Infectious complications of pressure-induced skin and soft tissue injury

INTRODUCTION — Pressure ulcers are localized areas of tissue necrosis that tend to develop when soft tissue is compressed between a bony prominence and an external surface for a prolonged period of time [1]. They are a significant problem in critically ill patients, older adults, and in persons with spinal cord injury.

Pressure ulcers cause pain, decrease quality of life, and lead to significant morbidity and prolonged hospital stays, in part due to complicating infection. Infected pressure ulcers are a common problem, occurring in 4 to 6 percent of nursing home patients in two series [1,2].

The infectious complications of pressure ulcers are reviewed in this topic. The epidemiology, pathogenesis, clinical manifestations, staging, prevention, and treatment of noninfected pressure skin and soft tissue injuries are discussed separately. (See "Epidemiology, pathogenesis, and risk assessment of pressure-induced skin and soft tissue injury" and "Prevention of pressure-induced skin and soft tissue injury" and "Clinical staging and general management of pressure-induced skin and soft tissue injury".)

Pressure ulcers that occur in the feet of patients with severe neuropathy and/or vascular insufficiency, often due to diabetes mellitus, are discussed separately. (See "Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities".)

CLASSIFICATION AND TERMINOLOGY — The National Pressure Injury Advisory Panel made changes to its classification in April 2016 and suggested using the terminology "pressure injury" instead of "pressure ulcer" to describe these wounds. The details of the terminology are discussed elsewhere. (See "Clinical staging and general management of pressure-induced skin and soft tissue injury", section on 'Definitions and terminology'.)

We use the term "pressure ulcer" for the specific circumstance where the integrity of the skin surface is disrupted.

PATHOGENESIS — Local factors that contribute to infection of pressure ulcers include breaks in the integrity of the skin barrier, pressure-induced edema and tissue damage, and contamination from contiguous dirty areas, such as from fecal incontinence. Among patients with spinal cord injury, the majority of pressure ulcers develop in areas adjacent to the ischium, sacrum, and greater trochanter. Other common sites in immobile individuals include the heels, back of the head, and elbows [3]. (See "Epidemiology, pathogenesis, and risk assessment of pressure-induced skin and soft tissue injury".)

Colonization — Pressure ulcer colonization by microorganisms precedes development of infection. The ulcer is first colonized with skin flora, which is rapidly replaced by bacteria from the local environment and the urogenital or gastrointestinal tracts, often from direct fecal contamination [4].

Pressure ulcers are generally associated with a bacteria count of <10² colony forming units (CFU) per gram of tissue if cared for and kept free of necrotic tissue [5]. Higher concentrations of bacteria in pressure ulcers may inhibit normal wound healing without inducing a host response, a state known as critical colonization [6]. In one study, delayed healing of pressure ulcers occurred when bacterial counts were >10⁵ CFU per gram of tissue [7]. Quantitative bacterial counts to identify critical colonization, however, are not widely used in clinical practice.

The presence of biofilms is also being increasingly recognized as a cause of delayed healing [8]. Bacterial biofilms may form on the necrotic and avascular debris in pressure ulcers. Bacteria within these biofilms are protected from normal host defenses and have markedly reduced susceptibility to antibacterial therapy [9].

MICROBIOLOGY — Pressure ulcers, even those that are not infected, are colonized with multiple organisms. Therefore, infection of pressure ulcers is typically caused by multiple organisms. Organisms causing infection, however, are not always identical to those colonizing an ulcer surface.

A retrospective study of 168 surgical samples evaluated the microbiology of infected pressure ulcers in 101 spinal cord injury patients [10]. The predominant organisms were Enterobacter (29 percent), staphylococci (28 percent), and Enterococcus faecalis (16 percent). In a separate study of pressure ulcer-related bacteremia in spinal cord injury patients, the major organisms were staphylococci (including methicillin-resistant Staphylococcus aureus [MRSA], methicillin-susceptible S. aureus, and coagulase-negative staphylococci), streptococci, Proteus mirabilis, and anaerobes [11].

DETERMINING EXTENT OF INFECTION — Infection occurs when microorganisms invade normal tissues, replicate, and overwhelm host immune defenses. The extent of local infection associated with a pressure ulcer is variable. Infection may be limited to the base of a superficial ulcer, result in a rim of surrounding cellulitis, or progress to extensive infection and necrosis of deeper structures (including fascia, muscle, and bone).

A poorly healing superficial ulcer with increased drainage but no surrounding erythema is suggestive of a limited superficial infection of the ulcer base; spreading erythema around an ulcer is suggestive of cellulitis; and a deep ulcer with necrotic muscle, undermined tissue, or sinus tracts is characteristic of deeper infection of the soft tissue or bone. Clinical assessment should focus on identifying these features. However, the full extent of local infection may not be apparent until surgical debridement when adequate visualization of underlying tissue is achieved.

Determining extent of infection is important since the approach to evaluation and management varies depending on whether infection is superficial or deep (involving either soft tissue or bone). These are outlined below. (See 'Superficial infection' below and 'Soft tissue infection' below and 'Osteomyelitis' below.)

