Osteomyelitis associated with open fractures in adults

INTRODUCTION — Osteomyelitis may develop as a result of contamination of open fractures [1-3].

The epidemiology, microbiology, clinical manifestations, treatment, and prevention of osteomyelitis in the setting of open fractures will be reviewed here.

General principles of fracture management are discussed separately. (See "General principles of fracture management: Early and late complications", section on 'Open fractures' and "General principles of fracture management: Early and late complications", section on 'Osteomyelitis'.)

General issues related to osteomyelitis are discussed separately. (See "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis" and "Nonvertebral osteomyelitis in adults: Treatment".)

Issues related to prosthetic joint infections are discussed separately. (See "Prosthetic joint infection: Epidemiology, microbiology, clinical manifestations, and diagnosis" and "Prosthetic joint infection: Treatment".)

Issues related to infection following nail puncture are discussed separately. (See "Pseudomonas aeruginosa skin and soft tissue infections", section on 'Infection following nail puncture'.)

Issues related to injury associated with bites are discussed separately. (See "Animal bites (dogs, cats, and other mammals): Evaluation and management" and "Human bites: Evaluation and management".)

Issues related to injury associated with water are discussed separately. (See "Soft tissue infections following water exposure".)

EPIDEMIOLOGY — Osteomyelitis can occur in up to 25 percent of open fractures; the risk depends upon the following factors [4-10]:

●Severity of injury, including whether concurrent vascular and/or neurologic damage is present

●Degree of bacterial contamination

●Timing and adequacy of surgical debridement

●Administration of antibiotics (including the timing as well as the type)

●Diabetes mellitus

●Comminuted fracture

●Surgical incision >10 cm [11]

In one review including more than 1100 open fracture wounds, the risk of infection with open tibia fracture was twice as high as for open fracture of other sites (10.5 versus 5.3 percent) [7]. The infection rate after open hand fracture is relatively low; in one review including twelve articles (4 prospective, 8 retrospective) and 1669 open fractures of the hand, the infection rate was approximately 3 to 4 percent [12].

Infection results in a 1.2 to 6-fold increase in costs associated with fracture [13].

MICROBIOLOGY — Microorganisms can be introduced directly into bone in the setting of fracture or via contiguous spread from injury to overlying soft tissue. They proliferate in the presence of devitalized tissues containing clotted blood and necrotic bone.

Pathogens may include skin flora, environmental organisms, or nosocomial pathogens. The most common organisms include Staphylococcus aureus, coagulase-negative staphylococci, and aerobic gram-negative bacilli. Other less commonly implicated pathogens include enterococci, anaerobes, fungi, and mycobacteria [6,14-20]. If the fracture is associated with water, infection may be caused by Pseudomonas, Aeromonas, or Vibrio species (see "Soft tissue infections following water exposure"). Infections are polymicrobial in 25 to 35 percent of cases [21,22].

The microbiologic diagnosis is established via cultures obtained at the time of debridement for possible infection, rather than at the time of initial debridement following fracture. Cultures obtained at the time of initial debridement correlate with established pathogens of osteomyelitis in only 25 percent of cases [23,24]. Not all microbes colonizing the wound at the time of injury cause sustained infection in the bone, and pathogens not present at the initial injury may colonize and infect wounds subsequently.

CLINICAL MANIFESTATIONS — The approach to classification of open fractures is summarized in the table (table 1).

Acute osteomyelitis following fracture usually presents with gradual progression of dull localized pain over several days. Local findings (tenderness, warmth, erythema, swelling) and systemic symptoms (fever, rigors) may be present. Decreased range of motion, point tenderness, and joint effusions may be seen but are also present with uninfected fractures, making clinical diagnosis potentially difficult.

In some cases, osteomyelitis presents with few symptoms or signs. This is more common with subacute or chronic infections, with infections of the hip, pelvis, or vertebrae, and in young patients.

Chronic osteomyelitis may present with pain, erythema, or swelling, sometimes in association with a draining sinus tract. Fractures that are healing slower than expected or that remain extremely painful despite adequate immobilization may be a sign that osteomyelitis is present.

