demonstrating a higher reoperation rate in the castile soap group and no difference in outcomes with changes in fluid delivery pressure would seem to validate these recommendations.22 Cultures should not be routinely obtained if there are no signs or symptoms of infection. Foreign bodies within soft tissue may be observed without removal, provided there is no bone, vascular, pleural, or peritoneal involvement; entry and exit wounds <2 cm; and no evidence of infection.

The timing of surgical debridement has not been directly evaluated in the combat environment with regard to infectious outcomes. Rapid surgical debridement has long been regarded as the primary intervention for reducing infection risk.17,23 However, the literature shows conflicting information about the urgency of debridement. Multiple previous studies, including Lower Extremity Assessment Project data, have shown no difference in infection rates with varying times to debridement within 24 hours of injury.24 Recent prospective data from Canadian civilian trauma centers demonstrated risk of infection in open fractures related to increasing Gustilo grade, tibia/fibula fractures, but no difference with either time to surgery or time to antibiotics.25 The adequacy of the initial debridement is considered to be even more important than the timing by most expert authorities, though there are no published data to support this opinion given the complexity of the topic and the lack of reliable objective measures needed to study it. Extension of the wounds to directly visualize and explore the entire extent of the wound and remove all foreign debris and necrotic material is critical to prevent later infection. Current guidelines for the prevention of infection in combat-related injuries recommend that debridement be performed as early as feasible.19 Staged fixation, with the use of external fixation initially and definitive fixation after evacuation and stabilization, is currently the preferred strategy. This is shared by the international community.26,27 The current US military practice avoids internal fixation until after several debridements and is typically done later than performed by civilian trauma orthopedists.

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Antimicrobials are seen as an important adjunct to surgical management in the prevention of infection after combat-related extremity injuries. As in civilian guidelines, the recommendation in context of combat injuries is to administer tetanus vaccine (and immune globulin if indicated) and antibiotic prophylaxis as soon as possible after open fracture, ideally within 3 hours of injury.20,28,29 One recent study of open, type III tibia fractures indicated a higher risk of infection if antibiotics were delayed even past an hour.30 On the battlefield, this extends to a recommendation for point-of-injury antibiotics administered by a field medic if evacuation is anticipated to be delayed. Although short-course, antistaphylococcal antibiotic prophylaxis has been recommended after open fractures of long bones by multiple civilian guidelines, the data supporting prophylaxis are inconsistent, the study is highly heterogenous and there remains lack of consensus about the role of extended-spectrum gram-negative and Clostridial coverage in particular.28,29 The Eastern Association for the Surgery of Trauma guidelines recommend the addition of an aminoglycoside for type III fractures and high-dose penicillin for those with fecal contamination/farm-related injuries. However, guidelines published by the Surgical Infection Society, evaluating the same body of literature, indicate that the great preponderance of literature on the subject did not reflect current standards for surgical management and suffered from a number of methodologic flaws. Those authors' conclusion was that the data were insufficient to recommend additional gram-negative or Clostridial coverage based on type or grade of injury. The 2011 guidelines for combat-related extremity injury infection prevention take a similar approach, also recommending high-dose cefazolin only as prophylaxis, citing insufficient evidence to recommend enhanced gram-negative coverage, the likelihood of selecting for resistant pathogens, and the variable susceptibility profiles of bacteria recovered from these infections. Experience with prophylaxis in the combat setting has done little to resolve the question of ideal antibiotic prophylaxis. However, a recent evaluation from the Trauma Infectious Disease Outcomes Study cohort identified even cefazolin prophylaxis as a risk factor for colonization with MDR gram-negative organisms, with an odds ratio of 3.5 on logistic regression; this increased to 5.4 in the setting of the addition of a fluoroquinolone.31 With this in mind, we continue to recommend short courses of narrower-spectrum prophylaxis, for example, cefazolin for 1–3 days, for prophylaxis of open fractures sustained in the combat environment. Ongoing studies may provide further guidance as to whether antimicrobial therapy should be provided to patients with positive cultures at the time of wound coverage, as these correlate with subsequent infection.32

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Wound Management: Topical Therapies and Negative-Pressure Wound Therapy

