Chronic Osteomyelitis in Sacral Pressure Ulcers Management Review in QA Format

Key Points

• Most cases of reported osteomyelitis in stage 4 pressure ulcers are almost exclusively chronic and superficial (when depth is reported).
• Wound cultures or bone specimen cultures lack diagnostic sensitivity or specificity. Histopathological diagnosis is necessary to make an accurate diagnosis of osteomyelitis.
• Surgical debridement is the mainstay of treatment for chronic osteomyelitis. Duration of antibiotics in combination with surgical management is unclear but choice should consider bone and biofilm penetration.
• Shorter durations of antibiotics to treat the soft tissue infection should be considered in the absence of a concrete plan for wound coverage with primary closure or rotational flap.

Introduction

Pathogenesis

• The pathogenetic sequence can be divided into three major phases. This includes initial microbial invasion, whether exogenously or via a hematogenous route, followed by biofilm proliferation. Biofilm is a matrix of extracellular polymeric substances which provides protection from host defense mechanisms and antibiotics. This is followed by a local immune response to the bacterial biofilm with immunoglobulins and complements leading to activation of polymorphonuclear neutrophils (PMN) as well as production of proinflammatory cytokines. Finally, the bacterial invasion can release virulence factors affecting cell apoptosis, decreased proliferation of osteoblasts, and promotion of osteoclastogenesis. This ultimately leads to destruction of bone tissue [5,6].

• During early biofilm formation the microorganisms are mainly in an aerobic, planktonic state with a high metabolic activity. Once the biofilm is mature, organisms are mainly in an anaerobic state with significantly reduced metabolic activity [6]. They can also hide intracellularly, further limiting access. These properties define the chronicity of infection. Limited in vitro data exist regarding certain antibiotics with activity against bacteria in stationary phase and within biofilms [7].

• S. aureus biofilms secrete soluble molecules which directly impact osteoblasts by decreasing viability and osteogenic potential. S. aureus also secretes protein A (SpA) which is capable of binding to osteoblasts and inhibiting the proliferation and mineralization process. It also induces apoptosis in osteoblasts in vitro [6].

• Human beta-defensins are typically expressed in epithelial and bone tissue that play a key role as antimicrobial peptides and are part of the innate immunity. They are cationic peptides that interact with the anionic membrane of bacteria and encapsulated viral and fungal pathogens, leading to destruction of the cellular membrane and interference with intracellular functions. In extrapolating data from jaw osteomyelitis, Benedicta et al. determined osteomyelitis of the jaw to be a fairly rare event considering it is in a setting of exposed bone after tooth extraction that is exposed to a milieu of oral bacteria. There may be some genetic predisposition or immunosuppressive drug contribution leading to an insufficient immune response. This may lead to an insufficient production of certain beta-defensins. Thus, people on immunosuppressive therapy or with certain genetic predisposition may be more prone to developing chronic osteomyelitis [8].

• Both blood flow and neurological status are key local factors in determining progression to osteomyelitis. Local perfusion arterial networks provide nutrients and oxygen. This can be compromised by direct compression or shear forces that disrupt blood distribution. This combined with neurological insults that would normally allow for change in position to relieve the local pressure in a sensate patient leads to tissue ischemia and focal thrombosis [3].

• Local immune response to pathogens leads to infiltration by leukocytes which release enzymes and pro-inflammatory mediators to destroy the pathogens. This also leads to bone cells and matrix destruction as well as disruption of local blood flow. This results in an avascular area of necrotic, infected bone (sequestrum) and reactive, surrounding formation of new bound involucrum [3].

• Sequestrum is osseous tissue that lacks blood supply and therefore no longer has access to nutrients, to the immune system, or to system antibiotics. This acts essentially as a foreign body and a potential carrier for bacteria and biofilm. Surgical debridement is the only method for eradication [3].

Microbiology

• The most common organisms are Staphylococcus aureus, including MRSA, Staphylococcus epidermidis, Streptococcus, Pseudomonas, and enterobacteria as well as anaerobes [3]. Up to 30% of cultures can be polymicrobial [3]. However, even with limited data, most studies have found no association between treatment failure and culture positivity, so the utility of culture directed therapy in the setting of chronic osteomyelitis is unclear. Most of the failures were attributable to patient characteristics, wound management, and lack of source control [5,9,10].

• No, it is expected for bone exposed to the external environment to be colonized with bacteria and a wound swab, superficial or deep, is not sufficient to make a diagnosis of osteomyelitis [3].

• No, cultures of bone specimens are frequently contaminated with organisms residing in adjacent soft tissue [2].