After open fracture, non-union is the most common consequence and manifestation of osteomyelitis. Non-unions commonly present with persistent pain, swelling, or instability beyond the time when healing should normally have occurred. Nonunion is not always due to infection; other causes include lack of adequate blood supply, suboptimal bone alignment, and smoking.

Additional manifestations of osteomyelitis and non-union associated with fracture are discussed separately. (See "General principles of fracture management: Early and late complications", section on 'Osteomyelitis' and "General principles of fracture management: Early and late complications", section on 'Nonunion and malunion'.)

DIAGNOSIS — The approach to diagnosis of osteomyelitis following open fracture is the same as the approach to diagnosis of osteomyelitis due to other causes; this is discussed separately. (See "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis" and "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis".)

TREATMENT — Following a fracture, initial management of osteomyelitis or infected non-union consists of surgical debridement with irrigation, obtaining bone biopsy for culture, fracture fixation (if needed), and antimicrobial therapy tailored to culture and susceptibility data [17,25-35].

To achieve optimal union in the setting of concomitant osteomyelitis, it may be necessary to administer systemic antibiotic therapy for as long as fixation hardware remains in place. Once fracture union is achieved, fixation hardware should be removed (if possible), with additional debridement.

Antibiotic-impregnated beads may be used as adjunctive therapy in surgical management of trauma-associated osteomyelitis [36].

The approach to antibiotic therapy for patients with retained hardware is discussed separately. (See "Nonvertebral osteomyelitis in adults: Treatment", section on 'Retained hardware'.)

The approach to antibiotic therapy for patients with no retained hardware is discussed separately. (See "Nonvertebral osteomyelitis in adults: Treatment", section on 'No retained hardware'.)

Antibiotic selection and other issues related to treatment of osteomyelitis are discussed in detail separately. (See "Nonvertebral osteomyelitis in adults: Treatment", section on 'Antibiotic therapy'.)

PREVENTION — Measures for prevention of osteomyelitis following open fracture include prompt debridement, surgical fixation (if needed), and antibiotic therapy [1].

Initial fracture management — General principles of acute fracture management are discussed separately. (See "General principles of acute fracture management" and "General principles of fracture management: Early and late complications", section on 'Open fractures'.)

In general, initial fracture management consists of thorough irrigation and debridement. The optimal timing of debridement is uncertain; some have suggested that open fractures should be debrided within six hours of injury [37-39]. In one meta-analysis of observational and trial data, the risk of infection for tibial fractures was higher when debridement took place after 12 hours; for Gustilo type III-B fractures (table 1), risk of infection rose after 12 hours (odds ratio [OR] 1.51) and 24 hours (OR 2.17) [40].

The decision regarding use of fixation hardware for stabilization is made on a case-by-case basis.

At the time of initial debridement, there is no need for operative routine cultures. If subsequent debridement is performed for suspected infection, collection of operative cultures is warranted at that time. (See 'Microbiology' above.)

Once union is achieved, fixation hardware may be removed and additional debridement performed if needed. Final steps include bone grafting (if needed) and wound closure [26-35,41].

Primary closure may be reasonable for debrided wounds with no contamination, good residual soft tissue, and good vascular supply [42]. Delayed wound closure is generally warranted in Gustilo type II or III fractures (table 1).

Antibiotics after open fracture — The use of antimicrobial agents for dirty procedures or established infection is classified as treatment of presumed infection, rather than prophylaxis. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Wound classification'.)

Following open fracture, prompt administration of antibiotics (ideally within six hours) is warranted to reduce the risk of osteomyelitis [2,3,43-45]. This approach is supported by a meta-analysis including 913 patients with open fractures [41]; use of antibiotics was associated with an absolute reduction in infection of 0.08 (95% CI 0.04-0.12) [41].

Antibiotic selection — Antibiotic regimens for patients with open fractures are summarized in the table (table 2).