SUPERFICIAL INFECTION — Limited superficial infection of a pressure ulcer typically presents as a poorly healing ulcer, often with increased exudate or wound drainage without associated soft tissue erythema. Systemic manifestations, including fever, chills, and malaise, are not typically seen; if present, they suggest either a deeper local infection or an unrelated infection. The diagnosis is based on clinical features alone.

Most pressure ulcers with superficial infection can be treated with local wound care followed by a one- to two-week trial of topical antiseptics to reduce bacterial concentrations (algorithm 1) [12]. Local wound care includes debridement of necrotic tissue, use of a moist wound dressing, nutritional support, and pressure relief. (See "Clinical staging and general management of pressure-induced skin and soft tissue injury".)

Topical antiseptic agents that reduce bacterial counts without damaging the wound include silver sulfadiazine 1% cream and other silver compounds [13,14]. We typically use silver sulfadiazine. Dressings impregnated with silver, honey, or cadexomer iodine are reasonable alternatives to topical antiseptics. Oher antiseptic agents such as peroxide and chlorhexidine gluconate are cytotoxic to human fibroblasts, may delay healing, and are not recommended [4]. Povidone-iodine or other iodine-containing products are often used, although reports on their potential harm are mixed [15,16]. As opposed to topical antiseptics, topical antibiotics are generally not recommended due to concerns of adverse drug reactions and development of antibiotic resistance [17]. (See "Basic principles of wound management", section on 'Antiseptics and antimicrobial agents'.)

The above recommended approach is designed to reduce the microbial burden and is consistent with guidelines from the National Pressure Injury Advisory Panel [17]. However, evidence supporting the benefit of topical antiseptics is inconclusive, as reflected in a systematic review of 12 trials [15]. Furthermore, a subsequent meta-analysis of 39 studies was unable to determine specific dressings or topical agents that were most likely to heal pressure ulcers, and it was not clear that any were more effective than saline gauze [18].

If there is no clinical improvement with optimal wound care and topical antiseptics, then the wound should be carefully examined, consideration given to other diagnoses, and further workup pursued. This could include a soft tissue biopsy for culture and evaluation for underlying osteomyelitis. (See 'Diagnosis' below.)

SOFT TISSUE INFECTION

Clinical features — Soft tissue infection of pressure ulcers may manifest as one or more of the following signs or symptoms depending on the depth of infection: warmth, erythema, induration, necrosis, tenderness, purulent discharge, and a foul odor [19].

●Cellulitis (ie, infection limited to the epidermis, dermis, and subcutaneous fat) associated with pressure ulcers typically presents as a limited area of erythema, warmth, induration, or tenderness of the surrounding skin or superficial subcutaneous tissue. Systemic signs of infection including fever, chills, and malaise may or may not occur. Mental status changes, such as confusion or lethargy, may be noted in older adult patients. The presence of leukocytosis is variable.

●Involvement of deeper tissue, such as fascia and muscle, may cause tissue discoloration or frank necrosis. In some cases, necrosis of deep tissue may extend to bony surfaces. Often, systemic signs of infection (eg, fever) or sepsis are present, and occasionally these are the only presenting signs, since changes in the surrounding soft tissue can be subtle.

Bloodstream infection, with or without sepsis, may occur in patients with pressure ulcer-related soft tissue infections.

Diagnostic evaluation

Clinical suspicion and presumptive diagnosis — Diagnosis of soft tissue infection of a pressure ulcer is based on clinical features and is straightforward in patients with typical findings of erythema, warmth, induration, fluctuance, tenderness, drainage, odor, or tissue necrosis (see 'Clinical features' above). A higher index of suspicion may be necessary in cases in which the ulcer and surrounding tissue have not significantly worsened but the patient has symptoms of systemic infection (eg, fever, chills, malaise, mental status changes, leukocytosis) or sepsis. In such cases, the possibility of a pressure ulcer-related infection should be suspected if evaluation does not identify an alternate source of infection. Additional workup involves microbiologic evaluation, as discussed below. (See 'Microbiologic evaluation' below.)

Conversely, exudate alone without additional signs or symptoms of soft tissue or systemic involvement should prompt consideration of a limited, superficial infection amenable to local debridement and wound care. (See 'Superficial infection' above.)

Microbiologic evaluation — Identification of causal pathogen(s) with antimicrobial susceptibility testing is essential to ensure optimal antibiotic therapy. A challenge of microbiologic evaluation is distinguishing between bacterial invasion and colonization since all pressure ulcers are colonized with microorganisms.

The most useful specimen for culture is a biopsy of the deepest tissue involved in the infection. Sampling techniques for cultures include the following:

●Deep tissue biopsy obtained during surgical debridement – Surgical debridement is often necessary for management of pressure ulcer-associated infections, and deep tissue biopsies should be obtained at the time of debridement. Cultures of the biopsied tissue should be sent promptly to the laboratory in appropriate containers for both aerobic and anaerobic cultures. Surgically obtained deep tissue biopsies remain the gold standard for wound culture because they prevent culture contamination by bypassing colonizing bacteria on the surface of the ulcer [10,20-22]. Details regarding the technique for obtaining surgical wound cultures are found elsewhere. (See "Surgical management of pressure-induced skin and soft tissue injuries", section on 'Debridement'.)