Local delivery of antibiotics via beads or pouches remains attractive as a concept, but with few prospective and no clinical trial data to inform their use in combat trauma patients and with mixed data supporting use in civilian trauma.19 Their use is cautiously endorsed as an IB recommendation in the 2011 guidelines, “as long as the emphasis is still on surgical debridement and irrigation,” with a recommendation against other forms of topical therapy. After those guidelines were published, increasing concern for IFI drove Joint Trauma System Clinical Practice Guidelines to recommend the use of 0.0025% Dakin's solution as topical therapy for patients at highest risk, either via soaked dressings or as an instillation vacuum dressing.33 Negative-pressure wound therapy has become standard of care in US military facilities treating combat-injured patients. This has proven feasible and safe even during aeromedical evacuation. Ongoing questions remain about whether this practice reduces infection risk. Animal and human data have shown a higher rate of S. aureus recovery and lower rates of P. aeruginosa, for reasons that remain unexplained; whether these affect the risk of infection is unclear.34,35 However, given the role of S. aureus in orthopaedic infections in general, this certainly warrants further investigation. A number of studies have evaluated whether topical therapies in conjunction with negative-pressure wound therapy might influence infection risk. Although promising, issues of altered wound appearance, which may limit the ability to evaluate for infection, local tissue toxicity, and removal of eluted antimicrobials from beads and the wound bed by negative-pressure wound therapy, itself present ongoing challenges.19

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Infection Control and Prevention Practices

In 2004, it became apparent that injured service members were being infected with MDR gram-negative pathogens including A. baumannii-calcoaceticus, P. aeruginosa, and K. pneumoniae. Investigations to determine the source of these bacteria evaluated preinjury colonization and inoculation from the environment at the time of injury, with no evidence to suggest that these played a role.36–39 However, clonal spread of A. baumannii-calcoaceticus clearly took place as a nosocomial pathogen.40 Early data indicated significant differences between clinical cultures of US troops hospitalized at a combat support hospital and those cultures taken from longer term local national patients.41 Follow-up studies of both A. baumannii-calcoaceticus in Iraq and MDR gram-negative pathogens in Afghanistan have demonstrated that these are major colonizers in local patients, even at the time of admission to medical facilities.42,43 Deployments of infection control (IC) teams in 2008, 2009, and 2012 to evaluate practices in theater demonstrated consistent challenges in a number of areas, including predeployment training of those assigned to IC roles, microbiology support, and environmental disinfection support.44 Taken together, the body of literature evaluating the source of MDR colonization and infection in injured US service members implicates nosocomial transmission, which begins in theater in medical treatment facilities.

Despite the challenges inherent in providing care and performing surgery in a relatively dusty tent or makeshift operating room when compared with a conventional operating room in CONUS, it is also clear that application of basic IC practices in theater can have a meaningful impact on MDR transmission and rates of health-care–associated infections. Interventions including early discharge of local patients, emphasis on hand hygiene, antimicrobial stewardship, and environmental disinfection have been associated with decreased rates of colonization with MDR pathogens and some health-care–associated infections.44–46 The 2011 guidelines for infection prevention and control in deployed military medical treatment facilities identified several areas for improvement: IC expertise in theater, emphasis on basic IC measures, use of standardized procedures and guidelines, and antimicrobial control.47 Recommendations from these have inconsistently been applied, and vulnerabilities are likely to be greatest during periods of entry rather than stability. Our primary recommendation going forward would apply to both the combat environment and the civilian mass-casualty or disaster response operation: the development of a systematic, command-supported process to specifically address IC in such an environment. Without an identified individual accountable for this area and in the position to develop standards of practice, perform risk assessments, communicate with those responsible for overall operations, and drive research and quality improvement, such efforts are likely to be fragmented and met with limited success.

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Diagnosis and treatment of orthopaedic infections after combat injury largely mirror that in any other traumatic context. Skin and soft tissue infections may be either deep or superficial, and diagnosis remains predominantly clinical, characterized by local evidence of inflammation and frequently purulent drainage. Depth and extent of infection are primarily judged by direct visualization during operative debridement. Osteomyelitis may be clinically obvious, as in the case of necrotic bone, abscess, and sequestrum formation, or inferred on the basis of deep-wound infection contiguous with underlying bone and/or orthopaedic hardware. IFI should be suspected with ongoing wound necrosis after multiple debridements, particularly in higher risk patients (large amputation burden, massive transfusion requirements, extensive wound contamination).48