For patients with type I and type II fractures (table 1), antibiotic therapy should include activity against gram-positive organisms. Cefazolin is a reasonable regimen; for patients at risk for methicillin-resistant S. aureus (table 3), gram-positive coverage should consist of vancomycin (table 4). Dosing is summarized in the table (table 2).

For patients with type III fractures (table 1), antibiotic therapy should include activity against gram-negative organisms (in addition to gram-positive coverage outlined above) [2,46]. For example, ceftriaxone (monotherapy) is an acceptable regimen [2,47]. Dosing is summarized in the table (table 2).

For patients with open fracture associated with soil contamination, we favor addition of metronidazole to the above regimens, for coverage of Clostridium spp.

For patients with open fracture associated with freshwater contamination, we favor piperacillin-tazobactam for activity against gram-negative pathogens such as Pseudomonas and Aeromonas species.

For patients with open fracture associated with seawater contamination, we favor levofloxacin plus metronidazole for activity against Vibrio species. Dosing is summarized in the table (table 2).

Data to guide the above approach to antibiotic selection are limited, and the optimal approach is uncertain. Our approach is guided by the typical microbiology of such infections as well as general trends in antimicrobial resistance.

Duration — The duration of antibiotic therapy depends on the classification of the fracture (table 1) [2,3,48,49]:

●For Gustilo type I and II open fractures, antibiotics may be discontinued 24 hours after wound closure.

●For Gustilo type III open fractures, antibiotics may be discontinued after 72 hours or within a day after soft tissue injuries have been closed.

Prolonged administration of antibiotics does not reduce the risk of infection and can lead to the development of resistant organisms [3,50].

Tetanus prophylaxis — Open fractures are tetanus-prone wounds [51,52]. The patient's tetanus immunization status should be determined; tetanus toxoid, diphtheria-tetanus-acellular pertussis, booster tetanus toxoid-reduced diphtheria toxoid-acellular pertussis, or tetanus-diphtheria toxoids adsorbed should be administered as indicated (table 5). The need for tetanus immune globulin should also be assessed (table 5). (See "Tetanus".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Osteomyelitis and prosthetic joint infection in adults".)

SUMMARY AND RECOMMENDATIONS

●Pathogenesis and microbiology – Osteomyelitis may develop as a result of contamination of open fractures in up to 25 percent of cases. Microorganisms can be introduced directly into bone in the setting of open fractures or via contiguous spread from injury to overlying soft tissue. Pathogens may include skin flora, environmental organisms, or nosocomial pathogens. (See 'Epidemiology' above and 'Microbiology' above.)

●Clinical approach – The approach to classification of open fractures is summarized in the table (table 1). The approach to diagnosis of osteomyelitis following open fracture is the same as the approach to diagnosis of osteomyelitis due to other causes; this is discussed separately. (See 'Clinical manifestations' above and "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis".)

●Management – Following a fracture, initial management of osteomyelitis or infected non-union consists of surgical debridement with irrigation, obtaining bone biopsy for culture, fracture fixation (if needed), and antimicrobial therapy tailored to culture and susceptibility data. To achieve optimal union, it may be necessary to administer systemic antibiotic therapy for as long as fixation hardware remains in place. Once fracture union is achieved, fixation hardware should be removed (if possible), with additional debridement if needed. (See 'Treatment' above.)

●Prevention of osteomyelitis – Measures for prevention of osteomyelitis following open fracture include prompt debridement, surgical fixation (if needed), antibiotic therapy, and assessment regarding need for tetanus prophylaxis. (See 'Prevention' above.)

●Antibiotic selection – Following open fracture, prompt administration of antibiotics (ideally within six hours) is warranted to reduce the risk of osteomyelitis (table 2). For patients with type I and type II fractures, antibiotic therapy should include activity against gram-positive organisms. For patients with type III fractures, antibiotic therapy should include activity against gram-positive and gram-negative organisms. The duration of antibiotic therapy depends on the classification of the fracture. (See 'Antibiotics after open fracture' above.)