●Needle aspiration – Aspiration of material below the ulcer margin is a reasonable alternative to deep tissue biopsy in patients in whom surgery is not performed [20,21]. Local anesthesia should not be used during collection of the samples because of its potential antibacterial activity. Cultures from needle aspirations should be sent promptly to the laboratory in appropriate containers for both aerobic and anaerobic cultures.

In one study from 30 nursing home residents with infected pressure ulcers, excellent concordance was reported between cultures recovered by needle aspiration and those recovered by tissue biopsy; sensitivity and specificity of aspirate cultures were 93 and 99 percent, respectively [20]. However, another study of 72 pressure ulcers found that 43 percent of needle aspirations were positive for microorganisms compared to 63 percent of deep tissue biopsies, suggesting that needle aspiration may not be as highly sensitive as some studies suggest [23].

●Superficial swab cultures – Superficial swab cultures of pressure ulcers are not adequate to guide antibiotic therapy. Although swab cultures are frequently used to avoid pain or complications from aspiration or biopsy, results of swab cultures often reflect surface colonization rather than infection [21,22]. If performed, we only use results of swab cultures to determine the need for ongoing coverage of methicillin-resistant S. aureus (MRSA) if the patient is not otherwise known to be colonized and cultures of deeper samples are not available. For organisms other than MRSA, we do not use swab culture results to broaden or narrow empiric coverage.

Basing antibiotic regimens on swab cultures may result in inadequate or unnecessarily broad coverage. In one study, for example, the microbiology of 72 pressure ulcers was assessed by superficial swab and deep tissue biopsy [23]. More swab cultures were positive for microorganisms (96 percent) than deep tissue biopsies (63 percent), and the higher rate of positive cultures from swabs most likely represented colonization. In another study of 25 individuals with spinal cord injury and infected pressure ulcers, a 75 percent concordance rate was found between swab and biopsy cultures [22].

Additionally, swab cultures may not identify all infected pathogens identified by surgical biopsy. In a retrospective study of 77 patients who underwent both surgical biopsy and surface swab for culture, almost two-thirds of surgical specimens grew different bacterial species than surface swabs [10].

Identification of antimicrobial resistance among swab culture isolates may be useful in determining whether enhanced infection prevention and control interventions are necessary.

In addition to obtaining samples from the site of infection, blood cultures should be obtained during the initial evaluation of patients who have systemic symptoms such as fever.

Select radiologic imaging — Imaging is not necessary for evaluation of all patients with pressure ulcer-related soft tissue infections. However, in patients with systemic manifestations of infection, positive blood cultures, or indwelling medical devices (eg, cardiac valves, cardiac implantable electronic devices, vascular grafts, prosthetic joints), magnetic resonance imaging (MRI; or computed tomography if MRI is not feasible) may be useful in identifying underlying necrotic tissue or abscess requiring debridement that may represent an unrecognized focus of infection [20,23].

Imaging is also warranted when there is suspicion for underlying osteomyelitis. (See 'Clinical suspicion and initial evaluation' below.)

Management of soft tissue infection — Ulcers complicated by soft tissue infection require systemic antimicrobial therapy in addition to debridement of necrotic tissue.

Debridement — Full debridement of all necrotic tissue is essential to achieve control of associated soft tissue infection. For patients who present with sepsis, surgical debridement should be performed urgently. (See "Basic principles of wound management", section on 'Surgical'.)

Antibiotic therapy — Systemic antimicrobial therapy is warranted in patients with soft tissue infections (beyond a limited, superficial infection) associated with pressure ulcers. The anatomic location of the pressure ulcer (eg, sacrum, heel) and the setting of patient care are important considerations when making treatment decisions.

When possible, regimen selection should be based upon culture results, ideally cultures of deep tissue obtained at the time of debridement (see 'Microbiologic evaluation' above). Since culture results from debrided tissue are often not immediately available, initial antibiotic therapy is often empiric, with tailoring of antibiotics when results of culture and susceptibility testing become available.

●Mild cellulitis – In mild cases of cellulitis (eg, limited erythema of surrounding skin and no systemic signs of infection), a trial of empiric oral antibiotics is a reasonable initial step. An example of empiric oral regimen for cellulitis of the sacral/perineal area is as follows (other regimens that have similar spectra of activity are also appropriate):

•Amoxicillin-clavulanate (875/125 mg every 12 hours) plus either

Trimethoprim-sulfamethoxazole (two double-strength tablets every 12 hours) OR doxycycline (100 mg orally every 12 hours)

For individuals unable to tolerate amoxicillin-clavulanate, levofloxacin (500 to 750 mg orally once daily) can be substituted for amoxicillin-clavulanate in the above regimen.

Mild pressure injury-associated cellulitis not involving the sacrum or perineal area (eg, heel, extremity, skull) can often be treated like uncomplicated cellulitis. Further discussion of treatment of cellulitis is found elsewhere. (See "Acute cellulitis and erysipelas in adults: Treatment", section on 'Acute cellulitis'.)

●Severe cellulitis, deep infection, sepsis – In patients with more severe cellulitis and deeper soft tissue infection (eg, involving fascia and muscle) or systemic manifestations of sepsis, we suggest initial empiric therapy with parenteral antibiotics. Examples of empiric parenteral regimens include the following (other regimens that have similar spectra of activity are also appropriate):

•Vancomycin (15 to 20 mg/kg intravenously every 8 to 12 hours) or other MRSA-active agent (table 1);

PLUS

•Ceftazidime (2 g every eight hours) or cefepime (2 g every eight hours);

PLUS

•Metronidazole (500 mg intravenously or orally every eight hours). Given its high bioavailability, metronidazole may be given orally instead of intravenously if there is no concern for poor gastrointestinal absorption in the patient.