• It is expected for exposed bone to be colonized with bacteria. For this reason, a simple bedside wound swab of a chronic ulcer is not helpful to diagnose the presence of osteomyelitis. Osteomyelitis is an infectious condition characterized by both pathogenic organisms and a corresponding inflammatory or immune response within the bone [3]. When cultures were positive, quantitative bone cultures yielded a similar number of bacterial isolates and a comparable range of bacterial concentration in patients with osteomyelitis vs. those without osteomyelitis [2].

Clinical Findings

• No, duration of exposed bone does not by default assist in diagnosis of osteomyelitis and bone that is exposed over a longer period of time is not necessarily more likely to have osteomyelitis [3,11]. See discussion below.

• Traditionally, it was thought that exposed bone defined osteomyelitis but as discussed above both pathogen and histologic examinations are required for the diagnosis [3]. This is important when assessing various studies as the study definition of osteomyelitis impacts the prevalence of osteomyelitis in its patient population.
• Turk et al. [12] used four distinct categories in autopsy patients with stage 4 sacral pressure ulcers.
  • Full-thickness soft-tissue disease without osseous involvement (seven patients);
  • Increased osteoclastic activity and reactive bone formation with inflammatory cells (seven patients);
  • Fibrotic osseous involvement without evidence of osteomyelitis (one patient);
  • Osteomyelitis (13 patients).
• Even in patients defined as having osteomyelitis, only half had cortical involvement with chronic osteomyelitis and the rest with small foci of acute on chronic osteomyelitis without extensive bone destruction. If the cases of superficial chronic osteomyelitis are excluded, then even fewer cases remain and the location of osteomyelitis in those cases were focal and are not diffuse or extensive.
• Other authors looking at this found similarly low rates of osteomyelitis when defined by histology [2,3,11]. While other authors have reported higher rates of osteomyelitis, the data is unclear regarding location of disease including whether it was focal or diffuse [3].
• Thus, chronically exposed sacral bone by itself does not define active osteomyelitis.

Lab Findings

• The most common tests include erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and alpha-1 acid glycoprotein [5]. They are usually elevated but have low sensitivity and specificity. They may be helpful to assist in early diagnosis of postoperative bone infection and to assess the effectiveness of antibiotics during the course of antibiotic therapy [5].

• Most of the studies have shown histologically confirmed chronic osteomyelitis as typically being superficial or focal without deep or diffuse involvement [3]. On histology mild infiltrates of lymphocytes and plasma cells were seen involving mostly the superficial bone. Acute inflammatory cells were not observed in bone and tissue stains did not show any bacteria. Osteomyelitis was always associated with pressure-related changes, including the presence of encasing fibrotic tissue with some degree of chronic inflammation and reactive bone formation [2].

Imaging

• Many studies reference Larson et al. [13], who showed a combined sensitivity of plain film and CT to be only 61% and specificity of 69%. However, osteomyelitis was defined based on positive bone culture rather than histopathology. Additionally, radiologic studies up to 1 year prior to surgery were included. However, Lewis et al. [14] showed, among 52 patients, the sensitivity and specificity of plain films and CT was 18% and 100% and 11% and 90%, respectively, compared to bone biopsy at surgical debridement. Histopathologic osteomyelitis was defined as both osteonecrosis and inflammatory infiltration of the bone.

• It can be difficult to distinguish chronic osteomyelitis from reactive bone formation or healed osteomyelitis [3]. Brunel et al., with 44 pressure ulcers, found that MRI scans when compared to bone biopsy and histology as the reference were highly sensitive (94.3%) but poorly specific (22%) [15].

• Sugarman et al. found bone scans to be highly sensitive but poorly specific for osteomyelitis [11]. However, this study evaluated only 28 pressure ulcers. Lewis et al. also did not recommend bone scanning to diagnose osteomyelitis associated with pressure ulcers [14].

• Daniali et al. compared 26 patients with MRI diagnosed osteomyelitis to 21 patients with osteomyelitis diagnosed by intraoperative bone culture positivity. Osteomyelitis diagnosed via MRI compared to culture growth from an intraoperative specimen found no difference in surgical technique, perioperative management, or patient outcomes [16].

• Most of the data regarding true sensitivity and specificity of imaging techniques are poor with small sample sizes and comparison to bone culture rather than histopathology. There does not seem to be a clear or proven benefit to obtaining any radiographs strictly for the diagnosis of chronic osteomyelitis in a sacral pressure ulcer. Logically, even if an imaging test revealed true osteomyelitis, antibiotics would not be initiated simply based on this result. Surgical management would have to be pursued including debridement, revascularization, and wound coverage at which time a reliable diagnosis can be made via bone biopsy and histopathology [3,13,16].

Management