Management of acutely infected wounds is primarily surgical, relying on removal of remaining foreign bodies and debris, debridement of necrotic and devascularized tissue, and drainage of fluid collections; osteomyelitis frequently also involves orthopaedic hardware, which would ideally be removed or replaced given biofilm involvement. Multiple operative cultures of fluid and/or involved fluid collections should routinely be obtained; yield is highest if obtained before empiric antimicrobial treatment, though prophylaxis should not be deferred for this indication. Tissue samples are greatly preferred to swabs, particularly in early infections where polymicrobial contamination may be extensive. If IFI is suspected, debridement must be particularly aggressive, with biopsies and fungal cultures obtained. Multiple fungal species are frequently involved, including Aspergillus and Mucorales spp., so broad-spectrum antimould coverage is recommended in such instances (voriconazole and amphotericin recommended in current clinical practice guideline; posaconazole has also been used).33

Empiric antimicrobial treatment is typically broad spectrum, but therapy should be narrowed to the extent possible based on culture data. However, the extensive wound contamination often seen with these injuries frequently leads to challenges in narrowing antimicrobial coverage. Evaluations of wounds sustained in both Iraq and Afghanistan revealed gram-negative (and often polymicrobial) involvement early, with most recurrent or relapsed infections involving staphylococci.4,6,49 Low-virulence environmental gram-negative pathogens (eg, nonaeruginosa Pseudomonas spp.) are frequently found in contaminated wounds but do not result in clinical infections. Enterococcus is often recovered from early wounds but not present in fully established/relapsed infections; specific coverage for this is often withheld especially when an alternate, more virulent pathogen is concurrently found. Similarly, Candida spp. may be recovered, frequently in more severely injured patients, but without demonstrated serial cultures positivity or attributable mortality.50,51 Anaerobes are typically treated when cultured, although many may be resistant to therapy with no apparent difference in outcomes.52 Duration of antibiotic therapy is determined by the depth and extent of infection; superficial wound infections may require little more than debridement, deep-wound infections frequently require 1–2 weeks of systemic antibiotics, and osteomyelitis conventionally requires 4–6 weeks of therapy, often further prolonged in the setting of involved orthopaedic hardware. This desire to avoid the complications inherent to using internal fixation in a contaminated wound has led to an increased reliance on ringed external fixator systems in these patients, which are challenging to use, costly, and come with a high complication rate of their own.

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Although mechanisms of injury such as high-energy blasts from improved explosive devices are predominantly seen in combat casualties, recent episodes of intentional violence and natural disasters generating mass casualties have highlighted that similar injuries also take place in noncombat environments. Aside from recommendations for postexposure prophylaxis against blood-borne pathogen infections after mass casualties and suicide bombings, very little in the literature specifically addresses infection prevention in these populations.53 Infectious complications after injuries caused by natural disasters have frequently reported a predominance of gram-negative and nosocomial, multidrug-resistant pathogens, particularly associated with international transportation of injured patients.54–57 Increasingly, an association between natural disasters and IFI has been recognized, reported after tornados, earthquakes, tsunamis, and others.58–61 This is likely related to displacement of fungi from their natural habitat in conjunction with infliction of serious injuries, common in both explosive blasts and in natural disasters.

Several lessons in infection prevention from combat casualty care can inform these environments. First, although heavily contaminated wounds may be present, there is no indication to culture an uninfected-seeming wound. Wounds are likely to be initially colonized with multiple low-virulence pathogens, but established, mature infections typically involve staphylococci, and it is against these that antibiotic prophylaxis must be directed. MDR gram-negatives are often involved in initial infections; these should be assumed to be nosocomial transmission events, and attention must be paid to limiting duration and spectrum of prophylactic antimicrobial therapy and in enforcing basic infection prevention practices. IFI must be suspected in the event of progressive wound necrosis, particularly in high-energy wounds with gross organic environmental contamination and severely injured patients. Both surgical debridement and antimicrobial prophylaxis should be administered as soon as is feasible. Wound closure should be delayed for 3–5 days and definitive fixation deferred until stabilization and evacuation, if applicable.

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Despite significant advances in combat casualty care and improvements in mortality, extremity injuries remain common and in recent years have become increasingly complex. High-energy, heavily contaminated explosive blast injuries treated at various levels of care are at high risk for infectious complications and result in serious morbidity. Advances made in understanding of infectious complications in this context in the last 15 years serve to better inform combat casualty care and shed light on a number of unique aspects of civilian trauma care, particularly those involving natural disasters and intentional violence with high-energy injury patterns and blast mechanisms (Table 1).



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combat; military; trauma; osteomyelitis; infection; orthopaedic

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