Since many patients with pressure ulcers live in a hospital, nursing home, or institutional setting, antibiotic-resistant microorganisms are often responsible for their infections. Knowledge of antimicrobial resistance patterns in an institution is important in selecting therapy. For patients with sepsis who are known or suspected of having an infection due to an organism with extended-spectrum beta-lactamase (ESBL), using an empiric carbapenem (eg, meropenem 1 g intravenously every eight hours) in conjunction with vancomycin is reasonable. Additionally, empiric antipseudomonal coverage should be included for most patients, especially those whose ulcers grew Pseudomonas species on prior cultures. Of the above regimens, those that provide pseudomonal coverage contain ciprofloxacin (dosed at 750 mg every 12 hours), levofloxacin (dosed at 750 mg every 24 hours), ceftazidime, cefepime, or meropenem. For infections due to multidrug-resistant organisms, consultation with an infectious diseases specialist may be helpful. More information regarding management of ESBL and pseudomonal infections is found elsewhere. (See "Extended-spectrum beta-lactamases", section on 'Treatment options' and "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on 'Antibiotics with antipseudomonal activity'.)

Transition to oral therapy is appropriate when the patient has clinically responded with resolution of systemic signs of infection, regression of surrounding erythema, and improvement in the appearance of soft tissue. In some cases of limited deeper tissue involvement, initial antibiotics may be administered orally in conjunction with tissue debridement. Oral therapy options are outlined above. A lack of timely response to therapy should prompt consideration of requiring debridement and/or a need to alter antibiotics to appropriately target the infecting pathogen(s).

Antibiotics should be narrowed when culture and susceptibility results from tissue debridement are available. Data on optimal duration of treatment are limited. It should be based on rate of response, area affected, and whether there was associated bloodstream infection, and is typically 5 to 14 days.

We generally treat skin and soft tissue infections associated with pressure ulcers with broader spectrum antibiotic regimens than routine cellulitis given the polymicrobial nature of these infections. There are no trials evaluating the optimal systemic antibiotic regimen for pressure ulcer-related infection. Based on the microbiology, we typically include empiric coverage for MRSA, streptococci, enteric gram-negative organisms, and anaerobes. For patients with severe infection, we aim to empirically cover more resistant enteric gram-negative organisms because of risk of resistance associated with the health care exposures that most patients with pressure ulcers have. (See 'Microbiology' above.)

OSTEOMYELITIS — Osteomyelitis is a frequent complication of infected pressure ulcers and has been reported in 17 to 32 percent of patients [24,25].

Clinical features — Clinical features of osteomyelitis in the setting of a pressure ulcer are variable and often present with a poorly healing wound. There may be visible bone that may be soft on palpation, with or without associated soft tissue infection. Some patients may present with signs or symptoms of systemic infection (eg, fever, sepsis). However, delayed wound healing is occasionally the only sign of underlying osteomyelitis. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell count may be elevated, but a normal value does not rule out osteomyelitis. Although rare in resource-abundant nations where early diagnosis and initiation of antimicrobial therapy in patients with osteomyelitis typically occur, pathologic fracture can complicate osteomyelitis [26]. Further details on features of osteomyelitis are found elsewhere. (See "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)

Diagnosis

Clinical suspicion and initial evaluation — Osteomyelitis in the setting of pressure ulcers should be suspected when a chronic ulcer fails to heal, has exposed bone, or the patient experiences recurrent soft tissue infections associated with a chronic ulcer. Flap reconstruction failure, sepsis, and bloodstream infection may also be indicators of unrecognized osteomyelitis [27]. A complete blood count, ESR, CRP, and blood cultures should be obtained; these results, however, can be normal in patients with biopsy-proven osteomyelitis. Positive blood cultures should heighten suspicion of an underlying infection at the ulcer site and can provide microbiologic information to help guide therapy. Abnormal inflammatory markers can support the diagnosis. Nevertheless, patients with clinically suspected osteomyelitis should generally undergo further evaluation with magnetic resonance imaging (MRI). Radiologic findings consistent with osteomyelitis should generally prompt bone biopsy to confirm the diagnosis. (See 'Radiologic imaging' below and 'Bone biopsy' below and "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Diagnosis'.)

Although suggestive, exposed bone does not confirm a diagnosis of osteomyelitis in pressure ulcers. Several reports have found that stage 4 ulcers with exposed bone were consistent with histology-confirmed osteomyelitis in fewer than half of cases, with the rate in one report being as low as 17 percent [24,25,28]. Duration of the ulcer may also not be a reliable indication of an underlying diagnosis of osteomyelitis [24].

A diagnosis of osteomyelitis cannot reliably be made on the basis of clinical findings alone in patients with pressure ulcers. This issue was addressed in a study of 36 patients with pressure ulcers who were evaluated for osteomyelitis [25]. The clinical judgment of clinicians was accurate in diagnosing biopsy-proven osteomyelitis in only 56 percent of patients. There were no clinical signs or symptoms that correlated with a final diagnosis of osteomyelitis, including the presence of fever, bone exposure, duration of the ulcer, purulent drainage, leukocytosis, or elevated ESR.

Radiologic imaging — In patients with suspected osteomyelitis associated with pressure ulcers, we obtain MRI to assess for evidence of bony involvement; imaging can also provide useful anatomic detail in planning for surgical debridement, since it may show abscesses that need drainage. Findings consistent with osteomyelitis on radiographic imaging should generally prompt bone biopsy for histology to confirm the diagnosis and cultures to identify the infecting organism(s) and antibiotic susceptibilities. This is largely the same as the approach to osteomyelitis in general. (See "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Clinical approach'.)

If an MRI is performed and is negative for osteomyelitis, then pursuit of bone biopsy is not necessary; the patient should be evaluated for other factors that could be responsible for a nonhealing ulcer, such as need for alternative wound care management and/or additional debridement.

Use and selection of radiologic imaging studies in the diagnosis of osteomyelitis and radiographic findings indicative of osteomyelitis are discussed separately (see "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis"). However, there are specific considerations in making decisions on imaging studies in patients with suspected osteomyelitis related to pressure ulcer:

●Although MRI is the radiologic test of choice for evaluating potential osteomyelitis, and thus is our preferred modality for patients with suspected pressure ulcer-associated osteomyelitis, reports on its accuracy in this setting are varied. One study with 44 paralyzed patients revealed a high sensitivity and specificity of 98 percent and 89 percent, respectively, as compared with bone biopsy [29]; however, another study with 34 patients with 44 pressure ulcers showed a specificity of only 22 percent despite a high sensitivity of 94 percent [30]. This highlights the importance of histologic examination from a bone biopsy to definitively diagnose pressure ulcer-associated osteomyelitis.

●Plain radiography has a limited role in the diagnosis of pressure ulcer-associated osteomyelitis, since bone changes due to osteomyelitis may not be distinguishable from those due to pressure alone.

Bone biopsy — When osteomyelitis is suspected in patients with pressure ulcers, every effort should be made to obtain a bone biopsy, with histopathologic and microbial analysis, in order to confirm the diagnosis of osteomyelitis and guide the selection of antibiotic therapy. At least two specimens should be obtained: one for culture (for aerobic and anaerobic cultures) and the other for histopathology. No other modality (eg, radiographic study, swab cultures) or clinical feature (eg, exposed bone) can definitively make the diagnosis of osteomyelitis or inform antimicrobial decisions.

When obtaining a bone biopsy, we suggest withholding antimicrobial therapy for clinically stable patients until after bone samples have been obtained. Antibiotics given prior to bone biopsy may affect culture results. More information about the technique and timing of bone biopsy in relation to antibiotics is found above and elsewhere. (See "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Bone biopsy' and 'Microbiologic evaluation' above.)

Management of osteomyelitis

Site and coordination of care — Optimal management of individuals with pressure ulcer-associated osteomyelitis requires a multidisciplinary team, including surgical, infectious diseases, and wound care specialists. From the outset, the treatment team should collaborate with each patient to create an individualized treatment plan that meets the patient's goals of care.

Treatment courses are often prolonged and complex. Outpatient management can present challenges, including coordination of team members, home provision of wound care and antimicrobials, and transportation for patients who often have limited mobility. Creation of multidisciplinary clinics that include each type of specialist can facilitate communication among team members and streamline care for patients [31].

Hospitalization is generally reserved for patients with sepsis, extensive cellulitis, or deep soft tissue infection. The presence of a large or deep ulcer with or without osteomyelitis in an otherwise stable patient is not necessarily an indication for hospitalization.

Sepsis in patients with suspected or confirmed osteomyelitis — In patients with large pressure ulcers, exposed bone, or chronic osteomyelitis, sepsis may be erroneously attributed to osteomyelitis. Such individuals are often at risk of sepsis from multiple other etiologies (eg, urinary tract infection, pneumonia [11,32]). If examination of the wound does not reveal soft tissue infection, osteomyelitis should not be presumed to be the cause of sepsis. In this situation, we recommend a thorough workup for alternative etiologies which may include imaging to rule out deep abscess. When soft tissue infection or abscess is present, urgent antimicrobial therapy and surgical debridement are indicated as outlined elsewhere. (See 'Management of soft tissue infection' above.)

When sepsis is unrelated to underlying osteomyelitis, attention can turn to treating the osteomyelitis once the acute illness has resolved.

Long-term management — Long-term cure has been described with proper wound care and a combined medical and surgical approach, although data are limited on the overall success rate [33-35].

Wound management — Proper wound management is critical for successful treatment of pressure injury-associated osteomyelitis. Fundamental components include redistributing pressure, using appropriate dressings, preventing contamination, and optimizing nutrition. Additional adjunctive therapies of uncertain benefit include negative pressure wound therapy, fecal/urinary diversion, and others. Wound management is discussed in detail elsewhere. (See "Clinical staging and general management of pressure-induced skin and soft tissue injury", section on 'General care' and "Clinical staging and general management of pressure-induced skin and soft tissue injury", section on 'General wound management' and "Surgical management of pressure-induced skin and soft tissue injuries".)

Surgical therapy — To achieve long-term cure, surgical intervention is thought to be necessary. Optimally, surgical intervention achieves three goals: removal of infected tissue, collection of bone sample for histopathology and culture, and complete wound closure. Without complete wound closure, the patient remains at risk for recurrent osteomyelitis.

Surgical debridement supports wound healing by creating a wound bed that allows for the formation of granulation tissue over time. With careful post-operative wound management, wound closure can often be achieved. Sometimes, surgical tissue reconstruction using flaps to cover the ulcer can promote wound closure. Surgeons may elect to perform flap reconstruction during the initial debridement or in a subsequent surgery.

Despite the benefits of surgery, some patients may be best served by undergoing surgery without curative intent or foregoing surgery altogether. Patient characteristics and technical issues are considered when determining whether and which type of surgical intervention is appropriate:

●Patients' comorbidities can lead to poor surgical outcomes and may preclude surgical intervention. Such conditions are common in patients with pressure ulcer-associated osteomyelitis and should be addressed prior to surgery if possible.

●Technical factors may deter a surgeon from operating with curative intent, including the extent of necessary debridement, potential anatomic complications, and whether the size and location of the wound bed will allow eventual healing or reconstruction. Surgeons may elect to operate even if wound closure cannot be accomplished, particularly when surgical debridement is necessary to treat or prevent soft tissue infection.

Surgical management of pressure-induced injuries is discussed in further detail elsewhere. (See "Surgical management of pressure-induced skin and soft tissue injuries".)

Antimicrobial therapy — Our approach to antimicrobial therapy in this setting depends on the goals of care, quality of wound management, and extent of surgical debridement. When making antimicrobial decisions, the potential benefits of antibiotics must be weighed against potential harms, including side effects, Clostridioides difficile infection, and emergence of resistant organisms.

Few studies and no controlled trials are available to guide antimicrobial treatment decisions for these individuals. Given the dearth of data and the complexity of these patients, management varies considerably, even among infectious diseases specialists [36].

Timing and regimen selection — To optimize culture results, unless a patient is septic, we typically withhold antimicrobial therapy until after bone samples have been collected [37]. (See 'Bone biopsy' above.)

Once specimens have been collected, we initiate empiric therapy that targets methicillin-resistant S. aureus (MRSA), streptococci, enteric gram-negative organisms, and anaerobes. Typical regimens are the same as those described above for patients with pressure ulcer-associated deep soft tissue infection. (See 'Antibiotic therapy' above.)

Once cultures and sensitivities are available, antibiotics should be narrowed to target recovered pathogens. Additionally, because some anaerobes do not reliably grow in culture, we add metronidazole for the full treatment course if a narrowed regimen omits anaerobic coverage. Except for maintaining anaerobic coverage, specific regimens for culture-directed therapy follow the same principles as treatment of chronic osteomyelitis and are discussed in detail elsewhere (see "Nonvertebral osteomyelitis in adults: Treatment", section on 'Definitive therapy'). For individuals whose cultures do not grow a pathogen, we continue broad-spectrum antibiotics except we discontinue empiric MRSA coverage (eg, vancomycin).

We typically use parenteral antibiotics for these individuals. If parenteral therapy is challenging or too burdensome and isolated organisms are susceptible to highly bioavailable antibiotics (eg, fluoroquinolones), an oral antibiotic regimen is a reasonable alternative. Emerging data suggest that oral antibiotics may be adequate therapy for osteomyelitis. Details regarding oral therapy for osteomyelitis are discussed elsewhere. (See "Nonvertebral osteomyelitis in adults: Treatment", section on 'Systemic therapy'.)

Duration of therapy — No clinical trial data are available to define the optimal duration of therapy for pressure injury-associated osteomyelitis. Based on our experience, we tailor duration of therapy depending on whether surgery is performed and the underlying intent of surgery:

●Individuals who undergo full surgical debridement with anticipated wound closure – If the surgical team believes thorough debridement of all infected tissue and complete wound closure are achievable, antibiotic therapy should aim to cure any residual infection that may remain after debridement. For such patients, we suggest six weeks of antibiotics following debridement, as in the general approach to chronic osteomyelitis (see "Nonvertebral osteomyelitis in adults: Treatment", section on 'Residual infected bone present'). The timing of wound closure or flap placement does not impact the duration of antibiotics (ie, we do not prolong antibiotics past the six-week mark if closure is delayed).

●Individuals who undergo surgical debridement without anticipated wound closure – These patients typically have wounds so large or deep that the surgeon believes closure is not an option; in some cases debridement may be incomplete.

For some such patients, sustained resolution may be achievable with adequate debridement, pressure redistribution, and proper wound care. In these patients, we suggest continuing antibiotics for a full six-week course, particularly if they have improvement of the wound during therapy.

However, in some patients, sustained resolution seems unlikely despite antibiotics, often because of ongoing pressure injury, contamination of the wound (eg, from stool), or residual necrotic bone that was not able to be debrided. In these patients, we typically discontinue antibiotics once residual soft tissue infection has resolved, generally after 5 to 14 days.

●Individuals who undergo no surgical debridement – Surgeons and patients may elect not to undergo surgery or bone biopsy, often when the risk of adverse outcomes from surgery is elevated due to comorbidities or frailty. For these patients, we typically discontinue antibiotics once sepsis and soft tissue infection have resolved (generally 5 to 14 days). These patients are at high risk for recurrence of sepsis or soft tissue infection, and discussion between treatment teams and patients is imperative to ensure that treatment plans match each patient's goals of care. Further discussion of management of recurrent and refractory infection is found below. (See 'Refractory or recurrent osteomyelitis' below.)

This approach balances the likelihood of meaningful benefit from prolonged courses of antibiotics against the attendant risks. Specific risks from prolonged antibiotics include C. difficile infections which can have high morbidity and increase fecal contamination of the wound. Additionally, inadequately debrided infections that are exposed to prolonged antibiotics are likely to develop antibiotic resistance, making treatment of future infections much more difficult.

Although data are limited, the likelihood of benefit seems greatest when the nidus of infection is eliminated and the conditions that predisposed to the osteomyelitis are reversed or reversible.

Monitoring during antimicrobial treatment — Assessing clinical response to treatment primarily involves regular examination of the wound and exposed bone.

Like the general approach for chronic osteomyelitis, we obtain serum inflammatory markers (ESR and CRP) at the beginning and end of parenteral therapy. We do not routinely monitor weekly serum inflammatory markers during parenteral antimicrobial therapy. However, if there is clinical suspicion for treatment failure, inflammatory markers (in conjunction with clinical examination and radiographic imaging) may help to guide further management. Routine follow-up imaging is generally not recommended for monitoring response. Further detail regarding monitoring of therapy can be found elsewhere. (See "Nonvertebral osteomyelitis in adults: Treatment", section on 'Monitoring during treatment' and "Nonvertebral osteomyelitis in adults: Treatment", section on 'Evaluation at the end of treatment'.)

Monitoring for medication toxicity is warranted for patients on long-term parenteral antibiotic therapy; specific testing depends on the agents used (table 2).

Conservative (non-antibiotic) management in select patients — Some patients who have pressure-induced injuries live comfortably with stable untreated osteomyelitis. For these patients, we do not pursue either surgery or antibiotic therapy and instead continue proper wound management and follow closely for signs of worsening. The decision to pursue this approach is made in discussion with the patient with consideration of the benefits and risks of therapy.

Refractory or recurrent osteomyelitis — Unfortunately, refractory or recurrent osteomyelitis is not uncommon in individuals with pressure injuries.

Multiple factors should be addressed in individuals whose osteomyelitis recurs or fails to respond to therapy. Common causes include inability to relieve pressure on the wound, inadequate debridement, ongoing wound contamination, poor wound care, and underlying comorbidities that lead to poor wound healing. Rising inflammatory markers or progression of disease on imaging may help determine whether aggressive intervention is necessary versus improved wound care.

We suggest avoiding reinitiation of prolonged antibiotic therapy for osteomyelitis if other contributing conditions are not addressed. Associated soft tissue infection should be treated following the same protocols described above. (See 'Antimicrobial therapy' above.)

Without adequate debridement, wound closure, and wound management, continuous or repeated courses of antibiotics can be more harmful than helpful. Of particular concern in this population is the role that antibiotics play in selecting for resistant organisms and C. difficile.

If retreatment is considered, we suggest obtaining a new bone sample for histopathology and culture to guide direct antibiotic therapy. In an observational study of 44 episodes of recurrent pressure ulcer-associated infections, only six (14 percent) of recurrences were found to be caused by the original pathogen on repeat biopsy [38].

Tissue biopsy is also helpful for detection of concurrent carcinoma which is a rare complication of pressure injuries and chronic osteomyelitis. Physical examination and imaging may not be able to differentiate carcinoma from refractory infection. Further discussion regarding this complication is found below. (See 'Concurrent carcinoma' below.)

OTHER COMPLICATIONS

Bloodstream infection and other infections — Patients with pressure ulcers may develop bloodstream infection with or without clinical signs of sepsis (eg, unexplained fever, tachycardia, hypotension, and/or deterioration in mental status). The frequency of bloodstream infection and/or sepsis in patients with pressure ulcers is illustrated by the following retrospective studies in different patient populations:

●In 123 episodes of bloodstream infection in a chronic spinal cord injury population, the source was the decubitus ulcer in 21 (17 percent) [11].

●In 44 patients with HIV and pressure ulcers, 12 had bloodstream infection; in 6, the source was the pressure ulcer [32].

Other infectious complications of pressure ulcers include septic arthritis, endocarditis, and meningitis [29,39].

Concurrent carcinoma — Cases of carcinoma, including squamous cell carcinoma and sarcoma, at the site of chronic osteomyelitis have been reported, mostly in individuals with osteomyelitis of an extremity [40-43]. Histopathologic examination of a tissue biopsy can differentiate infection from carcinoma. The diagnosis should be considered in individuals whose infection unexpectedly fails to improve.

INFECTION CONTROL — Most pressure ulcers occur in institutionalized patients with spinal cord injuries or nursing home residents. Infection control is important in limiting the spread of resistant microorganisms by cross-contamination and in reducing colonization and infection rates of pressure ulcers. Recommendations include:

●Follow universal precautions that are appropriate for the health care setting and the patient's condition.

●Use clean gloves for each patient. When treating multiple ulcers on the same patient, attend to the most contaminated ulcer last (eg, in the perianal region). Remove gloves and wash hands between patients.

●Use sterile instruments to debride pressure ulcers.

●Use clean dressings, rather than sterile ones, to treat pressure ulcers, as long as dressing procedures comply with institutional infection control guidelines.

●Clean dressings may also be used in the home setting.

●Special isolation precautions for patients infected or colonized with methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococci, or extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacilli.

General issues of infection control are discussed in detail elsewhere. (See "Infection prevention: Precautions for preventing transmission of infection" and "Infection prevention: General principles" and "Infection prevention: General principles", section on 'General principles'.)

PREVENTION — The best strategy for preventing infections of pressure ulcers is to prevent formation of the pressure ulcer. This is one of the most important aspects of care of the poorly mobile or immobile patient. Efforts to minimize the extrinsic risk factors of pressure, friction, shear stress, and moisture are pivotal. Health care workers and family members who provide care should be educated on ways to reduce these extrinsic factors [19]. (See "Prevention of pressure-induced skin and soft tissue injury".)

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

●Microbiology – Infections associated with pressure ulcers are usually polymicrobial. The most common organisms include staphylococci, streptococci, enterococci, Enterobacter, Proteus, and anaerobes. (See 'Microbiology' above.)

●Clinical presentation and approach to diagnosis – Clinical presentation and diagnosis vary based on the depth of infection.

•Superficial infection – Superficial infection typically presents as a poorly healing ulcer with increased drainage but no surrounding erythema or systemic symptoms (eg, fever). (See 'Superficial infection' above.)

•Cellulitis – Cellulitis involves the skin structures (ie, epidermis, dermis, and subcutaneous fat) surrounding the ulcer. Clinical findings include erythema, warmth, induration, or tenderness with or without systemic symptoms. (See 'Clinical features' above and 'Diagnostic evaluation' above.)

•Deep soft tissue infection – Deep infection involves fascia or muscle, or abscess formation below the subcutaneous fat. Clinical findings may include tissue discoloration or necrosis, undermined tissue, or sinus tracts, with or without systemic symptoms or exposed bone. Magnetic resonance imaging (MRI) may be helpful for determining extent of infection (algorithm 1). (See 'Clinical features' above and 'Diagnostic evaluation' above.)

•Osteomyelitis – Presentation ranges from a poorly healing wound to exposed necrotic bone with or without systemic illness or surrounding soft tissue infection. MRI is useful to assess for evidence of osteomyelitis and extent of infection. Bone biopsy with culture and histopathology is necessary to make a definitive diagnosis (algorithm 1). (See 'Clinical features' above and 'Diagnosis' above.)

●Management – Optimal treatment requires a multidisciplinary team and careful consideration of the patient's goals of care.

•Wound care – For all infections, proper wound care is critical. (See 'Wound management' above.)

•Surgical intervention – Regardless of the depth of infection, surgical debridement is necessary if abscess or necrotic infected tissue is present. When surgery is performed, biopsies of the deepest area of infection should be sent for culture and histopathology. Wound closure, often by placement of a flap, is sometimes attempted to minimize recurrence (algorithm 1). (See 'Surgical therapy' above and 'Debridement' above.)

•Antimicrobial therapy – Empiric antimicrobial selection depends on the depth of infection and severity of illness. Once culture results return, antimicrobials are narrowed (algorithm 1).

-Superficial infection – For patients with superficial infection, we suggest a topical antimicrobial agent (eg, silver sulfadiazine 1% cream) for one to two weeks (Grade 2C). (See 'Superficial infection' above.)

-Cellulitis, deep soft tissue infection, or osteomyelitis – For empiric treatment, appropriate regimens are active against methicillin-resistant Staphylococcus aureus (MRSA), streptococci, enteric gram-negative organisms, and anaerobes.

For mild cellulitis without systemic symptoms, we suggest oral antibiotic treatment with amoxicillin-clavulanate plus either trimethoprim-sulfamethoxazole or doxycycline (Grade 2C). (See 'Antibiotic therapy' above.)

For severe cellulitis, deep soft tissue infection, or osteomyelitis, we suggest parenteral vancomycin plus ceftazidime or cefepime plus metronidazole (Grade 2C). If no osteomyelitis is present, transition to oral therapy is appropriate once clinical improvement has occurred. (See 'Antibiotic therapy' above and 'Timing and regimen selection' above.)

●Duration of therapy – The typical duration of antibiotics is 5 to 14 days for infection limited to the soft tissue and six weeks for osteomyelitis; the goal of treatment in these cases is sustained resolution of the infection.

However, for patients with osteomyelitis who do not undergo adequate debridement or wound closure and cannot mitigate ongoing pressure at the ulcer site, we suggest stopping antibiotics once any soft tissue infection has resolved rather than completing a full six-week course (Grade 2C). In such patients, sustained resolution of osteomyelitis is unlikely, and the risks of prolonged antibiotic therapy may outweigh the benefit. (See 'Antibiotic therapy' above and 'Timing and regimen selection' above.)

●Recurrent or refractory infection – In these situations, addressing predisposing factors (eg, ongoing pressure) and undebrided infected tissue is paramount to management. The antimicrobial approach is the same as that for initial infection. (See 'Management of soft tissue infection' above and 'Refractory or recurrent osteomyelitis' above.)